Lessons Learned from COVID-19 Trials – Should We Be Doing Clinical Trials Differently?

Abstract

The COVID-19 crisis led to a flurry of clinical trials activity. The COVID-Evidence database shows 2,814 COVID-19 randomized trials registered as of February 16, 2021. Most were small (only 18% have a planned sample size >500). Most remained uncompleted. Most provided no published results so far (only 283 trial publications as of 2/2021). Large, adaptive platform trials, in particular RECOVERY, have been far more efficient in producing timely evidence than the numerous small trials. Small randomized trials and observational non-randomized analyses have not had a successful track record and have generated misleading expectations. Different large trials on the same intervention have generally had consistent results. Rapid generation of evidence has led also to new challenges for systematic reviews and meta-analyses (e.g. rapid, living, and scoping reviews). Dissemination of results has also been accelerated, with wider use of preprints and with some premature risks from press releases. Pressure to regulatory agencies has mounted with massive emergency authorizations, but some of them have had to be revoked. Pandemic circumstances have disrupted the conduct of many non-COVID-19 trials; therefore, new methods have been developed and adopted more widely to facilite recruitment, consent, and overall trial conduct. Based on the COVID-19 experience, planning of several large, efficient trials, and wider use of adaptive designs may change the future of clinical research. Pragmatism, integration in clinical care, efficient administration, promotion of collaborative structures, and enhanced integration of existing data and facilities may be several of the legacies of COVID-19 on future randomized trials.