In Clinical pharmacology and therapeutics
For the development of COVID-19 drugs during the ongoing pandemic, speed is of essence while quality of evidence is of paramount importance. While thousands of COVID-19 trials were rapidly started, many are unlikely to provide robust statistical evidence and meet regulatory standards, e.g. because of lack of randomisation or insufficient power. This has led to an inefficient use of time and resources. With more coordination, the sheer number of patients in these trials might have generated convincing data for several investigational treatments. Collaborative platform trials, comparing several drugs to a shared control arm, are an attractive solution. Those trials can utilise a variety of adaptive design features in order to accelerate the finding of life-saving treatments. In this manuscript we discuss several possible designs, illustrate them via simulations and also discuss challenges, such as the heterogeneity of the target population, time-varying standard of care, and the potentially high number of false hypothesis rejections in Phase 2 and Phase 3. We provide corresponding regulatory perspectives on approval and reimbursement, and note that the optimal design of a platform trial will differ with our societal objective and by stakeholder. Hasty approvals may delay the development of better alternatives, while searching relentlessly for the single most efficacious treatment may indirectly diminish the number of lives saved as time is lost. We point out the need for incentivising developers to participate in collaborative evidence-generation initiatives when a positive return on investment is not met.
Collignon Olivier, Burman Carl-Fredrik, Posch Martin, Schiel Anja
COVID-19, adaptive designs, platform trial, regulatory policy, societal objectives