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 | Â | 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 | Â | 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 | Â | Â | 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 | Â | Â | Multiple biomarkers each paired with specific treatments | Target the appropriate to treatment within each patient group |
Does the treatment work? | ||||
Group sequential design | Â | 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 | Â | 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 |