A systematic review of randomised controlled trials with adaptive and traditional group sequential designs – applications in cardiovascular clinical trials

BMC Medical Research Methodology

Research

Christy Saju¹  Jufen Zhang² 

[1] School of Medicine, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishop Hall Lane, CM1 1SQ, Chelmsford, U.K.;School of Medicine, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Bishop Hall Lane, CM1 1SQ, Chelmsford, U.K.;School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, U.K.;

关键词: Systematic review;    Randomised controlled trials;    Trial designs;    Cardiology;    Interim analysis;   

DOI  :  10.1186/s12874-023-02024-1

 received in 2023-01-25, accepted in 2023-08-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTrial design plays a key role in clinical trials. Traditional group sequential design has been used in cardiovascular clinical trials over decades as the trials can potentially be stopped early, therefore, it can reduce pre-planned sample size and trial resources. In contrast, trials with adoptive designs provide greater flexibility and are more efficient due to the ability to modify trial design according to the interim analysis results. In this systematic review, we aim to explore characteristics of adaptive and traditional group sequential trials in practice and to gain an understanding how these trial designs are currently being reported in cardiology.MethodsPubMed, Embase and Cochrane Central Register of Controlled Trials database were searched from January 1980 to June 2022. Randomised controlled phase 2/3 trials with either adaptive or traditional group sequential design in patients with cardiovascular disease were included. Descriptive statistics were used to present the collected data.ResultsOf 456 articles found in the initial search, 56 were identified including 43 (76.8%) trials with traditional group sequential design and 13 (23.2%) with adaptive. Most trials were large, multicentre, led by the USA (50%) and Europe (28.6%), and were funded by companies (78.6%). For trials with group sequential design, frequency of interim analyses was determined mainly by the number of events (47%). 67% of the trials stopped early, in which 14 (32.6%) were due to efficacy, and 5 (11.6%) for futility. The commonly used stopping rule to terminate trials was O’Brien- Fleming-type alpha spending function (10 (23.3%)). For trials with adaptive designs, 54% of the trials stopped early, in which 4 (30.8%) were due to futility, and 2 (15.4%) for efficacy. Sample size re-estimation was commonly used (8 (61.5%)). In 69% of the trials, simulation including Bayesian approach was used to define the statistical stopping rules. The adaptive designs have been increasingly used (from 0 to 1999 to 38.6% after 2015 amongst adaptive trials). 25% of the trials reported “adaptive” in abstract or title of the studies.ConclusionsThe application of adaptive trials is increasingly popular in cardiovascular clinical trials. The reporting of adaptive design needs improving.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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