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  <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">v23i10e24722</article-id>
      <article-id pub-id-type="pmid">34714246</article-id>
      <article-id pub-id-type="doi">10.2196/24722</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>Supportive Care Interventions for People With Cancer Assisted by Digital Technology: Systematic Review</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Kukafka</surname>
            <given-names>Rita</given-names>
          </name>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Eysenbach</surname>
            <given-names>Gunther</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Wreglesworth</surname>
            <given-names>Nicholas</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Marthick</surname>
            <given-names>Michael</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Research in Implementation Science and eHealth Group</institution>
            <institution>Faculty of Medicine and Health</institution>
            <institution>University of Sydney</institution>
            <addr-line>Charles Perkins Centre</addr-line>
            <addr-line>John Hopkins Dr</addr-line>
            <addr-line>Camperdown, 2006</addr-line>
            <country>Australia</country>
            <phone>61 (02) 9351 2222</phone>
            <email>mmar7320@uni.sydney.edu.au</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1524-7968</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>McGregor</surname>
            <given-names>Deborah</given-names>
          </name>
          <degrees>MHS</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-2234-7331</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Alison</surname>
            <given-names>Jennifer</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff3" ref-type="aff">3</xref>
          <xref rid="aff4" ref-type="aff">4</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-2011-4756</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Cheema</surname>
            <given-names>Birinder</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff5" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-1979-590X</ext-link>
        </contrib>
        <contrib id="contrib5" contrib-type="author">
          <name name-style="western">
            <surname>Dhillon</surname>
            <given-names>Haryana</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff6" ref-type="aff">6</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-4039-5169</ext-link>
        </contrib>
        <contrib id="contrib6" contrib-type="author">
          <name name-style="western">
            <surname>Shaw</surname>
            <given-names>Tim</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-0783-1918</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Research in Implementation Science and eHealth Group</institution>
        <institution>Faculty of Medicine and Health</institution>
        <institution>University of Sydney</institution>
        <addr-line>Camperdown</addr-line>
        <country>Australia</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Faculty of Science, Medicine and Health</institution>
        <institution>University of Wollongong</institution>
        <addr-line>Wollongong</addr-line>
        <country>Australia</country>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution>Faculty of Medicine and Health</institution>
        <institution>University of Sydney</institution>
        <addr-line>Sydney</addr-line>
        <country>Australia</country>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution>Sydney Local Health District</institution>
        <addr-line>Sydney</addr-line>
        <country>Australia</country>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution>School of Health Sciences</institution>
        <institution>Western Sydney University</institution>
        <addr-line>Penrith</addr-line>
        <country>Australia</country>
      </aff>
      <aff id="aff6">
        <label>6</label>
        <institution>Centre for Medical Psychology &#38; Evidence-based Decision-making</institution>
        <institution>School of Psychology</institution>
        <institution>University of Sydney</institution>
        <addr-line>Sydney</addr-line>
        <country>Australia</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Michael Marthick <email>mmar7320@uni.sydney.edu.au</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <month>10</month>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>29</day>
        <month>10</month>
        <year>2021</year>
      </pub-date>
      <volume>23</volume>
      <issue>10</issue>
      <elocation-id>e24722</elocation-id>
      <history>
        <date date-type="received">
          <day>2</day>
          <month>10</month>
          <year>2020</year>
        </date>
        <date date-type="rev-request">
          <day>30</day>
          <month>10</month>
          <year>2020</year>
        </date>
        <date date-type="rev-recd">
          <day>1</day>
          <month>11</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>20</day>
          <month>9</month>
          <year>2021</year>
        </date>
      </history>
      <copyright-statement>©Michael Marthick, Deborah McGregor, Jennifer Alison, Birinder Cheema, Haryana Dhillon, Tim Shaw. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.10.2021.</copyright-statement>
      <copyright-year>2021</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 https://www.jmir.org/, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://www.jmir.org/2021/10/e24722" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>Although relatively new, digital health interventions are demonstrating rapid growth because of their ability to facilitate access and overcome issues of location, time, health status, and most recently, the impact of a major pandemic. With the increased uptake of digital technologies, digital health has the potential to improve the provision of supportive cancer care.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>This systematic review aims to evaluate digital health interventions for supportive cancer care.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>Published literature between 2000 and 2020 was systematically searched in MEDLINE, PubMed, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and Scopus. Eligible publications were randomized controlled trials of clinician-led digital health interventions to support adult cancer patients. The interventions included were determined by applying a digital health conceptual model. Studies were appraised for quality using the revised Cochrane risk of bias tool.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>Twenty randomized controlled trials met the inclusion criteria for the analysis. Interventions varied by duration, frequency, degree of technology use, and applied outcome measures. Interventions targeting a single tumor stream, predominantly breast cancer, and studies involving the implementation of remote symptom monitoring have dominated the results. In most studies, digital intervention resulted in significant positive outcomes in patient-reported symptoms, levels of fatigue and pain, health-related quality of life, functional capacity, and depression levels compared with the control.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Digital health interventions are helpful and effective for supportive care of patients with cancer. There is a need for high-quality research. Future endeavors could focus on the use of valid, standardized outcome measures, maintenance of methodological rigor, and strategies to improve patient and health professional engagement in the design and delivery of supportive digital health interventions.</p>
        </sec>
        <sec sec-type="trial registration">
          <title>Trial Registration</title>
          <p>PROSPERO CRD42020149730; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=149730</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>digital health</kwd>
        <kwd>telehealth</kwd>
        <kwd>eHealth</kwd>
        <kwd>neoplasm</kwd>
        <kwd>supportive care</kwd>
        <kwd>systematic review</kwd>
        <kwd>mobile phone</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <sec>
        <title>Background</title>
        <p>Approximately 18.1 million new cancer cases and 9.6 million cancer-related deaths occurred globally in 2018 [<xref ref-type="bibr" rid="ref1">1</xref>]. The rising tide of cancer diagnoses in many developed countries has been attributed to both population aging and the increasing prevalence of primary risk factors, including physical inactivity, obesity, and metabolic disease [<xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref2">2</xref>]. As the cancer population continues to grow, there is an urgent need to improve supportive care services [<xref ref-type="bibr" rid="ref2">2</xref>].</p>
        <p>Supportive care focuses on assisting people with cancer and their families to cope with the disease and its treatment [<xref ref-type="bibr" rid="ref3">3</xref>]. The management of cancer treatment-related symptoms and side effects and the maintenance of health-related quality of life from early diagnosis to end-of-life are key aims of supportive cancer care [<xref ref-type="bibr" rid="ref3">3</xref>,<xref ref-type="bibr" rid="ref4">4</xref>]. Supportive care interventions vary and may involve multidisciplinary team support, including doctors, nurses, pharmacists, and allied health professionals [<xref ref-type="bibr" rid="ref5">5</xref>]. Recently, a shared follow-up approach between primary and secondary providers has been promoted to successfully meet increasing demands for survivorship care [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref7">7</xref>], as innovative methods for long-term cancer care are constantly needed [<xref ref-type="bibr" rid="ref2">2</xref>].</p>
        <p>There have been ongoing attempts to improve access to supportive care cancer services through the use of digital health technology [<xref ref-type="bibr" rid="ref8">8</xref>]. Digital health interventions, with telemedicine as its oldest form dating back to the 1920s, have been increasing dramatically in recent years [<xref ref-type="bibr" rid="ref9">9</xref>]. The terms <italic>digital health</italic> and <italic>eHealth</italic> are frequently used interchangeably, with numerous varied definitions. Eysenbach [<xref ref-type="bibr" rid="ref10">10</xref>] defined eHealth as <italic>an emerging field in the intersection of medical informatics, public health, and business, referring to health services and information delivered or enhanced through the internet and related technologies</italic>. Elbert [<xref ref-type="bibr" rid="ref11">11</xref>] and McLean et al [<xref ref-type="bibr" rid="ref12">12</xref>] assert 3 key elements of digital health: (1) data obtained from the patient, (2) electronic transfer of data over a distance, and (3) patient-tailored feedback from a health care professional. Furthermore, a recent conceptual model proposed by Shaw et al [<xref ref-type="bibr" rid="ref13">13</xref>] acknowledges the role of telehealth consultations, web-based forums, mobile devices and apps, and social media, in enabling real-time communication between health professionals and consumers.</p>
        <p>Recent systematic reviews evaluating the impact of digital health interventions on health and health care costs provide promising evidence of effectiveness and cost-effectiveness [<xref ref-type="bibr" rid="ref11">11</xref>,<xref ref-type="bibr" rid="ref14">14</xref>]. Digital health has demonstrated potential in engaging people in their care [<xref ref-type="bibr" rid="ref15">15</xref>], including as a tool for the treatment and self-management training of chronically ill patients [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref17">17</xref>]. Digital health interventions have been shown to be effective for managing cancer-related fatigue [<xref ref-type="bibr" rid="ref18">18</xref>], may improve physical activity among cancer survivors [<xref ref-type="bibr" rid="ref19">19</xref>], and can lead to positive effects addressing the supportive cancer care needs of individuals with different preferences and priorities [<xref ref-type="bibr" rid="ref20">20</xref>]. Cancer survivors have been found to have a positive attitude toward digital health [<xref ref-type="bibr" rid="ref21">21</xref>], suggesting that digital health interventions have the potential to overcome common challenges associated with access to supportive care in this population. Health professional-led, digital health–enabled, supportive care interventions may prove particularly useful in increasing accessibility of services to those with limited access because of location, health, time, and public health emergencies [<xref ref-type="bibr" rid="ref22">22</xref>-<xref ref-type="bibr" rid="ref30">30</xref>]. Despite the abundance of recent digital health literature, there remains an acknowledged lack of quality evidence regarding the effectiveness of supportive digital health care interventions for people with cancer [<xref ref-type="bibr" rid="ref19">19</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref31">31</xref>-<xref ref-type="bibr" rid="ref33">33</xref>].</p>
      </sec>
      <sec>
        <title>Objective</title>
        <p>Over the past several decades, studies have investigated the implementation and effects of digital health interventions in people with cancer. In previous systematic reviews evaluated in 2013, the design features of supportive digital health interventions for patients with cancer [<xref ref-type="bibr" rid="ref20">20</xref>]; in 2014, the use of technology in cancer follow-up [<xref ref-type="bibr" rid="ref31">31</xref>]; in 2015 and 2017, the effect of telehealth interventions in cancer survivors’ general quality of life [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>], and in 2020, the benefits and limits of digital health for optimal supportive care in oncology [<xref ref-type="bibr" rid="ref35">35</xref>]. The last review by Aapro et al [<xref ref-type="bibr" rid="ref35">35</xref>] conducted an article search up to November 2018 and focused on the technical features of digital technologies. This is a rapidly growing area of health care because of advances in information technology and the uptake of digital technologies by both health professionals and patients. Therefore, this systematic review aims to explore the effect of supportive care interventions assisted by digital technologies on the outcomes of patients with cancer.</p>
      </sec>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Search Strategy</title>
        <p>This systematic review was registered in the PROSPERO (International Prospective Register of Systematic Reviews) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [<xref ref-type="bibr" rid="ref36">36</xref>]. A search wa<bold>s</bold> performed in August 2020, using the following web-based databases: MEDLINE (OvidSP, Wolters Kluwer), PubMed (National Center for Biotechnology Information, US National Library of Medicine), Embase (OvidSP, Wolters Kluwer), PsycINFO (American Psychological Association), Cochrane Central Register of Controlled Trials (John Wiley &#38; Sons), and Scopus (SciVerse, Elsevier). Three main keywords were searched: <italic>supportive care</italic>, <italic>digital health</italic>, and <italic>cancer patients</italic>. Additional search terms were included based on synonyms of these keywords and medical subject headings. <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref> indicates the search strategy used.</p>
      </sec>
      <sec>
        <title>Inclusion Criteria</title>
        <p>The inclusion criteria were as follows: (1) studies in English describing a randomized controlled trial (RCT), published between January 2000 and August 2020; (2) intervention recipients were adults with a diagnosis of cancer; (3) involved clinician-led digital health interventions; and (4) interventions implemented to provide supportive cancer care.</p>
        <p>The determination of digital health interventions was on the basis of the conceptual model of Shaw et al [<xref ref-type="bibr" rid="ref13">13</xref>], which consists of 3 core domains:</p>
        <list list-type="order">
          <list-item>
            <p>Health in our hands: Using digital technologies to monitor, track, and inform health, for example, smartphones, tablets, clinical devices, mobile sensors and wearables, apps, social media, and web-based information.</p>
          </list-item>
          <list-item>
            <p>Interacting for health: Using digital technologies to enable health communication among practitioners and between health professionals and clients or patients, for example, traditionally dominated by teleconferencing and videoconferencing, this domain increasingly includes a range of synchronous and asynchronous tools, such as SMS and push notifications from mobile apps, dedicated portals, social media platforms, and virtual or simulated therapy tools.</p>
          </list-item>
          <list-item>
            <p>Data enabling health: Collecting, managing, and using digital health data, for example, technologies that provide expanded knowledge and insights about the health of an individual, community, or population.</p>
          </list-item>
        </list>
        <p>To be included in the review, it was essential that the intervention satisfied the 2 domains <italic>health in our hands</italic> and <italic>interacting for health</italic>. The third domain, <italic>data enabling health</italic> was deemed nonessential because of the known inconsistent reporting of these criteria. The essential criterion <italic>health in our hands</italic> was captured in the <italic>Intervention</italic> column and outlines the nature of digital health experience. <italic>Interacting for health</italic> was captured in the <italic>Interactions</italic> column of review data and outlines the individuals involved in any form of communicative exchange that supports the health and well-being of the patient and caregiver.</p>
        <p>Studies with interventions involving automated systems, such as interactive voice response and similar web-based systems, to monitor symptoms were included if the intervention featured an internet or web-based component and triggered health professional or researcher involvement when a threshold, such as a pain score, was reached.</p>
      </sec>
      <sec>
        <title>Exclusion Criteria</title>
        <p>Studies were excluded if they were (1) not RCTs; (2) reported only self-managed interventions, patient-to-patient interventions, prevention tools, or alternative treatments, or (3) focused solely on interventions involving telephone delivery that replicated a clinical service.</p>
      </sec>
      <sec>
        <title>Data Extraction and Synthesis</title>
        <p>Two reviewers (MM and DM) independently reviewed the titles and abstracts, followed by a full-text review of all publications. In cases of disagreement, a consensus was sought through discussion. Disagreement persisted for 4 studies; therefore, a third reviewer (TS) was consulted to adjudicate.</p>
        <p>Endnote software (Clarivate Plc) [<xref ref-type="bibr" rid="ref37">37</xref>] was used to manage references, and Covidence software (Veritas Health Innovation Ltd) was used to import and extract studies [<xref ref-type="bibr" rid="ref38">38</xref>]. Two reviewers (MM and DM) independently applied the revised Cochrane risk of bias tool (The Cochrane Collaboration) [<xref ref-type="bibr" rid="ref39">39</xref>] to establish the quality of the included studies. A matrix was developed by the authors and applied in the collection and analysis of structured data. Matrix criteria also included whether a study adhered to the CONSORT (Consolidated Standards of Reporting Trials) eHealth Checklist [<xref ref-type="bibr" rid="ref40">40</xref>], a tool developed to improve the standard of reporting in digital health trials.</p>
      </sec>
      <sec>
        <title>Quality Assessment</title>
        <p>Using the revised Cochrane Collaboration’s tool for assessing risk of bias (RoB) in randomized trials (Risk of Bias 2.0) [<xref ref-type="bibr" rid="ref39">39</xref>], each study’s methodological quality was assessed in 5 major domains: randomization process, deviation from intentional interventions, missing outcomes, measurement of outcomes, and selection of reported results. The RoB for each domain was rated as <italic>some concerns</italic>, <italic>low</italic>, or <italic>high</italic>. The overall RoB for each study was rated as <italic>some concerns</italic> or <italic>high</italic>.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Study Selection</title>
        <p>The initial search generated 972 records. After title and abstract review, 135 publications were retained. The full text for each of these 135 publications was reviewed for eligibility, resulting in the identification of 17 publications. Three additional studies were found using a reference search, generating a total of 20 digital health–enabled supportive cancer care interventions for inclusion in the review (<xref rid="figure1" ref-type="fig">Figure 1</xref>).</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram of the search and study selection process. RCT: randomized controlled trial.</p>
          </caption>
          <graphic xlink:href="jmir_v23i10e24722_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Study Characteristics</title>
        <sec>
          <title>Population</title>
          <p>Details of the study design and characteristics are given in <xref ref-type="supplementary-material" rid="app2">Multimedia Appendix 2</xref> [<xref ref-type="bibr" rid="ref41">41</xref>-<xref ref-type="bibr" rid="ref60">60</xref>]. Although the search was published in 2000, the earliest result identified was published in 2007, and the remaining included studies were published after 2009. A total of 20 studies were conducted across 8 countries [<xref ref-type="bibr" rid="ref41">41</xref>-<xref ref-type="bibr" rid="ref48">48</xref>], with 11 from the United States. The sample sizes ranged from 52 to 516 participants, with a median of 118.</p>
          <p>Of the 20 included studies, 12 (60%) were designed for participants within a single tumor stream. Interventions for breast cancer were dominant, with a total of 9 studies [<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref46">46</xref>-<xref ref-type="bibr" rid="ref53">53</xref>]. A total of 2 studies identified were for lung cancer [<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref55">55</xref>]. Of those targeting multiple tumor types, 1 recruited participants with breast or prostate cancer [<xref ref-type="bibr" rid="ref45">45</xref>], and 1 recruited participants with lung, breast, or colorectal cancer [<xref ref-type="bibr" rid="ref44">44</xref>]. The remaining 8 studies included several tumor types, such as participants living with any type or stage of cancer [<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref56">56</xref>-<xref ref-type="bibr" rid="ref58">58</xref>] or those with solid tumors attending ambulatory oncology clinics for chemotherapy [<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref60">60</xref>].</p>
        </sec>
        <sec>
          <title>Intervention Design and Features</title>
          <p>The duration of interventions ranged from 4 weeks to 12 months, with a variable frequency of clinician-patient interactions ranging from biweekly to every 3 months. There were 5 studies involving the use of a web-based portal or web-based experience [<xref ref-type="bibr" rid="ref45">45</xref>,<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref48">48</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref57">57</xref>]; 8 studies included the use of a telephone or smartphone [<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref52">52</xref>-<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref59">59</xref>,<xref ref-type="bibr" rid="ref60">60</xref>]; 2 studies used a combination of web-based and telephone interactions [<xref ref-type="bibr" rid="ref51">51</xref>,<xref ref-type="bibr" rid="ref58">58</xref>]; 2 studies used social media networks or social networks [<xref ref-type="bibr" rid="ref51">51</xref>,<xref ref-type="bibr" rid="ref55">55</xref>]; and 4 studies used wearable activity trackers [<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref51">51</xref>-<xref ref-type="bibr" rid="ref53">53</xref>]. Multidisciplinary care was identified in 30% (6/20) of the publications [<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref56">56</xref>,<xref ref-type="bibr" rid="ref58">58</xref>]. The study by Børøsund et al [<xref ref-type="bibr" rid="ref46">46</xref>] was nurse-led, with referrals to either physicians or social workers. Uni-disciplinary interactions dominated, with 5 nurse-led [<xref ref-type="bibr" rid="ref45">45</xref>,<xref ref-type="bibr" rid="ref48">48</xref>,<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref56">56</xref>,<xref ref-type="bibr" rid="ref60">60</xref>], 1 social worker-led [<xref ref-type="bibr" rid="ref49">49</xref>], and 1 led with a medical specialist experienced in mindfulness program delivery [<xref ref-type="bibr" rid="ref42">42</xref>]. Bruggeman-Everts et al [<xref ref-type="bibr" rid="ref41">41</xref>] involved a psychologist or physiotherapist assigned to participants in different arms of the study. Steel et al [<xref ref-type="bibr" rid="ref57">57</xref>] outlined a collaborative care intervention, whereby a care coordinator provided information to the patient’s medical team, as well as patients and caregivers. The interventions included digital health tutoring, psychotherapy, nursing support, remote exercise or rehabilitation program delivery, and digital mindfulness.</p>
          <p>Digital supportive care interventions included interactive voice response, tele and video counseling, internet-based patient-provider communication, exercise based on the internet, support systems, symptom monitoring, and self-management, mobile phone-based remote monitoring, and activity monitoring with tracking devices. The programs included digital health tutoring, psychotherapy, nursing support, remote exercise, rehabilitation program delivery, and digital mindfulness interventions. All varied in terms of design, features, and use of multimedia components. Only 2 publications referred to the CONSORT Digital Health Checklist [<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref55">55</xref>].</p>
        </sec>
      </sec>
      <sec>
        <title>RoB Assessment</title>
        <p>With regard to the overall RoB, no included studies were rated as <italic>low</italic> overall RoB; instead, 8 had <italic>some concerns</italic>, and 12 were <italic>high risk</italic>. A summary of the RoB assessment can be found in <xref ref-type="supplementary-material" rid="app3">Multimedia Appendix 3</xref> [<xref ref-type="bibr" rid="ref41">41</xref>-<xref ref-type="bibr" rid="ref60">60</xref>], describing the methodological quality of each domain according to the Cochrane tool for assessing RoB in randomized trials (RoB 2.0). <xref rid="figure2" ref-type="fig">Figures 2</xref> and <xref rid="figure3" ref-type="fig">3</xref> describe a graphical representation of the RoB assessments. <xref rid="figure2" ref-type="fig">Figure 2</xref> includes studies in which an intention-to-treat analysis was performed, whereas <xref rid="figure3" ref-type="fig">Figure 3</xref> contains studies with a per-protocol analysis.</p>
        <fig id="figure2" position="float">
          <label>Figure 2</label>
          <caption>
            <p>Risk of bias in studies with intention-to-treat analysis.</p>
          </caption>
          <graphic xlink:href="jmir_v23i10e24722_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
        <fig id="figure3" position="float">
          <label>Figure 3</label>
          <caption>
            <p>Risk of bias in studies with per-protocol analysis.</p>
          </caption>
          <graphic xlink:href="jmir_v23i10e24722_fig3.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Intervention Outcomes</title>
        <sec>
          <title>Overview</title>
          <p>Interventions were analyzed according to the before-after test design, with most of the interventions including repeated measurement points. Although 20 studies were included, the interventions and outcomes were heterogeneous and did not enable meta-analyses. Outcomes were synthetized using a model for quality of life among cancer survivors developed by Ferrell and Dow [<xref ref-type="bibr" rid="ref61">61</xref>,<xref ref-type="bibr" rid="ref62">62</xref>]. The model encompasses dimensions of physical, psychological, social, and spiritual well-being, specifying the content for each dimension in the context of cancer survivors. Details of the intervention outcomes and statistically significant results are presented in <xref ref-type="table" rid="table1">Table 1</xref>.</p>
          <table-wrap position="float" id="table1">
            <label>Table 1</label>
            <caption>
              <p>Intervention outcomes.</p>
            </caption>
            <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
              <col width="150"/>
              <col width="290"/>
              <col width="270"/>
              <col width="290"/>
              <thead>
                <tr valign="top">
                  <td>Author</td>
                  <td>Primary and secondary outcomes (grouped)</td>
                  <td>Measures</td>
                  <td>Results</td>
                </tr>
              </thead>
              <tbody>
                <tr valign="top">
                  <td>Anderson et al [<xref ref-type="bibr" rid="ref47">47</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Pain</p>
                      </list-item>
                      <list-item>
                        <p>Sleep</p>
                      </list-item>
                      <list-item>
                        <p>Fatigue</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>MDASI<sup>a</sup></p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Decreased pain severity from baseline to time point 1 (0.6 vs 2.3; <italic>P</italic>=.03; 95% CI 0.13 to 3.3) and from baseline to time point 2 (1.2 vs 3.5; <italic>P</italic>=.02; 95% CI 0.47 to 4.2) in the intervention group.</p>
                      </list-item>
                      <list-item>
                        <p>Improved reported sleep.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Badger et al [<xref ref-type="bibr" rid="ref49">49</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Depression</p>
                      </list-item>
                      <list-item>
                        <p>Symptom distress</p>
                      </list-item>
                      <list-item>
                        <p>Social well-being; spiritual well-being</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>CES-D<sup>b</sup>; GSDS<sup>c</sup>; Social and spiritual; Well-being scales</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Depression, symptoms, and spiritual well-being improved in intervention groups (<italic>P</italic>=.01). No between-group differences. Social well-being improved for tele and video groups.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Børøsund et al [<xref ref-type="bibr" rid="ref46">46</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Symptom distress</p>
                      </list-item>
                      <list-item>
                        <p>Anxiety</p>
                      </list-item>
                      <list-item>
                        <p>Depression</p>
                      </list-item>
                      <list-item>
                        <p>Self-efficacy</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>MSAS<sup>d</sup></p>
                      </list-item>
                      <list-item>
                        <p>HADS<sup>e</sup></p>
                      </list-item>
                      <list-item>
                        <p>CBI<sup>f</sup></p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>WebChoice lower symptom distress (−0.16, 95% CI −.25 to −0.06; <italic>P</italic>=.001), anxiety (−0.79, 95% CI −1.49 to −0.09; <italic>P</italic>=.03), and depression (−0.79, 95% CI 1.18 to −0.05; <italic>P</italic>=.03) compared with control.</p>
                      </list-item>
                      <list-item>
                        <p>Internet-based communication group lower depression (−0.69, 95% CI −1.32 to −0.05; <italic>P</italic>=.03) compared with usual care. No change in symptom distress or anxiety.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Bruggeman-Everts et al [<xref ref-type="bibr" rid="ref41">41</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Fatigue severity</p>
                      </list-item>
                      <list-item>
                        <p>Mental health</p>
                      </list-item>
                      <list-item>
                        <p>Distress</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>CIS-FS<sup>g</sup></p>
                      </list-item>
                      <list-item>
                        <p>The positive and negative affect schedule</p>
                      </list-item>
                      <list-item>
                        <p>HADS</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Clinically changes in fatigue severity in 66% (41/62) of patients in home-based physiotherapist guided protocol (AAF<sup>h</sup>), 49% (27/55) of patients in web-based psychologist-guided intervention (eMBCT<sup>i</sup>), and 12% (6/50) of patients in psycho-education e-mails only.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Cheville et al [<xref ref-type="bibr" rid="ref58">58</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Functional capacity</p>
                      </list-item>
                      <list-item>
                        <p>Pain</p>
                      </list-item>
                      <list-item>
                        <p>HRQoL<sup>j</sup></p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>AM-PAC<sup>k</sup></p>
                      </list-item>
                      <list-item>
                        <p>BPI<sup>l</sup></p>
                      </list-item>
                      <list-item>
                        <p>5-item EQ-5D-3L</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Telerehabilitation by physical therapist-physician team (intervention group 1) improved function (difference, 1.3; 95% CI 0.08 to 2.35; <italic>P</italic>=.03) and quality of life (difference, 0.04; 95% CI 0.004 to 0.071; <italic>P</italic>=.01) compared with control.</p>
                      </list-item>
                      <list-item>
                        <p>Intervention groups 1 and 2 showed reduced pain interference and average intensity (intervention group 1, −0.4; 95% CI −0.78 to −0.07; <italic>P</italic>=.02; and intervention group 2, −0.5; 95% CI −0.84 to −0.11; <italic>P</italic>=.006).</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Cleeland et al [<xref ref-type="bibr" rid="ref54">54</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Symptom threshold events</p>
                      </list-item>
                      <list-item>
                        <p>Cumulative distribution of symptom threshold events</p>
                      </list-item>
                      <list-item>
                        <p>Symptom severity</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>MDASI</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Both groups had decreased symptom threshold events, control group reported more events at the end of the study period. For both groups together, the effect size of reduction in symptom severity was 0.72, effect size of 0.68 in the control group and 0.75 in the intervention group.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Dong et al [<xref ref-type="bibr" rid="ref51">51</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>HRQoL</p>
                      </list-item>
                      <list-item>
                        <p>Muscle strength</p>
                      </list-item>
                      <list-item>
                        <p>Cardiorespiratory capacity</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>SF-36<sup>m</sup></p>
                      </list-item>
                      <list-item>
                        <p>Stand-up or sit-down chair test and arm lifting test (30 seconds)</p>
                      </list-item>
                      <list-item>
                        <p>Modified Bruce treadmill protocol</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>CEIBISMS<sup>n</sup> intervention showed improvements after 12 weeks in role-physical (<italic>P</italic>=.009), general health (<italic>P</italic>=.02), mental health (<italic>P</italic>=.01), vitality (<italic>P</italic>=.01) and health transition (<italic>P</italic>=.007).</p>
                      </list-item>
                      <list-item>
                        <p>In comparison with control group, differences in vitality (<italic>P</italic>=.009), mental health (<italic>P</italic>=.001), and health transition (<italic>P</italic>=.048).</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Freeman et al [<xref ref-type="bibr" rid="ref50">50</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>HRQoL</p>
                      </list-item>
                      <list-item>
                        <p>Functional capacity</p>
                      </list-item>
                      <list-item>
                        <p>Fatigue, sleep</p>
                      </list-item>
                      <list-item>
                        <p>Spiritual well-being</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>SF-36</p>
                      </list-item>
                      <list-item>
                        <p>FACT-B<sup>o</sup></p>
                      </list-item>
                      <list-item>
                        <p>FACIT-F<sup>p</sup> and cog</p>
                      </list-item>
                      <list-item>
                        <p>FACT-Sp<sup>q</sup></p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Less fatigue (<italic>P</italic>=.002), cognitive dysfunction (<italic>P</italic>=.001), and sleep disturbance (<italic>P</italic>&#60;.001) for both intervention groups compared with control.</p>
                      </list-item>
                      <list-item>
                        <p>No differences between live delivery and telemedicine delivery of therapy.</p>
                      </list-item>
                      <list-item>
                        <p>No group effect on overall quality of life; however, there was a time effect.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Galiano-Castillo et al [<xref ref-type="bibr" rid="ref43">43</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Functional capacity</p>
                      </list-item>
                      <list-item>
                        <p>Cognitive function</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>6-minute walk test</p>
                      </list-item>
                      <list-item>
                        <p>Trail making test</p>
                      </list-item>
                      <list-item>
                        <p>ACT<sup>r</sup></p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>After intervention, the telerehabilitation group had significantly improved distances as well as percentage of predicted 6-minute walk test compared with the control group (<italic>P</italic>&#60;.001).</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Gustafson et al [<xref ref-type="bibr" rid="ref55">55</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Caregiver surveys reporting patient symptom distress</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Modified ESAS<sup>s</sup></p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Caregivers in the CHESS<sup>t</sup> arm consistently reported lower patient physical symptom distress than caregivers in the internet arm at 4 months (<italic>P</italic>=.03); and at 6 months (<italic>P</italic>=.004)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Kearney et al [<xref ref-type="bibr" rid="ref44">44</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>6 chemotherapy-related symptoms</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Common toxicity criteria adverse events chemotherapy symptom assessment scale</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Difference between groups in fatigue, higher in the control group (OR<sup>u</sup> 2.29, 95% CI 1.04 to 5.05; <italic>P</italic>=.04) and in hand-foot syndrome lower in control group (OR control or intervention 0.39, 95% CI 0.17 to 0.92; <italic>P</italic>=.03)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Kroenke et al [<xref ref-type="bibr" rid="ref56">56</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Depression</p>
                      </list-item>
                      <list-item>
                        <p>Pain severity</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>HSCL-20<sup>v</sup></p>
                      </list-item>
                      <list-item>
                        <p>BPI</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Improvements for the intervention group: &#62;30% decrease in pain index (<italic>P</italic>&#60;.001) and &#62;50% decrease in the depression scale (<italic>P</italic>&#60;.001). Effect size between-group differences at 3 months was 0.67 (95% CI 0.33 to 1.02) for pain and 0.42 (95% CI 0.16 to 0.69) for depression.</p>
                      </list-item>
                      <list-item>
                        <p>Intervention group had better outcomes for several HrQoL domains, including mental health, vitality, anxiety, and physical symptom burden.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Lynch [<xref ref-type="bibr" rid="ref52">52</xref>]<sup>w</sup></td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Vigorous physical activity (MVPA<sup>x</sup>)</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Actigraph and activPAL accelerometers</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Between-group difference in MVPA at T2 (69 min/week; 95% CI 22 to 116); decreased total time of sitting 37 min/day (95% CI −72 to −2) and prolonged bouts of sitting 42 min/day (95% CI −83 to −2), favoring the intervention group</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Vallance [<xref ref-type="bibr" rid="ref53">53</xref>]<sup>w</sup></td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>HRQoL</p>
                      </list-item>
                      <list-item>
                        <p>Fatigue</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>FACT-B</p>
                      </list-item>
                      <list-item>
                        <p>FACIT-F</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Intervention group improvement in fatigue at T2 4.6 (95% CI 1.3 to 7.8). Within groups: intervention group, increase in fatigue at T2 5.1 (95% CI 2.0 to 8.2) and at T-3 3.3 (95% CI 0.1 to 6.41). No effects on HRQoL.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Mooney et al [<xref ref-type="bibr" rid="ref59">59</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Symptom severity</p>
                      </list-item>
                      <list-item>
                        <p>Distress</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Single item scale</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>No significant difference between symptom severity or distress scores between groups.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Ruland et al [<xref ref-type="bibr" rid="ref45">45</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Symptom distress</p>
                      </list-item>
                      <list-item>
                        <p>Depression</p>
                      </list-item>
                      <list-item>
                        <p>Self-efficacy</p>
                      </list-item>
                      <list-item>
                        <p>HRQoL</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>MSAS-SF<sup>y</sup></p>
                      </list-item>
                      <list-item>
                        <p>Centre for Epidemiological Cancer Behavior Inventory Studies-Depression Scale 15 d</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Decreased distress on one subscale of MSAS.</p>
                      </list-item>
                      <list-item>
                        <p>Group differences on symptom distress were significant for the MSAS-SF (slope estimate, −0.052, 95% CI −0.101 to −0.004; t244=4.42; <italic>P</italic>=.04). There were no significant within- or between-group differences on the other MSAS-SF subscales.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Sikorskii et al [<xref ref-type="bibr" rid="ref60">60</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Symptom severity</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>MDASI</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Decreased symptom severity across both intervention groups after 10 weeks. No between-group differences. Effect sizes were similar for NASM<sup>z</sup> (0.56) and ATSM<sup>aa</sup> (0.59)</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Steel et al [<xref ref-type="bibr" rid="ref57">57</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Depression</p>
                      </list-item>
                      <list-item>
                        <p>Pain</p>
                      </list-item>
                      <list-item>
                        <p>Serum cytokine levels natural killer cell numbers</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>CES-D</p>
                      </list-item>
                      <list-item>
                        <p>BPI</p>
                      </list-item>
                      <list-item>
                        <p>Functional assessment of cancer therapy–anemia, and hepatobiliary</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Reductions in pain (Cohen d=0.62), fatigue (Cohen d=0.26), depression (Cohen d=0.71), and significant changes in HRQoL with an effect size of Cohen d=0.99 at 6 months follow-up (<italic>P</italic>=.05) when compared with those in the enhanced usual care arm at 6 months.</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Wheelock et al [<xref ref-type="bibr" rid="ref48">48</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Time between symptoms</p>
                      </list-item>
                      <list-item>
                        <p>Health care use</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Clinic visits</p>
                      </list-item>
                      <list-item>
                        <p>Health service use</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Did not meet primary objective, no difference in health service use</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Zernicke et al [<xref ref-type="bibr" rid="ref42">42</xref>]</td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Feasibility</p>
                      </list-item>
                      <list-item>
                        <p>Mood</p>
                      </list-item>
                      <list-item>
                        <p>Stress</p>
                      </list-item>
                      <list-item>
                        <p>Posttraumatic growth inventory</p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Monitoring interest, eligibility, and participation</p>
                      </list-item>
                      <list-item>
                        <p>Profile of mood states</p>
                      </list-item>
                      <list-item>
                        <p>CSOSI<sup>ab</sup></p>
                      </list-item>
                    </list>
                  </td>
                  <td>
                    <list list-type="bullet">
                      <list-item>
                        <p>Significant improvements and moderate effect sizes in the web-based MBCR<sup>ac</sup> group relative to controls for mood disturbance (Cohen d=0.44; <italic>P</italic>=.049), stress (Cohen d=0.49; <italic>P</italic>=.02), spirituality (Cohen d=0.37; <italic>P</italic>=.04), and mindfully acting with awareness (Cohen d=0.50; <italic>P</italic>=.03).</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="table1fn1">
                <p><sup>a</sup>MDASI: MD Anderson symptom inventory.</p>
              </fn>
              <fn id="table1fn2">
                <p><sup>b</sup>CES-D: Center for Epidemiological Studies-Depression.</p>
              </fn>
              <fn id="table1fn3">
                <p><sup>c</sup>GSDS: General Sleep Disturbance Scale.</p>
              </fn>
              <fn id="table1fn4">
                <p><sup>d</sup>MSAS: Memorial Symptom Assessment Scale.</p>
              </fn>
              <fn id="table1fn5">
                <p><sup>e</sup>HADS: Hospital Anxiety And Depression Scale.</p>
              </fn>
              <fn id="table1fn6">
                <p><sup>f</sup>CBI: Cancer Behavioral Inventory.</p>
              </fn>
              <fn id="table1fn7">
                <p><sup>g</sup>CIS-FS: Checklist Individual Strength-Fatigue Severity.</p>
              </fn>
              <fn id="table1fn8">
                <p><sup>h</sup>AAF: Ambulant Activity Feedback</p>
              </fn>
              <fn id="table1fn9">
                <p><sup>i</sup>eMBCT: Web-based Mindfulness-Based Cognitive Therapy.</p>
              </fn>
              <fn id="table1fn10">
                <p><sup>j</sup>HRQoL: health-related quality of life.</p>
              </fn>
              <fn id="table1fn11">
                <p><sup>k</sup>AM-PAC: Activity Measure for Postacute Care.</p>
              </fn>
              <fn id="table1fn12">
                <p><sup>l</sup>BPI: Brief Pain Inventory.</p>
              </fn>
              <fn id="table1fn13">
                <p><sup>m</sup>SF-36: 36-item Short Form Health Survey.</p>
              </fn>
              <fn id="table1fn14">
                <p><sup>n</sup>CEIBISMS: combined exercise intervention based on internet and social media software.</p>
              </fn>
              <fn id="table1fn15">
                <p><sup>o</sup>FACT-B: Functional Assessment of Cancer Therapy–Breast.</p>
              </fn>
              <fn id="table1fn16">
                <p><sup>p</sup>FACIT-F: Functional Assessment of Chronic Illness Therapy–Fatigue.</p>
              </fn>
              <fn id="table1fn17">
                <p><sup>q</sup>FACT-Sp: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being.</p>
              </fn>
              <fn id="table1fn18">
                <p><sup>r</sup>ACT: acceptance and commitment therapy.</p>
              </fn>
              <fn id="table1fn19">
                <p><sup>s</sup>ESAS: Edmonton Symptom Assessment Score.</p>
              </fn>
              <fn id="table1fn20">
                <p><sup>t</sup>CHESS: Comprehensive Health Enhancement Support System.</p>
              </fn>
              <fn id="table1fn21">
                <p><sup>u</sup>OR: odds ratio.</p>
              </fn>
              <fn id="table1fn22">
                <p><sup>v</sup>HSCL-20: Hopkins Symptom Checklist Depression Scale.</p>
              </fn>
              <fn id="table1fn23">
                <p><sup>w</sup>Lynch [<xref ref-type="bibr" rid="ref52">52</xref>] and Vallance [<xref ref-type="bibr" rid="ref53">53</xref>] are 2 publications with different outcomes of the same randomized controlled trial.</p>
              </fn>
              <fn id="table1fn24">
                <p><sup>x</sup>MVPA: moderate-to-vigorous intensity physical activity.</p>
              </fn>
              <fn id="table1fn25">
                <p><sup>y</sup>MSAS-SF: Memorial Symptom Assessment Scale – Short Form</p>
              </fn>
              <fn id="table1fn26">
                <p><sup>z</sup>NASM: nurse-assisted symptom management</p>
              </fn>
              <fn id="table1fn27">
                <p><sup>aa</sup>ATSM: automated telephone symptom management</p>
              </fn>
              <fn id="table1fn28">
                <p><sup>ab</sup>CSOSI: Calgary Symptoms of Stress Inventory.</p>
              </fn>
              <fn id="table1fn29">
                <p><sup>ac</sup>MBCR: mindfulness-based cancer recovery.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Physical Well-being</title>
          <p>Despite measuring similar outcomes, heterogeneous self-reported instruments were used across the studies. Control or reduction of symptoms and maintenance of function and independence comprise this domain. A total of 16 studies reported statistically significant changes in outcomes within the physical well-being domain [<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref43">43</xref>-<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref52">52</xref>-<xref ref-type="bibr" rid="ref58">58</xref>,<xref ref-type="bibr" rid="ref60">60</xref>]. Furthermore, 4 studies showed a significant reduction in pain [<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref56">56</xref>-<xref ref-type="bibr" rid="ref58">58</xref>], of which 3 used the Brief Pain Inventory [<xref ref-type="bibr" rid="ref56">56</xref>-<xref ref-type="bibr" rid="ref58">58</xref>]. Decreased fatigue was reported in 4 studies, favoring the intervention groups [<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref53">53</xref>]. The most common outcome measure reported was clustered symptom changes, as referenced in 6 studies [<xref ref-type="bibr" rid="ref45">45</xref>,<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref60">60</xref>]. Finally, functional capacity-related outcomes were significant in 3 studies [<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref52">52</xref>,<xref ref-type="bibr" rid="ref58">58</xref>].</p>
        </sec>
        <sec>
          <title>Health-Related Quality of Life</title>
          <p>Health-related quality of life was the second most common domain, with significant improvements for the intervention group referenced in 4 studies [<xref ref-type="bibr" rid="ref51">51</xref>,<xref ref-type="bibr" rid="ref56">56</xref>-<xref ref-type="bibr" rid="ref58">58</xref>].</p>
        </sec>
        <sec>
          <title>Psychological Well-being</title>
          <p>The most common outcome in this domain reporting significant improvements in the 4 interventions was depression [<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref56">56</xref>,<xref ref-type="bibr" rid="ref57">57</xref>]. Anxiety was reduced compared with the control group in one study [<xref ref-type="bibr" rid="ref46">46</xref>], and significant improvements in mood disturbance were observed in one study [<xref ref-type="bibr" rid="ref42">42</xref>].</p>
        </sec>
        <sec>
          <title>Social and Spiritual Well-being</title>
          <p>A single study reported a significant improvement in social well-being in the intervention group [<xref ref-type="bibr" rid="ref49">49</xref>]. Badger et al [<xref ref-type="bibr" rid="ref49">49</xref>] was also the only study that evaluated spiritual well-being changes, resulting in statistically significant improvements for the intervention group but no between-group differences.</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Principal Findings</title>
        <sec>
          <title>Overview</title>
          <p>In the studies integrated in this review, the interventions included digital health education, psychotherapy, nursing support, remote exercise, rehabilitation program delivery, and digital mindfulness interventions. All interventions satisfied the domains <italic>health in our hands</italic> and <italic>interacting for health</italic> of the digital health model by Shaw et al [<xref ref-type="bibr" rid="ref13">13</xref>]. Digital supportive care interventions have been shown to improve cancer-related symptoms [<xref ref-type="bibr" rid="ref45">45</xref>,<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref55">55</xref>,<xref ref-type="bibr" rid="ref60">60</xref>], pain [<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref56">56</xref>-<xref ref-type="bibr" rid="ref58">58</xref>], fatigue [<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref50">50</xref>,<xref ref-type="bibr" rid="ref53">53</xref>], health-related quality of life [<xref ref-type="bibr" rid="ref51">51</xref>,<xref ref-type="bibr" rid="ref56">56</xref>-<xref ref-type="bibr" rid="ref58">58</xref>], functional capacity [<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref52">52</xref>,<xref ref-type="bibr" rid="ref58">58</xref>], and depression [<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref49">49</xref>,<xref ref-type="bibr" rid="ref56">56</xref>,<xref ref-type="bibr" rid="ref57">57</xref>]. Only 2 RCTs included in this review did not report significant changes in one or more outcomes [<xref ref-type="bibr" rid="ref48">48</xref>,<xref ref-type="bibr" rid="ref59">59</xref>].</p>
        </sec>
        <sec>
          <title>Digital Supportive Cancer Care Interventions</title>
          <p>The digital interventions reviewed have been shown to be beneficial and independent of disease and demographic factors. This is similar to findings reported in other reviews [<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref63">63</xref>] and meta-analyses [<xref ref-type="bibr" rid="ref34">34</xref>]. In addition, the use of technology for cancer follow-up appears to be acceptable to patients, is clinically safe [<xref ref-type="bibr" rid="ref31">31</xref>], and improves health knowledge and self-management practices [<xref ref-type="bibr" rid="ref64">64</xref>]. However, such interventions vary in design and features, most lack or fail to report theoretical frameworks, and they use outcome measures making pooling or comparison between studies difficult. Another issue when comparing digital supportive care interventions is that it may be possible that interventions vary in their efficacy across different populations and technologies used for delivery. Furthermore, past studies have reported potential challenges impacting the implementation of digital health care, such as technical problems, lack of technology knowledge, and data security [<xref ref-type="bibr" rid="ref65">65</xref>], which need to be considered when planning future studies. Recent systematic reviews concluded that a range of strategies should be implemented in digital supportive care [<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref63">63</xref>] and general digital health interventions [<xref ref-type="bibr" rid="ref66">66</xref>]. The study by O’Connor et al [<xref ref-type="bibr" rid="ref66">66</xref>] recommends increasing public awareness of different technologies and understanding of how they work, personalization of care, clinical accreditation of interventions, improving focus on health literacy, and safeguarding privacy of personal information as key areas for investigation. Key areas for digital supportive care design and implementation noted in previous cancer-related reviews that should be further explored are mechanisms for participant feedback to drive the co-design of digital interventions [<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref67">67</xref>], the efficiency of delivering relevant and tailored health care information [<xref ref-type="bibr" rid="ref65">65</xref>], and ways to integrate supportive care services at all stages of the cancer treatment pathway [<xref ref-type="bibr" rid="ref35">35</xref>].</p>
          <p>A supportive digital care intervention model should be underpinned by a theoretical framework that anticipates not only the outcomes and the tools to measure these, but also the process of achieving the outcomes from a particular intervention [<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref68">68</xref>]. However, many studies do not address the validity of patient-reported health outcomes, and most of them use self-reported measures in pre-post test design, which leaves them at a RoB. This might be in part because one of the main challenges in the development of an evidence-based digital supportive cancer care intervention is the velocity of technology development in comparison with the often-long process of conducting and evaluating clinical trials.</p>
        </sec>
        <sec>
          <title>Digital Health for Chronic Disease Care</title>
          <p>Evidence from the research and implementation of digital health interventions across other disease groups may facilitate the transferability of digitally enabled supportive cancer care. Cancer is a chronic disease for many people [<xref ref-type="bibr" rid="ref69">69</xref>]. Applications of research findings in other chronic diseases, such as cardiovascular disease [<xref ref-type="bibr" rid="ref70">70</xref>], hypertension [<xref ref-type="bibr" rid="ref12">12</xref>], and diabetes [<xref ref-type="bibr" rid="ref71">71</xref>], which have a larger evidence base in digital health–enabled interventions with positive effects, should be used where possible. A recent systematic review [<xref ref-type="bibr" rid="ref72">72</xref>] focused on the broader application of these symptom-reporting systems within multiple patient groups and concluded that although further research needs to be completed, most studies reported positive health outcomes. For example, in the case of diabetes, Greenwood et al [<xref ref-type="bibr" rid="ref71">71</xref>] found that the most effective digital interventions incorporated all components of a technology-assisted self-management feedback loop, connected people with diabetes and their health care team using two-way communication, analyzed patient-generated health data, tailored education programs, and individualized feedback. A 2018 systematic review focused on using remote monitoring in people with a history of type 2 diabetes [<xref ref-type="bibr" rid="ref73">73</xref>] significantly improved glycated hemoglobin and self-management. Evidence from diabetes research seems more cohesive, in part, because the outcomes of lowering glucose levels and glycated hemoglobin allow homogeneous measurement across studies.</p>
          <p>Several successful digital health interventions focus on both behavior change and increasing patient engagement [<xref ref-type="bibr" rid="ref74">74</xref>,<xref ref-type="bibr" rid="ref75">75</xref>]. Barello [<xref ref-type="bibr" rid="ref75">75</xref>] concluded that most studies failed to account for the complexity of patient engagement and that a more holistic approach might help maximize the potential of digital health technology [<xref ref-type="bibr" rid="ref75">75</xref>]. Another recent review focused on mobile health apps for chronic disease management and found that regular symptom assessments, automated reminders, and feedback loops were common features, with most studies reporting significant improvement in health outcomes [<xref ref-type="bibr" rid="ref73">73</xref>].</p>
        </sec>
      </sec>
      <sec>
        <title>Current Challenges and Need for Quality Information</title>
        <p>This review compiles evidence regarding the potential of digital health interventions for supportive cancer care in different settings, including remote areas and emergency situations [<xref ref-type="bibr" rid="ref33">33</xref>]. However, the challenges facing public health systems worldwide in terms of emergencies, such as the COVID-19 pandemic, have rapidly increased the use of digital health interventions [<xref ref-type="bibr" rid="ref29">29</xref>]. Health care systems, including cancer care, are adapting in response to the need for social distancing, lockdowns, and other public health initiatives. Cancer clinics have reduced clinical appointments, administration encounters, and postponed elective cancer surgeries [<xref ref-type="bibr" rid="ref28">28</xref>], which has increased the need for follow-up and management without visiting hospitals [<xref ref-type="bibr" rid="ref76">76</xref>]. This situation has advanced the use of digital health and telehealth apps and programs worldwide [<xref ref-type="bibr" rid="ref30">30</xref>]. Digital supportive cancer care has been implemented out of necessity and is becoming a common delivery model [<xref ref-type="bibr" rid="ref77">77</xref>]. Two of the suggested strategies to enable supportive cancer care during COVID-19 are (1) empowering patients and caregivers through the use of digital communication and (2) increasing the use of existing digital health platforms [<xref ref-type="bibr" rid="ref28">28</xref>].</p>
        <p>There is an urgent need to agree on relevant outcomes, methods of assessment, and there is a need for improved quality of primary studies and RCTs, as shown by our quality assessment. The lack of high-quality randomized trials identified in this review reflects the ongoing problem of low-quality research. Moreover, only 2 of the included publications referenced the CONSORT Digital Health Checklist, which was published in 2011. Only 3 included studies were published before 2011, making it disappointing that most later publications failed to reference this standard. Comments of Dickinson in BMC Cancer [<xref ref-type="bibr" rid="ref31">31</xref>] remain relevant in 2020:</p>
        <disp-quote>
          <p>Nevertheless, there are surprisingly few randomized trials given the explosion in technological innovation in recent years. It could be that technology is evolving so fast that potential innovative technological interventions become outdated before they can mature sufficiently to be subjected to randomized trials.</p>
        </disp-quote>
        <p>This insight has been recurrent in different systematic reviews [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref74">74</xref>].</p>
      </sec>
      <sec>
        <title>Strengths and Limitations</title>
        <p>Although the review was a rigorous evaluation of RCTs, there were a small number of included studies that indicated there may be significant literature in the phase I or II feasibility spectrum. Although 20 studies were included, the interventions and outcomes were heterogeneous and did not enable meta-analyses. Owing to the nature of this review, there was also a heterogeneous population, variable outcome measures, variable study quality, and methodological limitations. These characteristics have been found to contribute to a lack of evidence regarding the benefits of digital health [<xref ref-type="bibr" rid="ref19">19</xref>]. It is difficult to draw conclusions and synthesize studies with inconsistent outcome measures, and a systematic approach to using standardized measures is required. The CONSORT Digital Health Checklist should be used routinely. The review was limited to studies written in English. Therefore, it is possible that research papers published in other parts of the world were missed. As with many studies in oncology, this review found that breast cancer survivorship dominated. Thus, the development of supportive care interventions across other tumor streams is required. As most of the included studies were conducted in the United States and Europe, it is unclear whether the findings from these studies can be generalized to other countries and populations, particularly in developing nations.</p>
      </sec>
      <sec>
        <title>Future Directions</title>
        <p>Living well with cancer has gained greater relevance as the survival rates of many cancer types are increasing. The future of digital health in oncology supportive care brings a range of new and exciting possibilities. There is a need to evaluate the efficacy and efficiency of digital interventions in real-world conditions and standardize a core set of outcomes included in all studies to facilitate comparisons between interventions and digital technologies.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>Digital health–enabled supportive cancer care is capable of improving health-related quality of life, symptom burden including self-report of pain and fatigue, depression, and, to a lesser extent, functional capacity. Supportive digital interventions in the field of cancer are being used and have been reported to be helpful for patients, independent of other factors. However, there is a need for higher quality research and clearer reporting than is evident in the current RCTs. Future research should focus on using valid, standardized outcome measures, increasing the methodological rigor of studies undertaken, and the development and evaluation of strategies to improve both patient and health professional engagement in the design and delivery of supportive digital health interventions.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group>
      <supplementary-material id="app1">
        <label>Multimedia Appendix 1</label>
        <p>Search strategy.</p>
        <media xlink:href="jmir_v23i10e24722_app1.docx" xlink:title="DOCX File , 52 KB"/>
      </supplementary-material>
      <supplementary-material id="app2">
        <label>Multimedia Appendix 2</label>
        <p>Population and intervention characteristics.</p>
        <media xlink:href="jmir_v23i10e24722_app2.docx" xlink:title="DOCX File , 35 KB"/>
      </supplementary-material>
      <supplementary-material id="app3">
        <label>Multimedia Appendix 3</label>
        <p>Summary of risk of bias assessment.</p>
        <media xlink:href="jmir_v23i10e24722_app3.docx" xlink:title="DOCX File , 96 KB"/>
      </supplementary-material>
    </app-group>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">CONSORT</term>
          <def>
            <p>Consolidated Standards of Reporting Trials</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">PRISMA</term>
          <def>
            <p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">PROSPERO</term>
          <def>
            <p>International Prospective Register of Systematic Reviews</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">RCT</term>
          <def>
            <p>randomized controlled trial</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">RoB</term>
          <def>
            <p>risk of bias</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <fn-group>
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