Design of platform trials with a change in the control treatment arm

Platform trials are an efficient way of testing multiple treatments. We consider platform trials where, if a treatment is found to be superior to the control, it will become the new standard of care. The remaining treatments are then tested against this new control. In this setting, one can either keep the information on both the new standard of care and the other active treatments before the control is changed or discard this information when testing for benefit of the remaining treatments. We show analytically and numerically, retaining the information collected before the change in control can be detrimental to the power in a frequentist multi-arm multi-stage trial. Specifically, we consider the overall power, the probability that the active treatment with the greatest treatment effect is found during the trial, and the conditional power, the probability a given treatment is found superior against the current control. Also studied is the conditional type I error, the probability a given treatment is incorrectly found superior against the current control. We prove when retaining the information decreases both the overall and conditional power but also decreases the conditional type I error. A motivating example is then studied. Based on these observations, we discuss different aspects to consider when deciding whether to run a continuous platform trial or run an inherently new trial using the same trial infrastructure.

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Publication Details

Journal
Biometrics
Published
2025-04-02
DOI
https://doi.org/10.1093/biomtc/ujaf073
Citations
1
Primary Topic
Statistical Methods in Clinical Trials
Type
article
Field-Weighted Citation Impact
2.63

Funders

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article

Design of platform trials with a change in the control treatment arm

Thomas Jaki, Pavel Mozgunov, Peter Greenstreet, Alun Bedding
1 citations
Biometrics
Statistical Methods in Clinical Trials
2.63
article

Design of platform trials with a change in the control treatment arm

Thomas Jaki, Pavel Mozgunov, Peter Greenstreet, Alun Bedding
article en
1 citations

Abstract

Platform trials are an efficient way of testing multiple treatments. We consider platform trials where, if a treatment is found to be superior to the control, it will become the new standard of care. The remaining treatments are then tested against this new control. In this setting, one can either keep the information on both the new standard of care and the other active treatments before the control is changed or discard this information when testing for benefit of the remaining treatments. We show analytically and numerically, retaining the information collected before the change in control can be detrimental to the power in a frequentist multi-arm multi-stage trial. Specifically, we consider the overall power, the probability that the active treatment with the greatest treatment effect is found during the trial, and the conditional power, the probability a given treatment is found superior against the current control. Also studied is the conditional type I error, the probability a given treatment is incorrectly found superior against the current control. We prove when retaining the information decreases both the overall and conditional power but also decreases the conditional type I error. A motivating example is then studied. Based on these observations, we discuss different aspects to consider when deciding whether to run a continuous platform trial or run an inherently new trial using the same trial infrastructure.

BiometricsVol. 81(2)
University of Cambridge (GB), Ottawa Hospital (CA), MRC Biostatistics Unit (GB), University of Regensburg (DE), Lancaster University (GB)
National Institute for Health and Care Research, Department of Health and Social Care, Canadian Institutes of Health Research, Medical Research Council, Engineering and Physical Sciences Research Council
Industry, innovation and infrastructure
Openalex Percentile: Top 11%
Statistical Methods in Clinical Trials
2.63
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