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Table 1 Glossary of adaptive designs and descriptions of their typical applications

From: Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs

Method a.k.a Phase of development Definition Targeted benefits
What is a safe dose?
Continual re-assessment method CRM I Dose-escalation design for finding the maximum tolerated dose (MTD) More accurate and precise estimation of the MTD than with 3+3 designs, more patients treated at or close to the MTD
Escalation with overdose control EWOC I Dose-escalation design to find MTD using an allocation criterion to avoid overdosing More accurate and precise estimation of the MTD than with 3+3 designs, avoiding undesirable overdosing of patients
Which is the best treatment of multiple options?
Adaptive treatment switching   II/III Allow trial participants to switch from allocated treatment to an alternative More trial participants receive preferred treatment
Drop the loser DTL II/III Drop inferior treatment arms (control group typically retained) Fewer trial participants assigned to less effective treatments
Multi-arm multi-stage trial MAMS II/III Compare multiple treatments to a common control, allow for early stopping for efficacy or futility Common control requires fewer patients than conducting separate trials, early stopping for efficacy or futility
MCP-Mod   II Combination of multiple comparisons and modelling approaches to establish dose-response model Efficient use of available data vs pairwise comparisons
Response-adaptive randomisation Adaptive allocation, RAR II/III Shift allocation ratio towards more promising treatment(s) More trial participants receive effective treatment
Which patients will benefit?
Basket trials    Examine a single experimental treatment in multiple sub-types of a biomarker Identify and target biomarker sub-types that benefit from the treatment
Biomarker adaptive Adaptive signature II/III Identify and utilise biomarker information to modify trial in progress to target population Target the correct patient population
Covariate-adjusted response adaptive CARA II/III Shift allocation ratio towards promising treatment(s) using covariate information More trial participants receive effective treatment
Population enrichment Adaptive enrichment II/III Allow for selection of target population during the trial based on pre-defined patient populations Target the correct patient population
Umbrella trials    Multiple biomarkers each paired with specific treatments Target the appropriate to treatment within each patient group
Does the treatment work?
Group sequential design   II/III Early stopping for futility or efficacy Reduction in the expected sample size, typically allowing for faster trials requiring fewer patients (for a small increase in the possible maximum sample size)
Sample size re-assessment Sample size re-estimation/re-calculation II/III Mid-course adjustment of the sample size, in either a blinded or unblinded fashion Raise the probability of a successful trial
Broader topics in adaptive designs
Bayesian adaptive   I/II/III Bayesian methodology may be incorporated into many other designs in the analysis and/or the interim decision-making Lower sample size due to utilisation of prior information
Seamless design Portfolio decision-making I/II/III Merge trials from different phases of development, e.g. phase I/II or phase II/III, can be inferentially and/or operationally seamless (Inferential) More efficient use of data from each phase of clinical development/(operational) faster clinical development process and moving between stages