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.
Journal
Clinical and translational gastroenterology
ISSN: 2155-384X
Titre abrégé: Clin Transl Gastroenterol
Pays: United States
ID NLM: 101532142
Informations de publication
Date de publication:
01 Nov 2023
01 Nov 2023
Historique:
received:
07
04
2023
accepted:
02
08
2023
medline:
30
11
2023
pubmed:
14
8
2023
entrez:
14
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37578211
doi: 10.14309/ctg.0000000000000629
pii: 01720094-990000000-00184
pmc: PMC10684248
doi:
Types de publication
Meta-Analysis
Systematic Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00629Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
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