Pride and Prejudice during the COVID-19 Pandemic: The Misfortune of Inappropriate Clinical Trial Design

J Epidemiol Glob Health. 2021 Mar;11(1):15-19. doi: 10.2991/jegh.k.200729.001. Epub 2020 Aug 7.

Abstract

Coronavirus Disease 2019 (COVID-19) is a rapidly evolving global pandemic for which more than a thousand clinical trials have been registered to secure therapeutic effectiveness, expeditiously. Most of these are single-center non-randomized studies rather than multi-center, randomized controlled trials. Single-arm trials have several limitations and may be conducted when spontaneous improvement is not anticipated, small placebo effect exists, and randomization to a placebo is not ethical. In an emergency where saving lives takes precedence, it is ethical to conduct trials with any scientifically proven design, however, safety must not be compromised. A phase II or III trial can be conducted directly in a pandemic with appropriate checkpoints and stopping rules. COVID-19 has two management paradigms- antivirals, or treatment of its complications. Simultaneous assessment of two different treatments can be done using 2 × 2 factorial schema. World Health Organization's SOLIDARITY trial is a classic example of the global research protocol which can evaluate the preferred treatment to combat COVID-19 pandemic. Short of that, a trial design must incorporate the practicality of the intervention used, and an appropriate primary endpoint which should ideally be a clinical outcome. Collaboration between institutions is needed more than ever to successfully execute and accrue in randomized trials.

Keywords: COVID-19; Clinical trials; multi-center; primary endpoint; single-arm.

MeSH terms

  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment*
  • Early Termination of Clinical Trials / methods
  • Ethics
  • Humans
  • Information Dissemination* / ethics
  • Information Dissemination* / methods
  • Non-Randomized Controlled Trials as Topic* / ethics
  • Non-Randomized Controlled Trials as Topic* / methods
  • Non-Randomized Controlled Trials as Topic* / standards
  • Research Design* / standards
  • Research Design* / trends
  • SARS-CoV-2
  • Safety Management* / ethics
  • Safety Management* / standards