Rethinking Composite End Points in Clinical Trials: Insights From Patients and Trialists
BACKGROUND—Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers. METHODS AND RESULTS—We asked 785 cardiovascular patients and 164 clinical trial authors to assign...
Gespeichert in:
| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2014-10, Vol.130 (15), p.1254-1261 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1261 |
|---|---|
| container_issue | 15 |
| container_start_page | 1254 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 130 |
| creator | Stolker, Joshua M Spertus, John A Cohen, David J Jones, Philip G Jain, Kaushik K Bamberger, Emily Lonergan, Brady B Chan, Paul S |
| description | BACKGROUND—Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers.
METHODS AND RESULTS—We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 “spending weights” across 5 common adverse events comprising composite end points in cardiovascular trialsdeath, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant’s ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P |
| doi_str_mv | 10.1161/CIRCULATIONAHA.113.006588 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1609306780</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1609306780</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3067-e863558357771380605c16dbe02f70a39b42d4c9da1ec4d1ef8c8ca26f2ee1f43</originalsourceid><addsrcrecordid>eNpVkFtLAzEQhYMotl7-gqxvvqxOkk2y61tZWi0UFang25JmZ23sXmqypfjvTa0KPg1z5jtz4BBySeGaUklv8ulz_jIbzaePD6P7UdD4NYAUaXpAhlSwJE4Ezw7JEACyWHHGBuTE-_ewSq7EMRkwwQAYhSF5fcZ-aduVbd-ivGvWnbc9RuO2jJ462_Y-sm2U17a1RtfR3Fld-9to2nr7tgzHieua6En3FneoDq5vxPren5GjKsB4_jNPyctkPM_v49nj3TQfzWLDQaoYU8mFSLlQSlGeggRhqCwXCKxSoHm2SFiZmKzUFE1SUqxSkxrNZMUQaZXwU3K1_7t23ccGfV801husa91it_EFlZDtklIIaLZHjeu8d1gVa2cb7T4LCsWu2OJ_sUHjxb7Y4L34idksGiz_nL9NBiDZA9uu7tH5Vb3ZoiuWqOt-Gb4AcKAqZkATCqAg3kmKfwEs6YTZ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1609306780</pqid></control><display><type>article</type><title>Rethinking Composite End Points in Clinical Trials: Insights From Patients and Trialists</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Journals@Ovid Ovid Autoload</source><creator>Stolker, Joshua M ; Spertus, John A ; Cohen, David J ; Jones, Philip G ; Jain, Kaushik K ; Bamberger, Emily ; Lonergan, Brady B ; Chan, Paul S</creator><creatorcontrib>Stolker, Joshua M ; Spertus, John A ; Cohen, David J ; Jones, Philip G ; Jain, Kaushik K ; Bamberger, Emily ; Lonergan, Brady B ; Chan, Paul S</creatorcontrib><description>BACKGROUND—Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers.
METHODS AND RESULTS—We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 “spending weights” across 5 common adverse events comprising composite end points in cardiovascular trialsdeath, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant’s ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P<0.001 for all comparisons).
CONCLUSIONS—Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.113.006588</identifier><identifier>PMID: 25200210</identifier><language>eng</language><publisher>United States: by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><subject>Aged ; Aged, 80 and over ; Angina, Unstable - mortality ; Angina, Unstable - prevention & control ; Clinical Trials as Topic - psychology ; Data Collection ; Endpoint Determination - psychology ; Female ; Health Personnel - psychology ; Hospitalization ; Humans ; Male ; Myocardial Infarction - mortality ; Myocardial Infarction - prevention & control ; Patient Preference ; Patient-Centered Care ; Patients - psychology ; Percutaneous Coronary Intervention ; Risk Factors ; Stroke - mortality ; Stroke - prevention & control</subject><ispartof>Circulation (New York, N.Y.), 2014-10, Vol.130 (15), p.1254-1261</ispartof><rights>2014 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><rights>2014 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3067-e863558357771380605c16dbe02f70a39b42d4c9da1ec4d1ef8c8ca26f2ee1f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25200210$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stolker, Joshua M</creatorcontrib><creatorcontrib>Spertus, John A</creatorcontrib><creatorcontrib>Cohen, David J</creatorcontrib><creatorcontrib>Jones, Philip G</creatorcontrib><creatorcontrib>Jain, Kaushik K</creatorcontrib><creatorcontrib>Bamberger, Emily</creatorcontrib><creatorcontrib>Lonergan, Brady B</creatorcontrib><creatorcontrib>Chan, Paul S</creatorcontrib><title>Rethinking Composite End Points in Clinical Trials: Insights From Patients and Trialists</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>BACKGROUND—Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers.
METHODS AND RESULTS—We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 “spending weights” across 5 common adverse events comprising composite end points in cardiovascular trialsdeath, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant’s ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P<0.001 for all comparisons).
CONCLUSIONS—Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angina, Unstable - mortality</subject><subject>Angina, Unstable - prevention & control</subject><subject>Clinical Trials as Topic - psychology</subject><subject>Data Collection</subject><subject>Endpoint Determination - psychology</subject><subject>Female</subject><subject>Health Personnel - psychology</subject><subject>Hospitalization</subject><subject>Humans</subject><subject>Male</subject><subject>Myocardial Infarction - mortality</subject><subject>Myocardial Infarction - prevention & control</subject><subject>Patient Preference</subject><subject>Patient-Centered Care</subject><subject>Patients - psychology</subject><subject>Percutaneous Coronary Intervention</subject><subject>Risk Factors</subject><subject>Stroke - mortality</subject><subject>Stroke - prevention & control</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkFtLAzEQhYMotl7-gqxvvqxOkk2y61tZWi0UFang25JmZ23sXmqypfjvTa0KPg1z5jtz4BBySeGaUklv8ulz_jIbzaePD6P7UdD4NYAUaXpAhlSwJE4Ezw7JEACyWHHGBuTE-_ewSq7EMRkwwQAYhSF5fcZ-aduVbd-ivGvWnbc9RuO2jJ462_Y-sm2U17a1RtfR3Fld-9to2nr7tgzHieua6En3FneoDq5vxPren5GjKsB4_jNPyctkPM_v49nj3TQfzWLDQaoYU8mFSLlQSlGeggRhqCwXCKxSoHm2SFiZmKzUFE1SUqxSkxrNZMUQaZXwU3K1_7t23ccGfV801husa91it_EFlZDtklIIaLZHjeu8d1gVa2cb7T4LCsWu2OJ_sUHjxb7Y4L34idksGiz_nL9NBiDZA9uu7tH5Vb3ZoiuWqOt-Gb4AcKAqZkATCqAg3kmKfwEs6YTZ</recordid><startdate>20141007</startdate><enddate>20141007</enddate><creator>Stolker, Joshua M</creator><creator>Spertus, John A</creator><creator>Cohen, David J</creator><creator>Jones, Philip G</creator><creator>Jain, Kaushik K</creator><creator>Bamberger, Emily</creator><creator>Lonergan, Brady B</creator><creator>Chan, Paul S</creator><general>by the American College of Cardiology Foundation and the American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20141007</creationdate><title>Rethinking Composite End Points in Clinical Trials: Insights From Patients and Trialists</title><author>Stolker, Joshua M ; Spertus, John A ; Cohen, David J ; Jones, Philip G ; Jain, Kaushik K ; Bamberger, Emily ; Lonergan, Brady B ; Chan, Paul S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3067-e863558357771380605c16dbe02f70a39b42d4c9da1ec4d1ef8c8ca26f2ee1f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angina, Unstable - mortality</topic><topic>Angina, Unstable - prevention & control</topic><topic>Clinical Trials as Topic - psychology</topic><topic>Data Collection</topic><topic>Endpoint Determination - psychology</topic><topic>Female</topic><topic>Health Personnel - psychology</topic><topic>Hospitalization</topic><topic>Humans</topic><topic>Male</topic><topic>Myocardial Infarction - mortality</topic><topic>Myocardial Infarction - prevention & control</topic><topic>Patient Preference</topic><topic>Patient-Centered Care</topic><topic>Patients - psychology</topic><topic>Percutaneous Coronary Intervention</topic><topic>Risk Factors</topic><topic>Stroke - mortality</topic><topic>Stroke - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stolker, Joshua M</creatorcontrib><creatorcontrib>Spertus, John A</creatorcontrib><creatorcontrib>Cohen, David J</creatorcontrib><creatorcontrib>Jones, Philip G</creatorcontrib><creatorcontrib>Jain, Kaushik K</creatorcontrib><creatorcontrib>Bamberger, Emily</creatorcontrib><creatorcontrib>Lonergan, Brady B</creatorcontrib><creatorcontrib>Chan, Paul S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stolker, Joshua M</au><au>Spertus, John A</au><au>Cohen, David J</au><au>Jones, Philip G</au><au>Jain, Kaushik K</au><au>Bamberger, Emily</au><au>Lonergan, Brady B</au><au>Chan, Paul S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rethinking Composite End Points in Clinical Trials: Insights From Patients and Trialists</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2014-10-07</date><risdate>2014</risdate><volume>130</volume><issue>15</issue><spage>1254</spage><epage>1261</epage><pages>1254-1261</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><abstract>BACKGROUND—Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers.
METHODS AND RESULTS—We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 “spending weights” across 5 common adverse events comprising composite end points in cardiovascular trialsdeath, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant’s ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P<0.001 for all comparisons).
CONCLUSIONS—Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.</abstract><cop>United States</cop><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub><pmid>25200210</pmid><doi>10.1161/CIRCULATIONAHA.113.006588</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2014-10, Vol.130 (15), p.1254-1261 |
| issn | 0009-7322 1524-4539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1609306780 |
| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | Aged Aged, 80 and over Angina, Unstable - mortality Angina, Unstable - prevention & control Clinical Trials as Topic - psychology Data Collection Endpoint Determination - psychology Female Health Personnel - psychology Hospitalization Humans Male Myocardial Infarction - mortality Myocardial Infarction - prevention & control Patient Preference Patient-Centered Care Patients - psychology Percutaneous Coronary Intervention Risk Factors Stroke - mortality Stroke - prevention & control |
| title | Rethinking Composite End Points in Clinical Trials: Insights From Patients and Trialists |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T15%3A44%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Rethinking%20Composite%20End%20Points%20in%20Clinical%20Trials:%20Insights%20From%20Patients%20and%20Trialists&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=Stolker,%20Joshua%20M&rft.date=2014-10-07&rft.volume=130&rft.issue=15&rft.spage=1254&rft.epage=1261&rft.pages=1254-1261&rft.issn=0009-7322&rft.eissn=1524-4539&rft_id=info:doi/10.1161/CIRCULATIONAHA.113.006588&rft_dat=%3Cproquest_cross%3E1609306780%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1609306780&rft_id=info:pmid/25200210&rfr_iscdi=true |