<?xml version="1.0" encoding="utf-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "http://dtd.nlm.nih.gov/publishing/2.0/journalpublishing.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="review-article" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JMIR</journal-id>
      <journal-id journal-id-type="nlm-ta">J Med Internet Res</journal-id>
      <journal-title>Journal of Medical Internet Research</journal-title>
      <issn pub-type="epub">1438-8871</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v21i7e14676</article-id>
      <article-id pub-id-type="pmid">31267981</article-id>
      <article-id pub-id-type="doi">10.2196/14676</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Review</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Virtual Patient Simulations in Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Eysenbach</surname>
            <given-names>Gunther</given-names>
          </name>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Marusic</surname>
            <given-names>Ana</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Liaw</surname>
            <given-names>Sok Ying</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Sobocan</surname>
            <given-names>Monika</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="author" id="contrib1">
          <name name-style="western">
            <surname>Kononowicz</surname>
            <given-names>Andrzej A</given-names>
          </name>
          <degrees>MSc, PhD</degrees>
          <xref rid="aff01" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0003-2956-2093</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib2">
          <name name-style="western">
            <surname>Woodham</surname>
            <given-names>Luke A</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff02" ref-type="aff">2</xref>
          <xref rid="aff03" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0003-4170-2925</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib3">
          <name name-style="western">
            <surname>Edelbring</surname>
            <given-names>Samuel</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff03" ref-type="aff">3</xref>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff05" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0002-1110-0782</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib4">
          <name name-style="western">
            <surname>Stathakarou</surname>
            <given-names>Natalia</given-names>
          </name>
          <degrees>MSc</degrees>
          <xref rid="aff03" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0002-7159-5801</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib5">
          <name name-style="western">
            <surname>Davies</surname>
            <given-names>David</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff06" ref-type="aff">6</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0002-7573-2762</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib6">
          <name name-style="western">
            <surname>Saxena</surname>
            <given-names>Nakul</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff07" ref-type="aff">7</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0002-6717-4975</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib7">
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>Lorainne</given-names>
          </name>
          <degrees>MD, MSc, PhD</degrees>
          <xref rid="aff08" ref-type="aff">8</xref>
          <xref rid="aff09" ref-type="aff">9</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0001-8414-7664</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib8">
          <name name-style="western">
            <surname>Carlstedt-Duke</surname>
            <given-names>Jan</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff10" ref-type="aff">10</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0001-7784-5296</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib9" corresp="yes">
          <name name-style="western">
            <surname>Car</surname>
            <given-names>Josip</given-names>
          </name>
          <degrees>MD, PhD, FRCPE, FFPH</degrees>
          <xref rid="aff11" ref-type="aff">11</xref>
          <address>
            <institution>Centre for Population Health Sciences</institution>
            <institution>Lee Kong Chian School of Medicine</institution>
            <institution>Nanyang Technological University</institution>
            <addr-line>11 Mandalay Road, Clinical Science Building</addr-line>
            <addr-line>Singapore,</addr-line>
            <country>Singapore</country>
            <phone>65 6340 2480</phone>
            <email>josip.car@ntu.edu.sg</email>
          </address>
          <xref rid="aff12" ref-type="aff">12</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0001-8969-371X</ext-link>
        </contrib>
        <contrib contrib-type="author" id="contrib10">
          <name name-style="western">
            <surname>Zary</surname>
            <given-names>Nabil</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff13" ref-type="aff">13</xref>
          <xref rid="aff14" ref-type="aff">14</xref>
          <ext-link ext-link-type="orcid">http://orcid.org/0000-0001-8999-6999</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution>Department of Bioinformatics and Telemedicine, Jagiellonian University Medical College</institution>
        <addr-line>Kraków</addr-line>
        <country>Poland</country>
      </aff>
      <aff id="aff02">
        <label>2</label>
        <institution>Institute of Medical and Biomedical Education, St George’s, University of London</institution>
        <addr-line>London</addr-line>
        <country>United Kingdom</country>
      </aff>
      <aff id="aff03">
        <label>3</label>
        <institution>Department of Learning, Informatics, Management and Ethics, Karolinska Institutet</institution>
        <addr-line>Stockholm</addr-line>
        <country>Sweden</country>
      </aff>
      <aff id="aff04">
      <label>4</label>
      <institution>Department of Medical and Health Sciences</institution>
      <institution>Linköping University</institution>  
      <addr-line>Linköping</addr-line>
      <country>Sweden</country></aff>
      <aff id="aff05">
      <label>5</label>
      <institution>Learning and Professional Development Group</institution>
      <institution>School of Health Sciences</institution>  
      <institution>Örebro University</institution>  
      <addr-line>Örebro</addr-line>
      <country>Sweden</country></aff>
      <aff id="aff06">
        <label>6</label>
        <institution>Warwick Medical School, University of Warwick</institution>
        <addr-line>Coventry</addr-line>
        <country>United Kingdom</country>
      </aff>
      <aff id="aff07">
        <label>7</label>
        <institution>Health Services and Outcomes Research, National Healthcare Group</institution>
        <addr-line>Singapore</addr-line>
        <country>Singapore</country>
      </aff>
      <aff id="aff08">
        <label>8</label>
        <institution>Family Medicine and Primary Care, Lee Kong Chian School of Medicine, Nanyang Technological University</institution>
        <addr-line>Singapore</addr-line>
        <country>Singapore</country>
      </aff>
      <aff id="aff09">
        <label>9</label>
        <institution>Department of Primary Care and Public Health, School of Public Health, Imperial College London</institution>
        <addr-line>London</addr-line>
        <country>United Kingdom</country>
      </aff>
      <aff id="aff10">
        <label>10</label>
        <institution>President’s Office, Nanyang Technological University</institution>
        <addr-line>Singapore</addr-line>
        <country>Singapore</country>
      </aff>
      <aff id="aff11">
      <label>11</label>
      <institution>Centre for Population Health Sciences</institution>
      <institution>Lee Kong Chian School of Medicine</institution>  
      <institution>Nanyang Technological University</institution>  
      <addr-line>Singapore</addr-line>
      <country>Singapore</country></aff>
      <aff id="aff12">
        <label>12</label>
        <institution>Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London</institution>
        <addr-line>London</addr-line>
        <country>United Kingdom</country>
      </aff>
      <aff id="aff13">
      <label>13</label>
      <institution>Games for Health Innovations Centre</institution>
      <institution>Lee Kong Chian School of Medicine</institution>  
      <institution>Nanyang Technological University</institution>  
      <addr-line>Singapore</addr-line>
      <country>Singapore</country></aff>
      <aff id="aff14">
        <label>14</label>
        <institution>Mohammed Bin Rashid University of Medicine and Health Sciences</institution>
        <addr-line>Dubai</addr-line>
        <country>United Arab Emirates</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Josip Car 
        <email>josip.car@ntu.edu.sg</email></corresp>
      </author-notes>
      <pub-date pub-type="collection"><month>07</month><year>2019</year></pub-date>
      <pub-date pub-type="epub">
        <day>02</day>
        <month>07</month>
        <year>2019</year>
      </pub-date>
      <volume>21</volume>
      <issue>7</issue>
      <elocation-id>e14676</elocation-id>
      <!--history from ojs - api-xml-->
      <history>
        <date date-type="received">
          <day>10</day>
          <month>5</month>
          <year>2019</year>
        </date>
        <date date-type="rev-request">
          <day>31</day>
          <month>5</month>
          <year>2019</year>
        </date>
        <date date-type="rev-recd">
          <day>6</day>
          <month>6</month>
          <year>2019</year>
        </date>
        <date date-type="accepted">
          <day>8</day>
          <month>6</month>
          <year>2019</year>
        </date>
      </history>
      <copyright-statement>©Andrzej A Kononowicz, Luke A Woodham, Samuel Edelbring, Natalia Stathakarou, David Davies, Nakul Saxena, Lorainne Tudor Car, Jan Carlstedt-Duke, Josip Car, Nabil Zary. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.07.2019.</copyright-statement>
      <copyright-year>2019</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://www.jmir.org/2019/7/e14676/" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>Virtual patients are interactive digital simulations of clinical scenarios for the purpose of health professions education. There is no current collated evidence on the effectiveness of this form of education.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>The goal of this study was to evaluate the effectiveness of virtual patients compared with traditional education, blended with traditional education, compared with other types of digital education, and design variants of virtual patients in health professions education. The outcomes of interest were knowledge, skills, attitudes, and satisfaction.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>We performed a systematic review on the effectiveness of virtual patient simulations in pre- and postregistration health professions education following Cochrane methodology. We searched 7 databases from the year 1990 up to September 2018. No language restrictions were applied. We included randomized controlled trials and cluster randomized trials. We independently selected studies, extracted data, and assessed risk of bias and then compared the information in pairs. We contacted study authors for additional information if necessary. All pooled analyses were based on random-effects models.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>A total of 51 trials involving 4696 participants met our inclusion criteria. Furthermore, 25 studies compared virtual patients with traditional education, 11 studies investigated virtual patients as blended learning, 5 studies compared virtual patients with different forms of digital education, and 10 studies compared different design variants. The pooled analysis of studies comparing the effect of virtual patients to traditional education showed similar results for knowledge (standardized mean difference [SMD]=0.11, 95% CI −0.17 to 0.39, I<sup>2</sup>=74%, n=927) and favored virtual patients for skills (SMD=0.90, 95% CI 0.49 to 1.32, I<sup>2</sup>=88%, n=897). Studies measuring attitudes and satisfaction predominantly used surveys with item-by-item comparison. Trials comparing virtual patients with different forms of digital education and design variants were not numerous enough to give clear recommendations. Several methodological limitations in the included studies and heterogeneity contributed to a generally low quality of evidence.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge. The skills that improved were clinical reasoning, procedural skills, and a mix of procedural and team skills. We found evidence of effectiveness in both high-income and low- and middle-income countries, demonstrating the global applicability of virtual patients. Further research should explore the utility of different design variants of virtual patients.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>computer simulation</kwd>
        <kwd>professional education</kwd>
        <kwd>computer-assisted instruction</kwd>
        <kwd>systematic review</kwd>
        <kwd>meta-analysis</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <sec>
        <title>Background</title>
        <p>Health care education is confronted with many global challenges. Shorter hospital stays, specialization of care, higher patient safety measures, and shortage of clinical teachers all diminish the traditional opportunities for the training of health professions through direct patient contact [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref2">2</xref>]. Early health professions education is often dominated by theoretical presentations with insufficient connection to clinical practice [<xref ref-type="bibr" rid="ref3">3</xref>]. The need to increase numbers and quality of the health workforce is especially visible in low-and-middle-income countries, where the need to scale up high-quality health education and introduce educational innovations is most pressing [<xref ref-type="bibr" rid="ref4">4</xref>]. Therefore, the global medical education community is perpetually searching for methods that can be applied to improve the relevance, increase the spread, and accelerate the educational process for health professions [<xref ref-type="bibr" rid="ref5">5</xref>].</p>
        <p>Digital education (often referred to as e-learning) is “the act of teaching and learning by means of digital technologies” [<xref ref-type="bibr" rid="ref6">6</xref>]. It encompasses a multitude of educational concepts, approaches, methods, and technologies. Digital health education comprises, for example, offline learning, mobile learning, serious games, or virtual reality environments. We have conducted this systematic review as part of a review series on digital health education [<xref ref-type="bibr" rid="ref6">6</xref>-<xref ref-type="bibr" rid="ref19">19</xref>] and focused it on the simulation modality called <italic>virtual patients</italic>.</p>
        <p>Virtual patients are defined as interactive computer simulations of real-life clinical scenarios for the purpose of health professions training, education, or assessment [<xref ref-type="bibr" rid="ref20">20</xref>]. This broad definition encompasses a variety of systems that use different technologies and address various learning needs [<xref ref-type="bibr" rid="ref21">21</xref>]. The learner is cast into the role of a health care provider who makes decisions about the type and order of clinical information acquired, differential diagnosis, and management and follow-up of the patient. Virtual patients are hypothesized to primarily address learning needs in clinical reasoning [<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref23">23</xref>]. However, an influence of the use of virtual patients on other educational outcomes has been reported in previous literature [<xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref24">24</xref>].</p>
        <p>The educational use of virtual patients may be understood through experiential learning theory [<xref ref-type="bibr" rid="ref25">25</xref>,<xref ref-type="bibr" rid="ref26">26</xref>]. Following this theoretical model of action and reflection, virtual patients expose learners to simulated clinical experiences, providing mechanisms for information gathering and clinical decision making in a safe environment [<xref ref-type="bibr" rid="ref27">27</xref>]. Exposing the learner to many simulated clinical scenarios supports learning diagnostic processes [<xref ref-type="bibr" rid="ref28">28</xref>] while acquainting learners with a standardized set of clinical conditions common in the population, but rare or nonaccessible in highly specialized teaching hospitals [<xref ref-type="bibr" rid="ref29">29</xref>].</p>
        <p>Some concerns have been raised about educational use of virtual patients. Virtual patients should not replace but complement contact with real patients [<xref ref-type="bibr" rid="ref27">27</xref>]. There are concerns around the use of virtual patients potentially resulting in less empathic learners [<xref ref-type="bibr" rid="ref30">30</xref>]. The use of unfamiliar technology as part of virtual patients’ education can represent a barrier to learning, even for younger generations [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref32">32</xref>]. Virtual patients may also prove ineffective when technological objectives drive teaching instead of being motivated by learning needs [<xref ref-type="bibr" rid="ref33">33</xref>].</p>
        <p>This virtual patient simulation review has been preceded by several narrative reviews [<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref34">34</xref>-<xref ref-type="bibr" rid="ref37">37</xref>] and 2 systematic reviews with meta-analyses [<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref39">39</xref>]. Our preliminary literature analysis showed that the number of studies including the term <italic>virtual patient</italic> or <italic>virtual patients</italic> has more than doubled on the MEDLINE database in comparison with available evidence provided in previous systematic reviews (February 2009 [<xref ref-type="bibr" rid="ref38">38</xref>] and July 2010 [<xref ref-type="bibr" rid="ref39">39</xref>]). Thus, our review will update the evidence base with studies not included in previous analyses.</p>
      </sec>
      <sec>
        <title>Objectives</title>
        <p>The objective of this review was to evaluate the effectiveness of virtual patient simulation for delivering pre- and postregistration health care professions education using the following comparisons:</p>
        <list list-type="order">
          <list-item>
            <p>Virtual patient versus traditional education</p>
          </list-item>
          <list-item>
            <p>Virtual patient blended learning versus traditional education</p>
          </list-item>
          <list-item>
            <p>Virtual patient versus other types of digital education</p>
          </list-item>
          <list-item>
            <p>Virtual patient design comparison</p>
          </list-item>
        </list>
        <p>By traditional education, we mean all nondigital educational methods. This includes lectures, reading exercises, group discussion in classroom, and nondigital simulation as standardized patients or mannequin-based training. Virtual patient blended learning is the addition of virtual patients as a supplement to traditional education when the control intervention uses nondigital education methods only. Other types of digital education may include interventions such as video recordings, Web-based tutorials, or virtual classrooms.</p>
        <p>We assessed the impact of virtual patient interventions on learners’ knowledge, skills, attitude, and satisfaction. Our secondary objective was to assess the cost-effectiveness, patient outcomes, and adverse effects of these interventions.</p>
      </sec>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Protocol and Registration</title>
        <p>While conducting the review, we adhered to the Cochrane methodology [<xref ref-type="bibr" rid="ref40">40</xref>], followed a published protocol [<xref ref-type="bibr" rid="ref41">41</xref>], and presented results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [<xref ref-type="bibr" rid="ref42">42</xref>].</p>
      </sec>
      <sec>
        <title>Eligibility Criteria</title>
        <p>We included randomized controlled trials (RCTs) and cluster RCTs (cRCTs). We excluded crossover trials because of the high likelihood of carryover effect.</p>
        <p>Participants in the included studies had to be enrolled in a pre- or postregistration health-related education or training program (see glossary in <xref ref-type="app" rid="app1">Multimedia Appendix 1</xref>). This included students from disciplines such as medicine, dentistry, nursing and midwifery, medical diagnostic and treatment technology, physiotherapy and rehabilitation, and pharmacy.</p>
        <p>This review focused on screen-based virtual patient simulations that form a computerized, dynamically unfolding representation of patient cases. A virtual patient simulation is introduced by a case description and might contain answers given by the patient, clinical data (eg, laboratory results, medical images), and descriptions of patients’ signs and symptoms. Only the representations of the patient as a whole were of interest, rather than studies that focused on single parts of the body. As a matter of a policy followed in the Digital Health Education Collaboration [<xref ref-type="bibr" rid="ref6">6</xref>] and aiming at avoiding duplication of reviews, we deliberately excluded virtual patients in 3-dimensional (3D) virtual learning environments from this study. We judged that a higher level of immersion of learners in 3D virtual environments, connected with potential technical challenges (eg, difficulties in navigating such environments, lags because of increased computational time or limited internet bandwidth), was likely to influence the educational outcomes and therefore merited a separate analysis covered already by the virtual reality review [<xref ref-type="bibr" rid="ref13">13</xref>] of this Digital Health Education Collaboration series. We also excluded those virtual patient interventions which require nonstandard equipment (eg, haptic devices, mannequins) or those virtual patients which are human controlled (eg, simulated email correspondence or chat room conversations). We excluded studies in which virtual patients were just a small part of the intervention and those in which the influence of virtual patients was not evaluated separately.</p>
        <p>Furthermore, 2-arm RCTs comparing virtual patients with a control group not involved in any type of subject-related learning activity were not considered eligible as previous meta-analyses have already shown a large positive effect when virtual patients were compared with no intervention [<xref ref-type="bibr" rid="ref38">38</xref>].</p>
        <p>We decided to introduce to the review a comparison of virtual patients blended learning with traditional education as a consequence of the discussion in the community on the need to eliminate traditional types of learning activities to make space for virtual patients. For instance, Berman et al [<xref ref-type="bibr" rid="ref29">29</xref>] noticed that the students’ subjective learning effect perceptions and satisfaction with integration were lower at universities that increased the workload of students by adding virtual patients without releasing time resources in the curriculum. As most of health professions education is conducted on campus, an integrated effect of virtual patients is possible. Blending virtual patients with traditional education is challenging and qualitatively different than a nonintervention control group comparison.</p>
        <p>Eligible primary outcomes were students’ (1) knowledge, (2) skills, (3) attitudes, and (4) satisfaction—together representing clinical competencies measured post intervention with validated or nonvalidated instruments. Secondary outcomes were (1) economic cost and cost-effectiveness, (2) patient outcomes, and (3) observed adverse effects.</p>
      </sec>
      <sec>
        <title>Search Methods for Identification of Studies</title>
        <p>We searched the following 7 databases: MEDLINE (via Ovid), EMBASE (via Elsevier), The Cochrane Library (via Wiley), PsycINFO (via Ovid), Educational Resource Information Centre (ERIC; via Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL; via EBSCO), and Web of Science Core Collection (via Thomson Reuters). We adapted the MEDLINE strategy and keywords presented in <xref ref-type="app" rid="app2">Multimedia Appendix 2</xref> for use with each of the databases above. We searched databases from the year 1990 to September 20, 2018 to highlight recent developments and did not apply language restrictions. For all included studies, we searched references lists and conducted author and citation searches. We searched lists of references from other identified relevant systematic reviews while running our electronic searches.</p>
      </sec>
      <sec>
        <title>Data Collection and Analysis</title>
        <sec>
          <title>Data Selection, Extraction, and Management</title>
          <p>The search results were combined in a single EndNote library (version X7; Thomson Reuters) [<xref ref-type="bibr" rid="ref43">43</xref>]. Overall, 2 authors independently screened titles and abstracts to identify potentially eligible studies. In the next phase, full-text versions of these papers were retrieved and 2 review authors independently assessed these papers against eligibility criteria. We piloted data extraction to maximize consistency in the information extracted. Disagreements were resolved through discussion. A third review author was consulted to arbitrate when differences in opinion arose. All relevant data were extracted using a structured form in Microsoft Excel. We contacted study authors for crucial missing information, particularly if required to judge inclusion criteria and study outcomes.</p>
        </sec>
        <sec>
          <title>Data Items</title>
          <p>Information was extracted from each included study on (1) the characteristics of study participants (field of study; stage of education: pre/postregistered; year of study; and country where the study was conducted and its World Bank income category: high-income/low-and-middle-income country), (2) the type of outcome measure (type of tool used to measure outcome and information on whether the tool was validated), (3) the type of virtual patient intervention (topic and language of presented virtual patient simulations; information on whether the language of virtual patient was native to the majority of participants; source of virtual patient simulations: internal/external; was the study an individual or group assignment, and in case of group assignments, the number of students in a group; whether access to virtual patient simulation was from home or in a computer laboratory; number of virtual patient cases presented; time when the virtual patients were available; and duration of use of virtual patients), and (4) the type of virtual patient system (name of the system; navigation scheme: linear, branched, and free access; control mechanism: menu-based, keyboard, or speech recognition; feedback delivery and timing; and whether video clips where included in virtual patient cases). A glossary of the terms in use in the review may be found in <xref ref-type="app" rid="app1">Multimedia Appendix 1</xref>.</p>
        </sec>
        <sec>
          <title>Measures of Treatment Effect</title>
          <p>We reported the treatment effects for continuous outcomes as mean values and SDs post intervention in each intervention group, along with the number of participants and <italic>P</italic> values. As the studies presented data using different tools, the mean differences were recalculated into standardized mean difference (SMD). We interpreted the effect size as small (SMD=0.2), moderate (SMD=0.5), and large (SMD=0.8) effect sizes [<xref ref-type="bibr" rid="ref40">40</xref>]. If studies had multiple arms and no clear main comparison, we compared the virtual patient intervention arm with the most common control arm, excluding the nonintervention and mixed-intervention controls. If that was impossible to decide, we selected the least active control arm. If multiple outcomes in the same category (knowledge, skills, attitudes, and outcomes) were reported, we selected the primary measure, and if that was impossible, we calculated the mean value of all measures. For papers that reported median and range for the outcomes, we converted these to mean and SD using methods described by Wan [<xref ref-type="bibr" rid="ref44">44</xref>]. If a study did not report SD but provided CIs, we estimated SD from those using a method described in previous literature [<xref ref-type="bibr" rid="ref40">40</xref>].</p>
        </sec>
        <sec>
          <title>Data Synthesis and Analysis</title>
          <p>Owing to the significant differences between studies, we employed a random-effects model in the meta-analysis using Review Manager (version 5.3; The Nordic Cochrane Centre) [<xref ref-type="bibr" rid="ref45">45</xref>]. We displayed the results of the meta-analysis in forest plots and evaluated heterogeneity numerically using I<sup>2</sup> statistics. For comparisons with more than 10 outcomes in the meta-analysis, we attempted a subgroup analysis. As the planned 15 subgroup analyses in the protocol [<xref ref-type="bibr" rid="ref41">41</xref>] did not explain the heterogeneity, we visualized the outcomes using albatross plots [<xref ref-type="bibr" rid="ref46">46</xref>]. These plots were implemented using a script created for the purpose of the study by one of the review authors (AK) in the statistical package R (version 3.4.3; R Foundation for Statistical Computing) [<xref ref-type="bibr" rid="ref47">47</xref>]. This explorative approach resulted in a new subgroup analysis in which we divided the control interventions into active (group discussion, mannequin-based simulation) and passive (lectures, reading assignments). Findings unsuitable for inclusion in a meta-analysis (eg, comparison of individual items in surveys) were presented using a narrative synthesis.</p>
        </sec>
        <sec>
          <title>Assessment of Risk of Bias</title>
          <p>Two authors independently assessed the risk of bias using the Cochrane tool [<xref ref-type="bibr" rid="ref40">40</xref>]. We considered the following domains: random sequence generation, allocation sequence concealment, blinding of participants or personnel, blinding to outcome assessment, completeness of outcome data, selective outcome reporting, and other sources of bias (eg, differences in baseline evaluation, volunteer bias, commercial grants). For cRCTs, we also assessed the risk of the following additional biases: recruitment bias, baseline imbalance, loss of clusters, incorrect analysis, and comparability with individually randomized trials. The publication bias in our review was difficult to investigate in a formal way because of high levels of heterogeneity which limit the interpretation possibilities of funnel plots.</p>
        </sec>
        <sec>
          <title>Summary of Findings Tables</title>
          <p>We prepared <italic>summary of findings</italic> tables to present results of the meta-analysis [<xref ref-type="bibr" rid="ref40">40</xref>]. We presented the results for major comparisons of the review and for each of the major primary outcomes. We considered the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to assess the quality of the evidence and downgraded the quality where appropriate [<xref ref-type="bibr" rid="ref40">40</xref>].</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Included Studies</title>
        <p>Our searches yielded a total of 44,054 citations, and 51 studies with 4696 participants were included (<xref ref-type="fig" rid="figure1">Figure 1</xref>). Overall, 2 reports described results already included in the review [<xref ref-type="bibr" rid="ref48">48</xref>,<xref ref-type="bibr" rid="ref49">49</xref>].</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) study flow diagram.</p>
          </caption>
          <graphic xlink:href="jmir_v21i7e14676_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Types of Studies</title>
        <p>All included studies were published in peer-reviewed journals. All included studies had an RCT design, with the exception of 3 cRCTs [<xref ref-type="bibr" rid="ref50">50</xref>-<xref ref-type="bibr" rid="ref52">52</xref>].</p>
      </sec>
      <sec>
        <title>Types of Comparisons</title>
        <p>A total of 25 studies compared virtual patients with traditional education [<xref ref-type="bibr" rid="ref53">53</xref>-<xref ref-type="bibr" rid="ref77">77</xref>], 11 compared a blend of virtual patients and traditional education with traditional education [<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref52">52</xref>,<xref ref-type="bibr" rid="ref78">78</xref>-<xref ref-type="bibr" rid="ref86">86</xref>], 5 studies compared virtual patients with different forms of digital health education [<xref ref-type="bibr" rid="ref51">51</xref>,<xref ref-type="bibr" rid="ref87">87</xref>-<xref ref-type="bibr" rid="ref90">90</xref>], and 10 studies compared different types of virtual patient interventions [<xref ref-type="bibr" rid="ref91">91</xref>-<xref ref-type="bibr" rid="ref100">100</xref>].</p>
        <p>The traditional education control group involved a reading assignment in 6 studies [<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref60">60</xref>,<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref67">67</xref>-<xref ref-type="bibr" rid="ref69">69</xref>]; 4 studies each involving a lecture [<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref66">66</xref>,<xref ref-type="bibr" rid="ref72">72</xref>,<xref ref-type="bibr" rid="ref77">77</xref>], group assignment [<xref ref-type="bibr" rid="ref53">53</xref>,<xref ref-type="bibr" rid="ref65">65</xref>,<xref ref-type="bibr" rid="ref71">71</xref>,<xref ref-type="bibr" rid="ref73">73</xref>], and mannequin-based training [<xref ref-type="bibr" rid="ref58">58</xref>,<xref ref-type="bibr" rid="ref64">64</xref>,<xref ref-type="bibr" rid="ref70">70</xref>,<xref ref-type="bibr" rid="ref76">76</xref>]; and 1 each involving standardized patients [<xref ref-type="bibr" rid="ref74">74</xref>] and ward-based education [<xref ref-type="bibr" rid="ref75">75</xref>]. In 5 studies, the intervention was a mix of different forms of traditional education (eg, lecture, small group assignment, and mannequin-based training) [<xref ref-type="bibr" rid="ref54">54</xref>-<xref ref-type="bibr" rid="ref57">57</xref>,<xref ref-type="bibr" rid="ref61">61</xref>].</p>
        <p>The digital education control group was in 2 studies—a Web tutorial or course [<xref ref-type="bibr" rid="ref88">88</xref>,<xref ref-type="bibr" rid="ref90">90</xref>] and video recording [<xref ref-type="bibr" rid="ref87">87</xref>,<xref ref-type="bibr" rid="ref89">89</xref>]—and in 1 study, a mix of traditional lectures and Web materials including video clips [<xref ref-type="bibr" rid="ref51">51</xref>] was used.</p>
        <p>Studies comparing different types of virtual patients contrasted narrative with problem-solving structure of virtual patients [<xref ref-type="bibr" rid="ref91">91</xref>]; virtual patients with and without usability enhancements [<xref ref-type="bibr" rid="ref94">94</xref>]; different forms of feedback in virtual patients [<xref ref-type="bibr" rid="ref95">95</xref>,<xref ref-type="bibr" rid="ref96">96</xref>]; worked with unworked versions of virtual patients [<xref ref-type="bibr" rid="ref97">97</xref>]; differences between self-determined and mandatory access to virtual patients [<xref ref-type="bibr" rid="ref98">98</xref>]; virtual patients collections in which all the cases were presented at once to those automatically activated spaced in time [<xref ref-type="bibr" rid="ref99">99</xref>]; effects of virtual patient solving with virtual patient construction exercises [<xref ref-type="bibr" rid="ref100">100</xref>]; linear versus branched design of virtual patients [<xref ref-type="bibr" rid="ref92">92</xref>]; and finally the addition of representation scaffolding (see glossary in <xref ref-type="app" rid="app1">Multimedia Appendix 1</xref>) to virtual patients [<xref ref-type="bibr" rid="ref93">93</xref>].</p>
        <p>Furthermore, 41 studies had 2 study arms (see the first table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>), 7 studies had 3 arms [<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref88">88</xref>,<xref ref-type="bibr" rid="ref91">91</xref>,<xref ref-type="bibr" rid="ref95">95</xref>-<xref ref-type="bibr" rid="ref98">98</xref>], and 3 studies had 4 arms [<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref65">65</xref>,<xref ref-type="bibr" rid="ref67">67</xref>].</p>
      </sec>
      <sec>
        <title>Types of Participants</title>
        <p>In total, 41 studies involved preregistered professionals (see the first table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>), with 8 studies focused on postregistered participants [<xref ref-type="bibr" rid="ref68">68</xref>,<xref ref-type="bibr" rid="ref69">69</xref>,<xref ref-type="bibr" rid="ref74">74</xref>,<xref ref-type="bibr" rid="ref76">76</xref>,<xref ref-type="bibr" rid="ref78">78</xref>,<xref ref-type="bibr" rid="ref90">90</xref>,<xref ref-type="bibr" rid="ref94">94</xref>,<xref ref-type="bibr" rid="ref97">97</xref>]; 2 studies involved both pre- and postregistered participants [<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref87">87</xref>].</p>
        <p>In 37 out of 51 studies, participants were from the field of medicine. The studies from fields other than medicine were as follows: 6 studies in nursing [<xref ref-type="bibr" rid="ref58">58</xref>,<xref ref-type="bibr" rid="ref64">64</xref>,<xref ref-type="bibr" rid="ref70">70</xref>,<xref ref-type="bibr" rid="ref73">73</xref>,<xref ref-type="bibr" rid="ref78">78</xref>,<xref ref-type="bibr" rid="ref80">80</xref>]; 2 in pharmacy [<xref ref-type="bibr" rid="ref53">53</xref>,<xref ref-type="bibr" rid="ref92">92</xref>]; and 1 each in physical therapy [<xref ref-type="bibr" rid="ref61">61</xref>], osteopathic medicine [<xref ref-type="bibr" rid="ref84">84</xref>], and dentistry [<xref ref-type="bibr" rid="ref83">83</xref>]. In addition, 3 studies involved interprofessional education [<xref ref-type="bibr" rid="ref74">74</xref>,<xref ref-type="bibr" rid="ref76">76</xref>,<xref ref-type="bibr" rid="ref90">90</xref>].</p>
        <p>A total of 44 out of 51 studies were conducted in high-income countries; 19 were from the United States (see the first table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>); 5 from Germany [<xref ref-type="bibr" rid="ref65">65</xref>,<xref ref-type="bibr" rid="ref82">82</xref>,<xref ref-type="bibr" rid="ref93">93</xref>,<xref ref-type="bibr" rid="ref98">98</xref>,<xref ref-type="bibr" rid="ref99">99</xref>]; 3 each from Australia [<xref ref-type="bibr" rid="ref52">52</xref>,<xref ref-type="bibr" rid="ref70">70</xref>,<xref ref-type="bibr" rid="ref91">91</xref>] and Sweden [<xref ref-type="bibr" rid="ref83">83</xref>,<xref ref-type="bibr" rid="ref85">85</xref>,<xref ref-type="bibr" rid="ref87">87</xref>]; 2 each from Canada [<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref60">60</xref>], the Netherlands [<xref ref-type="bibr" rid="ref86">86</xref>,<xref ref-type="bibr" rid="ref88">88</xref>], and the United Kingdom [<xref ref-type="bibr" rid="ref66">66</xref>,<xref ref-type="bibr" rid="ref77">77</xref>]; and 1 study was conducted each in Belgium and Switzerland [<xref ref-type="bibr" rid="ref92">92</xref>], Denmark [<xref ref-type="bibr" rid="ref100">100</xref>], France [<xref ref-type="bibr" rid="ref54">54</xref>], Hong Kong [<xref ref-type="bibr" rid="ref51">51</xref>], Japan [<xref ref-type="bibr" rid="ref67">67</xref>], Poland [<xref ref-type="bibr" rid="ref50">50</xref>], Singapore [<xref ref-type="bibr" rid="ref64">64</xref>], and Slovenia [<xref ref-type="bibr" rid="ref71">71</xref>]. From the 7 studies conducted in low-and-middle-income countries, 3 were from China [<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref73">73</xref>,<xref ref-type="bibr" rid="ref80">80</xref>], 2 from Colombia [<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref56">56</xref>], and 1 each from the Republic of South Africa [<xref ref-type="bibr" rid="ref94">94</xref>] and Iran [<xref ref-type="bibr" rid="ref75">75</xref>].</p>
        <p>In <xref ref-type="app" rid="app4">Multimedia Appendix 4</xref> we present the technical characteristics of virtual patient systems, topics of educational content presented, applied instructional design methods, setting of use, information on the validity of outcome measurement, and applied educational theories in the included studies. <xref ref-type="app" rid="app5">Multimedia Appendix 5</xref> summarizes the reasons for excluding studies following a review of their full-text versions.</p>
      </sec>
      <sec>
        <title>Effects of Interventions</title>
        <sec>
          <title>Knowledge</title>
          <p>In total, 33 studies assessed outcomes of knowledge. In all studies, knowledge was measured using paper-based tests (see the second table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>). In 19 studies, the test consisted of multiple-choice questions (MCQs). Other knowledge test designs contained multiple-response questions [<xref ref-type="bibr" rid="ref100">100</xref>], true/false questions [<xref ref-type="bibr" rid="ref50">50</xref>], and key feature format questions [<xref ref-type="bibr" rid="ref82">82</xref>]. In 4 studies, the participants had to formulate free-text answers [<xref ref-type="bibr" rid="ref75">75</xref>,<xref ref-type="bibr" rid="ref85">85</xref>,<xref ref-type="bibr" rid="ref94">94</xref>,<xref ref-type="bibr" rid="ref99">99</xref>]. In 4 studies [<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref66">66</xref>,<xref ref-type="bibr" rid="ref93">93</xref>,<xref ref-type="bibr" rid="ref97">97</xref>], the knowledge tests comprised a mix of different formats. Li et al [<xref ref-type="bibr" rid="ref63">63</xref>] used a combination of multiple-choice and short answer questions; Miedzybrodzka et al [<xref ref-type="bibr" rid="ref66">66</xref>] used MCQs and modified essays; Harris et al [<xref ref-type="bibr" rid="ref97">97</xref>] applied MCQs with confidence levels combined with script concordance testing questions; and Braun et al [<xref ref-type="bibr" rid="ref93">93</xref>] used a test consisting of multiple-choice items, key feature problems, and problem-solving tasks. Secomb et al [<xref ref-type="bibr" rid="ref70">70</xref>] measured cognitive growth using a survey requiring selection of the most significant items regarding learning environment preferences. In 3 studies [<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref73">73</xref>,<xref ref-type="bibr" rid="ref92">92</xref>], the nature of the knowledge test was unclear. In the case of MCQs in which the nature of items was unclear or mixed, we classified the outcome as knowledge instead of, for example, clinical reasoning skills, but the borderline between those was sometimes blurred. Meta-knowledge (eg, knowledge about the clinical reasoning process itself) was classified as knowledge outcomes following the framework by Kraiger [<xref ref-type="bibr" rid="ref101">101</xref>].</p>
          <p>The effects of interventions on knowledge outcomes are summarized in the second table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>.</p>
          <sec>
            <title>Virtual Patient Versus Traditional Education</title>
            <p>In 4 [<xref ref-type="bibr" rid="ref60">60</xref>,<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref67">67</xref>,<xref ref-type="bibr" rid="ref72">72</xref>] of 18 studies comparing virtual patients with traditional education, the intervention resulted in more positive knowledge outcomes. In 2, the control group attended a lecture [<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref72">72</xref>], whereas in the remaining 2 studies, students participated in a reading exercise [<xref ref-type="bibr" rid="ref60">60</xref>,<xref ref-type="bibr" rid="ref67">67</xref>]. In 1 study [<xref ref-type="bibr" rid="ref53">53</xref>], the control intervention arm (Problem-based learning (PBL) small group discussion) had significantly better results than the virtual patient intervention (SMD=−0.65, 95% CI −1.02 to −0.28, <italic>P=</italic>.001). In the remaining 13 studies, the difference did not reach a statistically significant level (see the second table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>).</p>
            <p>We excluded 2 studies [<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref65">65</xref>] from our meta-analysis because of missing crucial outcome data. Jeimy et al [<xref ref-type="bibr" rid="ref59">59</xref>] presented outcomes of a knowledge test compared item-by-item and the study was therefore excluded from the meta-analysis. We also excluded 1 study [<xref ref-type="bibr" rid="ref72">72</xref>] owing to its outlier value of SMD=12.5 being most likely because of reporting error and excluded another study [<xref ref-type="bibr" rid="ref70">70</xref>] as we regarded meta-knowledge as very different from the other types of core knowledge outcomes.</p>
            <p>The pooled effect for knowledge outcomes (SMD=0.11, 95% CI −0.17 to 0.39, I<sup>2</sup>=74%, n=927; <xref ref-type="fig" rid="figure2">Figure 2</xref>) suggests that virtual patient interventions are as efficient as traditional education.</p>
            <fig id="figure2" position="float">
              <label>Figure 2</label>
              <caption>
                <p>Forest plot of virtual patient to traditional education comparison for knowledge outcomes. df: degrees of freedom; IV: interval variable; random: random effects model.</p>
              </caption>
              <graphic xlink:href="jmir_v21i7e14676_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
            </fig>
          </sec>
          <sec>
            <title>Virtual Patient Blended Learning Versus Traditional Education</title>
            <p>In 4 [<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref52">52</xref>,<xref ref-type="bibr" rid="ref80">80</xref>,<xref ref-type="bibr" rid="ref82">82</xref>] of the 5 studies comparing virtual patients as a supplement with traditional education in the domain of knowledge, the group having the additional resource scored better than the control group. Only in 1 study [<xref ref-type="bibr" rid="ref85">85</xref>] did the addition of virtual patients not lead to statistically significant difference in knowledge outcomes (<italic>P</italic>=.11).</p>
            <p>The pooled effect for knowledge outcomes (SMD=0.73, 95% CI 0.24 to 1.22, I<sup>2</sup>=81%, n=439; <xref ref-type="fig" rid="figure3">Figure 3</xref>) suggests moderate effects preferring the mix of virtual patients with traditional education over traditional education alone.</p>
            <fig id="figure3" position="float">
              <label>Figure 3</label>
              <caption>
                <p>Forest plot of virtual patient blended learning to traditional education comparison for knowledge outcomes. df: degrees of freedom; IV: interval variable; random: random effects model; VP: virtual patients.</p>
              </caption>
              <graphic xlink:href="jmir_v21i7e14676_fig3.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
            </fig>
          </sec>
          <sec>
            <title>Virtual Patient Versus Other Types of Digital Education</title>
            <p>A total of 2 studies compared the difference in knowledge outcomes between virtual patients and digital health education interventions. Courteille et al [<xref ref-type="bibr" rid="ref87">87</xref>] compared virtual patients with a video-recorded lecture, whereas Trudeau et al [<xref ref-type="bibr" rid="ref90">90</xref>] compared with a static Web course. Neither of these comparisons showed significant differences in knowledge outcomes.</p>
          </sec>
          <sec>
            <title>Virtual Patient Design Comparison</title>
            <p>In total, 8 studies focused on detecting the difference between variants of virtual patient design in the domain of knowledge. Only in 1 study by Friedman et al [<xref ref-type="bibr" rid="ref96">96</xref>] were the differences at a statistically significant level. In this study, the pedagogic design of virtual patients was better than problem-solving and high-fidelity designs (<italic>P</italic>&lt;.01). Comparing linear and branched virtual patients [<xref ref-type="bibr" rid="ref92">92</xref>], scaffolded versus nonscaffolded [<xref ref-type="bibr" rid="ref93">93</xref>], worked and unworked examples [<xref ref-type="bibr" rid="ref97">97</xref>], virtual patient with usability extensions [<xref ref-type="bibr" rid="ref94">94</xref>], self-determined versus mandatory integration [<xref ref-type="bibr" rid="ref98">98</xref>], spaced versus nonspaced release of cases [<xref ref-type="bibr" rid="ref99">99</xref>], and virtual patient solving versus virtual patient design exercises [<xref ref-type="bibr" rid="ref100">100</xref>] resulted in no significant differences in knowledge outcomes.</p>
          </sec>
        </sec>
        <sec>
          <title>Skills</title>
          <p>A total of 28 studies assessed skills outcomes (see the third table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>). Skills were assessed by performance on a mannequin in 9 studies [<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref64">64</xref>,<xref ref-type="bibr" rid="ref68">68</xref>,<xref ref-type="bibr" rid="ref69">69</xref>,<xref ref-type="bibr" rid="ref73">73</xref>,<xref ref-type="bibr" rid="ref80">80</xref>,<xref ref-type="bibr" rid="ref82">82</xref>,<xref ref-type="bibr" rid="ref88">88</xref>], by performance on a live standardized patient in 8 studies [<xref ref-type="bibr" rid="ref57">57</xref>,<xref ref-type="bibr" rid="ref67">67</xref>,<xref ref-type="bibr" rid="ref78">78</xref>,<xref ref-type="bibr" rid="ref81">81</xref>,<xref ref-type="bibr" rid="ref89">89</xref>,<xref ref-type="bibr" rid="ref91">91</xref>,<xref ref-type="bibr" rid="ref95">95</xref>,<xref ref-type="bibr" rid="ref100">100</xref>], and performance on virtual patients [<xref ref-type="bibr" rid="ref93">93</xref>] and real patients [<xref ref-type="bibr" rid="ref83">83</xref>] in 1 study each. In 6 studies, outcomes were measured by a written assignment involving description of photographed clinical cases [<xref ref-type="bibr" rid="ref63">63</xref>], radiographs [<xref ref-type="bibr" rid="ref65">65</xref>], carrying out and structuring a mental state examination based on videotaped material [<xref ref-type="bibr" rid="ref77">77</xref>], solving paper cases [<xref ref-type="bibr" rid="ref74">74</xref>,<xref ref-type="bibr" rid="ref86">86</xref>], and a modular paper-based test [<xref ref-type="bibr" rid="ref75">75</xref>]. In 2 studies [<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref56">56</xref>], outcomes were measured by a mix of paper cases and virtual patients. Kumta et al [<xref ref-type="bibr" rid="ref51">51</xref>] combined computer-based assessment, objective structured clinical examination (OSCE), and clinical examination comprising patients in the ward into 1 score.</p>
          <p>The effects of interventions on skills outcomes are summarized in the third table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>.</p>
          <sec>
            <title>Virtual Patient Versus Traditional Education</title>
            <p>In 9 of 14 studies comparing virtual patients with traditional education, the intervention resulted in better skills outcomes (see the third table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>). The virtual patient intervention showed larger effects than lectures [<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref77">77</xref>], reading exercises [<xref ref-type="bibr" rid="ref67">67</xref>-<xref ref-type="bibr" rid="ref69">69</xref>], group discussions [<xref ref-type="bibr" rid="ref73">73</xref>], and activities comprising traditional methods, including lectures or hands-on training with mannequins [<xref ref-type="bibr" rid="ref54">54</xref>-<xref ref-type="bibr" rid="ref56">56</xref>].</p>
            <p>Those skills which improved were clinical reasoning [<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref56">56</xref>,<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref77">77</xref>], procedural skills [<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref67">67</xref>-<xref ref-type="bibr" rid="ref69">69</xref>], and a mix of procedural and team skills [<xref ref-type="bibr" rid="ref73">73</xref>].</p>
            <p>We did not include in the meta-analysis 2 studies with incomplete reported data [<xref ref-type="bibr" rid="ref65">65</xref>,<xref ref-type="bibr" rid="ref74">74</xref>]. We also excluded skills outcomes from the study by Haerling [<xref ref-type="bibr" rid="ref58">58</xref>] as these were available for a randomly selected subgroup only and from Wang et al [<xref ref-type="bibr" rid="ref76">76</xref>] as they were measured for teams of students only and not individually.</p>
            <p>The pooled effect on skills outcomes was (SMD=0.90, 95% CI 0.49 to 1.32, I<sup>2</sup>=88%, n=897; <xref ref-type="fig" rid="figure4">Figure 4</xref>). Overall, this suggests that virtual patients have moderate to large positive effects in comparison with traditional education in the investigated types of skills.</p>
            <fig id="figure4" position="float">
              <label>Figure 4</label>
              <caption>
                <p>Forest plot of virtual patient to traditional education comparison for skills outcomes. df: degrees of freedom; IV: interval variable; random: random effects model; VP: virtual patients.</p>
              </caption>
              <graphic xlink:href="jmir_v21i7e14676_fig4.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
            </fig>
          </sec>
          <sec>
            <title>Virtual Patient Blended Learning Versus Traditional Education</title>
            <p>In 3 [<xref ref-type="bibr" rid="ref82">82</xref>,<xref ref-type="bibr" rid="ref83">83</xref>,<xref ref-type="bibr" rid="ref86">86</xref>] out of 7 studies, the groups using virtual patients blended learning scored better than the control group in the skills domain. Lehmann et al [<xref ref-type="bibr" rid="ref82">82</xref>] demonstrated significantly improved procedural skills (<italic>P</italic>&lt;.001), whereas Weverling et al [<xref ref-type="bibr" rid="ref86">86</xref>] reported on improved clinical reasoning skills (<italic>P</italic>&lt;.001) and Schittek Janda et al [<xref ref-type="bibr" rid="ref83">83</xref>] on communication skills (<italic>P</italic>&lt;.01). Furthermore, 2 studies [<xref ref-type="bibr" rid="ref78">78</xref>,<xref ref-type="bibr" rid="ref80">80</xref>] involving nursing students showed no significant difference. The study by Bryant et al [<xref ref-type="bibr" rid="ref78">78</xref>] evaluated communication skills (<italic>P</italic>=.38), whereas Gu et al [<xref ref-type="bibr" rid="ref80">80</xref>] measured procedural skills (<italic>P</italic>&gt;.05). We excluded 3 studies [<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref81">81</xref>,<xref ref-type="bibr" rid="ref83">83</xref>] from the meta-analysis because of insufficient data provided in the report or item-by-item comparison of a skills checklist.</p>
            <p>The pooled effect for skills outcomes (SMD=0.60, 95% CI −0.07 to 1.27, I<sup>2</sup>=83%, n=247; <xref ref-type="fig" rid="figure5">Figure 5</xref>) suggests that virtual patients blended with traditional education have moderate positive effects in comparison with traditional education alone.</p>
            <fig id="figure5" position="float">
              <label>Figure 5</label>
              <caption>
                <p>Forest plot of virtual patient blended learning to traditional education comparison for skills outcomes. df: degrees of freedom; IV: interval variable; random: random effects model; VP: virtual patients.</p>
              </caption>
              <graphic xlink:href="jmir_v21i7e14676_fig5.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
            </fig>
          </sec>
          <sec>
            <title>Virtual Patient Versus Other Types of Digital Education</title>
            <p>Out of 3 studies comparing skills outcomes in virtual patients with other types of digital education studies, Kumta et al [<xref ref-type="bibr" rid="ref51">51</xref>] showed a significant difference (<italic>P</italic>&lt;.001). In this study, virtual patients were better than a range of different traditional teaching methods supplemented by Web content that included video clips, PowerPoint presentations, digital notes, and handouts. The target outcomes were clinical skills assessed by OSCE stations and examination of patients in the wards. In a study by Dankbaar et al [<xref ref-type="bibr" rid="ref88">88</xref>], virtual patients were not significantly better in teaching procedural skill than an electronic module only (<italic>P</italic>&gt;.05). Finally, in the study by Foster et al [<xref ref-type="bibr" rid="ref89">89</xref>], virtual patients showed no significant difference when compared with video recordings in teaching communication skills (<italic>P</italic>&gt;.05).</p>
          </sec>
          <sec>
            <title>Virtual Patient Design Comparison</title>
            <p>From the 4 studies that compared the influence of different virtual patient designs on skills outcomes, Foster et al [<xref ref-type="bibr" rid="ref95">95</xref>] showed that virtual patients with emphatic feedback were significantly better in training communication skills than those virtual patients without feedback (<italic>P</italic>&lt;.03). In the study by Bearman et al [<xref ref-type="bibr" rid="ref91">91</xref>], narrative virtual patients were significantly better than problem-solving virtual patients in conveying communication skills (<italic>P</italic>=.03). In a study by Braun et al [<xref ref-type="bibr" rid="ref93">93</xref>], the addition of representational scaffolding to a virtual patient intervention significantly improved diagnostic efficiency (<italic>P</italic>=.045). Finally, in the study by Tolsgaard et al [<xref ref-type="bibr" rid="ref100">100</xref>], there was no significant difference in integrated clinical performance when students constructed or solved virtual patients (<italic>P</italic>=.54).</p>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>Attitudes</title>
        <p>A total of 11 studies reported attitudinal outcomes (see the third table in <xref ref-type="app" rid="app1">Multimedia Appendix 1</xref>). The attitudes related to confidence, preparedness, comfort, self-efficacy, and perceived ability in topics such as history taking and clinical breast examination [<xref ref-type="bibr" rid="ref79">79</xref>], diagnostic and management abilities [<xref ref-type="bibr" rid="ref59">59</xref>], contrast reaction management and teamwork [<xref ref-type="bibr" rid="ref76">76</xref>], ethical, legal, and communication issues [<xref ref-type="bibr" rid="ref57">57</xref>,<xref ref-type="bibr" rid="ref81">81</xref>], opioid therapy [<xref ref-type="bibr" rid="ref90">90</xref>], cultural competence [<xref ref-type="bibr" rid="ref84">84</xref>], procedural knowledge in pediatric basic life support [<xref ref-type="bibr" rid="ref82">82</xref>], performing pharmacy triage [<xref ref-type="bibr" rid="ref92">92</xref>], caring for distress disorders patients [<xref ref-type="bibr" rid="ref74">74</xref>], and anxiety [<xref ref-type="bibr" rid="ref77">77</xref>].</p>
        <p>The effects of interventions on attitudinal outcomes are presented in the fourth table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>. Furthermore, 3 studies presented pooled scores on students‘ self-assessment. In the study by Lehmann et al [<xref ref-type="bibr" rid="ref82">82</xref>], students felt more confident in their knowledge and skills on performing pediatric basic life support with additional access to virtual patients that supplemented their traditional course (<italic>P</italic>&lt;.001). There were no significant differences in the remaining 2 studies focusing on communication-related self-efficacy [<xref ref-type="bibr" rid="ref81">81</xref>] and attitudes related to opioid therapy [<xref ref-type="bibr" rid="ref90">90</xref>].</p>
        <p>In the study by Williams et al [<xref ref-type="bibr" rid="ref77">77</xref>], more items related to self-assessment of competences (in dealing with ethical aspects and managing anxiety) were scored lower in the virtual patient group than in the traditional education groups. There were no differences in analyzed items related to attitudes in 4 studies [<xref ref-type="bibr" rid="ref57">57</xref>,<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref74">74</xref>,<xref ref-type="bibr" rid="ref79">79</xref>]. In the study by Smith et al [<xref ref-type="bibr" rid="ref84">84</xref>], the results regarding attitudes toward clinical cultural competence were presented separately for bilingual and English-speaking students, which makes it difficult to aggregate not knowing the number of bilingual students in each study group. However, the descriptive conclusion of the authors was that general cultural competence measures were the same for the virtual patient and control group. In 2 studies [<xref ref-type="bibr" rid="ref76">76</xref>,<xref ref-type="bibr" rid="ref92">92</xref>], the results were compared item-by-item and only within the groups (pre/posttest), not between the study groups.</p>
      </sec>
      <sec>
        <title>Satisfaction</title>
        <p>In total, 17 studies measured satisfaction resulting from an intervention (see the fifth table in <xref ref-type="app" rid="app3">Multimedia Appendix 3</xref>). All outcomes in this category were measured by satisfaction questionnaires. Different facets of satisfaction were measured, which we classified in the following 5 dimensions: general impression (global score or willingness to recommend), comfort in use (learning style preference, engagement or motivation, positive climate or safety, and enjoyment or pleasure), integration in curriculum (time constraints, relevance, and level of difficulty), academic factors (feedback quality, structure, and clarity), and satisfaction with technical features (usability and information technology readiness).</p>
        <p>In 4 out of 17 studies evaluating the satisfaction of students receiving a virtual patient intervention, the result was presented as 1 aggregated score of several items. Furthermore, 3 of those studies compared different design variants of virtual patients. In the study by Friedman et al [<xref ref-type="bibr" rid="ref96">96</xref>], the pedagogic format (menus, guided) resulted in higher satisfaction scores than the high-fidelity (free text, unguided) format (<italic>P</italic>&lt;.01). There was no statistically significant difference between the virtual patients with and without usability enhancements [<xref ref-type="bibr" rid="ref94">94</xref>] (<italic>P</italic>=.13) and solving versus constructing virtual patients [<xref ref-type="bibr" rid="ref100">100</xref>] (<italic>P</italic>=.46). One study [<xref ref-type="bibr" rid="ref58">58</xref>] presented comparison of virtual patients with mannequin-based training using a single score for student satisfaction and self-confidence in learning, showing no difference between the simulation modalities (<italic>P</italic>=.11).</p>
        <p>In the remaining 13 out 17 studies, the survey responses were compared item-by-item. In 4 studies, the majority of the items indicated preference for the virtual patient intervention, in comparison with lecture [<xref ref-type="bibr" rid="ref63">63</xref>], reading assignment [<xref ref-type="bibr" rid="ref67">67</xref>], video-based learning [<xref ref-type="bibr" rid="ref89">89</xref>], and Web tutorial [<xref ref-type="bibr" rid="ref88">88</xref>]. In 7 studies, most items were indifferent between the groups [<xref ref-type="bibr" rid="ref53">53</xref>,<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref65">65</xref>,<xref ref-type="bibr" rid="ref66">66</xref>,<xref ref-type="bibr" rid="ref74">74</xref>,<xref ref-type="bibr" rid="ref92">92</xref>]. In 1 study [<xref ref-type="bibr" rid="ref76">76</xref>], most items (5 out of 6) in a satisfaction survey were better rated in the mannequin-based training than in the virtual patient group.</p>
      </sec>
      <sec>
        <title>Secondary Outcomes</title>
        <p>One study had cost-effectiveness as an outcome [<xref ref-type="bibr" rid="ref58">58</xref>]. In 9 studies, statements were made regarding the cost of the intervention—either monetary or in development time [<xref ref-type="bibr" rid="ref53">53</xref>,<xref ref-type="bibr" rid="ref60">60</xref>,<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref64">64</xref>-<xref ref-type="bibr" rid="ref66">66</xref>,<xref ref-type="bibr" rid="ref79">79</xref>,<xref ref-type="bibr" rid="ref95">95</xref>]. Only 1 study provided numerical data on both types of intervention [<xref ref-type="bibr" rid="ref95">95</xref>]. The comparison was qualitative in 3 studies [<xref ref-type="bibr" rid="ref64">64</xref>,<xref ref-type="bibr" rid="ref65">65</xref>,<xref ref-type="bibr" rid="ref78">78</xref>]. In 5 studies, estimations of costs were made for the virtual patient group without contrasting it with the cost of the control intervention [<xref ref-type="bibr" rid="ref53">53</xref>,<xref ref-type="bibr" rid="ref60">60</xref>,<xref ref-type="bibr" rid="ref62">62</xref>,<xref ref-type="bibr" rid="ref66">66</xref>,<xref ref-type="bibr" rid="ref79">79</xref>]. None of the included studies had patient outcomes or adverse effects as the main outcome measure. Even though none of the studies reported direct patient outcomes, in 2 studies, the participants were observed by raters while performing tasks on real patients as an outcome assessment [<xref ref-type="bibr" rid="ref51">51</xref>,<xref ref-type="bibr" rid="ref83">83</xref>]. In the study by Kumta et al [<xref ref-type="bibr" rid="ref51">51</xref>], the score was included in more complex assessment (including MCQ tests and OSCE examination) and the patient-related outcome was not explicitly reported. In the study by Schittek Janda et al [<xref ref-type="bibr" rid="ref83">83</xref>], first year students of dentistry were asked to perform history taking with real patients and were rated by the instructor. The patients’ perspective was, however, not considered. Even though none of the studies had adverse effects as the major outcome, 6 studies [<xref ref-type="bibr" rid="ref53">53</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref67">67</xref>,<xref ref-type="bibr" rid="ref70">70</xref>,<xref ref-type="bibr" rid="ref84">84</xref>,<xref ref-type="bibr" rid="ref88">88</xref>] reported findings related to noticed unexpected effects of the intervention.</p>
        <sec>
          <title>Cost</title>
          <p>Haerling [<xref ref-type="bibr" rid="ref58">58</xref>] showed a better cost-utility ratio of US $1.08 for virtual patients versus US $3.62 for the mannequin-based training. Foster et al [<xref ref-type="bibr" rid="ref95">95</xref>] compared the cost of human-provided (Mechanical Turk) feedback with backstory video feedback; the cost of human answers was US $0.05 per question assisted, whereas videos required 4 hours of development time and the license cost of a video game (Sims 3 by Electronic Arts). This does not provide a direct answer to the question of which method was more cost-efficient as it depends on the number of participants and time of use. It is also important to notice that the human-generated feedback in virtual patients showed positive effects on the communication skills outcomes, whereas the backstory video did not. Bryant et al [<xref ref-type="bibr" rid="ref78">78</xref>] estimated, but without providing numerical evidence, that the cost of a virtual patient was similar to that of a course text that was eliminated by the new intervention. Liaw et al [<xref ref-type="bibr" rid="ref64">64</xref>], without providing concrete numbers, noticed that despite “initial startup costs for developing the virtual patient simulation, its implementation was less resource intensive than the mannequin-based simulation.” The cost savings were because of reduced instructor time, use of expensive equipment, or simulation facilities. Maleck et al [<xref ref-type="bibr" rid="ref65">65</xref>] saw cost savings in the virtual patient group because of spared radiograph printouts. The cost of the virtual patient intervention was expressed in hours of work; in 2 cases, the cost was 12 to 15 hours per virtual patient [<xref ref-type="bibr" rid="ref53">53</xref>,<xref ref-type="bibr" rid="ref60">60</xref>]; in 1 case it was 15 to 30 hours [<xref ref-type="bibr" rid="ref62">62</xref>] and 100 hours in another [<xref ref-type="bibr" rid="ref66">66</xref>]. The cost expressed in amounts of money was estimated at US $500 for content development and technical implementation [<xref ref-type="bibr" rid="ref62">62</xref>] and US $4800 for a total clerkship restructuring, including adding virtual patients [<xref ref-type="bibr" rid="ref60">60</xref>]. It is worth noticing that in both cases the virtual patients were developed by students. Deladisma et al [<xref ref-type="bibr" rid="ref79">79</xref>] used in their study a virtual patient system that involved a speech recognition engine, tracked user’s body movements, and projected a life-sized avatar on the wall. The cost of the technology used in the pilot study (including 2 networked personal computers, 1 data projector, and 2 Web cameras) was estimated in 2006 to be less than US $7000 [<xref ref-type="bibr" rid="ref102">102</xref>].</p>
        </sec>
        <sec>
          <title>Patient Outcomes</title>
          <p>In the study by Schittek Janda et al [<xref ref-type="bibr" rid="ref83">83</xref>], an experienced clinician rated the professional behavior (language precision, order of question, and empathy) of first year students’ of dentistry toward real patients as significantly higher (<italic>P</italic>&lt;.01) in the group having access to a supplementary virtual patient case than in the group that underwent standard instruction.</p>
        </sec>
        <sec>
          <title>Adverse Effects</title>
          <p>Dankbaar et al [<xref ref-type="bibr" rid="ref88">88</xref>] hypothesize based on their study results that high-fidelity virtual patients may increase motivation, but at the same time be more distracting for novice students and by that impede learning. Authors of 2 studies [<xref ref-type="bibr" rid="ref70">70</xref>,<xref ref-type="bibr" rid="ref84">84</xref>] observe that the language of virtual patients might be a significant factor showing greater effects on nonnative English speaking and bilingual learners than in native English speakers. In the study by Qayumi et al [<xref ref-type="bibr" rid="ref67">67</xref>], it is observed that that lower-achieving students benefit more from virtual patients than high performers. In the study by Botezatu et al [<xref ref-type="bibr" rid="ref55">55</xref>], students knowing about the possibility of being assessed by virtual patients opposed being tested with paper cases. In the study by Al-Dahir et al [<xref ref-type="bibr" rid="ref53">53</xref>], it is observed that analysis of individual learner traces in the virtual patient system negates benefits of social learning.</p>
        </sec>
      </sec>
      <sec>
        <title>Subgroup Analysis</title>
        <p>None of the initially planned subgroup analyses explained the heterogeneity of the results.</p>
        <p>Among many analyzed aspects, we looked into differences regarding the efficiency of learning with virtual patients between the health professions disciplines. Most of the located studies involved students of medicine as participants. For instance, when comparing virtual patients with traditional education in the domain of skills, out of the 12 outcomes included for subgroup analyses, only 2 were from other health profession disciplines than medicine (ie, studies from nursing [<xref ref-type="bibr" rid="ref64">64</xref>,<xref ref-type="bibr" rid="ref73">73</xref>]). When analyzing knowledge outcomes out of the 12 included studies, 4 were nonmedical but represented 3 very different disciplines, nursing [<xref ref-type="bibr" rid="ref58">58</xref>,<xref ref-type="bibr" rid="ref73">73</xref>], pharmacy [<xref ref-type="bibr" rid="ref53">53</xref>], and physiotherapy [<xref ref-type="bibr" rid="ref61">61</xref>]. The conducted subgroup analyses showed no significant differences between the subgroups and high heterogeneity.</p>
        <p>While analyzing aspects of instructional design implemented in the virtual patient scenarios, we were able to locate a very balanced number of studies implementing the narrative and problem-solving designs [<xref ref-type="bibr" rid="ref91">91</xref>] in the domain of knowledge outcomes (6 studies in each branch). Yet, the pooled results showed no difference (narrative: SMD=0.12, 95% CI −0.41 to 0.64, I<sup>2</sup>=85%, n=525 versus problem solving: SMD=0.11, 95% CI −0.17 to 0.38, I<sup>2</sup>=51%, n=520; subgroup differences <italic>P</italic>=.97). Interestingly, when looking into the domain of skills outcomes, all studies had either the problem-solving or unclear design (in 2 cases). This might be an indication that narrative (linear, branched) virtual patients are seen as being better suited for knowledge outcomes rather than skills.</p>
        <fig id="figure6" position="float">
          <label>Figure 6</label>
          <caption>
            <p>Albatross plot for studies comparing virtual patient with traditional education for knowledge outcomes. SMD: standardized mean difference.</p>
          </caption>
          <graphic xlink:href="jmir_v21i7e14676_fig6.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
        <p>Finally, we were unable to see any pattern in efficiency when analyzing the timing of feedback as being either during activity or post activity. However, in almost half of the studies, we were unable to decide, based on the description of the intervention, which model of feedback was implemented or whether the study had a mixed (during/post activity) mode of providing feedback.</p>
        <p>To further explore the reasons for heterogeneity, we visualized the outcomes in the form of albatross plots of the knowledge and skills outcomes for virtual patients to traditional education comparisons. <xref ref-type="fig" rid="figure6">Figure 6</xref> presents an albatross plot for knowledge and <xref ref-type="fig" rid="figure7">Figure 7</xref> for skills outcomes. Comparisons of virtual patients to passive forms of learning (reading exercises and lectures) tended to display large positive effect sizes, whereas those comparing virtual patients to active learning (group discussion or mannequin-based learning) show small effects or even negative effects (left hand side in the <xref ref-type="fig" rid="figure6">Figures 6</xref> and <xref ref-type="fig" rid="figure7">7</xref> and <xref ref-type="app" rid="app6">Multimedia Appendix 6</xref>).</p>
        <fig id="figure7" position="float">
          <label>Figure 7</label>
          <caption>
            <p>Albatross plot for studies comparing virtual patient with traditional education for skills outcome. SMD: standardized mean difference.</p>
          </caption>
          <graphic xlink:href="jmir_v21i7e14676_fig7.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Risk of Bias</title>
        <p>Following the Cochrane methodology [<xref ref-type="bibr" rid="ref40">40</xref>], we have assessed the risk of bias in all included studies. The results of the analysis are summarized in <xref ref-type="fig" rid="figure8">Figure 8</xref>.</p>
        <p>Overall, we do not consider allocation bias as a significant issue in the review as most of the studies either described an adequate randomization method (17 of 51 studies) or even when the description was unclear (31 of 51), it was judged unlikely that the randomization was seriously flawed. Performance bias in comparisons with traditional education is an issue but at the same time is impossible to avoid in this type of research. The blinding of participants in virtual patient design comparisons is possible, but those studies are still relatively uncommon (n=10). The risk of assessor bias was avoided in many studies by using automated or formalized assessment instruments. Consequently, we assessed the risk as low in 42 of 51 studies. However, it is often unclear whether the instruments (eg, MCQ tests, assessment rubrics) were properly validated. We felt that in the majority of studies, attrition bias was within acceptable levels (low risk in 36 of 51 studies). This does not exclude volunteer bias, which is likely to be common, but its influence is difficult to estimate. As there is little tradition of publishing protocols in medical education research, it was problematic to assess selective reporting bias, but we judged the risk as low in 35 out of 51 studies. We were unable to reliably assess publication bias considering the high heterogeneity of studies. None of the cRCT studies considered in the statistical analysis had corrections for clustering, but we have decreased the number of participants in those studies using a method from the Cochrane Handbook to compensate for that. We present more details of the risk of bias analysis in <xref ref-type="app" rid="app7">Multimedia Appendix 7</xref>.</p>
        <p>We rated down the quality of evidence for knowledge and skills outcomes in virtual patients to traditional education comparison because of the high heterogeneity of included studies and limitations in study design (lack of participant blinding, nonvalidated instruments, and potential volunteer bias). For attitudinal and satisfaction outcomes and for other types of comparisons, we additionally rated down the quality as the outcomes were presented as independent items in questionnaires that were not amenable to statistical analysis or the analyses contained just a handful of studies and the CIs were wide. Summary of findings table (GRADE) are presented in <xref ref-type="app" rid="app8">Multimedia Appendix 8</xref>.</p>
        <fig id="figure8" position="float">
          <label>Figure 8</label>
          <caption>
            <p>Risk of bias summary (+ low risk of bias; - high risk of bias, ? unclear risk of bias).</p>
          </caption>
          <graphic xlink:href="jmir_v21i7e14676_fig8.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Principal Findings</title>
        <p>The aim of this review was to evaluate the effectiveness of virtual patients in comparison with other existing educational methods.</p>
        <p>There is low quality evidence that virtual patients are at least as effective as traditional education for knowledge outcome and more effective for skills outcomes. On the basis of the visual analysis of albatross plots, we may hypothesize that replacing passive forms of traditional education with virtual patients brings more benefit than replacing active learning methods. We collected positive evidence of effectiveness from both high-income and low-and-middle-income countries demonstrating the global applicability of virtual patients. Students were generally satisfied with the use of virtual patients, but we also located studies in our review where the use of virtual patients was connected with diminished confidence.</p>
        <p>The strength of our systematic review is the broad perspective which shows the landscape of RCTs in the domain of virtual patients. Our systematic review updates the evidence on virtual patient effectiveness, which was last summarized in a meta-analysis almost a decade ago.</p>
      </sec>
      <sec>
        <title>Limitations</title>
        <p>The limitation of our work is that the wide scope of the review does not allow nuances in the studies to be explored in detail. We were unable to make a firm assessment of publication bias. The high heterogeneity of the results leads to the conclusion that without further consideration of needs and implementation details, we cannot expect that the introduction of virtual patients will always lead to detectable positive outcomes. Evidence to determine the effective factors is sparse and represented by only 10 studies in our review, with very diverse research questions.</p>
        <p>Our review is limited by the decision to exclude crossover design studies. However, this has been discussed in detail in the potential biases in the review process section in <xref ref-type="app" rid="app7">Multimedia Appendix 7</xref>. We excluded studies published before 1991 as we consider the technology available before the World Wide Web to be materially different from that currently available. Finally, we are limited by the sparse description of the interventions in some of the papers, which occasionally might have led to misclassification of the studies.</p>
      </sec>
      <sec>
        <title>Comparison With Prior Work</title>
        <p>Extending the results of the meta-analysis by Cook et al [<xref ref-type="bibr" rid="ref38">38</xref>] and in agreement with the one by Consorti et al [<xref ref-type="bibr" rid="ref39">39</xref>], our review shows that virtual patients have an overall positive pooled effect when compared with some other types of traditional educational methods. Our observations regarding the influence of the type of outcome (knowledge/skills) and comparison (active/passive traditional learning) supplement the evidence in the previous reviews [<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref39">39</xref>], which included studies until 2010. This time point divides the evidence collected in 2 parts: (1) time already covered by previous reviews (1991-2010) and (2) time not included in the previous reviews (2011-2018). It is interesting to note that, though the former timeframe spans over 20 years compared with 8 years in the latter, more studies were included from the latter period, 22 studies (until 2010) versus 29 studies (after 2010). This demonstrates increased interest in virtual patients and medical education in general. The research community around digital health education has long been criticized for publishing media-comparative studies [<xref ref-type="bibr" rid="ref103">103</xref>,<xref ref-type="bibr" rid="ref104">104</xref>]. Media-comparative research aims to make comparisons between different media formats such as paper, face-to-face, and digital education [<xref ref-type="bibr" rid="ref104">104</xref>]. Both Friedman and Cook argue [<xref ref-type="bibr" rid="ref103">103</xref>,<xref ref-type="bibr" rid="ref104">104</xref>] that the limitations of this type of comparison boils down to the inability to produce an adequate control group as interventions are bound to be influenced by too many confounding factors to be generalizable. Even though there are still many media-comparative studies, the number of studies comparing different forms of digital education seem to increase: 3/22 (14%) until 2010 versus 11/29 (38%) after 2010. The number of studies in which students worked from home as an intervention has also increased; before 2011 there was just 1/16 (6%; in 6 studies it was unclear), whereas after 2011, it was 11/22 (50%; in 7 studies it was unclear) studies. However, this potentially raises concerns about how controlled the interventions and measures were, and thus the validity of the conclusions.</p>
        <p>Our observation that virtual patient simulations predominantly effect skills rather than knowledge outcomes can be interpreted as an indication that for lower levels of Bloom's taxonomy [<xref ref-type="bibr" rid="ref105">105</xref>], (<italic>remember, understands</italic>) there is little added value of introducing virtual patients when compared with traditional methods of education. Virtual patients can have greater impact when applied where knowledge is combined with skills and applied in problem solving, and when direct patient contact is not yet possible. We found little evidence to support the use of virtual patients at higher levels of the taxonomy. We also warn against using our result in justifying diminished hours of bedside teaching as this was investigated in just 1 study [<xref ref-type="bibr" rid="ref75">75</xref>] and did not show positive outcomes. Consequently, virtual patients can be said to be a modality for learning in which learners actively use and train their clinical reasoning and critical thinking abilities before bedside learning, as was previously suggested in their critical literature review by Cook and Triola [<xref ref-type="bibr" rid="ref22">22</xref>].</p>
        <p>The perceptions of students toward studying with virtual patients are generally positive. However, some exceptions can be noted. In 1 study [<xref ref-type="bibr" rid="ref77">77</xref>], students were less confident in their skills when compared with facilitated group discussion and lecture. This is in contrast with no observable differences or even better performance in the virtual patient group when considering the objective outcomes in those studies. This could be explained by disbelief in the effectiveness of the new computer-based methods of learning or anxiety of losing direct patient contact.</p>
        <p>The results of our subgroup analysis, though inconsistent, encourage the introduction of more active forms of education. Yet, we note that the range from active to passive learning forms a continuum, and the decision on how to classify each intervention is hampered by sparse descriptions in the reports. Nevertheless, questioning the utility of passive learning is not a new finding and is observed elsewhere, for instance, in the literature on the flipped-classroom learning approach [<xref ref-type="bibr" rid="ref106">106</xref>]. As the effects of comparing virtual patients with other forms of active learning were small and we could not detect any other variables explaining the heterogeneity, it seems reasonable to individually consider other factors such as cost of use, time flexibility, personnel shortage, and availability in different settings (eg, students’ homes or locations remote from academic centers) when determining which methods to use.</p>
        <p>The need for more guidance within virtual patient simulations is apparent in studies differing by instructional methods where narrative virtual patient design was better than more autonomous problem-oriented designs [<xref ref-type="bibr" rid="ref91">91</xref>]. Feedback given by humans at distance in a virtual patient system was better than an animated backstory in increasing empathy [<xref ref-type="bibr" rid="ref95">95</xref>], whereas more active constructing virtual patients with more time on a task but no feedback had no more positive result on the outcomes than learning from a virtual patient scenario [<xref ref-type="bibr" rid="ref100">100</xref>]. This reminds us that presenting realistic patient scenarios with a great degree of freedom cannot be an excuse for neglecting guidance in relation to learning objectives [<xref ref-type="bibr" rid="ref107">107</xref>,<xref ref-type="bibr" rid="ref108">108</xref>].</p>
      </sec>
      <sec>
        <title>Outlook</title>
        <p>We join the plea of Friedman [<xref ref-type="bibr" rid="ref103">103</xref>] and Cook [<xref ref-type="bibr" rid="ref104">104</xref>] to abandon media-comparative research as it is difficult to interpret and we instead encourage greater focus on exploring the utility of different design variants of virtual patient simulations. The current knowledge on the influence of these factors is sparse. A carefully planned study backed up in sound educational theory should provide many valuable research opportunities. However, sufficiently powered samples are needed, as the effects are likely to be small. The second consideration pertains to the need to use previously validated measurement tools that are well-aligned with the learning objectives. Comparisons of outcomes in tools on an item-by-item basis is methodologically questionable and makes the aggregations of results difficult in systematic reviews. We also call for more studies in other health professions disciplines than medicine, as our subgroup analysis showed that evidence of virtual patient effectiveness in such programs as nursing, physiotherapy, or pharmacy is underrepresented. Investigations into patient outcomes and cost-effectiveness of virtual patients are not yet explored directly and form a key avenue for future efforts.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge outcomes as traditional education. Education with virtual patients provides an active form of learning that is beneficial for clinical reasoning skills. Implementations vary and are likely to be broad across pre- and postregistration education, although current studies do not provide clear guidance on when to use virtual patients. We recommend further research be focused on exploring the utility of different design variants of virtual patients.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group>
      <app id="app1">
        <title>Multimedia Appendix 1</title>
        <p>Glossary.</p>
        <media xlink:href="jmir_v21i7e14676_app1.doc" xlink:title="DOC File, 76KB"/>
      </app>
      <app id="app2">
        <title>Multimedia Appendix 2</title>
        <p>MEDLINE (Ovid) search strategy.</p>
        <media xlink:href="jmir_v21i7e14676_app2.doc" xlink:title="DOC File, 47KB"/>
      </app>
      <app id="app3">
        <title>Multimedia Appendix 3</title>
        <p>Summary of included studies.</p>
        <media xlink:href="jmir_v21i7e14676_app3.doc" xlink:title="DOC File, 291KB"/>
      </app>
      <app id="app4">
        <title>Multimedia Appendix 4</title>
        <p>Summary of technical and educational features of included studies.</p>
        <media xlink:href="jmir_v21i7e14676_app4.doc" xlink:title="DOC File, 458KB"/>
      </app>
      <app id="app5">
        <title>Multimedia Appendix 5</title>
        <p>Summary of excluded studies.</p>
        <media xlink:href="jmir_v21i7e14676_app5.doc" xlink:title="DOC File, 60KB"/>
      </app>
      <app id="app6">
        <title>Multimedia Appendix 6</title>
        <p>Subgroup analysis details.</p>
        <media xlink:href="jmir_v21i7e14676_app6.doc" xlink:title="DOC File, 66KB"/>
      </app>
      <app id="app7">
        <title>Multimedia Appendix 7</title>
        <p>Quality of the evidence.</p>
        <media xlink:href="jmir_v21i7e14676_app7.doc" xlink:title="DOC File, 89KB"/>
      </app>
      <app id="app8">
        <title>Multimedia Appendix 8</title>
        <p>Summary of finding tables.</p>
        <media xlink:href="jmir_v21i7e14676_app8.doc" xlink:title="DOC File, 86KB"/>
      </app>
    </app-group>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">3D</term>
          <def>
            <p>3-dimensional</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">cRCT</term>
          <def>
            <p>cluster randomized controlled trials</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">GRADE</term>
          <def>
            <p>Grading of Recommendations Assessment, Development and Evaluation Working Group</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">MCQ</term>
          <def>
            <p>multiple-choice question</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">OSCE</term>
          <def>
            <p>objective structured clinical examination</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">RCT</term>
          <def>
            <p>randomized controlled trial</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">SMD</term>
          <def>
            <p>standardized mean difference</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>The authors wish to acknowledge the help of Jayne Alfredsson, Carina Georg, Anneliese Lilienthal, Italo Masiello, and Monika Semwal at the stage of protocol writing. The authors would like to thank Jim Campbell for his contribution to coordination and conceptual formation of the Digital Health Education Collaboration. The authors would also like to thank Carl Gornitzki, GunBrit Knutssön, and Klas Moberg from the University Library, Karolinska Institute, for developing the search strategy and Ram Chandra Bajpai from Nanyang Technological University for statistical consulting and Pawel Posadzki for his supportive feedback on the manuscript.</p>
      <p>At the time of the study, SE was affiliated with the Karolinska Institutet and Linköping University, and N Saxena was affiliated with Health Services and Outcomes Research, National Healthcare Group, Singapore, Singapore.</p>
    </ack>
    <fn-group>
      <fn fn-type="con">
        <p>JC conceived the idea for the review. AK drafted the protocol with substantial contributions from LW, SE, NS, DD, NSA, LTC, and NZ. The Digital Health Education Collaboration developed the search strategy, obtained copies of studies, and screened the studies. JC and JCD contributed to the coordination and conceptual formation of the Digital Health Education Collaboration. AK, LW, NS, and DD extracted data from studies and conducted the risk of bias assessment. LW contacted the authors in case of missing data. AK carried out the analysis of collected data. LTC provided methodological guidance. AK, LW, SE, NS, DD, LTC, and NZ interpreted the analysis and contributed to the discussion. AK drafted the final review with substantial contributions from all authors. All authors revised and approved the final version of review.</p>
      </fn>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
    <ref-list>
      <ref id="ref1">
        <label>1</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Ramani</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Leinster</surname>
            <given-names>S</given-names>
          </name>
        </person-group>
        <article-title>AMEE Guide no. 34: teaching in the clinical environment</article-title>
        <source>Med Teach</source>  
        <year>2008</year>  
        <month>01</month>  
        <volume>30</volume>  
        <issue>4</issue>  
        <fpage>347</fpage>  
        <lpage>64</lpage>  
        <pub-id pub-id-type="doi">10.1080/01421590802061613</pub-id>
        <pub-id pub-id-type="medline">18569655</pub-id>
        <pub-id pub-id-type="pii">792389225</pub-id></nlm-citation>
      </ref>
      <ref id="ref2">
        <label>2</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Moalem</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Salzman</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Ruan</surname>
            <given-names>DT</given-names>
          </name>
          <name name-style="western">
            <surname>Cherr</surname>
            <given-names>GS</given-names>
          </name>
          <name name-style="western">
            <surname>Freiburg</surname>
            <given-names>CB</given-names>
          </name>
          <name name-style="western">
            <surname>Farkas</surname>
            <given-names>RL</given-names>
          </name>
          <name name-style="western">
            <surname>Brewster</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>James</surname>
            <given-names>TA</given-names>
          </name>
        </person-group>
        <article-title>Should all duty hours be the same? Results of a national survey of surgical trainees</article-title>
        <source>J Am Coll Surg</source>  
        <year>2009</year>  
        <month>07</month>  
        <volume>209</volume>  
        <issue>1</issue>  
        <fpage>47</fpage>  
        <lpage>54, 54.e1-2</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.jamcollsurg.2009.02.053</pub-id>
        <pub-id pub-id-type="medline">19651062</pub-id>
        <pub-id pub-id-type="pii">S1072-7515(09)00223-3</pub-id></nlm-citation>
      </ref>
      <ref id="ref3">
        <label>3</label>
        <nlm-citation citation-type="book">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Dev</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Schleyer</surname>
            <given-names>T</given-names>
          </name>
        </person-group>
        <person-group person-group-type="editor">
          <name name-style="western">
            <surname>Shortliffe</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Cimino</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Computers in health care education</article-title>
        <source>Biomedical Informatics</source>  
        <year>2014</year>  
        <publisher-loc>London</publisher-loc>
        <publisher-name>Springer</publisher-name>
        <fpage>675</fpage>  
        <lpage>93</lpage> </nlm-citation>
      </ref>
      <ref id="ref4">
        <label>4</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Frenk</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Bhutta</surname>
            <given-names>ZA</given-names>
          </name>
          <name name-style="western">
            <surname>Cohen</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Crisp</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Evans</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Fineberg</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Garcia</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Ke</surname>
            <given-names>Y</given-names>
          </name>
          <name name-style="western">
            <surname>Kelley</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Kistnasamy</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Meleis</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Naylor</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Pablos-Mendez</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Reddy</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Scrimshaw</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Sepulveda</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Serwadda</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Zurayk</surname>
            <given-names>H</given-names>
          </name>
        </person-group>
        <article-title>Health professionals for a new century: transforming education to strengthen health systems in an interdependent world</article-title>
        <source>Lancet</source>  
        <year>2010</year>  
        <month>12</month>  
        <day>4</day>  
        <volume>376</volume>  
        <issue>9756</issue>  
        <fpage>1923</fpage>  
        <lpage>58</lpage>  
        <pub-id pub-id-type="doi">10.1016/S0140-6736(10)61854-5</pub-id>
        <pub-id pub-id-type="medline">21112623</pub-id>
        <pub-id pub-id-type="pii">S0140-6736(10)61854-5</pub-id></nlm-citation>
      </ref>
      <ref id="ref5">
        <label>5</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Crisp</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Gawanas</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Sharp</surname>
            <given-names>I</given-names>
          </name>
          <collab>Task Force for Scaling Up EducationTraining for Health Workers</collab>
        </person-group>
        <article-title>Training the health workforce: scaling up, saving lives</article-title>
        <source>Lancet</source>  
        <year>2008</year>  
        <month>02</month>  
        <day>23</day>  
        <volume>371</volume>  
        <issue>9613</issue>  
        <fpage>689</fpage>  
        <lpage>91</lpage>  
        <pub-id pub-id-type="doi">10.1016/S0140-6736(08)60309-8</pub-id>
        <pub-id pub-id-type="medline">18295028</pub-id>
        <pub-id pub-id-type="pii">S0140-6736(08)60309-8</pub-id></nlm-citation>
      </ref>
      <ref id="ref6">
        <label>6</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Carlstedt-Duke</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Posadzki</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Whiting</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Zary</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Atun</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Majeed</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Campbell</surname>
            <given-names>J</given-names>
          </name>
          <collab>Digital Health Education Collaboration</collab>
        </person-group>
        <article-title>Digital education in health professions: the need for overarching evidence synthesis</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>12</month>  
        <day>14</day>  
        <volume>21</volume>  
        <issue>2</issue>  
        <fpage>e12913</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/2/e12913/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12913</pub-id>
        <pub-id pub-id-type="medline">30762583</pub-id>
        <pub-id pub-id-type="pii">v21i2e12913</pub-id></nlm-citation>
      </ref>
      <ref id="ref7">
        <label>7</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Bajpai</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Bajpai</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Ho</surname>
            <given-names>AH</given-names>
          </name>
        </person-group>
        <article-title>Health professions' digital education: review of learning theories in randomized controlled trials by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>03</month>  
        <day>12</day>  
        <volume>21</volume>  
        <issue>3</issue>  
        <fpage>e12912</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/3/e12912/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12912</pub-id>
        <pub-id pub-id-type="medline">30860483</pub-id>
        <pub-id pub-id-type="pii">v21i3e12912</pub-id>
        <pub-id pub-id-type="pmcid">PMC6434396</pub-id></nlm-citation>
      </ref>
      <ref id="ref8">
        <label>8</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Dunleavy</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Nikolaou</surname>
            <given-names>CK</given-names>
          </name>
          <name name-style="western">
            <surname>Nifakos</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Atun</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Law</surname>
            <given-names>GC</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Mobile digital education for health professions: systematic review and meta-analysis by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>02</month>  
        <day>12</day>  
        <volume>21</volume>  
        <issue>2</issue>  
        <fpage>e12937</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/2/e12937/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12937</pub-id>
        <pub-id pub-id-type="medline">30747711</pub-id>
        <pub-id pub-id-type="pii">v21i2e12937</pub-id></nlm-citation>
      </ref>
      <ref id="ref9">
        <label>9</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Gentry</surname>
            <given-names>SV</given-names>
          </name>
          <name name-style="western">
            <surname>Gauthier</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>L'Estrade Ehrstrom</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Wortley</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Lilienthal</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Dauwels-Okutsu</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Nikolaou</surname>
            <given-names>CK</given-names>
          </name>
          <name name-style="western">
            <surname>Zary</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Campbell</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Serious gaming and gamification education in health professions: systematic review</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>03</month>  
        <day>28</day>  
        <volume>21</volume>  
        <issue>3</issue>  
        <fpage>e12994</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/3/e12994/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12994</pub-id>
        <pub-id pub-id-type="medline">30920375</pub-id>
        <pub-id pub-id-type="pii">v21i3e12994</pub-id>
        <pub-id pub-id-type="pmcid">PMC6458534</pub-id></nlm-citation>
      </ref>
      <ref id="ref10">
        <label>10</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>George</surname>
            <given-names>PP</given-names>
          </name>
          <name name-style="western">
            <surname>Zhabenko</surname>
            <given-names>O</given-names>
          </name>
          <name name-style="western">
            <surname>Kyaw</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Antoniou</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Posadzki</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Saxena</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Zary</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Lockwood</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Online digital education for postregistration training of medical doctors: systematic review by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>02</month>  
        <day>25</day>  
        <volume>21</volume>  
        <issue>2</issue>  
        <fpage>e13269</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/2/e13269/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/13269</pub-id>
        <pub-id pub-id-type="medline">30801252</pub-id>
        <pub-id pub-id-type="pii">v21i2e13269</pub-id></nlm-citation>
      </ref>
      <ref id="ref11">
        <label>11</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Huang</surname>
            <given-names>Z</given-names>
          </name>
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Lee</surname>
            <given-names>SY</given-names>
          </name>
          <name name-style="western">
            <surname>Tee</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Ong</surname>
            <given-names>W</given-names>
          </name>
          <name name-style="western">
            <surname>Tan</surname>
            <given-names>WS</given-names>
          </name>
          <name name-style="western">
            <surname>Bajpai</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Digital health professions education on diabetes management: systematic review by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>02</month>  
        <day>21</day>  
        <volume>21</volume>  
        <issue>2</issue>  
        <fpage>e12997</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/2/e12997/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12997</pub-id>
        <pub-id pub-id-type="medline">30789348</pub-id>
        <pub-id pub-id-type="pii">v21i2e12997</pub-id></nlm-citation>
      </ref>
      <ref id="ref12">
        <label>12</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kyaw</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Posadzki</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Dunleavy</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Divakar</surname>
            <given-names>U</given-names>
          </name>
          <name name-style="western">
            <surname>Hervatis</surname>
            <given-names>V</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Offline digital education for medical students: systematic review and meta-analysis by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>03</month>  
        <day>25</day>  
        <volume>21</volume>  
        <issue>3</issue>  
        <fpage>e13165</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/3/e13165/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/13165</pub-id>
        <pub-id pub-id-type="medline">30907731</pub-id>
        <pub-id pub-id-type="pii">v21i3e13165</pub-id>
        <pub-id pub-id-type="pmcid">PMC6452290</pub-id></nlm-citation>
      </ref>
      <ref id="ref13">
        <label>13</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kyaw</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Saxena</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Posadzki</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Vseteckova</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Nikolaou</surname>
            <given-names>CK</given-names>
          </name>
          <name name-style="western">
            <surname>George</surname>
            <given-names>PP</given-names>
          </name>
          <name name-style="western">
            <surname>Divakar</surname>
            <given-names>U</given-names>
          </name>
          <name name-style="western">
            <surname>Masiello</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Kononowicz</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Zary</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Virtual reality for health professions education: systematic review and meta-analysis by the Digital Health Education collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>01</month>  
        <day>22</day>  
        <volume>21</volume>  
        <issue>1</issue>  
        <fpage>e12959</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/1/e12959/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12959</pub-id>
        <pub-id pub-id-type="medline">30668519</pub-id>
        <pub-id pub-id-type="pii">v21i1e12959</pub-id>
        <pub-id pub-id-type="pmcid">PMC6362387</pub-id></nlm-citation>
      </ref>
      <ref id="ref14">
        <label>14</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Lall</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Rees</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Law</surname>
            <given-names>GC</given-names>
          </name>
          <name name-style="western">
            <surname>Dunleavy</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Cotic</surname>
            <given-names>Ž</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Influences on the implementation of mobile learning for medical and nursing education: qualitative systematic review by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>02</month>  
        <day>28</day>  
        <volume>21</volume>  
        <issue>2</issue>  
        <fpage>e12895</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/2/e12895/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12895</pub-id>
        <pub-id pub-id-type="medline">30816847</pub-id>
        <pub-id pub-id-type="pii">v21i2e12895</pub-id></nlm-citation>
      </ref>
      <ref id="ref15">
        <label>15</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Martinengo</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Yeo</surname>
            <given-names>NJY</given-names>
          </name>
          <name name-style="western">
            <surname>Tang</surname>
            <given-names>ZQ</given-names>
          </name>
          <name name-style="western">
            <surname>Markandran</surname>
            <given-names>KD</given-names>
          </name>
          <name name-style="western">
            <surname>Kyaw</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Digital education for the management of chronic wounds in health care professionals: protocol for a systematic review by the Digital Health Education Collaboration</article-title>
        <source>JMIR Res Protoc</source>  
        <year>2019</year>  
        <month>03</month>  
        <day>25</day>  
        <volume>8</volume>  
        <issue>3</issue>  
        <fpage>e12488</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.researchprotocols.org/2019/3/e12488/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12488</pub-id>
        <pub-id pub-id-type="medline">30907743</pub-id>
        <pub-id pub-id-type="pii">v8i3e12488</pub-id>
        <pub-id pub-id-type="pmcid">PMC6452282</pub-id></nlm-citation>
      </ref>
      <ref id="ref16">
        <label>16</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Posadzki</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Bala</surname>
            <given-names>MM</given-names>
          </name>
          <name name-style="western">
            <surname>Kyaw</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Divakar</surname>
            <given-names>U</given-names>
          </name>
          <name name-style="western">
            <surname>Koperny</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Sliwka</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Offline digital education for postregistration health professions: systematic review and meta-analysis by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>04</month>  
        <day>24</day>  
        <volume>21</volume>  
        <issue>4</issue>  
        <fpage>e12968</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/4/e12968/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12968</pub-id>
        <pub-id pub-id-type="medline">31017584</pub-id>
        <pub-id pub-id-type="pii">v21i4e12968</pub-id></nlm-citation>
      </ref>
      <ref id="ref17">
        <label>17</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Whiting</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Bajpai</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Bajpai</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Kyaw</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Digital education for health professions on smoking cessation management: systematic review by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>03</month>  
        <day>4</day>  
        <volume>21</volume>  
        <issue>3</issue>  
        <fpage>e13000</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/3/e13000/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/13000</pub-id>
        <pub-id pub-id-type="medline">30829576</pub-id>
        <pub-id pub-id-type="pii">v21i3e13000</pub-id></nlm-citation>
      </ref>
      <ref id="ref18">
        <label>18</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Kyaw</surname>
            <given-names>BM</given-names>
          </name>
          <name name-style="western">
            <surname>Dunleavy</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Smart</surname>
            <given-names>NA</given-names>
          </name>
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Rotgans</surname>
            <given-names>JI</given-names>
          </name>
          <name name-style="western">
            <surname>Low-Beer</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Campbell</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Digital problem-based learning in health professions: systematic review and meta-analysis by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>02</month>  
        <day>28</day>  
        <volume>21</volume>  
        <issue>2</issue>  
        <fpage>e12945</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/2/e12945/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12945</pub-id>
        <pub-id pub-id-type="medline">30816846</pub-id>
        <pub-id pub-id-type="pii">v21i2e12945</pub-id></nlm-citation>
      </ref>
      <ref id="ref19">
        <label>19</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Wahabi</surname>
            <given-names>HA</given-names>
          </name>
          <name name-style="western">
            <surname>Esmaeil</surname>
            <given-names>SA</given-names>
          </name>
          <name name-style="western">
            <surname>Bahkali</surname>
            <given-names>KH</given-names>
          </name>
          <name name-style="western">
            <surname>Titi</surname>
            <given-names>MA</given-names>
          </name>
          <name name-style="western">
            <surname>Amer</surname>
            <given-names>YS</given-names>
          </name>
          <name name-style="western">
            <surname>Fayed</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Jamal</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Zakaria</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Siddiqui</surname>
            <given-names>AR</given-names>
          </name>
          <name name-style="western">
            <surname>Semwal</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>LT</given-names>
          </name>
          <name name-style="western">
            <surname>Posadzki</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Medical doctors' offline computer-assisted digital education: systematic review by the Digital Health Education Collaboration</article-title>
        <source>J Med Internet Res</source>  
        <year>2019</year>  
        <month>03</month>  
        <day>1</day>  
        <volume>21</volume>  
        <issue>3</issue>  
        <fpage>e12998</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2019/3/e12998/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/12998</pub-id>
        <pub-id pub-id-type="medline">30821689</pub-id>
        <pub-id pub-id-type="pii">v21i3e12998</pub-id>
        <pub-id pub-id-type="pmcid">PMC6418481</pub-id></nlm-citation>
      </ref>
      <ref id="ref20">
        <label>20</label>
        <nlm-citation citation-type="web">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Ellaway</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Candler</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Greene</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Smothers</surname>
            <given-names>V</given-names>
          </name>
        </person-group>
        <source>MedBiquitous</source>  
        <access-date>2019-05-10</access-date>
        <comment>An Architectural Model for MedBiquitous Virtual Patients 
        <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://tinyurl.com/jpewpbt">http://tinyurl.com/jpewpbt</ext-link>
        <ext-link ext-link-type="webcite" xlink:href="6qkBNcQGi"/></comment> </nlm-citation>
      </ref>
      <ref id="ref21">
        <label>21</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kononowicz</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Zary</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Edelbring</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Corral</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Hege</surname>
            <given-names>I</given-names>
          </name>
        </person-group>
        <article-title>Virtual patients - what are we talking about? A framework to classify the meanings of the term in healthcare education</article-title>
        <source>BMC Med Educ</source>  
        <year>2015</year>  
        <volume>15</volume>  
        <fpage>11</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.biomedcentral.com/1472-6920/15/11"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1186/s12909-015-0296-3</pub-id>
        <pub-id pub-id-type="medline">25638167</pub-id>
        <pub-id pub-id-type="pii">s12909-015-0296-3</pub-id>
        <pub-id pub-id-type="pmcid">PMC4318546</pub-id></nlm-citation>
      </ref>
      <ref id="ref22">
        <label>22</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Cook</surname>
            <given-names>DA</given-names>
          </name>
          <name name-style="western">
            <surname>Triola</surname>
            <given-names>MM</given-names>
          </name>
        </person-group>
        <article-title>Virtual patients: a critical literature review and proposed next steps</article-title>
        <source>Med Educ</source>  
        <year>2009</year>  
        <month>04</month>  
        <volume>43</volume>  
        <issue>4</issue>  
        <fpage>303</fpage>  
        <lpage>11</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1365-2923.2008.03286.x</pub-id>
        <pub-id pub-id-type="medline">19335571</pub-id>
        <pub-id pub-id-type="pii">MED3286</pub-id></nlm-citation>
      </ref>
      <ref id="ref23">
        <label>23</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Posel</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>McGee</surname>
            <given-names>JB</given-names>
          </name>
          <name name-style="western">
            <surname>Fleiszer</surname>
            <given-names>DM</given-names>
          </name>
        </person-group>
        <article-title>Twelve tips to support the development of clinical reasoning skills using virtual patient cases</article-title>
        <source>Med Teach</source>  
        <year>2014</year>  
        <month>12</month>  
        <day>19</day>  
        <fpage>1</fpage>  
        <lpage>6</lpage>  
        <pub-id pub-id-type="doi">10.3109/0142159X.2014.993951</pub-id>
        <pub-id pub-id-type="medline">25523009</pub-id></nlm-citation>
      </ref>
      <ref id="ref24">
        <label>24</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Berman</surname>
            <given-names>NB</given-names>
          </name>
          <name name-style="western">
            <surname>Durning</surname>
            <given-names>SJ</given-names>
          </name>
          <name name-style="western">
            <surname>Fischer</surname>
            <given-names>MR</given-names>
          </name>
          <name name-style="western">
            <surname>Huwendiek</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Triola</surname>
            <given-names>MM</given-names>
          </name>
        </person-group>
        <article-title>The role for virtual patients in the future of medical education</article-title>
        <source>Acad Med</source>  
        <year>2016</year>  
        <month>09</month>  
        <volume>91</volume>  
        <issue>9</issue>  
        <fpage>1217</fpage>  
        <lpage>22</lpage>  
        <pub-id pub-id-type="doi">10.1097/ACM.0000000000001146</pub-id>
        <pub-id pub-id-type="medline">26959224</pub-id></nlm-citation>
      </ref>
      <ref id="ref25">
        <label>25</label>
        <nlm-citation citation-type="book">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kolb</surname>
            <given-names>DA</given-names>
          </name>
        </person-group>
        <source>Experiential Learning: Experience As The Source Of Learning And Development</source>  
        <year>1984</year>  
        <publisher-loc>Upper Saddle River, New Jersey</publisher-loc>
        <publisher-name>Prentice Hall</publisher-name></nlm-citation>
      </ref>
      <ref id="ref26">
        <label>26</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Yardley</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Teunissen</surname>
            <given-names>PW</given-names>
          </name>
          <name name-style="western">
            <surname>Dornan</surname>
            <given-names>T</given-names>
          </name>
        </person-group>
        <article-title>Experiential learning: AMEE Guide No. 63</article-title>
        <source>Med Teach</source>  
        <year>2012</year>  
        <volume>34</volume>  
        <issue>2</issue>  
        <fpage>e102</fpage>  
        <lpage>15</lpage>  
        <pub-id pub-id-type="doi">10.3109/0142159X.2012.650741</pub-id>
        <pub-id pub-id-type="medline">22289008</pub-id></nlm-citation>
      </ref>
      <ref id="ref27">
        <label>27</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Edelbring</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Dastmalchi</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Hult</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Lundberg</surname>
            <given-names>IE</given-names>
          </name>
          <name name-style="western">
            <surname>Dahlgren</surname>
            <given-names>LO</given-names>
          </name>
        </person-group>
        <article-title>Experiencing virtual patients in clinical learning: a phenomenological study</article-title>
        <source>Adv Health Sci Educ Theory Pract</source>  
        <year>2011</year>  
        <month>08</month>  
        <volume>16</volume>  
        <issue>3</issue>  
        <fpage>331</fpage>  
        <lpage>45</lpage>  
        <pub-id pub-id-type="doi">10.1007/s10459-010-9265-0</pub-id>
        <pub-id pub-id-type="medline">21656337</pub-id></nlm-citation>
      </ref>
      <ref id="ref28">
        <label>28</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Norman</surname>
            <given-names>G</given-names>
          </name>
        </person-group>
        <article-title>Research in clinical reasoning: past history and current trends</article-title>
        <source>Med Educ</source>  
        <year>2005</year>  
        <month>04</month>  
        <volume>39</volume>  
        <issue>4</issue>  
        <fpage>418</fpage>  
        <lpage>27</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1365-2929.2005.02127.x</pub-id>
        <pub-id pub-id-type="medline">15813765</pub-id>
        <pub-id pub-id-type="pii">MED2127</pub-id></nlm-citation>
      </ref>
      <ref id="ref29">
        <label>29</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Berman</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Fall</surname>
            <given-names>LH</given-names>
          </name>
          <name name-style="western">
            <surname>Smith</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Levine</surname>
            <given-names>DA</given-names>
          </name>
          <name name-style="western">
            <surname>Maloney</surname>
            <given-names>CG</given-names>
          </name>
          <name name-style="western">
            <surname>Potts</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Siegel</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Foster-Johnson</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Integration strategies for using virtual patients in clinical clerkships</article-title>
        <source>Acad Med</source>  
        <year>2009</year>  
        <month>07</month>  
        <volume>84</volume>  
        <issue>7</issue>  
        <fpage>942</fpage>  
        <lpage>9</lpage>  
        <pub-id pub-id-type="doi">10.1097/ACM.0b013e3181a8c668</pub-id>
        <pub-id pub-id-type="medline">19550193</pub-id>
        <pub-id pub-id-type="pii">00001888-200907000-00030</pub-id></nlm-citation>
      </ref>
      <ref id="ref30">
        <label>30</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kenny</surname>
            <given-names>NP</given-names>
          </name>
          <name name-style="western">
            <surname>Beagan</surname>
            <given-names>BL</given-names>
          </name>
        </person-group>
        <article-title>The patient as text: a challenge for problem-based learning</article-title>
        <source>Med Educ</source>  
        <year>2004</year>  
        <month>10</month>  
        <volume>38</volume>  
        <issue>10</issue>  
        <fpage>1071</fpage>  
        <lpage>9</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1365-2929.2004.01956.x</pub-id>
        <pub-id pub-id-type="medline">15461652</pub-id>
        <pub-id pub-id-type="pii">MED1956</pub-id></nlm-citation>
      </ref>
      <ref id="ref31">
        <label>31</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Button</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Harrington</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Belan</surname>
            <given-names>I</given-names>
          </name>
        </person-group>
        <article-title>E-learning &amp; information communication technology (ICT) in nursing education: a review of the literature</article-title>
        <source>Nurse Educ Today</source>  
        <year>2014</year>  
        <month>10</month>  
        <volume>34</volume>  
        <issue>10</issue>  
        <fpage>1311</fpage>  
        <lpage>23</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.nedt.2013.05.002</pub-id>
        <pub-id pub-id-type="medline">23786869</pub-id>
        <pub-id pub-id-type="pii">S0260-6917(13)00165-2</pub-id></nlm-citation>
      </ref>
      <ref id="ref32">
        <label>32</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Watson</surname>
            <given-names>JA</given-names>
          </name>
          <name name-style="western">
            <surname>Pecchioni</surname>
            <given-names>LL</given-names>
          </name>
        </person-group>
        <article-title>Digital natives and digital media in the college classroom: assignment design and impacts on student learning</article-title>
        <source>Educ Media Int</source>  
        <year>2011</year>  
        <month>12</month>  
        <volume>48</volume>  
        <issue>4</issue>  
        <fpage>307</fpage>  
        <lpage>20</lpage>  
        <pub-id pub-id-type="doi">10.1080/09523987.2011.632278</pub-id></nlm-citation>
      </ref>
      <ref id="ref33">
        <label>33</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Schifferdecker</surname>
            <given-names>KE</given-names>
          </name>
          <name name-style="western">
            <surname>Berman</surname>
            <given-names>NB</given-names>
          </name>
          <name name-style="western">
            <surname>Fall</surname>
            <given-names>LH</given-names>
          </name>
          <name name-style="western">
            <surname>Fischer</surname>
            <given-names>MR</given-names>
          </name>
        </person-group>
        <article-title>Adoption of computer-assisted learning in medical education: the educators' perspective</article-title>
        <source>Med Educ</source>  
        <year>2012</year>  
        <month>11</month>  
        <volume>46</volume>  
        <issue>11</issue>  
        <fpage>1063</fpage>  
        <lpage>73</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1365-2923.2012.04350.x</pub-id>
        <pub-id pub-id-type="medline">23078683</pub-id></nlm-citation>
      </ref>
      <ref id="ref34">
        <label>34</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Baumann-Birkbeck</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Florentina</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Karatas</surname>
            <given-names>O</given-names>
          </name>
          <name name-style="western">
            <surname>Sun</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Tang</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Thaung</surname>
            <given-names>V</given-names>
          </name>
          <name name-style="western">
            <surname>McFarland</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Bernaitis</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Khan</surname>
            <given-names>SA</given-names>
          </name>
          <name name-style="western">
            <surname>Grant</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Anoopkumar-Dukie</surname>
            <given-names>S</given-names>
          </name>
        </person-group>
        <article-title>Appraising the role of the virtual patient for therapeutics health education</article-title>
        <source>Curr Pharm Teach Learn</source>  
        <year>2017</year>  
        <month>12</month>  
        <volume>9</volume>  
        <issue>5</issue>  
        <fpage>934</fpage>  
        <lpage>44</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.cptl.2017.05.012</pub-id>
        <pub-id pub-id-type="medline">29233327</pub-id>
        <pub-id pub-id-type="pii">S1877-1297(16)30164-2</pub-id></nlm-citation>
      </ref>
      <ref id="ref35">
        <label>35</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Cendan</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Lok</surname>
            <given-names>B</given-names>
          </name>
        </person-group>
        <article-title>The use of virtual patients in medical school curricula</article-title>
        <source>Adv Physiol Educ</source>  
        <year>2012</year>  
        <month>03</month>  
        <volume>36</volume>  
        <issue>1</issue>  
        <fpage>48</fpage>  
        <lpage>53</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://advan.physiology.org/cgi/pmidlookup?view=long&amp;pmid=22383412"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1152/advan.00054.2011</pub-id>
        <pub-id pub-id-type="medline">22383412</pub-id>
        <pub-id pub-id-type="pii">36/1/48</pub-id>
        <pub-id pub-id-type="pmcid">PMC3776425</pub-id></nlm-citation>
      </ref>
      <ref id="ref36">
        <label>36</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Poulton</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Balasubramaniam</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <article-title>Virtual patients: a year of change</article-title>
        <source>Med Teach</source>  
        <year>2011</year>  
        <month>01</month>  
        <volume>33</volume>  
        <issue>11</issue>  
        <fpage>933</fpage>  
        <lpage>7</lpage>  
        <pub-id pub-id-type="doi">10.3109/0142159X.2011.613501</pub-id>
        <pub-id pub-id-type="medline">22022903</pub-id></nlm-citation>
      </ref>
      <ref id="ref37">
        <label>37</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Saleh</surname>
            <given-names>N</given-names>
          </name>
        </person-group>
        <article-title>The value of virtual patients in medical education</article-title>
        <source>Ann Behav Sci Med Educ</source>  
        <year>2010</year>  
        <month>10</month>  
        <day>16</day>  
        <volume>16</volume>  
        <issue>2</issue>  
        <fpage>29</fpage>  
        <lpage>31</lpage>  
        <pub-id pub-id-type="doi">10.1007/BF03355129</pub-id></nlm-citation>
      </ref>
      <ref id="ref38">
        <label>38</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Cook</surname>
            <given-names>DA</given-names>
          </name>
          <name name-style="western">
            <surname>Erwin</surname>
            <given-names>PJ</given-names>
          </name>
          <name name-style="western">
            <surname>Triola</surname>
            <given-names>MM</given-names>
          </name>
        </person-group>
        <article-title>Computerized virtual patients in health professions education: a systematic review and meta-analysis</article-title>
        <source>Acad Med</source>  
        <year>2010</year>  
        <month>10</month>  
        <volume>85</volume>  
        <issue>10</issue>  
        <fpage>1589</fpage>  
        <lpage>602</lpage>  
        <pub-id pub-id-type="doi">10.1097/ACM.0b013e3181edfe13</pub-id>
        <pub-id pub-id-type="medline">20703150</pub-id></nlm-citation>
      </ref>
      <ref id="ref39">
        <label>39</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Consorti</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Mancuso</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Nocioni</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Piccolo</surname>
            <given-names>A</given-names>
          </name>
        </person-group>
        <article-title>Efficacy of virtual patients in medical education: a meta-analysis of randomized studies</article-title>
        <source>Comput Educ</source>  
        <year>2012</year>  
        <month>11</month>  
        <volume>59</volume>  
        <issue>3</issue>  
        <fpage>1001</fpage>  
        <lpage>8</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.compedu.2012.04.017</pub-id></nlm-citation>
      </ref>
      <ref id="ref40">
        <label>40</label>
        <nlm-citation citation-type="book">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Higgins</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Green</surname>
            <given-names>S</given-names>
          </name>
        </person-group>
        <source>Cochrane Handbook For Systematic Reviews Of Interventions</source>  
        <year>2008</year>  
        <publisher-loc>Chichester, England</publisher-loc>
        <publisher-name>John Wiley &amp; Sons</publisher-name></nlm-citation>
      </ref>
      <ref id="ref41">
        <label>41</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kononowicz</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Woodham</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Georg</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Edelbring</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Stathakarou</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Davies</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Masiello</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Saxena</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Tudor Car</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Car</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Zary</surname>
            <given-names>N</given-names>
          </name>
        </person-group>
        <article-title>Virtual patient simulations for health professional education</article-title>
        <source>Cochrane Database Syst Rev</source>  
        <year>2016</year>  
        <month>05</month>  
        <day>19</day>  
        <issue>5</issue>  
        <fpage>CD012194</fpage>  
        <pub-id pub-id-type="doi">10.1002/14651858.CD012194</pub-id></nlm-citation>
      </ref>
      <ref id="ref42">
        <label>42</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Liberati</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Altman</surname>
            <given-names>DG</given-names>
          </name>
          <name name-style="western">
            <surname>Tetzlaff</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Mulrow</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Gøtzsche</surname>
            <given-names>PC</given-names>
          </name>
          <name name-style="western">
            <surname>Ioannidis</surname>
            <given-names>JP</given-names>
          </name>
          <name name-style="western">
            <surname>Clarke</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Devereaux</surname>
            <given-names>PJ</given-names>
          </name>
          <name name-style="western">
            <surname>Kleijnen</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Moher</surname>
            <given-names>D</given-names>
          </name>
        </person-group>
        <article-title>The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration</article-title>
        <source>PLoS Med</source>  
        <year>2009</year>  
        <month>07</month>  
        <day>21</day>  
        <volume>6</volume>  
        <issue>7</issue>  
        <fpage>e1000100</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://dx.plos.org/10.1371/journal.pmed.1000100"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1371/journal.pmed.1000100</pub-id>
        <pub-id pub-id-type="medline">19621070</pub-id>
        <pub-id pub-id-type="pmcid">PMC2707010</pub-id></nlm-citation>
      </ref>
      <ref id="ref43">
        <label>43</label>
        <nlm-citation citation-type="web">
        <source>EndNote X7</source>  
        <year>2016</year>  
        <access-date>2019-05-10</access-date>
        <publisher-loc>Philadelphia, PA</publisher-loc>
        <publisher-name>Thomson Reuters</publisher-name>
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://endnote.com/">https://endnote.com/</ext-link>
        </comment> </nlm-citation>
      </ref>
      <ref id="ref44">
        <label>44</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Wan</surname>
            <given-names>X</given-names>
          </name>
          <name name-style="western">
            <surname>Wang</surname>
            <given-names>W</given-names>
          </name>
          <name name-style="western">
            <surname>Liu</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Tong</surname>
            <given-names>T</given-names>
          </name>
        </person-group>
        <article-title>Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range</article-title>
        <source>BMC Med Res Methodol</source>  
        <year>2014</year>  
        <month>12</month>  
        <day>19</day>  
        <volume>14</volume>  
        <fpage>135</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-14-135"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1186/1471-2288-14-135</pub-id>
        <pub-id pub-id-type="medline">25524443</pub-id>
        <pub-id pub-id-type="pii">1471-2288-14-135</pub-id>
        <pub-id pub-id-type="pmcid">PMC4383202</pub-id></nlm-citation>
      </ref>
      <ref id="ref45">
        <label>45</label>
        <nlm-citation citation-type="web">
        <source>Cochrane Community</source>  
        <year>2014</year>  
        <access-date>2019-05-10</access-date>
        <publisher-loc>Copenhagen, Denmark</publisher-loc>
        <publisher-name>The Nordic Cochrane Centre</publisher-name>
        <comment>Review Manager (RevMan) Version 5.3 
        <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://community.cochrane.org/help/tools-and-software/revman-5">https://community.cochrane.org/help/tools-and-software/revman-5</ext-link></comment> </nlm-citation>
      </ref>
      <ref id="ref46">
        <label>46</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Harrison</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Jones</surname>
            <given-names>HE</given-names>
          </name>
          <name name-style="western">
            <surname>Martin</surname>
            <given-names>RM</given-names>
          </name>
          <name name-style="western">
            <surname>Lewis</surname>
            <given-names>SJ</given-names>
          </name>
          <name name-style="western">
            <surname>Higgins</surname>
            <given-names>JP</given-names>
          </name>
        </person-group>
        <article-title>The albatross plot: a novel graphical tool for presenting results of diversely reported studies in a systematic review</article-title>
        <source>Res Synth Methods</source>  
        <year>2017</year>  
        <month>09</month>  
        <volume>8</volume>  
        <issue>3</issue>  
        <fpage>281</fpage>  
        <lpage>9</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/28453179"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1002/jrsm.1239</pub-id>
        <pub-id pub-id-type="medline">28453179</pub-id>
        <pub-id pub-id-type="pmcid">PMC5599982</pub-id></nlm-citation>
      </ref>
      <ref id="ref47">
        <label>47</label>
        <nlm-citation citation-type="web">
        <source>R: A Language and Environment for Statistical Computing</source>  
        <year>2017</year>  
        <access-date>2019-05-10</access-date>
        <publisher-loc>Vienna, Austria</publisher-loc>
        <publisher-name>R Core Team</publisher-name>
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://www.r-project.org/">https://www.r-project.org/</ext-link>
        </comment> </nlm-citation>
      </ref>
      <ref id="ref48">
        <label>48</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kurihara</surname>
            <given-names>Y</given-names>
          </name>
          <name name-style="western">
            <surname>Kuramoto</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Matsuura</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Miki</surname>
            <given-names>Y</given-names>
          </name>
          <name name-style="western">
            <surname>Oda</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Seo</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Watabe</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Qayumi</surname>
            <given-names>AK</given-names>
          </name>
        </person-group>
        <article-title>Academic performance and comparative effectiveness of computer- and textbook-based self-instruction</article-title>
        <source>Stud Health Technol Inform</source>  
        <year>2004</year>  
        <volume>107</volume>  
        <issue>Pt 2</issue>  
        <fpage>894</fpage>  
        <lpage>7</lpage>  
        <pub-id pub-id-type="medline">15360941</pub-id>
        <pub-id pub-id-type="pii">D040004039</pub-id></nlm-citation>
      </ref>
      <ref id="ref49">
        <label>49</label>
        <nlm-citation citation-type="confproc">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Succar</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Grigg</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>A new vision for teaching ophthalmology in the medical curriculum: The Virtual Ophthalmology clinic</article-title>
        <year>2010</year>  
        <conf-name>ASCILITE Conference</conf-name>
        <conf-date>December 5-8, 2010</conf-date>
        <conf-loc>Sydney, Australia</conf-loc>
        <fpage>944</fpage>  
        <lpage>7</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1442-9071.2010.02415.x</pub-id></nlm-citation>
      </ref>
      <ref id="ref50">
        <label>50</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kononowicz</surname>
            <given-names>AA</given-names>
          </name>
          <name name-style="western">
            <surname>Krawczyk</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Cebula</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Dembkowska</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Drab</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Fraczek</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Stachoń</surname>
            <given-names>AJ</given-names>
          </name>
          <name name-style="western">
            <surname>Andres</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>Effects of introducing a voluntary virtual patient module to a basic life support with an automated external defibrillator course: a randomised trial</article-title>
        <source>BMC Med Educ</source>  
        <year>2012</year>  
        <month>06</month>  
        <day>18</day>  
        <volume>12</volume>  
        <fpage>41</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://bmcmededuc.biomedcentral.com/articles/10.1186/1472-6920-12-41"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1186/1472-6920-12-41</pub-id>
        <pub-id pub-id-type="medline">22709278</pub-id>
        <pub-id pub-id-type="pii">1472-6920-12-41</pub-id>
        <pub-id pub-id-type="pmcid">PMC3408380</pub-id></nlm-citation>
      </ref>
      <ref id="ref51">
        <label>51</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kumta</surname>
            <given-names>SM</given-names>
          </name>
          <name name-style="western">
            <surname>Tsang</surname>
            <given-names>PL</given-names>
          </name>
          <name name-style="western">
            <surname>Hung</surname>
            <given-names>LK</given-names>
          </name>
          <name name-style="western">
            <surname>Cheng</surname>
            <given-names>JCY</given-names>
          </name>
        </person-group>
        <article-title>Fostering critical thinking skills through a web-based tutorial programme for final year medical students--A randomized controlled study</article-title>
        <source>J Educ Multimed Hypermedia</source>  
        <year>2003</year>  
        <volume>12</volume>  
        <issue>3</issue>  
        <fpage>267</fpage>  
        <lpage>73</lpage> </nlm-citation>
      </ref>
      <ref id="ref52">
        <label>52</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Succar</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Zebington</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Billson</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Byth</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Barrie</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>McCluskey</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Grigg</surname>
            <given-names>J</given-names>
          </name>
        </person-group>
        <article-title>The impact of the Virtual Ophthalmology Clinic on medical students' learning: a randomised controlled trial</article-title>
        <source>Eye (Lond)</source>  
        <year>2013</year>  
        <month>10</month>  
        <volume>27</volume>  
        <issue>10</issue>  
        <fpage>1151</fpage>  
        <lpage>7</lpage>  
        <pub-id pub-id-type="doi">10.1038/eye.2013.143</pub-id>
        <pub-id pub-id-type="medline">23867718</pub-id>
        <pub-id pub-id-type="pii">eye2013143</pub-id>
        <pub-id pub-id-type="pmcid">PMC3806573</pub-id></nlm-citation>
      </ref>
      <ref id="ref53">
        <label>53</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Al-Dahir</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Bryant</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Kennedy</surname>
            <given-names>KB</given-names>
          </name>
          <name name-style="western">
            <surname>Robinson</surname>
            <given-names>DS</given-names>
          </name>
        </person-group>
        <article-title>Online virtual-patient cases versus traditional problem-based learning in advanced pharmacy practice experiences</article-title>
        <source>Am J Pharm Educ</source>  
        <year>2014</year>  
        <month>05</month>  
        <day>15</day>  
        <volume>78</volume>  
        <issue>4</issue>  
        <fpage>76</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/24850938"/>
        </comment>  
        <pub-id pub-id-type="doi">10.5688/ajpe78476</pub-id>
        <pub-id pub-id-type="medline">24850938</pub-id>
        <pub-id pub-id-type="pii">ajpe76</pub-id>
        <pub-id pub-id-type="pmcid">PMC4028585</pub-id></nlm-citation>
      </ref>
      <ref id="ref54">
        <label>54</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Bonnetain</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Boucheix</surname>
            <given-names>JM</given-names>
          </name>
          <name name-style="western">
            <surname>Hamet</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Freysz</surname>
            <given-names>M</given-names>
          </name>
        </person-group>
        <article-title>Benefits of computer screen-based simulation in learning cardiac arrest procedures</article-title>
        <source>Med Educ</source>  
        <year>2010</year>  
        <month>07</month>  
        <volume>44</volume>  
        <issue>7</issue>  
        <fpage>716</fpage>  
        <lpage>22</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1365-2923.2010.03708.x</pub-id>
        <pub-id pub-id-type="medline">20636591</pub-id>
        <pub-id pub-id-type="pii">MED3708</pub-id></nlm-citation>
      </ref>
      <ref id="ref55">
        <label>55</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Botezatu</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Hult</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Tessma</surname>
            <given-names>MK</given-names>
          </name>
          <name name-style="western">
            <surname>Fors</surname>
            <given-names>UGH</given-names>
          </name>
        </person-group>
        <article-title>Virtual patient simulation for learning and assessment: superior results in comparison with regular course exams</article-title>
        <source>Med Teach</source>  
        <year>2010</year>  
        <volume>32</volume>  
        <issue>10</issue>  
        <fpage>845</fpage>  
        <lpage>50</lpage>  
        <pub-id pub-id-type="doi">10.3109/01421591003695287</pub-id>
        <pub-id pub-id-type="medline">20854161</pub-id></nlm-citation>
      </ref>
      <ref id="ref56">
        <label>56</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Botezatu</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Hult</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Tessma</surname>
            <given-names>MK</given-names>
          </name>
          <name name-style="western">
            <surname>Fors</surname>
            <given-names>U</given-names>
          </name>
        </person-group>
        <article-title>Virtual patient simulation: knowledge gain or knowledge loss?</article-title>
        <source>Med Teach</source>  
        <year>2010</year>  
        <volume>32</volume>  
        <issue>7</issue>  
        <fpage>562</fpage>  
        <lpage>8</lpage>  
        <pub-id pub-id-type="doi">10.3109/01421590903514630</pub-id>
        <pub-id pub-id-type="medline">20653378</pub-id></nlm-citation>
      </ref>
      <ref id="ref57">
        <label>57</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Fleetwood</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Vaught</surname>
            <given-names>W</given-names>
          </name>
          <name name-style="western">
            <surname>Feldman</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Gracely</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Kassutto</surname>
            <given-names>Z</given-names>
          </name>
          <name name-style="western">
            <surname>Novack</surname>
            <given-names>D</given-names>
          </name>
        </person-group>
        <article-title>MedEthEx Online: a computer-based learning program in medical ethics and communication skills</article-title>
        <source>Teach Learn Med</source>  
        <year>2000</year>  
        <volume>12</volume>  
        <issue>2</issue>  
        <fpage>96</fpage>  
        <lpage>104</lpage>  
        <pub-id pub-id-type="doi">10.1207/S15328015TLM1202_7</pub-id>
        <pub-id pub-id-type="medline">11228685</pub-id></nlm-citation>
      </ref>
      <ref id="ref58">
        <label>58</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Haerling</surname>
            <given-names>KA</given-names>
          </name>
        </person-group>
        <article-title>Cost-utility analysis of virtual and mannequin-based simulation</article-title>
        <source>Simul Healthc</source>  
        <year>2018</year>  
        <month>02</month>  
        <volume>13</volume>  
        <issue>1</issue>  
        <fpage>33</fpage>  
        <lpage>40</lpage>  
        <pub-id pub-id-type="doi">10.1097/SIH.0000000000000280</pub-id>
        <pub-id pub-id-type="medline">29373382</pub-id></nlm-citation>
      </ref>
      <ref id="ref59">
        <label>59</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Jeimy</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Wang</surname>
            <given-names>JY</given-names>
          </name>
          <name name-style="western">
            <surname>Richardson</surname>
            <given-names>L</given-names>
          </name>
        </person-group>
        <article-title>Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study</article-title>
        <source>BMC Res Notes</source>  
        <year>2018</year>  
        <month>06</month>  
        <day>5</day>  
        <volume>11</volume>  
        <issue>1</issue>  
        <fpage>357</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-018-3463-x"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1186/s13104-018-3463-x</pub-id>
        <pub-id pub-id-type="medline">29871699</pub-id>
        <pub-id pub-id-type="pii">10.1186/s13104-018-3463-x</pub-id>
        <pub-id pub-id-type="pmcid">PMC5989465</pub-id></nlm-citation>
      </ref>
      <ref id="ref60">
        <label>60</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kandasamy</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Fung</surname>
            <given-names>K</given-names>
          </name>
        </person-group>
        <article-title>Interactive internet-based cases for undergraduate otolaryngology education</article-title>
        <source>Otolaryngol Head Neck Surg</source>  
        <year>2009</year>  
        <month>03</month>  
        <volume>140</volume>  
        <issue>3</issue>  
        <fpage>398</fpage>  
        <lpage>402</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.otohns.2008.11.033</pub-id>
        <pub-id pub-id-type="medline">19248951</pub-id>
        <pub-id pub-id-type="pii">S0194-5998(08)01645-8</pub-id></nlm-citation>
      </ref>
      <ref id="ref61">
        <label>61</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kinney</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Keskula</surname>
            <given-names>DR</given-names>
          </name>
          <name name-style="western">
            <surname>Perry</surname>
            <given-names>JF</given-names>
          </name>
        </person-group>
        <article-title>The effect of a computer assisted instructional program on physical therapy students</article-title>
        <source>J Allied Health</source>  
        <year>1997</year>  
        <volume>26</volume>  
        <issue>2</issue>  
        <fpage>57</fpage>  
        <lpage>61</lpage>  
        <pub-id pub-id-type="medline">9268782</pub-id></nlm-citation>
      </ref>
      <ref id="ref62">
        <label>62</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Leong</surname>
            <given-names>SL</given-names>
          </name>
          <name name-style="western">
            <surname>Baldwin</surname>
            <given-names>CD</given-names>
          </name>
          <name name-style="western">
            <surname>Adelman</surname>
            <given-names>AM</given-names>
          </name>
        </person-group>
        <article-title>Integrating web-based computer cases into a required clerkship: development and evaluation</article-title>
        <source>Acad Med</source>  
        <year>2003</year>  
        <month>03</month>  
        <volume>78</volume>  
        <issue>3</issue>  
        <fpage>295</fpage>  
        <lpage>301</lpage>  
        <pub-id pub-id-type="medline">12634211</pub-id></nlm-citation>
      </ref>
      <ref id="ref63">
        <label>63</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Li</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Li</surname>
            <given-names>QL</given-names>
          </name>
          <name name-style="western">
            <surname>Li</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>ML</given-names>
          </name>
          <name name-style="western">
            <surname>Xie</surname>
            <given-names>HF</given-names>
          </name>
          <name name-style="western">
            <surname>Li</surname>
            <given-names>YP</given-names>
          </name>
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>X</given-names>
          </name>
        </person-group>
        <article-title>Comparison of three problem-based learning conditions (real patients, digital and paper) with lecture-based learning in a dermatology course: a prospective randomized study from China</article-title>
        <source>Med Teach</source>  
        <year>2013</year>  
        <volume>35</volume>  
        <issue>2</issue>  
        <fpage>e963</fpage>  
        <lpage>70</lpage>  
        <pub-id pub-id-type="doi">10.3109/0142159X.2012.719651</pub-id>
        <pub-id pub-id-type="medline">23009254</pub-id></nlm-citation>
      </ref>
      <ref id="ref64">
        <label>64</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Liaw</surname>
            <given-names>SY</given-names>
          </name>
          <name name-style="western">
            <surname>Chan</surname>
            <given-names>SW</given-names>
          </name>
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Hooi</surname>
            <given-names>SC</given-names>
          </name>
          <name name-style="western">
            <surname>Siau</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <article-title>Comparison of virtual patient simulation with mannequin-based simulation for improving clinical performances in assessing and managing clinical deterioration: randomized controlled trial</article-title>
        <source>J Med Internet Res</source>  
        <year>2014</year>  
        <volume>16</volume>  
        <issue>9</issue>  
        <fpage>e214</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2014/9/e214,"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/jmir.3322</pub-id>
        <pub-id pub-id-type="medline">25230684</pub-id>
        <pub-id pub-id-type="pii">v16i9e214</pub-id>
        <pub-id pub-id-type="pmcid">PMC4180357</pub-id></nlm-citation>
      </ref>
      <ref id="ref65">
        <label>65</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Maleck</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Fischer</surname>
            <given-names>MR</given-names>
          </name>
          <name name-style="western">
            <surname>Kammer</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Zeiler</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Mangel</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Schenk</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Pfeifer</surname>
            <given-names>KJ</given-names>
          </name>
        </person-group>
        <article-title>Do computers teach better? A media comparison study for case-based teaching in radiology</article-title>
        <source>Radiographics</source>  
        <year>2001</year>  
        <volume>21</volume>  
        <issue>4</issue>  
        <fpage>1025</fpage>  
        <lpage>32</lpage>  
        <pub-id pub-id-type="doi">10.1148/radiographics.21.4.g01jl091025</pub-id>
        <pub-id pub-id-type="medline">11452078</pub-id></nlm-citation>
      </ref>
      <ref id="ref66">
        <label>66</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Miedzybrodzka</surname>
            <given-names>Z</given-names>
          </name>
          <name name-style="western">
            <surname>Hamilton</surname>
            <given-names>NM</given-names>
          </name>
          <name name-style="western">
            <surname>Gregory</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Milner</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Frade</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Sinclair</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Mollison</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Haites</surname>
            <given-names>N</given-names>
          </name>
        </person-group>
        <article-title>Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach</article-title>
        <source>Eur J Hum Genet</source>  
        <year>2001</year>  
        <month>12</month>  
        <volume>9</volume>  
        <issue>12</issue>  
        <fpage>953</fpage>  
        <lpage>6</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://dx.doi.org/10.1038/sj.ejhg.5200751"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1038/sj.ejhg.5200751</pub-id>
        <pub-id pub-id-type="medline">11840198</pub-id></nlm-citation>
      </ref>
      <ref id="ref67">
        <label>67</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Qayumi</surname>
            <given-names>AK</given-names>
          </name>
          <name name-style="western">
            <surname>Kurihara</surname>
            <given-names>Y</given-names>
          </name>
          <name name-style="western">
            <surname>Imai</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Pachev</surname>
            <given-names>G</given-names>
          </name>
          <name name-style="western">
            <surname>Seo</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Hoshino</surname>
            <given-names>Y</given-names>
          </name>
          <name name-style="western">
            <surname>Cheifetz</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Matsuura</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Momoi</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Saleem</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Lara-Guerra</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Miki</surname>
            <given-names>Y</given-names>
          </name>
          <name name-style="western">
            <surname>Kariya</surname>
            <given-names>Y</given-names>
          </name>
        </person-group>
        <article-title>Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience)</article-title>
        <source>Med Educ</source>  
        <year>2004</year>  
        <month>10</month>  
        <volume>38</volume>  
        <issue>10</issue>  
        <fpage>1080</fpage>  
        <lpage>8</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1365-2929.2004.01957.x</pub-id>
        <pub-id pub-id-type="medline">15461653</pub-id>
        <pub-id pub-id-type="pii">MED1957</pub-id></nlm-citation>
      </ref>
      <ref id="ref68">
        <label>68</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Schwid</surname>
            <given-names>HA</given-names>
          </name>
          <name name-style="western">
            <surname>Rooke</surname>
            <given-names>GA</given-names>
          </name>
          <name name-style="western">
            <surname>Ross</surname>
            <given-names>BK</given-names>
          </name>
          <name name-style="western">
            <surname>Sivarajan</surname>
            <given-names>M</given-names>
          </name>
        </person-group>
        <article-title>Use of a computerized advanced cardiac life support simulator improves retention of advanced cardiac life support guidelines better than a textbook review</article-title>
        <source>Crit Care Med</source>  
        <year>1999</year>  
        <month>04</month>  
        <volume>27</volume>  
        <issue>4</issue>  
        <fpage>821</fpage>  
        <lpage>4</lpage>  
        <pub-id pub-id-type="medline">10321676</pub-id></nlm-citation>
      </ref>
      <ref id="ref69">
        <label>69</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Schwid</surname>
            <given-names>HA</given-names>
          </name>
          <name name-style="western">
            <surname>Rooke</surname>
            <given-names>GA</given-names>
          </name>
          <name name-style="western">
            <surname>Michalowski</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Ross</surname>
            <given-names>BK</given-names>
          </name>
        </person-group>
        <article-title>Screen-based anesthesia simulation with debriefing improves performance in a mannequin-based anesthesia simulator</article-title>
        <source>Teach Learn Med</source>  
        <year>2001</year>  
        <volume>13</volume>  
        <issue>2</issue>  
        <fpage>92</fpage>  
        <lpage>6</lpage>  
        <pub-id pub-id-type="doi">10.1207/S15328015TLM1302_4</pub-id>
        <pub-id pub-id-type="medline">11302037</pub-id></nlm-citation>
      </ref>
      <ref id="ref70">
        <label>70</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Secomb</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>McKenna</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Smith</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <article-title>The effectiveness of simulation activities on the cognitive abilities of undergraduate third-year nursing students: a randomised control trial</article-title>
        <source>J Clin Nurs</source>  
        <year>2012</year>  
        <month>12</month>  
        <volume>21</volume>  
        <issue>23-24</issue>  
        <fpage>3475</fpage>  
        <lpage>84</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1365-2702.2012.04257.x</pub-id>
        <pub-id pub-id-type="medline">23145517</pub-id></nlm-citation>
      </ref>
      <ref id="ref71">
        <label>71</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Sobocan</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Turk</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Dinevski</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Hojs</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Balon</surname>
            <given-names>BP</given-names>
          </name>
        </person-group>
        <article-title>Problem-based learning in internal medicine: virtual patients or paper-based problems?</article-title>
        <source>Intern Med J</source>  
        <year>2017</year>  
        <month>01</month>  
        <volume>47</volume>  
        <issue>1</issue>  
        <fpage>99</fpage>  
        <lpage>103</lpage>  
        <pub-id pub-id-type="doi">10.1111/imj.13304</pub-id>
        <pub-id pub-id-type="medline">27800653</pub-id></nlm-citation>
      </ref>
      <ref id="ref72">
        <label>72</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Subramanian</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Timberlake</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Mittakanti</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Lara</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Brandt</surname>
            <given-names>ML</given-names>
          </name>
        </person-group>
        <article-title>Novel educational approach for medical students: improved retention rates using interactive medical software compared with traditional lecture-based format</article-title>
        <source>J Surg Educ</source>  
        <year>2012</year>  
        <volume>69</volume>  
        <issue>2</issue>  
        <fpage>253</fpage>  
        <lpage>6</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.jsurg.2011.12.007</pub-id>
        <pub-id pub-id-type="medline">22365876</pub-id>
        <pub-id pub-id-type="pii">S1931-7204(11)00358-8</pub-id></nlm-citation>
      </ref>
      <ref id="ref73">
        <label>73</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Tao</surname>
            <given-names>H</given-names>
          </name>
        </person-group>
        <article-title>Computer-based simulative training system—a new approach to teaching pre-hospital trauma care</article-title>
        <source>J Med Coll PLA</source>  
        <year>2011</year>  
        <month>12</month>  
        <volume>26</volume>  
        <issue>6</issue>  
        <fpage>335</fpage>  
        <lpage>44</lpage>  
        <pub-id pub-id-type="doi">10.1016/S1000-1948(12)60029-X</pub-id></nlm-citation>
      </ref>
      <ref id="ref74">
        <label>74</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Triola</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Feldman</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Kalet</surname>
            <given-names>AL</given-names>
          </name>
          <name name-style="western">
            <surname>Zabar</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Kachur</surname>
            <given-names>EK</given-names>
          </name>
          <name name-style="western">
            <surname>Gillespie</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Anderson</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Griesser</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Lipkin</surname>
            <given-names>M</given-names>
          </name>
        </person-group>
        <article-title>A randomized trial of teaching clinical skills using virtual and live standardized patients</article-title>
        <source>J Gen Intern Med</source>  
        <year>2006</year>  
        <month>05</month>  
        <volume>21</volume>  
        <issue>5</issue>  
        <fpage>424</fpage>  
        <lpage>9</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0884-8734&amp;date=2006&amp;volume=21&amp;issue=5&amp;spage=424"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1111/j.1525-1497.2006.00421.x</pub-id>
        <pub-id pub-id-type="medline">16704382</pub-id>
        <pub-id pub-id-type="pii">JGI421</pub-id>
        <pub-id pub-id-type="pmcid">PMC1484797</pub-id></nlm-citation>
      </ref>
      <ref id="ref75">
        <label>75</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Vash</surname>
            <given-names>JH</given-names>
          </name>
          <name name-style="western">
            <surname>Yunesian</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Shariati</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Keshvari</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Harirchi</surname>
            <given-names>I</given-names>
          </name>
        </person-group>
        <article-title>Virtual patients in undergraduate surgery education: a randomized controlled study</article-title>
        <source>ANZ J Surg</source>  
        <year>2007</year>  
        <volume>77</volume>  
        <issue>1-2</issue>  
        <fpage>54</fpage>  
        <lpage>9</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1445-2197.2006.03978.x</pub-id>
        <pub-id pub-id-type="medline">17295822</pub-id>
        <pub-id pub-id-type="pii">ANS3978</pub-id></nlm-citation>
      </ref>
      <ref id="ref76">
        <label>76</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Wang</surname>
            <given-names>CL</given-names>
          </name>
          <name name-style="western">
            <surname>Chinnugounder</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Hippe</surname>
            <given-names>DS</given-names>
          </name>
          <name name-style="western">
            <surname>Zaidi</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>O'Malley</surname>
            <given-names>RB</given-names>
          </name>
          <name name-style="western">
            <surname>Bhargava</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Bush</surname>
            <given-names>WH</given-names>
          </name>
        </person-group>
        <article-title>Comparative effectiveness of hands-on versus computer simulation-based training for contrast media reactions and teamwork skills</article-title>
        <source>J Am Coll Radiol</source>  
        <year>2017</year>  
        <month>01</month>  
        <volume>14</volume>  
        <issue>1</issue>  
        <fpage>103</fpage>  
        <lpage>10.e3</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.jacr.2016.07.013</pub-id>
        <pub-id pub-id-type="medline">27815053</pub-id>
        <pub-id pub-id-type="pii">S1546-1440(16)30606-8</pub-id></nlm-citation>
      </ref>
      <ref id="ref77">
        <label>77</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Williams</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Aubin</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Harkin</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Cottrell</surname>
            <given-names>D</given-names>
          </name>
        </person-group>
        <article-title>A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture</article-title>
        <source>Med Educ</source>  
        <year>2001</year>  
        <month>09</month>  
        <volume>35</volume>  
        <issue>9</issue>  
        <fpage>847</fpage>  
        <lpage>54</lpage>  
        <pub-id pub-id-type="medline">11555222</pub-id>
        <pub-id pub-id-type="pii">med960</pub-id></nlm-citation>
      </ref>
      <ref id="ref78">
        <label>78</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Bryant</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Miller</surname>
            <given-names>CL</given-names>
          </name>
          <name name-style="western">
            <surname>Henderson</surname>
            <given-names>D</given-names>
          </name>
        </person-group>
        <article-title>Virtual clinical simulations in an online advanced health appraisal course</article-title>
        <source>Clin Simul Nurs</source>  
        <year>2015</year>  
        <month>10</month>  
        <volume>11</volume>  
        <issue>10</issue>  
        <fpage>437</fpage>  
        <lpage>444</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.ecns.2015.08.002</pub-id></nlm-citation>
      </ref>
      <ref id="ref79">
        <label>79</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Deladisma</surname>
            <given-names>AM</given-names>
          </name>
          <name name-style="western">
            <surname>Gupta</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Kotranza</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Bittner</surname>
            <given-names>JG</given-names>
          </name>
          <name name-style="western">
            <surname>Imam</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Swinson</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Gucwa</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Nesbit</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Lok</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Pugh</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Lind</surname>
            <given-names>DS</given-names>
          </name>
        </person-group>
        <article-title>A pilot study to integrate an immersive virtual patient with a breast complaint and breast examination simulator into a surgery clerkship</article-title>
        <source>Am J Surg</source>  
        <year>2009</year>  
        <month>01</month>  
        <volume>197</volume>  
        <issue>1</issue>  
        <fpage>102</fpage>  
        <lpage>6</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.amjsurg.2008.08.012</pub-id>
        <pub-id pub-id-type="medline">19101251</pub-id>
        <pub-id pub-id-type="pii">S0002-9610(08)00700-9</pub-id></nlm-citation>
      </ref>
      <ref id="ref80">
        <label>80</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Gu</surname>
            <given-names>Y</given-names>
          </name>
          <name name-style="western">
            <surname>Zou</surname>
            <given-names>Z</given-names>
          </name>
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>X</given-names>
          </name>
        </person-group>
        <article-title>The Effects of vSIM for Nursing™ as a teaching strategy on fundamentals of nursing education in undergraduates</article-title>
        <source>Clin Simul Nurs</source>  
        <year>2017</year>  
        <month>04</month>  
        <volume>13</volume>  
        <issue>4</issue>  
        <fpage>194</fpage>  
        <lpage>7</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.ecns.2017.01.005</pub-id></nlm-citation>
      </ref>
      <ref id="ref81">
        <label>81</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kaltman</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Talisman</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Pennestri</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Syverson</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Arthur</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Vovides</surname>
            <given-names>Y</given-names>
          </name>
        </person-group>
        <article-title>Using technology to enhance teaching of patient-centered interviewing for early medical students</article-title>
        <source>Simul Healthc</source>  
        <year>2018</year>  
        <month>06</month>  
        <volume>13</volume>  
        <issue>3</issue>  
        <fpage>188</fpage>  
        <lpage>94</lpage>  
        <pub-id pub-id-type="doi">10.1097/SIH.0000000000000304</pub-id>
        <pub-id pub-id-type="medline">29771814</pub-id></nlm-citation>
      </ref>
      <ref id="ref82">
        <label>82</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Lehmann</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Thiessen</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Frick</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Bosse</surname>
            <given-names>HM</given-names>
          </name>
          <name name-style="western">
            <surname>Nikendei</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Hoffmann</surname>
            <given-names>GF</given-names>
          </name>
          <name name-style="western">
            <surname>Tönshoff</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Huwendiek</surname>
            <given-names>S</given-names>
          </name>
        </person-group>
        <article-title>Improving pediatric basic life support performance through blended learning with web-based virtual patients: randomized controlled trial</article-title>
        <source>J Med Internet Res</source>  
        <year>2015</year>  
        <month>07</month>  
        <day>2</day>  
        <volume>17</volume>  
        <issue>7</issue>  
        <fpage>e162</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.jmir.org/2015/7/e162/"/>
        </comment>  
        <pub-id pub-id-type="doi">10.2196/jmir.4141</pub-id>
        <pub-id pub-id-type="medline">26139388</pub-id>
        <pub-id pub-id-type="pii">v17i7e162</pub-id>
        <pub-id pub-id-type="pmcid">PMC4526972</pub-id></nlm-citation>
      </ref>
      <ref id="ref83">
        <label>83</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Schittek Janda</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Mattheos</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Nattestad</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Wagner</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Nebel</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Färbom</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Lê</surname>
            <given-names>D</given-names>
          </name>
          <name name-style="western">
            <surname>Attström</surname>
            <given-names>R</given-names>
          </name>
        </person-group>
        <article-title>Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills</article-title>
        <source>Eur J Dent Educ</source>  
        <year>2004</year>  
        <month>08</month>  
        <volume>8</volume>  
        <issue>3</issue>  
        <fpage>111</fpage>  
        <lpage>9</lpage>  
        <pub-id pub-id-type="doi">10.1111/j.1600-0579.2004.00339.x</pub-id>
        <pub-id pub-id-type="medline">15233775</pub-id>
        <pub-id pub-id-type="pii">EJE339</pub-id></nlm-citation>
      </ref>
      <ref id="ref84">
        <label>84</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Smith</surname>
            <given-names>BD</given-names>
          </name>
          <name name-style="western">
            <surname>Silk</surname>
            <given-names>K</given-names>
          </name>
        </person-group>
        <article-title>Cultural competence clinic: an online, interactive, simulation for working effectively with Arab American Muslim patients</article-title>
        <source>Acad Psychiatry</source>  
        <year>2011</year>  
        <volume>35</volume>  
        <issue>5</issue>  
        <fpage>312</fpage>  
        <lpage>6</lpage>  
        <pub-id pub-id-type="doi">10.1176/appi.ap.35.5.312</pub-id>
        <pub-id pub-id-type="medline">22007089</pub-id>
        <pub-id pub-id-type="pii">35/5/312</pub-id></nlm-citation>
      </ref>
      <ref id="ref85">
        <label>85</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Wahlgren</surname>
            <given-names>CF</given-names>
          </name>
          <name name-style="western">
            <surname>Edelbring</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Fors</surname>
            <given-names>U</given-names>
          </name>
          <name name-style="western">
            <surname>Hindbeck</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Ståhle</surname>
            <given-names>M</given-names>
          </name>
        </person-group>
        <article-title>Evaluation of an interactive case simulation system in dermatology and venereology for medical students</article-title>
        <source>BMC Med Educ</source>  
        <year>2006</year>  
        <volume>6</volume>  
        <fpage>40</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.biomedcentral.com/1472-6920/6/40"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1186/1472-6920-6-40</pub-id>
        <pub-id pub-id-type="medline">16907972</pub-id>
        <pub-id pub-id-type="pii">1472-6920-6-40</pub-id>
        <pub-id pub-id-type="pmcid">PMC1590009</pub-id></nlm-citation>
      </ref>
      <ref id="ref86">
        <label>86</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Weverling</surname>
            <given-names>GJ</given-names>
          </name>
          <name name-style="western">
            <surname>Stam</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>ten Cate</surname>
            <given-names>TJ</given-names>
          </name>
          <name name-style="western">
            <surname>van Crevel</surname>
            <given-names>H</given-names>
          </name>
        </person-group>
        <article-title>[Computer-assisted education in problem-solving in neurology; a randomized educational study]</article-title>
        <source>Ned Tijdschr Geneeskd</source>  
        <year>1996</year>  
        <month>02</month>  
        <day>24</day>  
        <volume>140</volume>  
        <issue>8</issue>  
        <fpage>440</fpage>  
        <lpage>3</lpage>  
        <pub-id pub-id-type="medline">8720819</pub-id></nlm-citation>
      </ref>
      <ref id="ref87">
        <label>87</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Courteille</surname>
            <given-names>O</given-names>
          </name>
          <name name-style="western">
            <surname>Fahlstedt</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Ho</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Hedman</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Fors</surname>
            <given-names>U</given-names>
          </name>
          <name name-style="western">
            <surname>von Holst</surname>
            <given-names>H</given-names>
          </name>
          <name name-style="western">
            <surname>Felländer-Tsai</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Möller</surname>
            <given-names>H</given-names>
          </name>
        </person-group>
        <article-title>Learning through a virtual patient vs recorded lecture: a comparison of knowledge retention in a trauma case</article-title>
        <source>Int J Med Educ</source>  
        <year>2018</year>  
        <month>03</month>  
        <day>28</day>  
        <volume>9</volume>  
        <fpage>86</fpage>  
        <lpage>92</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://www.ijme.net/pmid/29599421"/>
        </comment>  
        <pub-id pub-id-type="doi">10.5116/ijme.5aa3.ccf2</pub-id>
        <pub-id pub-id-type="medline">29599421</pub-id>
        <pub-id pub-id-type="pii">ijme.9.8692</pub-id>
        <pub-id pub-id-type="pmcid">PMC5951773</pub-id></nlm-citation>
      </ref>
      <ref id="ref88">
        <label>88</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Dankbaar</surname>
            <given-names>ME</given-names>
          </name>
          <name name-style="western">
            <surname>Alsma</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Jansen</surname>
            <given-names>EE</given-names>
          </name>
          <name name-style="western">
            <surname>van Merrienboer</surname>
            <given-names>JJ</given-names>
          </name>
          <name name-style="western">
            <surname>van Saase</surname>
            <given-names>JL</given-names>
          </name>
          <name name-style="western">
            <surname>Schuit</surname>
            <given-names>SC</given-names>
          </name>
        </person-group>
        <article-title>An experimental study on the effects of a simulation game on students' clinical cognitive skills and motivation</article-title>
        <source>Adv Health Sci Educ Theory Pract</source>  
        <year>2016</year>  
        <month>08</month>  
        <volume>21</volume>  
        <issue>3</issue>  
        <fpage>505</fpage>  
        <lpage>21</lpage>  
        <pub-id pub-id-type="doi">10.1007/s10459-015-9641-x</pub-id>
        <pub-id pub-id-type="medline">26433730</pub-id>
        <pub-id pub-id-type="pii">10.1007/s10459-015-9641-x</pub-id>
        <pub-id pub-id-type="pmcid">PMC4923100</pub-id></nlm-citation>
      </ref>
      <ref id="ref89">
        <label>89</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Foster</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Chaudhary</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Murphy</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Lok</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Waller</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Buckley</surname>
            <given-names>PF</given-names>
          </name>
        </person-group>
        <article-title>The use of simulation to teach suicide risk assessment to health profession trainees—rationale, methodology, and a proof of concept demonstration with a virtual patient</article-title>
        <source>Acad Psychiatry</source>  
        <year>2015</year>  
        <month>12</month>  
        <volume>39</volume>  
        <issue>6</issue>  
        <fpage>620</fpage>  
        <lpage>9</lpage>  
        <pub-id pub-id-type="doi">10.1007/s40596-014-0185-9</pub-id>
        <pub-id pub-id-type="medline">25026950</pub-id>
        <pub-id pub-id-type="pii">10.1007/s40596-014-0185-9</pub-id></nlm-citation>
      </ref>
      <ref id="ref90">
        <label>90</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Trudeau</surname>
            <given-names>KJ</given-names>
          </name>
          <name name-style="western">
            <surname>Hildebrand</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Garg</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Chiauzzi</surname>
            <given-names>E</given-names>
          </name>
          <name name-style="western">
            <surname>Zacharoff</surname>
            <given-names>KL</given-names>
          </name>
        </person-group>
        <article-title>A randomized controlled trial of the effects of online pain management education on primary care providers</article-title>
        <source>Pain Med</source>  
        <year>2017</year>  
        <month>12</month>  
        <day>1</day>  
        <volume>18</volume>  
        <issue>4</issue>  
        <fpage>680</fpage>  
        <lpage>92</lpage>  
        <pub-id pub-id-type="doi">10.1093/pm/pnw271</pub-id>
        <pub-id pub-id-type="medline">28034967</pub-id>
        <pub-id pub-id-type="pii">pnw271</pub-id></nlm-citation>
      </ref>
      <ref id="ref91">
        <label>91</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Bearman</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Cesnik</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Liddell</surname>
            <given-names>M</given-names>
          </name>
        </person-group>
        <article-title>Random comparison of 'virtual patient' models in the context of teaching clinical communication skills</article-title>
        <source>Med Educ</source>  
        <year>2001</year>  
        <month>09</month>  
        <volume>35</volume>  
        <issue>9</issue>  
        <fpage>824</fpage>  
        <lpage>32</lpage>  
        <pub-id pub-id-type="medline">11555219</pub-id></nlm-citation>
      </ref>
      <ref id="ref92">
        <label>92</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Berger</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Bawab</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>de Mooij</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Widmer</surname>
            <given-names>DS</given-names>
          </name>
          <name name-style="western">
            <surname>Szilas</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>de Vriese</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Bugnon</surname>
            <given-names>O</given-names>
          </name>
        </person-group>
        <article-title>An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students</article-title>
        <source>Curr Pharm Teach Learn</source>  
        <year>2018</year>  
        <month>12</month>  
        <volume>10</volume>  
        <issue>3</issue>  
        <fpage>267</fpage>  
        <lpage>76</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.cptl.2017.11.002</pub-id>
        <pub-id pub-id-type="medline">29764629</pub-id>
        <pub-id pub-id-type="pii">S1877-1297(16)30383-5</pub-id></nlm-citation>
      </ref>
      <ref id="ref93">
        <label>93</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Braun</surname>
            <given-names>LT</given-names>
          </name>
          <name name-style="western">
            <surname>Zottmann</surname>
            <given-names>JM</given-names>
          </name>
          <name name-style="western">
            <surname>Adolf</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Lottspeich</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Then</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>Wirth</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Fischer</surname>
            <given-names>MR</given-names>
          </name>
          <name name-style="western">
            <surname>Schmidmaier</surname>
            <given-names>R</given-names>
          </name>
        </person-group>
        <article-title>Representation scaffolds improve diagnostic efficiency in medical students</article-title>
        <source>Med Educ</source>  
        <year>2017</year>  
        <month>11</month>  
        <volume>51</volume>  
        <issue>11</issue>  
        <fpage>1118</fpage>  
        <lpage>26</lpage>  
        <pub-id pub-id-type="doi">10.1111/medu.13355</pub-id>
        <pub-id pub-id-type="medline">28585351</pub-id></nlm-citation>
      </ref>
      <ref id="ref94">
        <label>94</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Davids</surname>
            <given-names>MR</given-names>
          </name>
          <name name-style="western">
            <surname>Chikte</surname>
            <given-names>UM</given-names>
          </name>
          <name name-style="western">
            <surname>Halperin</surname>
            <given-names>ML</given-names>
          </name>
        </person-group>
        <article-title>Effect of improving the usability of an e-learning resource: a randomized trial</article-title>
        <source>Adv Physiol Educ</source>  
        <year>2014</year>  
        <month>06</month>  
        <volume>38</volume>  
        <issue>2</issue>  
        <fpage>155</fpage>  
        <lpage>60</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://www.physiology.org/doi/full/10.1152/advan.00119.2013?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub%3dpubmed"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1152/advan.00119.2013</pub-id>
        <pub-id pub-id-type="medline">24913451</pub-id>
        <pub-id pub-id-type="pii">38/2/155</pub-id>
        <pub-id pub-id-type="pmcid">PMC4056166</pub-id></nlm-citation>
      </ref>
      <ref id="ref95">
        <label>95</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Foster</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Chaudhary</surname>
            <given-names>N</given-names>
          </name>
          <name name-style="western">
            <surname>Kim</surname>
            <given-names>T</given-names>
          </name>
          <name name-style="western">
            <surname>Waller</surname>
            <given-names>JL</given-names>
          </name>
          <name name-style="western">
            <surname>Wong</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Borish</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Cordar</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Lok</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Buckley</surname>
            <given-names>PF</given-names>
          </name>
        </person-group>
        <article-title>Using virtual patients to teach empathy: a randomized controlled study to enhance medical students' empathic communication</article-title>
        <source>Simul Healthc</source>  
        <year>2016</year>  
        <month>06</month>  
        <volume>11</volume>  
        <issue>3</issue>  
        <fpage>181</fpage>  
        <lpage>9</lpage>  
        <pub-id pub-id-type="doi">10.1097/SIH.0000000000000142</pub-id>
        <pub-id pub-id-type="medline">26841278</pub-id></nlm-citation>
      </ref>
      <ref id="ref96">
        <label>96</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Friedman</surname>
            <given-names>CP</given-names>
          </name>
          <name name-style="western">
            <surname>France</surname>
            <given-names>CL</given-names>
          </name>
          <name name-style="western">
            <surname>Drossman</surname>
            <given-names>DD</given-names>
          </name>
        </person-group>
        <article-title>A randomized comparison of alternative formats for clinical simulations</article-title>
        <source>Med Decis Making</source>  
        <year>1991</year>  
        <volume>11</volume>  
        <issue>4</issue>  
        <fpage>265</fpage>  
        <lpage>72</lpage>  
        <pub-id pub-id-type="doi">10.1177/0272989X9101100404</pub-id>
        <pub-id pub-id-type="medline">1766329</pub-id></nlm-citation>
      </ref>
      <ref id="ref97">
        <label>97</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Harris</surname>
            <given-names>JM</given-names>
          </name>
          <name name-style="western">
            <surname>Sun</surname>
            <given-names>H</given-names>
          </name>
        </person-group>
        <article-title>A randomized trial of two e-learning strategies for teaching substance abuse management skills to physicians</article-title>
        <source>Acad Med</source>  
        <year>2013</year>  
        <month>09</month>  
        <volume>88</volume>  
        <issue>9</issue>  
        <fpage>1357</fpage>  
        <lpage>62</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/23887001"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1097/ACM.0b013e31829e7ec6</pub-id>
        <pub-id pub-id-type="medline">23887001</pub-id>
        <pub-id pub-id-type="pmcid">PMC3769087</pub-id></nlm-citation>
      </ref>
      <ref id="ref98">
        <label>98</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Mahnken</surname>
            <given-names>AH</given-names>
          </name>
          <name name-style="western">
            <surname>Baumann</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Meister</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Schmitt</surname>
            <given-names>V</given-names>
          </name>
          <name name-style="western">
            <surname>Fischer</surname>
            <given-names>MR</given-names>
          </name>
        </person-group>
        <article-title>Blended learning in radiology: is self-determined learning really more effective?</article-title>
        <source>Eur J Radiol</source>  
        <year>2011</year>  
        <month>06</month>  
        <volume>78</volume>  
        <issue>3</issue>  
        <fpage>384</fpage>  
        <lpage>7</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.ejrad.2010.12.059</pub-id>
        <pub-id pub-id-type="medline">21288674</pub-id>
        <pub-id pub-id-type="pii">S0720-048X(11)00008-8</pub-id></nlm-citation>
      </ref>
      <ref id="ref99">
        <label>99</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Maier</surname>
            <given-names>EM</given-names>
          </name>
          <name name-style="western">
            <surname>Hege</surname>
            <given-names>I</given-names>
          </name>
          <name name-style="western">
            <surname>Muntau</surname>
            <given-names>AC</given-names>
          </name>
          <name name-style="western">
            <surname>Huber</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Fischer</surname>
            <given-names>MR</given-names>
          </name>
        </person-group>
        <article-title>What are effects of a spaced activation of virtual patients in a pediatric course?</article-title>
        <source>BMC Med Educ</source>  
        <year>2013</year>  
        <month>03</month>  
        <day>28</day>  
        <volume>13</volume>  
        <fpage>45</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://bmcmededuc.biomedcentral.com/articles/10.1186/1472-6920-13-45"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1186/1472-6920-13-45</pub-id>
        <pub-id pub-id-type="medline">23537162</pub-id>
        <pub-id pub-id-type="pii">1472-6920-13-45</pub-id>
        <pub-id pub-id-type="pmcid">PMC3639235</pub-id></nlm-citation>
      </ref>
      <ref id="ref100">
        <label>100</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Tolsgaard</surname>
            <given-names>MG</given-names>
          </name>
          <name name-style="western">
            <surname>Jepsen</surname>
            <given-names>RMHG</given-names>
          </name>
          <name name-style="western">
            <surname>Rasmussen</surname>
            <given-names>MB</given-names>
          </name>
          <name name-style="western">
            <surname>Kayser</surname>
            <given-names>L</given-names>
          </name>
          <name name-style="western">
            <surname>Fors</surname>
            <given-names>U</given-names>
          </name>
          <name name-style="western">
            <surname>Laursen</surname>
            <given-names>LC</given-names>
          </name>
          <name name-style="western">
            <surname>Svendsen</surname>
            <given-names>JH</given-names>
          </name>
          <name name-style="western">
            <surname>Ringsted</surname>
            <given-names>C</given-names>
          </name>
        </person-group>
        <article-title>The effect of constructing versus solving virtual patient cases on transfer of learning: a randomized trial</article-title>
        <source>Perspect Med Educ</source>  
        <year>2016</year>  
        <month>02</month>  
        <volume>5</volume>  
        <issue>1</issue>  
        <fpage>33</fpage>  
        <lpage>8</lpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/26754313"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1007/s40037-015-0242-4</pub-id>
        <pub-id pub-id-type="medline">26754313</pub-id>
        <pub-id pub-id-type="pii">10.1007/s40037-015-0242-4</pub-id>
        <pub-id pub-id-type="pmcid">PMC4754215</pub-id></nlm-citation>
      </ref>
      <ref id="ref101">
        <label>101</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kraiger</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Ford</surname>
            <given-names>JK</given-names>
          </name>
          <name name-style="western">
            <surname>Salas</surname>
            <given-names>E</given-names>
          </name>
        </person-group>
        <article-title>Application of cognitive, skill-based, and affective theories of learning outcomes to new methods of training evaluation</article-title>
        <source>J Appl Psychol</source>  
        <year>1993</year>  
        <volume>78</volume>  
        <issue>2</issue>  
        <fpage>311</fpage>  
        <lpage>28</lpage>  
        <pub-id pub-id-type="doi">10.1037/0021-9010.78.2.311</pub-id>
        <pub-id pub-id-type="medline">31070385</pub-id></nlm-citation>
      </ref>
      <ref id="ref102">
        <label>102</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Stevens</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Hernandez</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Johnsen</surname>
            <given-names>K</given-names>
          </name>
          <name name-style="western">
            <surname>Dickerson</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Raij</surname>
            <given-names>A</given-names>
          </name>
          <name name-style="western">
            <surname>Harrison</surname>
            <given-names>C</given-names>
          </name>
          <name name-style="western">
            <surname>DiPietro</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Allen</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Ferdig</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Foti</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Jackson</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Shin</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Cendan</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Watson</surname>
            <given-names>R</given-names>
          </name>
          <name name-style="western">
            <surname>Duerson</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Lok</surname>
            <given-names>B</given-names>
          </name>
          <name name-style="western">
            <surname>Cohen</surname>
            <given-names>M</given-names>
          </name>
          <name name-style="western">
            <surname>Wagner</surname>
            <given-names>P</given-names>
          </name>
          <name name-style="western">
            <surname>Lind</surname>
            <given-names>DS</given-names>
          </name>
        </person-group>
        <article-title>The use of virtual patients to teach medical students history taking and communication skills</article-title>
        <source>Am J Surg</source>  
        <year>2006</year>  
        <month>06</month>  
        <volume>191</volume>  
        <issue>6</issue>  
        <fpage>806</fpage>  
        <lpage>11</lpage>  
        <pub-id pub-id-type="doi">10.1016/j.amjsurg.2006.03.002</pub-id>
        <pub-id pub-id-type="medline">16720154</pub-id>
        <pub-id pub-id-type="pii">S0002-9610(06)00204-2</pub-id></nlm-citation>
      </ref>
      <ref id="ref103">
        <label>103</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Friedman</surname>
            <given-names>CP</given-names>
          </name>
        </person-group>
        <article-title>The research we should be doing</article-title>
        <source>Acad Med</source>  
        <year>1994</year>  
        <month>06</month>  
        <volume>69</volume>  
        <issue>6</issue>  
        <fpage>455</fpage>  
        <lpage>7</lpage>  
        <pub-id pub-id-type="medline">8003158</pub-id></nlm-citation>
      </ref>
      <ref id="ref104">
        <label>104</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Cook</surname>
            <given-names>DA</given-names>
          </name>
        </person-group>
        <article-title>The research we still are not doing: an agenda for the study of computer-based learning</article-title>
        <source>Acad Med</source>  
        <year>2005</year>  
        <month>06</month>  
        <volume>80</volume>  
        <issue>6</issue>  
        <fpage>541</fpage>  
        <lpage>8</lpage>  
        <pub-id pub-id-type="medline">15917356</pub-id>
        <pub-id pub-id-type="pii">80/6/541</pub-id></nlm-citation>
      </ref>
      <ref id="ref105">
        <label>105</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Krathwohl</surname>
            <given-names>DR</given-names>
          </name>
        </person-group>
        <article-title>A revision of Bloom's taxonomy: an overview</article-title>
        <source>Theory Pract</source>  
        <year>2002</year>  
        <month>11</month>  
        <volume>41</volume>  
        <issue>4</issue>  
        <fpage>212</fpage>  
        <lpage>8</lpage>  
        <pub-id pub-id-type="doi">10.1207/s15430421tip4104_2</pub-id></nlm-citation>
      </ref>
      <ref id="ref106">
        <label>106</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Chen</surname>
            <given-names>F</given-names>
          </name>
          <name name-style="western">
            <surname>Lui</surname>
            <given-names>AM</given-names>
          </name>
          <name name-style="western">
            <surname>Martinelli</surname>
            <given-names>SM</given-names>
          </name>
        </person-group>
        <article-title>A systematic review of the effectiveness of flipped classrooms in medical education</article-title>
        <source>Med Educ</source>  
        <year>2017</year>  
        <month>06</month>  
        <volume>51</volume>  
        <issue>6</issue>  
        <fpage>585</fpage>  
        <lpage>97</lpage>  
        <pub-id pub-id-type="doi">10.1111/medu.13272</pub-id>
        <pub-id pub-id-type="medline">28488303</pub-id></nlm-citation>
      </ref>
      <ref id="ref107">
        <label>107</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Kirschner</surname>
            <given-names>PA</given-names>
          </name>
          <name name-style="western">
            <surname>Sweller</surname>
            <given-names>J</given-names>
          </name>
          <name name-style="western">
            <surname>Clark</surname>
            <given-names>RE</given-names>
          </name>
        </person-group>
        <article-title>Why minimal guidance during instruction does not work: an analysis of the failure of constructivist, discovery, problem-based, experiential, and inquiry-based teaching</article-title>
        <source>Educ Psychol</source>  
        <year>2006</year>  
        <month>06</month>  
        <volume>41</volume>  
        <issue>2</issue>  
        <fpage>75</fpage>  
        <lpage>86</lpage>  
        <pub-id pub-id-type="doi">10.1207/s15326985ep4102_1</pub-id></nlm-citation>
      </ref>
      <ref id="ref108">
        <label>108</label>
        <nlm-citation citation-type="journal">
        <person-group person-group-type="author">
          <name name-style="western">
            <surname>Edelbring</surname>
            <given-names>S</given-names>
          </name>
          <name name-style="western">
            <surname>Wahlström</surname>
            <given-names>R</given-names>
          </name>
        </person-group>
        <article-title>Dynamics of study strategies and teacher regulation in virtual patient learning activities: a cross sectional survey</article-title>
        <source>BMC Med Educ</source>  
        <year>2016</year>  
        <month>04</month>  
        <day>23</day>  
        <volume>16</volume>  
        <fpage>122</fpage>  
        <comment>
          <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:type="simple" xlink:href="https://bmcmededuc.biomedcentral.com/articles/10.1186/s12909-016-0644-y"/>
        </comment>  
        <pub-id pub-id-type="doi">10.1186/s12909-016-0644-y</pub-id>
        <pub-id pub-id-type="medline">27108089</pub-id>
        <pub-id pub-id-type="pii">10.1186/s12909-016-0644-y</pub-id>
        <pub-id pub-id-type="pmcid">PMC4842289</pub-id></nlm-citation>
      </ref>
    </ref-list>
  </back>
</article>
