A Comparison of Treatment Effect Sizes in Matched Phase 2 and Phase 3 Trials of Advanced Therapeutics in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis
Phase 2 trials are fundamental to the rational and efficient design of phase 3 trials. We aimed to determine the relationship of treatment effect size estimates from phase 2 and phase 3 clinical trials on advanced therapeutics in inflammatory bowel disease. MEDLINE, EMBASE, CENTRAL, and the Cochrane...
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| Veröffentlicht in: | Clinical and translational gastroenterology 2023-11, Vol.14 (11), p.e00629-e00629 |
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| container_title | Clinical and translational gastroenterology |
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| creator | Hanzel, Jurij Solitano, Virginia Zou, Lily Zou, G Y Peyrin-Biroulet, Laurent Danese, Silvio Singh, Siddharth Ma, Christopher Wils, Pauline Jairath, Vipul |
| description | Phase 2 trials are fundamental to the rational and efficient design of phase 3 trials. We aimed to determine the relationship of treatment effect size estimates from phase 2 and phase 3 clinical trials on advanced therapeutics in inflammatory bowel disease.
MEDLINE, EMBASE, CENTRAL, and the Cochrane library were searched from inception to December 19, 2022, to identify paired phase 2 and 3 placebo-controlled induction studies of advanced therapeutics for Crohn's disease (CD) and ulcerative colitis (UC). Treatment effect sizes were expressed as a risk ratio (RR) between the active arm and placebo arm. For the same therapeutics, RRs from phase 2 trials were divided by the RR from phase 3 trial to quantify the relationship of effect sizes between phases.
Twenty-two studies (9 phase 2 trials, 13 phase 3 trials) were included for CD and 30 studies (12 phase 2 trials, 18 phase 3 trials) for UC. In UC (pooled RR 0.72; 95% confidence interval: 0.58-0.86; RR |
| doi_str_mv | 10.14309/ctg.0000000000000629 |
| format | Article |
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MEDLINE, EMBASE, CENTRAL, and the Cochrane library were searched from inception to December 19, 2022, to identify paired phase 2 and 3 placebo-controlled induction studies of advanced therapeutics for Crohn's disease (CD) and ulcerative colitis (UC). Treatment effect sizes were expressed as a risk ratio (RR) between the active arm and placebo arm. For the same therapeutics, RRs from phase 2 trials were divided by the RR from phase 3 trial to quantify the relationship of effect sizes between phases.
Twenty-two studies (9 phase 2 trials, 13 phase 3 trials) were included for CD and 30 studies (12 phase 2 trials, 18 phase 3 trials) for UC. In UC (pooled RR 0.72; 95% confidence interval: 0.58-0.86; RR <1 indicates smaller treatment effect sizes in phase 2 trials), but not CD (pooled RR 1.01; 95% confidence interval: 0.84-1.18), phase 2 trials systematically underestimated treatment effect sizes for the primary endpoint compared with phase 3 trials. The underestimation was observed for clinical, but not endoscopic, endpoints in UC.
Treatment effect sizes for the primary and clinical endpoints were similar across clinical trial phases in CD, but not UC, where only endoscopic endpoints were comparable. This will help inform clinical development plans and future trial design.</description><identifier>ISSN: 2155-384X</identifier><identifier>EISSN: 2155-384X</identifier><identifier>DOI: 10.14309/ctg.0000000000000629</identifier><identifier>PMID: 37578211</identifier><language>eng</language><publisher>United States: Wolters Kluwer</publisher><subject>Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Colitis, Ulcerative - drug therapy ; Crohn Disease - drug therapy ; Humans ; Induction Chemotherapy ; Inflammatory Bowel Diseases - drug therapy ; Remission Induction ; Review</subject><ispartof>Clinical and translational gastroenterology, 2023-11, Vol.14 (11), p.e00629-e00629</ispartof><rights>Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.</rights><rights>2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-fab653605f2de647bea581756df2ef77420b88608b99ae5b6ee76f75c83723f93</citedby><cites>FETCH-LOGICAL-c412t-fab653605f2de647bea581756df2ef77420b88608b99ae5b6ee76f75c83723f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684248/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10684248/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37578211$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hanzel, Jurij</creatorcontrib><creatorcontrib>Solitano, Virginia</creatorcontrib><creatorcontrib>Zou, Lily</creatorcontrib><creatorcontrib>Zou, G Y</creatorcontrib><creatorcontrib>Peyrin-Biroulet, Laurent</creatorcontrib><creatorcontrib>Danese, Silvio</creatorcontrib><creatorcontrib>Singh, Siddharth</creatorcontrib><creatorcontrib>Ma, Christopher</creatorcontrib><creatorcontrib>Wils, Pauline</creatorcontrib><creatorcontrib>Jairath, Vipul</creatorcontrib><title>A Comparison of Treatment Effect Sizes in Matched Phase 2 and Phase 3 Trials of Advanced Therapeutics in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis</title><title>Clinical and translational gastroenterology</title><addtitle>Clin Transl Gastroenterol</addtitle><description>Phase 2 trials are fundamental to the rational and efficient design of phase 3 trials. We aimed to determine the relationship of treatment effect size estimates from phase 2 and phase 3 clinical trials on advanced therapeutics in inflammatory bowel disease.
MEDLINE, EMBASE, CENTRAL, and the Cochrane library were searched from inception to December 19, 2022, to identify paired phase 2 and 3 placebo-controlled induction studies of advanced therapeutics for Crohn's disease (CD) and ulcerative colitis (UC). Treatment effect sizes were expressed as a risk ratio (RR) between the active arm and placebo arm. For the same therapeutics, RRs from phase 2 trials were divided by the RR from phase 3 trial to quantify the relationship of effect sizes between phases.
Twenty-two studies (9 phase 2 trials, 13 phase 3 trials) were included for CD and 30 studies (12 phase 2 trials, 18 phase 3 trials) for UC. In UC (pooled RR 0.72; 95% confidence interval: 0.58-0.86; RR <1 indicates smaller treatment effect sizes in phase 2 trials), but not CD (pooled RR 1.01; 95% confidence interval: 0.84-1.18), phase 2 trials systematically underestimated treatment effect sizes for the primary endpoint compared with phase 3 trials. The underestimation was observed for clinical, but not endoscopic, endpoints in UC.
Treatment effect sizes for the primary and clinical endpoints were similar across clinical trial phases in CD, but not UC, where only endoscopic endpoints were comparable. This will help inform clinical development plans and future trial design.</description><subject>Clinical Trials, Phase II as Topic</subject><subject>Clinical Trials, Phase III as Topic</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Crohn Disease - drug therapy</subject><subject>Humans</subject><subject>Induction Chemotherapy</subject><subject>Inflammatory Bowel Diseases - drug therapy</subject><subject>Remission Induction</subject><subject>Review</subject><issn>2155-384X</issn><issn>2155-384X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1u1DAUhSMEolXpI4C8ZJNiO_FP2KBhKFCpFYgOEjvrxrnuGCXxYHumGp6IxyQz_dGAN77SPd85lk9RvGT0jNUVbd7YfHNGD4_kzZPimDMhykrXP54ezEfFaUo_d6Kact00z4ujSgmlOWPHxZ8ZmYdhBdGnMJLgyCIi5AHHTM6dQ5vJtf-NifiRXEG2S-zI1yUkJJzA-DBXE-WhTzt-1m1gtJNsscQIK1xnb_f4xeh6GAbIIW7J-3CLPfngE078W3K9TRmnlbfkG2483u7NrzBDORuh3yafXhTP3BSBp_f3SfH94_li_rm8_PLpYj67LG3NeC4dtFJUkgrHO5S1ahGEZkrIznF0StWctlpLqtumARStRFTSKWF1pXjlmuqkeHfnu1q3A3Z2-okIvVlFP0DcmgDe_LsZ_dLchI1hVOqa13pyeH3vEMOvNaZsBp8s9j2MGNbJcC2oYlo2uzBxJ7UxpBTRPeYwavZNm6lp83_TE_fq8JGP1EOv1V-HsKby</recordid><startdate>20231101</startdate><enddate>20231101</enddate><creator>Hanzel, Jurij</creator><creator>Solitano, Virginia</creator><creator>Zou, Lily</creator><creator>Zou, G Y</creator><creator>Peyrin-Biroulet, Laurent</creator><creator>Danese, Silvio</creator><creator>Singh, Siddharth</creator><creator>Ma, Christopher</creator><creator>Wils, Pauline</creator><creator>Jairath, Vipul</creator><general>Wolters Kluwer</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><scope>5PM</scope></search><sort><creationdate>20231101</creationdate><title>A Comparison of Treatment Effect Sizes in Matched Phase 2 and Phase 3 Trials of Advanced Therapeutics in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis</title><author>Hanzel, Jurij ; Solitano, Virginia ; Zou, Lily ; Zou, G Y ; Peyrin-Biroulet, Laurent ; Danese, Silvio ; Singh, Siddharth ; Ma, Christopher ; Wils, Pauline ; Jairath, Vipul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-fab653605f2de647bea581756df2ef77420b88608b99ae5b6ee76f75c83723f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Clinical Trials, Phase II as Topic</topic><topic>Clinical Trials, Phase III as Topic</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Crohn Disease - drug therapy</topic><topic>Humans</topic><topic>Induction Chemotherapy</topic><topic>Inflammatory Bowel Diseases - drug therapy</topic><topic>Remission Induction</topic><topic>Review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hanzel, Jurij</creatorcontrib><creatorcontrib>Solitano, Virginia</creatorcontrib><creatorcontrib>Zou, Lily</creatorcontrib><creatorcontrib>Zou, G Y</creatorcontrib><creatorcontrib>Peyrin-Biroulet, Laurent</creatorcontrib><creatorcontrib>Danese, Silvio</creatorcontrib><creatorcontrib>Singh, Siddharth</creatorcontrib><creatorcontrib>Ma, Christopher</creatorcontrib><creatorcontrib>Wils, Pauline</creatorcontrib><creatorcontrib>Jairath, Vipul</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and translational gastroenterology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hanzel, Jurij</au><au>Solitano, Virginia</au><au>Zou, Lily</au><au>Zou, G Y</au><au>Peyrin-Biroulet, Laurent</au><au>Danese, Silvio</au><au>Singh, Siddharth</au><au>Ma, Christopher</au><au>Wils, Pauline</au><au>Jairath, Vipul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Comparison of Treatment Effect Sizes in Matched Phase 2 and Phase 3 Trials of Advanced Therapeutics in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis</atitle><jtitle>Clinical and translational gastroenterology</jtitle><addtitle>Clin Transl Gastroenterol</addtitle><date>2023-11-01</date><risdate>2023</risdate><volume>14</volume><issue>11</issue><spage>e00629</spage><epage>e00629</epage><pages>e00629-e00629</pages><issn>2155-384X</issn><eissn>2155-384X</eissn><abstract>Phase 2 trials are fundamental to the rational and efficient design of phase 3 trials. We aimed to determine the relationship of treatment effect size estimates from phase 2 and phase 3 clinical trials on advanced therapeutics in inflammatory bowel disease.
MEDLINE, EMBASE, CENTRAL, and the Cochrane library were searched from inception to December 19, 2022, to identify paired phase 2 and 3 placebo-controlled induction studies of advanced therapeutics for Crohn's disease (CD) and ulcerative colitis (UC). Treatment effect sizes were expressed as a risk ratio (RR) between the active arm and placebo arm. For the same therapeutics, RRs from phase 2 trials were divided by the RR from phase 3 trial to quantify the relationship of effect sizes between phases.
Twenty-two studies (9 phase 2 trials, 13 phase 3 trials) were included for CD and 30 studies (12 phase 2 trials, 18 phase 3 trials) for UC. In UC (pooled RR 0.72; 95% confidence interval: 0.58-0.86; RR <1 indicates smaller treatment effect sizes in phase 2 trials), but not CD (pooled RR 1.01; 95% confidence interval: 0.84-1.18), phase 2 trials systematically underestimated treatment effect sizes for the primary endpoint compared with phase 3 trials. The underestimation was observed for clinical, but not endoscopic, endpoints in UC.
Treatment effect sizes for the primary and clinical endpoints were similar across clinical trial phases in CD, but not UC, where only endoscopic endpoints were comparable. This will help inform clinical development plans and future trial design.</abstract><cop>United States</cop><pub>Wolters Kluwer</pub><pmid>37578211</pmid><doi>10.14309/ctg.0000000000000629</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Clinical Trials, Phase II as Topic Clinical Trials, Phase III as Topic Colitis, Ulcerative - drug therapy Crohn Disease - drug therapy Humans Induction Chemotherapy Inflammatory Bowel Diseases - drug therapy Remission Induction Review |
| title | A Comparison of Treatment Effect Sizes in Matched Phase 2 and Phase 3 Trials of Advanced Therapeutics in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis |
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