How individual participant data meta-analyses have influenced trial design, conduct, and analysis
Identifieur interne : 002494 ( Pmc/Curation ); précédent : 002493; suivant : 002495How individual participant data meta-analyses have influenced trial design, conduct, and analysis
Auteurs : Jayne F. Tierney [Royaume-Uni] ; Jean-Pierre Pignon [France] ; Francois Gueffyier [France] ; Mike Clarke [Royaume-Uni] ; Lisa Askie ; Claire L. Vale [Royaume-Uni] ; Sarah Burdett [Royaume-Uni]Source :
- Journal of Clinical Epidemiology [ 0895-4356 ] ; 2015.
Abstract
To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer.
Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses.
We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials.
IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials.
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DOI: 10.1016/j.jclinepi.2015.05.024
PubMed: 26186982
PubMed Central: 4635379
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Lisa Askie<affiliation><nlm:aff id="aff6">NHMRC Clinical Trials Centre, ABN 15 211 513 464, Locked Bag 77, Camperdown, NSW 1450 Australia</nlm:aff><wicri:noCountry code="subfield">NSW 1450 Australia</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">How individual participant data meta-analyses have influenced trial design, conduct, and analysis</title><author><name sortKey="Tierney, Jayne F" sort="Tierney, Jayne F" uniqKey="Tierney J" first="Jayne F." last="Tierney">Jayne F. Tierney</name><affiliation wicri:level="1"><nlm:aff id="aff1">MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH</wicri:regionArea></affiliation></author><author><name sortKey="Pignon, Jean Pierre" sort="Pignon, Jean Pierre" uniqKey="Pignon J" first="Jean-Pierre" last="Pignon">Jean-Pierre Pignon</name><affiliation wicri:level="1"><nlm:aff id="aff2">LNCC plateforme de méta-analyse en oncologie, Service de Biostatistique et d’Epidemiologie, Gustave-Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>LNCC plateforme de méta-analyse en oncologie, Service de Biostatistique et d’Epidemiologie, Gustave-Roussy, Villejuif</wicri:regionArea></affiliation></author><author><name sortKey="Gueffyier, Francois" sort="Gueffyier, Francois" uniqKey="Gueffyier F" first="Francois" last="Gueffyier">Francois Gueffyier</name><affiliation wicri:level="1"><nlm:aff id="aff3">Université Claude Bernard Lyon 1/Université de Lyon, 69365 Lyon Cedex 07, Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Claude Bernard Lyon 1/Université de Lyon, 69365 Lyon Cedex 07, Lyon</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Service de Pharmacologie Clinique, Hospices Civils de Lyon, Bron cedex, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service de Pharmacologie Clinique, Hospices Civils de Lyon, Bron cedex</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Mike" sort="Clarke, Mike" uniqKey="Clarke M" first="Mike" last="Clarke">Mike Clarke</name><affiliation wicri:level="1"><nlm:aff id="aff5">All-Ireland Hub for Trials Methodology Research, Queen's University Belfast, University Road, Belfast BT7 1NN, Northern Ireland, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>All-Ireland Hub for Trials Methodology Research, Queen's University Belfast, University Road, Belfast BT7 1NN, Northern Ireland</wicri:regionArea></affiliation></author><author><name sortKey="Askie, Lisa" sort="Askie, Lisa" uniqKey="Askie L" first="Lisa" last="Askie">Lisa Askie</name><affiliation><nlm:aff id="aff6">NHMRC Clinical Trials Centre, ABN 15 211 513 464, Locked Bag 77, Camperdown, NSW 1450 Australia</nlm:aff><wicri:noCountry code="subfield">NSW 1450 Australia</wicri:noCountry></affiliation></author><author><name sortKey="Vale, Claire L" sort="Vale, Claire L" uniqKey="Vale C" first="Claire L." last="Vale">Claire L. Vale</name><affiliation wicri:level="1"><nlm:aff id="aff1">MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH</wicri:regionArea></affiliation></author><author><name sortKey="Burdett, Sarah" sort="Burdett, Sarah" uniqKey="Burdett S" first="Sarah" last="Burdett">Sarah Burdett</name><affiliation wicri:level="1"><nlm:aff id="aff1">MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26186982</idno><idno type="pmc">4635379</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4635379</idno><idno type="RBID">PMC:4635379</idno><idno type="doi">10.1016/j.jclinepi.2015.05.024</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">002644</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002644</idno><idno type="wicri:Area/Pmc/Curation">002494</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002494</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">How individual participant data meta-analyses have influenced trial design, conduct, and analysis</title><author><name sortKey="Tierney, Jayne F" sort="Tierney, Jayne F" uniqKey="Tierney J" first="Jayne F." last="Tierney">Jayne F. Tierney</name><affiliation wicri:level="1"><nlm:aff id="aff1">MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH</wicri:regionArea></affiliation></author><author><name sortKey="Pignon, Jean Pierre" sort="Pignon, Jean Pierre" uniqKey="Pignon J" first="Jean-Pierre" last="Pignon">Jean-Pierre Pignon</name><affiliation wicri:level="1"><nlm:aff id="aff2">LNCC plateforme de méta-analyse en oncologie, Service de Biostatistique et d’Epidemiologie, Gustave-Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>LNCC plateforme de méta-analyse en oncologie, Service de Biostatistique et d’Epidemiologie, Gustave-Roussy, Villejuif</wicri:regionArea></affiliation></author><author><name sortKey="Gueffyier, Francois" sort="Gueffyier, Francois" uniqKey="Gueffyier F" first="Francois" last="Gueffyier">Francois Gueffyier</name><affiliation wicri:level="1"><nlm:aff id="aff3">Université Claude Bernard Lyon 1/Université de Lyon, 69365 Lyon Cedex 07, Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université Claude Bernard Lyon 1/Université de Lyon, 69365 Lyon Cedex 07, Lyon</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4">Service de Pharmacologie Clinique, Hospices Civils de Lyon, Bron cedex, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service de Pharmacologie Clinique, Hospices Civils de Lyon, Bron cedex</wicri:regionArea></affiliation></author><author><name sortKey="Clarke, Mike" sort="Clarke, Mike" uniqKey="Clarke M" first="Mike" last="Clarke">Mike Clarke</name><affiliation wicri:level="1"><nlm:aff id="aff5">All-Ireland Hub for Trials Methodology Research, Queen's University Belfast, University Road, Belfast BT7 1NN, Northern Ireland, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>All-Ireland Hub for Trials Methodology Research, Queen's University Belfast, University Road, Belfast BT7 1NN, Northern Ireland</wicri:regionArea></affiliation></author><author><name sortKey="Askie, Lisa" sort="Askie, Lisa" uniqKey="Askie L" first="Lisa" last="Askie">Lisa Askie</name><affiliation><nlm:aff id="aff6">NHMRC Clinical Trials Centre, ABN 15 211 513 464, Locked Bag 77, Camperdown, NSW 1450 Australia</nlm:aff><wicri:noCountry code="subfield">NSW 1450 Australia</wicri:noCountry></affiliation></author><author><name sortKey="Vale, Claire L" sort="Vale, Claire L" uniqKey="Vale C" first="Claire L." last="Vale">Claire L. Vale</name><affiliation wicri:level="1"><nlm:aff id="aff1">MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH</wicri:regionArea></affiliation></author><author><name sortKey="Burdett, Sarah" sort="Burdett, Sarah" uniqKey="Burdett S" first="Sarah" last="Burdett">Sarah Burdett</name><affiliation wicri:level="1"><nlm:aff id="aff1">MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Clinical Epidemiology</title><idno type="ISSN">0895-4356</idno><idno type="eISSN">1878-5921</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer.</p></sec><sec><title>Study Design and Setting</title><p>Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses.</p></sec><sec><title>Results</title><p>We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials.</p></sec><sec><title>Conclusions</title><p>IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Clarke, M" uniqKey="Clarke M">M. Clarke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cooper, N J" uniqKey="Cooper N">N.J. Cooper</name></author><author><name sortKey="Jones, D R" uniqKey="Jones D">D.R. Jones</name></author><author><name sortKey="Sutton, A J" uniqKey="Sutton A">A.J. Sutton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clarke, M" uniqKey="Clarke M">M. Clarke</name></author><author><name sortKey="Hopewell, S" uniqKey="Hopewell S">S. Hopewell</name></author><author><name sortKey="Chalmers, I" uniqKey="Chalmers I">I. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Epidemiol</journal-id><journal-id journal-id-type="iso-abbrev">J Clin Epidemiol</journal-id><journal-title-group><journal-title>Journal of Clinical Epidemiology</journal-title></journal-title-group><issn pub-type="ppub">0895-4356</issn><issn pub-type="epub">1878-5921</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26186982</article-id><article-id pub-id-type="pmc">4635379</article-id><article-id pub-id-type="publisher-id">S0895-4356(15)00268-1</article-id><article-id pub-id-type="doi">10.1016/j.jclinepi.2015.05.024</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>How individual participant data meta-analyses have influenced trial design, conduct, and analysis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Tierney</surname><given-names>Jayne F.</given-names></name><email>jayne.tierney@ucl.ac.uk</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author"><name><surname>Pignon</surname><given-names>Jean-Pierre</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Gueffyier</surname><given-names>Francois</given-names></name><xref rid="aff3" ref-type="aff">c</xref><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Clarke</surname><given-names>Mike</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Askie</surname><given-names>Lisa</given-names></name><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Vale</surname><given-names>Claire L.</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Burdett</surname><given-names>Sarah</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><collab>Cochrane IPD Meta-analysis Methods Group<contrib-group><contrib contrib-type="author"><name><surname>Alderson</surname><given-names>P.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Askie</surname><given-names>L.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bennett</surname><given-names>D.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Burdett</surname><given-names>S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Clarke</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Dias</surname><given-names>S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Emberson</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Gueyffier</surname><given-names>F.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Iorio</surname><given-names>A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Macleod</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Mol</surname><given-names>B.W.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Moons</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Parmar</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Perera</surname><given-names>R.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Phillips</surname><given-names>R.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Pignon</surname><given-names>J.P.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Rees</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Reitsma</surname><given-names>H.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Riley</surname><given-names>R.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Rovers</surname><given-names>M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Rydzewska</surname><given-names>L.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Schmid</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Shepperd</surname><given-names>S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Stenning</surname><given-names>S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Stewart</surname><given-names>L.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tierney</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tudur Smith</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Vale</surname><given-names>C.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Welge</surname><given-names>J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>White</surname><given-names>I.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Whiteley</surname><given-names>W.</given-names></name></contrib></contrib-group></collab></contrib></contrib-group><aff id="aff1"><label>a</label>MRC Clinical Trials Unit at UCL, Aviation House, 125 Kingsway, London WC2B 6NH, UK</aff><aff id="aff2"><label>b</label>LNCC plateforme de méta-analyse en oncologie, Service de Biostatistique et d’Epidemiologie, Gustave-Roussy, Villejuif, France</aff><aff id="aff3"><label>c</label>Université Claude Bernard Lyon 1/Université de Lyon, 69365 Lyon Cedex 07, Lyon, France</aff><aff id="aff4"><label>d</label>Service de Pharmacologie Clinique, Hospices Civils de Lyon, Bron cedex, France</aff><aff id="aff5"><label>e</label>All-Ireland Hub for Trials Methodology Research, Queen's University Belfast, University Road, Belfast BT7 1NN, Northern Ireland, UK</aff><aff id="aff6"><label>f</label>NHMRC Clinical Trials Centre, ABN 15 211 513 464, Locked Bag 77, Camperdown, NSW 1450 Australia</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Tel.: +0207-670-4724; fax: +0207-670-4685. <email>jayne.tierney@ucl.ac.uk</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>1</day><month>11</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>11</month><year>2015</year></pub-date><volume>68</volume><issue>11</issue><fpage>1325</fpage><lpage>1335</lpage><history><date date-type="accepted"><day>27</day><month>5</month><year>2015</year></date></history><permissions><copyright-statement>Crown Copyright © Published by Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2015</copyright-year><copyright-holder></copyright-holder><license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p></license></permissions><abstract><sec><title>Objectives</title><p>To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer.</p></sec><sec><title>Study Design and Setting</title><p>Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses.</p></sec><sec><title>Results</title><p>We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials.</p></sec><sec><title>Conclusions</title><p>IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials.</p></sec></abstract><kwd-group><title>Keywords</title><kwd>Individual participant data (IPD)</kwd><kwd>Systematic review</kwd><kwd>Meta-analysis</kwd><kwd>Trial conduct</kwd><kwd>Trial design</kwd><kwd>Trial analysis</kwd></kwd-group></article-meta></front><floats-group><table-wrap id="tbl1" position="float"><label>Table 1</label><caption><p>Further examples of the impact of IPD meta-analyses on trial design, conduct, analysis, and interpretation</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Example</th><th>Description of IPD meta-analyses</th><th>What was the impact?</th><th>Impact IPD specific</th></tr></thead><tbody><tr><td colspan="4"><italic>Trial design</italic></td></tr><tr><td> Breast cancer <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0035"><label>•</label><p>3 IPD meta-analyses comparing effects of hormonal therapy vs. non or two durations of this treatment for early breast cancer <xref rid="bib19" ref-type="bibr">[19]</xref>.</p></list-item><list-item id="u0040"><label>•</label><p>71 Trials and 80,273 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0045"><label>•</label><p>Informed choice of comparators in the ATLAS trial <xref rid="bib20" ref-type="bibr">[20]</xref>, <xref rid="bib21" ref-type="bibr">[21]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0050"><label>•</label><p>No</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Non–small cell lung cancer <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0055"><label>•</label><p>4 IPD meta-analyses investigating effects of adding chemotherapy to surgery; surgery and radiotherapy; radiotherapy and supportive care <xref rid="bib22" ref-type="bibr">[22]</xref>.</p></list-item><list-item id="u0060"><label>•</label><p>52 Trials and 9,387 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0065"><label>•</label><p>Informed the choice of comparators in new trials in locally advanced disease <xref rid="bib23" ref-type="bibr">[23]</xref>, <xref rid="bib24" ref-type="bibr">[24]</xref>.</p></list-item><list-item id="u0070"><label>•</label><p>Renewed enthusiasm for chemotherapy led to collaborations on new trials from IPD collaborative group <xref rid="bib25" ref-type="bibr">[25]</xref>, <xref rid="bib26" ref-type="bibr">[26]</xref>, <xref rid="bib27" ref-type="bibr">[27]</xref>, <xref rid="bib28" ref-type="bibr">[28]</xref>.</p></list-item><list-item id="u0075"><label>•</label><p>Control group survival and absolute survival benefits used as the basis for sample size calculation <xref rid="bib27" ref-type="bibr">[27]</xref>, <xref rid="bib28" ref-type="bibr">[28]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0080"><label>•</label><p>No</p></list-item><list-item id="u0085"><label>•</label><p>Yes</p></list-item><list-item id="u0090"><label>•</label><p>No</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Soft tissue sarcoma <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0095"><label>•</label><p>1 IPD meta-analysis investigating the effects of adding doxorubicin-based chemotherapy after local treatment <xref rid="bib29" ref-type="bibr">[29]</xref>.</p></list-item><list-item id="u0100"><label>•</label><p>14 Trials and 1,568 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0105"><label>•</label><p>Subgroup results helped define population in the RTOG 95-14 trial <xref rid="bib30" ref-type="bibr">[30]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0110"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Cervical cancer <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0115"><label>•</label><p>1 IPD meta-analysis investigating concomitant chemoradiotherapy vs. the same radiotherapy <xref rid="bib31" ref-type="bibr">[31]</xref>.</p></list-item><list-item id="u0120"><label>•</label><p>18 Trials and 4,818 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0125"><label>•</label><p>IPD meta-analysis and another trial together informed choice of comparators in the OUTBACK trial (ANZGOG 0902/GOG-0274/RTOG 1174).</p></list-item><list-item id="u0130"><label>•</label><p>Control group survival used as the basis for sample size calculation in the OUTBACK trial.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0135"><label>•</label><p>No</p></list-item><list-item id="u0140"><label>•</label><p>No</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Hypertension <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0145"><label>•</label><p>1 IPD meta-analysis investigating antihypertensive drugs in very elderly patients <xref rid="bib32" ref-type="bibr">[32]</xref>.</p></list-item><list-item id="u0150"><label>•</label><p>7 Trials and 1,670 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0155"><label>•</label><p>Subgroup results helped define the population in the HYVET trial <xref rid="bib33" ref-type="bibr">[33]</xref>, <xref rid="bib34" ref-type="bibr">[34]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0160"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Hypertension <xref rid="bib2" ref-type="bibr">[2]</xref></td><td><list list-type="simple"><list-item id="u0165"><label>•</label><p>1 IPD meta-analysis investigating the effect of antihypertensive treatment in patients having already suffered a stroke <xref rid="bib35" ref-type="bibr">[35]</xref>.</p></list-item><list-item id="u0170"><label>•</label><p>9 Trials and 6,752 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0175"><label>•</label><p>Subgroup results helped define population for the PROGRESS trial <xref rid="bib36" ref-type="bibr">[36]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0180"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Hypertension <xref rid="bib3" ref-type="bibr">[3]</xref></td><td><list list-type="simple"><list-item id="u0185"><label>•</label><p>1 IPD meta-analysis investigating diuretic vs. placebo-based treatment of hypertension for diabetes <xref rid="bib37" ref-type="bibr">[37]</xref>.</p></list-item><list-item id="u0190"><label>•</label><p>4 Trials and 18,097 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0195"><label>•</label><p>Subgroup results helped define population for the ADVANCE trial <xref rid="bib38" ref-type="bibr">[38]</xref>, <xref rid="bib39" ref-type="bibr">[39]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0200"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Head and neck <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0205"><label>•</label><p>1 IPD meta-analysis comparing conventional radiotherapy vs. altered fractionated radiotherapy for head and neck cancer <xref rid="bib40" ref-type="bibr">[40]</xref>.</p></list-item><list-item id="u0210"><label>•</label><p>15 Trials and 6,515 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0215"><label>•</label><p>Subgroup results helped define population of GORTEC-ELAN-RT (<ext-link ext-link-type="uri" xlink:href="ctgov:NCT01864850" id="interref0010b">NCT01864850</ext-link>) trial.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0220"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Small-cell lung cancer <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0225"><label>•</label><p>1 IPD meta-analysis comparing prophylactic cranial irradiation (PCI) vs. none in patients with small-cell lung cancer <xref rid="bib41" ref-type="bibr">[41]</xref>.</p></list-item><list-item id="u0230"><label>•</label><p>7 Trials and 987 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0235"><label>•</label><p>Informed choice of comparators in PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01 trial <xref rid="bib42" ref-type="bibr">[42]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0240"><label>•</label><p>No</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Breast cancer <xref rid="bib2" ref-type="bibr">[2]</xref></td><td><list list-type="simple"><list-item id="u0245"><label>•</label><p>1 IPD meta-analysis comparing radiotherapy and other treatments vs. the same other treatment with no radiotherapy <xref rid="bib43" ref-type="bibr">[43]</xref>.</p></list-item><list-item id="u0250"><label>•</label><p>40 RCTs and 19,582 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0255"><label>•</label><p>Informed choice of comparators in SUPREMO trial (ISRCTN 61145589).</p></list-item></list></td><td><list list-type="simple"><list-item id="u0260"><label>•</label><p>No</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Non–small cell lung cancer <xref rid="bib2" ref-type="bibr">[2]</xref></td><td><list list-type="simple"><list-item id="u0265"><label>•</label><p>1 IPD meta-analysis of postoperative radiotherapy vs. none <xref rid="bib44" ref-type="bibr">[44]</xref>.</p></list-item><list-item id="u0270"><label>•</label><p>11 RCTs and 2,343 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0275"><label>•</label><p>Subgroup results helped define population in the Lung ART trial (<ext-link ext-link-type="uri" xlink:href="ctgov:NCT00410683" id="interref0010c">NCT00410683</ext-link>)</p></list-item></list></td><td><list list-type="simple"><list-item id="u0280"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Stroke <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0285"><label>•</label><p>Prospective IPD meta-analysis comparing antidepressants vs. none in recovering stroke patients.</p></list-item><list-item id="u0290"><label>•</label><p>2 Trials and 4,600 patients (approx.).</p></list-item></list></td><td><list list-type="simple"><list-item id="u0295"><label>•</label><p>Prospective IPD meta-analysis led to common trial design of the two included trials<list list-type="simple"><list-item id="u0300"><label>○</label><p>Affinity—<ext-link ext-link-type="uri" xlink:href="http://www.affinitytrial.org" id="intref0015">www.affinitytrial.org</ext-link></p></list-item><list-item id="u0305"><label>○</label><p>FOCUS—<ext-link ext-link-type="uri" xlink:href="http://www.focustrial.org.uk" id="intref0020">www.focustrial.org.uk</ext-link></p></list-item></list></p></list-item></list></td><td><list list-type="simple"><list-item id="u0310"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Preterm neonates</td><td><list list-type="simple"><list-item id="u0315"><label>•</label><p>Prospective IPD meta-analysis comparing oxygen saturation given to extremely premature babies <xref rid="bib45" ref-type="bibr">[45]</xref>.</p></list-item><list-item id="u0320"><label>•</label><p>5 Trials and 5,000 patients (approx).</p></list-item></list></td><td><list list-type="simple"><list-item id="u0325"><label>•</label><p>Prospective IPD meta-analysis to achieve power for key outcomes.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0330"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td colspan="4"><italic>Trial conduct</italic></td></tr><tr><td> Colon cancer <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0335"><label>•</label><p>Prospective IPD meta-analysis comparing adjuvant fluorouracil and folinic acid vs. control for Dukes B and C colon cancer <xref rid="bib46" ref-type="bibr">[46]</xref>.</p></list-item><list-item id="u0340"><label>•</label><p>3 Trials and 1,493 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0345"><label>•</label><p>Prospective IPD meta-analysis used to achieve power for key outcome.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0350"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Stroke <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0355"><label>•</label><p>As above</p></list-item></list></td><td><list list-type="simple"><list-item id="u0360"><label>•</label><p>Collaborative design of prospective IPD meta-analysis study materials in the two included trials.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0365"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Non–small cell lung cancer <xref rid="bib3" ref-type="bibr">[3]</xref></td><td><list list-type="simple"><list-item id="u0370"><label>•</label><p>1 IPD meta-analysis of postoperative platinum-based chemotherapy vs. none for NSCLC <xref rid="bib47" ref-type="bibr">[47]</xref>.</p></list-item><list-item id="u0375"><label>•</label><p>2 Trials and 494 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0380"><label>•</label><p>Subgroup results used as rationale for trial stopping (IFCT 0801, TASTE (<ext-link ext-link-type="uri" xlink:href="ctgov:NCT00775385" id="interref0010d">NCT00775385</ext-link><xref rid="bib48" ref-type="bibr">[48]</xref>, <xref rid="bib49" ref-type="bibr">[49]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0385"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Preterm neonates</td><td><list list-type="simple"><list-item id="u0390"><label>•</label><p>As above</p></list-item></list></td><td><list list-type="simple"><list-item id="u0395"><label>•</label><p>Prospective IPD meta-analysis influenced aspects of the individual trials, for example, data collection and study materials.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0400"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td colspan="4"><italic>Trial analysis and interpretation</italic></td></tr><tr><td> Soft tissue sarcoma <xref rid="bib2" ref-type="bibr">[2]</xref></td><td><list list-type="simple"><list-item id="u0405"><label>•</label><p>IPD meta-analysis investigating the effects of adding doxorubicin-based chemotherapy after local treatment <xref rid="bib29" ref-type="bibr">[29]</xref>.</p></list-item><list-item id="u0410"><label>•</label><p>14 Trials and 1,568 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0415"><label>•</label><p>EORTC 62931 trial report uses results of meta-analysis and subsequent trials to places trial results in context <xref rid="bib50" ref-type="bibr">[50]</xref>.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0420"><label>•</label><p>No</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Stroke <xref rid="bib1" ref-type="bibr">[1]</xref></td><td><list list-type="simple"><list-item id="u0425"><label>•</label><p>As above</p></list-item></list></td><td><list list-type="simple"><list-item id="u0430"><label>•</label><p>Prospective IPD meta-analysis influenced planned analysis of two included trials.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0435"><label>•</label><p>Yes</p></list-item></list></td></tr><tr><td colspan="4">
</td></tr><tr><td> Bladder cancer</td><td><list list-type="simple"><list-item id="u0440"><label>•</label><p>IPD meta-analysis of adjuvant chemotherapy vs. none in bladder <xref rid="bib51" ref-type="bibr">[51]</xref>.</p></list-item><list-item id="u0445"><label>•</label><p>6 Trials and 491 patients.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0450"><label>•</label><p>EORTC 30994 trial report <xref rid="bib52" ref-type="bibr">[52]</xref> uses results of IPD meta-analyses and subsequent results to places trial results in context.</p></list-item></list></td><td><list list-type="simple"><list-item id="u0455"><label>•</label><p>No</p></list-item></list></td></tr></tbody></table><table-wrap-foot><fn><p><italic>Abbreviations</italic>: IPD, individual participant data; RCT, randomized controlled trial.</p></fn></table-wrap-foot></table-wrap><boxed-text id="tbox1"><label>Box 1</label><caption><title>Impact on trial design: choice of comparators, and reaching consensus and collaboration on the next trial</title></caption><p><list list-type="simple"><title>The individual participant data (IPD) meta-analyses</title><list-item id="o0010"><label>•</label><p>Five meta-analyses comparing the effects of different types of chemotherapy for advanced ovarian cancer <xref rid="bib12" ref-type="bibr">[12]</xref>.</p></list-item><list-item id="o0015"><label>•</label><p>One related meta-analysis comparing CAP (cyclophosphamide, doxorubicin, and cisplatin) with CP (cyclophosphamide and cisplatin) chemotherapy <xref rid="bib13" ref-type="bibr">[13]</xref>.</p></list-item><list-item id="o0020"><label>•</label><p>Together included ∼50 trials and ∼10,000 women.</p></list-item><list-item id="o0025"><label>•</label><p>Provided the first comprehensive synthesis of the effects of chemotherapy for advanced ovarian cancer.</p></list-item></list><list list-type="simple"><title>The pertinent results</title><list-item id="o0030"><label>•</label><p>Platinum-based chemotherapy better than nonplatinum chemotherapy <xref rid="bib12" ref-type="bibr">[12]</xref>.</p></list-item><list-item id="o0035"><label>•</label><p>Platinum-based combination chemotherapy better than single-agent platinum-based chemotherapy <xref rid="bib12" ref-type="bibr">[12]</xref>.</p></list-item><list-item id="o0040"><label>•</label><p>No clear difference between the effects of carboplatin and cisplatin when used as single agents or when substituted for one another in combination regimens <xref rid="bib12" ref-type="bibr">[12]</xref>.</p></list-item><list-item id="o0045"><label>•</label><p>CAP better than CP but dose of cisplatin in CAP regimen suboptimal because of toxicity <xref rid="bib13" ref-type="bibr">[13]</xref>.</p></list-item></list><list list-type="simple"><title>Impact on new trials</title><list-item id="o0050"><label>(1)</label><p>Informed choice of comparators in new trial.<list list-type="simple"><list-item id="u0460"><label>•</label><p>International Collaborative Ovarian Neoplasm 2 trial (ICON2) compared CAP with optimal dose carboplatin <xref rid="bib14" ref-type="bibr">[14]</xref>; the latter being less toxic than cisplatin.</p></list-item><list-item id="u0465"><label>•</label><p>In its time, ICON2 was the largest trial to be conducted in ovarian cancer and it showed definitely that carboplatin was an effective but less toxic treatment than CAP for women with advanced ovarian cancer.</p></list-item><list-item id="u0470"><label>•</label><p>Carboplatin was the control group comparator in the subsequent ICON3 trial <xref rid="bib15" ref-type="bibr">[15]</xref>.</p></list-item><list-item id="u0475"><label>•</label><p>Impact may have been possible using aggregate data.</p></list-item></list></p></list-item><list-item id="o0055"><label>(2)</label><p>Collaboration<list list-type="simple"><list-item id="u0480"><label>•</label><p>Large-scale collaboration was needed to achieve a trial of sufficient size and was formed from the meta-analyses collaborative groups.</p></list-item><list-item id="u0485"><label>•</label><p>A total of 1,526 patients in ICON2 were recruited by 132 centers in nine countries.</p></list-item><list-item id="u0490"><label>•</label><p>Collaborations and strategic planning of ovarian cancer trials (ICON 1–8) have continued long after the original meta-analysis.</p></list-item><list-item id="u0495"><label>•</label><p>Impact only possible because of the individual participant data approach.</p></list-item></list></p></list-item></list></p></boxed-text><boxed-text id="tbox2"><label>Box 2</label><caption><title>Impact on trial analysis and interpretation: validated prognostic factor used to stratify new trial analysis, which formed part of the final report</title></caption><p><list list-type="simple"><title>The individual participant data (IPD) meta-analysis</title><list-item id="o0060"><label>•</label><p>Eleven acute stroke trials, 5,843 participants fitting entry criteria <xref rid="bib16" ref-type="bibr">[16]</xref> from the Virtual International Stroke Archive (VISTA, <ext-link ext-link-type="uri" xlink:href="http://www.gla.ac.uk" id="intref0025">www.gla.ac.uk</ext-link>).</p></list-item></list><list list-type="simple"><title>Pertinent results</title><list-item id="o0065"><label>•</label><p>Prognostic model developed and validated using IPD.</p></list-item><list-item id="o0070"><label>•</label><p>Provided the predicted probability of a poor outcome at 6 months <xref rid="bib16" ref-type="bibr">[16]</xref>.</p></list-item></list><list list-type="simple"><title>Impact on new trials</title><list-item id="o0075"><label>(1)</label><p>Prognostic factor analysis informed trial analysis stratification.<list list-type="simple"><list-item id="u0500"><label>•</label><p>Predicted probability of a poor outcome used to stratify the analysis of IST-3 trial of thrombolysis vs. control.</p></list-item><list-item id="u0505"><label>•</label><p>Larger benefit of thrombolysis was seen with higher probability of a poor outcome <xref rid="bib17" ref-type="bibr">[17]</xref>.</p></list-item><list-item id="u0510"><label>•</label><p>Impact only possible because individual participant data were used.</p></list-item></list></p></list-item></list></p></boxed-text><boxed-text id="tbox3"><label>Box 3</label><caption><title>Impact on trial conduct: designed prospective individual participant data (IPD) meta-analysis of ongoing trials to achieve power, encourage continued recruitment, and inform trial analyses</title></caption><p><list list-type="simple"><title>The IPD meta-analysis</title><list-item id="o0080"><label>•</label><p>Adjuvant vs. salvage radiotherapy after radical prostatectomy for locally advanced prostate cancer.</p></list-item><list-item id="u0515"><label>•</label><p>Three trials (RADICALS [ISRCTN40814031], RAVES [<ext-link ext-link-type="uri" xlink:href="ctgov:NCT00860652" id="interref0010e">NCT00860652</ext-link>], GETUG-17 [<ext-link ext-link-type="uri" xlink:href="ctgov:NCT00667069" id="interref0010f">NCT00667069</ext-link>]) and ∼2,000 patients</p></list-item></list><list list-type="simple"><title>Impact on ongoing trials</title><list-item id="o0085"><label>(1)</label><p>To achieve power for key outcomes<list list-type="simple"><list-item id="u0525"><label>•</label><p>Trials are recruiting slowly and the prognosis of participants is better than expected, so a meta-analysis will help achieve sufficient power to detect an effect on survival.</p></list-item><list-item id="u0530"><label>•</label><p>Impact only possible because of individual participant data approach.</p></list-item></list></p></list-item><list-item id="o0090"><label>(2)</label><p>Informing the conduct<list list-type="simple"><list-item id="u0535"><label>•</label><p>Used to justify and encourage continued recruitment, follow-up, and funding of ongoing trials <xref rid="bib18" ref-type="bibr">[18]</xref>.</p></list-item></list></p></list-item><list-item id="o0095"><label>(3)</label><p>Informing the analysis<list list-type="simple"><list-item id="u0540"><label>•</label><p>Deciding on definition and analysis of intermediate outcomes.</p></list-item></list></p></list-item></list></p></boxed-text></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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