Platform trials to evaluate the benefit-risk of COVID-19 therapeutics: Successes, learnings, and recommendations for future pandemics.

BACKGROUND

In response to the COVID-19 global pandemic, multiple platform trials were initiated to accelerate evidence generation of potential therapeutic interventions. Given a rapidly evolving and dynamic pandemic, platform trials have a key advantage over traditional randomized trials: multiple interventions can be investigated under a master protocol sharing a common infrastructure.

METHODS

This paper focuses on nine platform trials that were instrumental in advancing care in COVID-19 in the hospital and community setting. A semi-structured qualitative interview was conducted with the principal investigators and lead statisticians of these trials. Information from the interviews and public sources were tabulated and summarized across trials, and recommendations for best practice for the next health crisis are provided.

RESULTS

Based on the information gathered takeaways were identified as 1) the existence of some aspect of trial design or conduct (e.g., existing network of investigators or colleagues, infrastructure for data capture and relevant statistical expertise) was a key success factor; 2) the choice of treatments (e.g., repurposed drugs) had major impact on the trials as did the choice of primary endpoint; and 3) the lack of coordination across trials was flagged as an area for improvement.

CONCLUSION

These trials deployed during the COVID-19 pandemic demonstrate how to achieve both speed and quality of evidence generation regarding clinical benefit (or not) of existing therapies to treat new pathogens in a pandemic setting. As a group, these trials identified treatments that worked, and many that did not, in a matter of months.

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest JB is an employee and shareholder of BMS, RL and FC are employees and shareholders of Eli Lilly, JL is an employee and shareholder of Takeda, PS is an employee and shareholder of Novartis, and MG is an employee and shareholder of Pfizer. This publication was neither originated, managed nor sponsored by the authors' employers. NZ reports personal fees from Bill and Melinda Gates Foundation, Genentech, BMS, ANOVA, ZS Associates, FDA, Cytokinetics, Intelligencia, Friends of Cancer Research and Pfizer, outside the submitted work. She was Strategic Advisor to FDA (Office of Commissioner) regarding RWD & COVID19 during the period of Sept 2020-Sept 2021. The article reflects her personal views, not those of the FDA. She was also a member of the executive committee of ICODA (International Covid19 Data Alliance) during the period of June 2020 -Dec 2022. She held/holds varying levels of stock equity in AstraZeneca, GSK, J&J, Merck, Moderna, Pfizer, Sanofi, Takeda, TranslateBio, Vaxart, Vir, Inovio [period Dec 2020-Dec 2022] and holds stock options in ANOVA. ERC reports personal fees from Bill and Melinda Gates Foundation, Cytel Corporation and DXOCRO LLC. SG declare no competing interest.