REVIEW   

Minerva Medica 2022 December;113(6):1000-7

DOI: 10.23736/S0026-4806.21.07566-2

Copyright © 2021 EDIZIONI MINERVA MEDICA

language: English

Use of placebo in clinical trials in COVID-19 pandemic times: considerations on pros, cons, challenges and limitations

William J. MOELLER ¹, Nicola POTERE ², Aldo BONAVENTURA ³, Alessandra VECCHIÈ ³, Yub R. SEDHAI ⁴, Roberto CARICCHIO ⁵, Antonio ABBATE ⁶ ✉

¹ College of William and Mary, Department of Chemistry, Williamsburg, VA, USA; ² Department of Medical, Oral and Biotechnological Sciences, G. D’Annunzio University, Chieti, Italy; ³ Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA; ⁴ Department of Internal Medicine, Division of Hospital Medicine, VCU School of Medicine, Richmond, VA, USA; ⁵ Division of Rheumatology, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; ⁶ C. Kenneth and Dianne Wright’ Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA

The ongoing coronavirus disease 2019 (COVID-19) pandemic has placed tremendous strain on health systems throughout the world. This has led to many clinical trials being launched in order to try to find ways to combat the disease. The unprecedented nature of the pandemic has been reflected in the methods used in some of these trials. Placebo-controlled randomized trials are considered the gold-standard, however, there are inherent challenges in the use of placebo, especially during COVID-19. We herein review the pros, cons, challenges and limitations of using placebo in clinical trials investigating treatments for COVID-19. We also discuss the importance of viewing research critically, examining the potential impact of placebo use or lack thereof, on blinding and possible biases. This becomes important as we assess the responses to the pandemic in preparation for a future pandemic. Although placebo-controlled clinical trials are the gold standard for clinical research, they may not be practically or ethically feasible during a pandemic. Choices accomplished to design many COVID-19 trials might reflect the unprecedently trying environment in which they were made. However, critical evaluation of the methodology and practice of scientific research remains a crucial part of the scientific process. Even when conducted as randomized double-blind studies, residual biases may exist and interfere with the study conduct and interpretation of the data. A critical review of all data remains essential to thoroughly assess the impact of a research study.

KEY WORDS: Placebo; COVID-19; Pandemics; SARS-CoV-2