The statistical design and analysis of pandemic platform trials: Implications for the future
Christopher J Lindsell, Matthew Shotwell, Kevin J Anstrom, Scott Berry, Erica Brittain, Frank E Harrell, Nancy Geller, Birgit Grund, Michael D Hughes, Prasanna Jagannathan, Eric Leifer, Carlee B Moser, Karen L Price, Michael Proschan, Thomas Stewart, Sonia Thomas, Giota Touloumi, Lisa Lavange
Journal of Clinical and Translational Science, doi:10.1017/cts.2024.514
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.
Author contributions. All authors contributed to the outline and content. CJL, MS, and LL drafted the manuscript, and all authors provided critical review and approved the final version. CJL takes responsibility for the manuscript as a whole. Funding statement. The ACTIV clinical trials referenced in this manuscript received funding from various US Government funding agencies. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the NIH. Competing interests. Dr Lindsell reported receiving grants to the institution from the National Center for Advancing Translational Sciences (NCATS) for the submitted work; grants to the institution from NIH and Department of Defense and research funds to the institution from the CDC, bioMerieux, AstraZeneca, AbbVie, Entegrion Inc., and Endpoint Health outside the submitted work; patents for risk stratification in sepsis and septic shock issued to Cincinnati Children's Hospital Medical Center; service on DSMBs unrelated to the current work; and stock options in Bioscape Digital unrelated to the current work. Dr Shotwell reported receiving grants to the institution from the National Heart, Lung, and Blood Institute (NHLBI) for the submitted work; grants to the institution from NIH and research funds from MedRegen LLC and Lupin Pharmaceuticals unrelated the submitted work; and service on DSMBs unrelated to the submitted..
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