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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">v23i6e26514</article-id>
      <article-id pub-id-type="pmid">34132641</article-id>
      <article-id pub-id-type="doi">10.2196/26514</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Letter to the Editor</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Letter to the Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Periodic Manual Algorithm Updates and Generalizability: A Developer’s Response. Comment on “Evaluation of Four Artificial Intelligence–Assisted Self-Diagnosis Apps on Three Diagnoses: Two-Year Follow-Up Study”</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Derrick</surname>
            <given-names>Thomas</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Ćirković</surname>
            <given-names>Aleksandar</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Gilbert</surname>
            <given-names>Stephen</given-names>
          </name>
          <degrees>BSc, BVMS, MRes, PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Ada Health</institution>
            <addr-line>Karl-Liebknecht-Str 1</addr-line>
            <addr-line>Berlin, 10178</addr-line>
            <country>Germany</country>
            <phone>49 017680396015</phone>
            <email>stephen.gilbert@ada.com</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1997-1689</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Fenech</surname>
            <given-names>Matthew</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-7933-4617</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Idris</surname>
            <given-names>Anisa</given-names>
          </name>
          <degrees>LLM, MPH, MBA</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-0355-6904</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Türk</surname>
            <given-names>Ewelina</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-3954-1210</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Ada Health</institution>
        <addr-line>Berlin</addr-line>
        <country>Germany</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Stephen Gilbert <email>stephen.gilbert@ada.com</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <month>6</month>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>16</day>
        <month>6</month>
        <year>2021</year>
      </pub-date>
      <volume>23</volume>
      <issue>6</issue>
      <elocation-id>e26514</elocation-id>
      <history>
        <date date-type="received">
          <day>15</day>
          <month>12</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>13</day>
          <month>5</month>
          <year>2021</year>
        </date>
      </history>
      <copyright-statement>©Stephen Gilbert, Matthew Fenech, Anisa Idris, Ewelina Türk. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 16.06.2021.</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/2021/6/e26514" xlink:type="simple"/>
      <related-article related-article-type="commentary-article" id="v22i12e18097" ext-link-type="doi" xlink:href="10.2196/18097" vol="22" page="e18097" xlink:type="simple">https://www.jmir.org/2020/12/e18097</related-article>
      <related-article related-article-type="commentary" id="v23i6e29336" ext-link-type="doi" xlink:href="10.2196/29336" vol="23" page="e29336" xlink:type="simple">https://www.jmir.org/2021/6/e29336</related-article>
      <kwd-group>
        <kwd>artificial intelligence</kwd>
        <kwd>machine learning</kwd>
        <kwd>mobile apps</kwd>
        <kwd>medical diagnosis</kwd>
        <kwd>mHealth</kwd>
        <kwd>symptom assessment</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <p>We have several comments on the recent publication of Ćirković [<xref ref-type="bibr" rid="ref1">1</xref>], in which repeated testing of four symptom assessment applications with clinical vignettes was carried out to look for “hints of ‘non-locked learning algorithms’.” As the developer of one of the symptom assessment applications studied by Ćirković [<xref ref-type="bibr" rid="ref1">1</xref>], we are supportive of studies evaluating app performance; however, there are important limitations in the methodology of this study.</p>
    <p>Most importantly, the methodology used in this study is not capable of addressing its main objective. The approach used to look for evidence of nonlocked algorithms was the quantification of differences in performance using 3 ophthalmology vignettes, first in 2018, then in 2020. This methodology, although highly limited due to the use of only 3 vignettes in one medical specialism, could be used to detect changes in app performance over time. It, however, cannot be used to distinguish between nonlocked algorithms and the manual updating of apps’ medical intelligence, through the normal process of the manual release of updated app versions. Medical device regulations and quality system requirements provide standard mechanisms through which apps can be further developed, validated, and released as updated versions. The manual of medical knowledge in this manner has been acknowledged by the manufacturers of all the apps studied by Ćirković [<xref ref-type="bibr" rid="ref1">1</xref>]. In response to previous independent vignettes studies [<xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref3">3</xref>], spokespeople for Your.MD and Babylon stated that they update their medical knowledge periodically, and this is also clear on Buoy’s website. In Gilbert et al [<xref ref-type="bibr" rid="ref4">4</xref>], the Ada app is described as having a knowledge base “built and reviewed by medical doctors in a curated process of knowledge integration from medical literature. It is being expanded continuously following this standardized process.”</p>
    <p>As is acknowledged in the limitations listed in Ćirković’s work [<xref ref-type="bibr" rid="ref1">1</xref>], the study used vignettes designed, entered, and with results adjudicated by a single clinician. This could result in bias and a narrow type of case. It is also acknowledged that 3 vignettes represent a small sample size for a vignettes study and that “standardized and transparent procedures” are needed for symptom assessment app–vignettes studies. We recently published a 200-vignette assessment of symptom assessment applications [<xref ref-type="bibr" rid="ref4">4</xref>], including those studied by Ćirković [<xref ref-type="bibr" rid="ref1">1</xref>], which used standardized and transparent procedures, including the separation of vignette design, entered and with results adjudication. It is our view that the effect of the limitations described by Ćirković [<xref ref-type="bibr" rid="ref1">1</xref>], together with only including ophthalmological cases, is that the accuracy results reported have limited generalizability or repeatability. Our own internal validation testing shows an improvement in Ada's medical intelligence in all-condition top-3 suggestion accuracy (also known as M3, as defined by Miller et al [<xref ref-type="bibr" rid="ref5">5</xref>]) of 4.8% between 2018 and 2020. We take account of all performance feedback we receive, and incorporate this, when judged appropriate by our medical knowledge experts, into updates of our app, through periodic releases of locked versions of our app.</p>
  </body>
  <back>
    <app-group/>
    <fn-group>
      <fn fn-type="conflict">
        <p>All authors are employees of Ada Health.</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>Ćirković</surname>
              <given-names>Aleksandar</given-names>
            </name>
          </person-group>
          <article-title>Evaluation of Four Artificial Intelligence-Assisted Self-Diagnosis Apps on Three Diagnoses: Two-Year Follow-Up Study</article-title>
          <source>J Med Internet Res</source>
          <year>2020</year>
          <month>12</month>
          <day>04</day>
          <volume>22</volume>
          <issue>12</issue>
          <fpage>e18097</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.jmir.org/2020/12/e18097/"/>
          </comment>
          <pub-id pub-id-type="doi">10.2196/18097</pub-id>
          <pub-id pub-id-type="medline">33275113</pub-id>
          <pub-id pub-id-type="pii">v22i12e18097</pub-id>
          <pub-id pub-id-type="pmcid">PMC7748958</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref2">
        <label>2</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Burgess</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Can you really trust the medical apps on your phone?</article-title>
          <source>Wired</source>
          <year>2017</year>
          <month>10</month>
          <day>1</day>
          <access-date>2020-12-15</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.wired.co.uk/article/health-apps-test-ada-yourmd-babylon-accuracy">https://www.wired.co.uk/article/health-apps-test-ada-yourmd-babylon-accuracy</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref3">
        <label>3</label>
        <nlm-citation citation-type="web">
          <article-title>What happened when Pulse tested symptom checker apps</article-title>
          <source>Pulse</source>
          <year>2019</year>
          <month>8</month>
          <day>30</day>
          <access-date>2020-12-15</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://www.pulsetoday.co.uk/news/analysis/what-happened-when-pulse-tested-symptom-checker-apps/20039333.article">http://www.pulsetoday.co.uk/news/analysis/what-happened-when-pulse-tested-symptom-checker-apps/20039333.article</ext-link>
          </comment>
        </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>Gilbert</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Mehl</surname>
              <given-names>Alicia</given-names>
            </name>
            <name name-style="western">
              <surname>Baluch</surname>
              <given-names>Adel</given-names>
            </name>
            <name name-style="western">
              <surname>Cawley</surname>
              <given-names>Caoimhe</given-names>
            </name>
            <name name-style="western">
              <surname>Challiner</surname>
              <given-names>Jean</given-names>
            </name>
            <name name-style="western">
              <surname>Fraser</surname>
              <given-names>Hamish</given-names>
            </name>
            <name name-style="western">
              <surname>Millen</surname>
              <given-names>Elizabeth</given-names>
            </name>
            <name name-style="western">
              <surname>Montazeri</surname>
              <given-names>Maryam</given-names>
            </name>
            <name name-style="western">
              <surname>Multmeier</surname>
              <given-names>Jan</given-names>
            </name>
            <name name-style="western">
              <surname>Pick</surname>
              <given-names>Fiona</given-names>
            </name>
            <name name-style="western">
              <surname>Richter</surname>
              <given-names>Claudia</given-names>
            </name>
            <name name-style="western">
              <surname>Türk</surname>
              <given-names>Ewelina</given-names>
            </name>
            <name name-style="western">
              <surname>Upadhyay</surname>
              <given-names>Shubhanan</given-names>
            </name>
            <name name-style="western">
              <surname>Virani</surname>
              <given-names>Vishaal</given-names>
            </name>
            <name name-style="western">
              <surname>Vona</surname>
              <given-names>Nicola</given-names>
            </name>
            <name name-style="western">
              <surname>Wicks</surname>
              <given-names>Paul</given-names>
            </name>
            <name name-style="western">
              <surname>Novorol</surname>
              <given-names>Claire</given-names>
            </name>
          </person-group>
          <article-title>How accurate are digital symptom assessment apps for suggesting conditions and urgency advice? A clinical vignettes comparison to GPs</article-title>
          <source>BMJ Open</source>
          <year>2020</year>
          <month>12</month>
          <day>16</day>
          <volume>10</volume>
          <issue>12</issue>
          <fpage>e040269</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://bmjopen.bmj.com/lookup/pmidlookup?view=long&#38;pmid=33328258"/>
          </comment>
          <pub-id pub-id-type="doi">10.1136/bmjopen-2020-040269</pub-id>
          <pub-id pub-id-type="medline">33328258</pub-id>
          <pub-id pub-id-type="pii">bmjopen-2020-040269</pub-id>
          <pub-id pub-id-type="pmcid">PMC7745523</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>Miller</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Gilbert</surname>
              <given-names>Stephen</given-names>
            </name>
            <name name-style="western">
              <surname>Virani</surname>
              <given-names>Vishaal</given-names>
            </name>
            <name name-style="western">
              <surname>Wicks</surname>
              <given-names>Paul</given-names>
            </name>
          </person-group>
          <article-title>Patients' Utilization and Perception of an Artificial Intelligence-Based Symptom Assessment and Advice Technology in a British Primary Care Waiting Room: Exploratory Pilot Study</article-title>
          <source>JMIR Hum Factors</source>
          <year>2020</year>
          <month>07</month>
          <day>10</day>
          <volume>7</volume>
          <issue>3</issue>
          <fpage>e19713</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://humanfactors.jmir.org/2020/3/e19713/"/>
          </comment>
          <pub-id pub-id-type="doi">10.2196/19713</pub-id>
          <pub-id pub-id-type="medline">32540836</pub-id>
          <pub-id pub-id-type="pii">v7i3e19713</pub-id>
          <pub-id pub-id-type="pmcid">PMC7382011</pub-id>
        </nlm-citation>
      </ref>
    </ref-list>
  </back>
</article>
