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. 2025 Jul;69(6):e70044.
doi: 10.1111/aas.70044.

Adaptations and Heterogeneity of Treatment Effects in Platform Trials-Protocol for Two Methodological Studies

Tine Sylvest Meyhoff  1 , Aksel Karl Georg Jensen  1   2 , Anders Perner  1   3 , Ewan C Goligher  4 , Marion K Campbell  5 , Morten Hylander Møller  1   3 , Anders Granholm  1   2
Affiliations

Adaptations and Heterogeneity of Treatment Effects in Platform Trials-Protocol for Two Methodological Studies

Tine Sylvest Meyhoff et al. Acta Anaesthesiol Scand. 2025 Jul.

Abstract

Background: Adaptive platform trials bring opportunities for improved infrastructure and effective advancement in medical care but are methodologically complex. Assessment of heterogeneity of treatment effects (HTE) according to participant characteristics and adaptations, including adaptive stopping, are important methodological features in these trials, which may be approached in multiple ways. We aim to characterise the assessment of HTE and use of adaptations, including their key methodological features, in adaptive platform trials.

Methods: This protocol outlines two methodological studies, which will be based on a common, systematic literature search and data extraction. We will include adaptive platform trials conducted from 2005 onwards. Screening and data extraction will be performed independently and in duplicate. In Study I, we will assess methods used to evaluate HTE, and in Study II, we will assess adaptations and stopping rules in the included trials.

Discussion: The two proposed methodological studies will provide an overview of important methodological features regarding the assessment of HTE and adaptations used in adaptive platform trials. Better knowledge of available methods to assess these features can improve the conditions for designing adaptive platform trials and identify areas for further development.

Keywords: adaptive analyses; adaptive platform trial; heterogeneity of treatment effects.

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Conflict of interest statement

T.S.M., A.K.G.J., A.P., M.H.M., and A.G. are involved in the design and conduct of the adaptive Intensive Care Platform Trial (INCEPT) (www.incept.dk). INCEPT has received grants from the Novo Nordisk Foundation and Sygeforsikringen “danmark,” and additional support from Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond, and Dagmar Marshalls Fond. Specific domains on INCEPT have received grants from Danmarks Frie Forskningsfond. The Department of Intensive Care at Rigshospitalet has received grants from the Novo Nordisk Foundation for other projects. M.K.C. is Chair of the UK NIHR/MRC Better Methods Better Research Funding Panel and has received multiple grants for the conduct of clinical trials from the UK NIHR programme. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Screening and inclusion flowchart. [Applicable for both studies] mock figure. Mock screening and inclusion flowchart adapted from the PRISMA flowchart [20]. The flow of screening will be common for Studies I and II, including the final number of platform trials included. CTIS, Clinical Trials Information System; EU CTR, EU Clinical Trials Register.
See this image and copyright information in PMC

References

    1. Pallmann P., Bedding A. W., Choodari‐Oskooei B., et al., “Adaptive Designs in Clinical Trials: Why Use Them, and How to Run and Report Them,” BMC Medicine 16, no. 1 (2018): 29, 10.1186/S12916-018-1017-7. - DOI - PMC - PubMed
    1. Pitre T., Cheng S., Cusano E., et al., “Methodology and Design of Platform Trials: A Meta‐Epidemiological Study,” Journal of Clinical Epidemiology 157 (2023): 1–12, 10.1016/J.JCLINEPI.2023.02.010. - DOI - PMC - PubMed
    1. Granholm A., Jensen A. K. G., Lange T., Perner A., Møller M. H., and Kaas‐Hansen B. S., “Designing and Evaluating Advanced Adaptive Randomised Clinical Trials: A Practical Guide,” arXiv (2025): 2501.08765, 10.48550/arXiv.2501.08765. - DOI
    1. Granholm A., Kaas‐Hansen B. S., Lange T., et al., “An Overview of Methodological Considerations Regarding Adaptive Stopping, Arm Dropping, and Randomization in Clinical Trials,” Journal of Clinical Epidemiology 153 (2023): 45–54, 10.1016/j.jclinepi.2022.11.002. - DOI - PubMed
    1. Angus D. C., Alexander B. M., Berry S., et al., “Adaptive Platform Trials: Definition, Design, Conduct and Reporting Considerations,” Nature Reviews. Drug Discovery 18 (2019): 797–807, 10.1038/S41573-019-0034-3. - DOI - PubMed