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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