Economic considerations in designs and modifications of multiarm, multistage adaptive and adaptive platform randomized controlled trials: A systematic literature review

Objectives: There is uncertainty around whether, and under what circumstances, there is value in embedding economic considerations into multiarm, multistage (MAMS) adaptive, and adaptive platform trial designs. This systematic review was conducted to assess the analytical methods and factors that are considered when incorporating health economic analyses when designing and modifying MAMS adaptive and adaptive platform trials.

Methods: The review searched for health economic analyses, including planned analyses, of interventions assessed through MAMS adaptive, and adaptive platform trials. The search for articles was conducted in EMBASE, MEDLINE, Web of Science, Scopus, and ClinicalTrials.gov electronic databases from their inception to 7 August 2023. The screening for articles was conducted by 2 blinded reviewers who followed a predetermined screening process. A narrative synthesis was conducted on the methods used in the analysis and how the results informed the trial designs and modifications.

Results: The review included 17 articles, of which 4 were the results of economic evaluations, whereas 13 were economic evaluation protocols. No trial was reported using pretrial economic evaluations to inform the trial designs. In 14 articles, it was possible to estimate the costs and benefits of the interventions at the interim analysis stages. There were only 5 interim cost-effectiveness analyses, and 3 of these had informed decisions to drop or maintain trial arms.

Conclusions: Health economics is being embedded in some MAMS adaptive and adaptive platform trials to inform trial modifications. Nevertheless, the use of economic evidence is limited, both by design and circumstance, despite its potential importance in adopting decisions.