Definitions of types of adaptive designs23
| Type of adaptive design | Definition |
| Adaptive dose-finding | These trials allocate patients to multiple different treatment doses and patient responses are assessed at interim analyses. Trial design is then adapted to allocate more patients to the treatment doses of interest, reducing allocation of patients to doses that appear non-informative. These studies usually occur in early-phase research to identify doses used in subsequent studies. |
| Adaptive hypothesis | A study design in which trial hypotheses are adapted in response to interim analysis results. For example, adaptive hypothesis trials could involve a preplanned shift from a single hypothesis to multiple hypotheses, preplanned switching between the null hypothesis and the alternative hypothesis or preplanned switching between the primary and secondary study endpoints. |
| Adaptive group sequential | In these variants on classical group sequential studies, results are analysed at interim analyses, with prespecified options of making adaptations such as sample size re-estimation, modification/deletion/addition of treatment arms, changing study endpoints, modifying dose and/or treatment duration or adapting randomisation schedules. |
| Adaptive randomisation | A study design in which accumulating results are observed and the randomisation scheme is adjusted so that patients enrolled later in the trial have a higher probability of being randomised to the treatment arm that was more effective among earlier patients in the trial. |
| Seamless Phase II/III | A study design that combines the objectives of the Phase II investigational stage with the Phase III efficacy or confirmatory stage into a single study protocol moving from one stage to the second stage without stopping the patient enrolment process. |
| Adaptive treatment-switching | A study design allowing the investigator to switch a patient’s treatment from an initial assignment to an alternative treatment due to apparent lack of efficacy, disease progression or safety issues associated with the initial treatment. |
| Biomarker adaptive | This method allows adaptations to trial design based on interim analysis of the treatment responses of biomarkers, such as genomic markers. This design can be used to select patient populations for subsequent trials, identify the natural course of a disease, achieve early detection of a disease and/or help in developing personalised medicine. |
| Pick-the-winner/drop-the-loser | A study design that allows for dropping the inferior treatment group(s), modifying treatment arms and/or adding additional arms based on the review of accumulating data at interim analysis. |
| Sample size re-estimation | A study design using a flexible sample size adjustment or re-estimation based on interim analysis of accumulating data. |
| Multiple adaptive | This refers to a trial that incorporates multiple adaptive designs into a single study. |