Table 1 Overview of adaptive designs with examples of trials that employed these methods
From: Adaptive designs in clinical trials: why use them, and how to run and report them
Design | Idea | Examples |
|---|---|---|
Continual reassessment method | Model-based dose escalation to estimate the maximum tolerated dose | |
Group-sequential | Include options to stop the trial early for safety, futility or efficacy | DEVELOP-UK [139] |
Sample size re-estimation | Adjust sample size to ensure the desired power | DEVELOP-UK [139] |
Multi-arm multi-stage | Explore multiple treatments, doses, durations or combinations with options to ‘drop losers’ or ‘select winners’ early | TAILoR [31], STAMPEDE [67, 140], COMPARE [141], 18-F PET study [142] |
Population enrichment | Narrow down recruitment to patients more likely to benefit (most) from the treatment | |
Biomarker-adaptive | Incorporate information from or adapt on biomarkers | |
Adaptive randomisation | Shift allocation ratio towards more promising or informative treatment(s) | |
Adaptive dose-ranging | Shift allocation ratio towards more promising or informative dose(s) | DILfrequency [146] |
Seamless phase I/II | Combine safety and activity assessment into one trial | |
Seamless phase II/III | Combine selection and confirmatory stages into one trial | Case studies in [133] |