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.

Author(s) :

Hanzel, Jurij [Auteur]
University Medical Centre Ljubljana [Ljubljana, Slovenia] [UMCL]
Solitano, Virginia [Auteur]
University of Western Ontario [UWO]
Humanitas University [Milan] [Hunimed]
Zou, Lily [Auteur]
University of Waterloo [Waterloo]
Zou, G. Y. [Auteur]
University of Western Ontario [UWO]
Peyrin-Biroulet, Laurent [Auteur]
Centre Hospitalier Universitaire de Nancy [CHU Nancy]
Danese, Silvio [Auteur]
IRCCS Ospedale San Raffaele [Milan, Italy]
Singh, Singh [Auteur]
University of California [San Diego] [UC San Diego]
Ma, Christopher [Auteur]
University of Calgary
Wils, Pauline [Auteur]
Hôpital Claude Huriez [Lille]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Jairath, Vipul [Auteur]
University of Western Ontario [UWO]

Journal title :

Clinical and translational gastroenterology

Abbreviated title :

Clin Transl Gastroenterol

Publication date :

2023-08-15

ISSN :

2155-384X

English abstract : [en]

INTRODUCTION: 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 ...
Show more >INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-02-01T22:04:25Z
2024-03-11T15:09:33Z