Problems interpreting some COVID-19 clinical trials
As the COVID-19 pandemic began sweeping around the world, many clinical trials were initiated to test drugs that were already approved for one condition (usually to treat viral infections or inflammatory diseases) for treating COVID-19.
Given the emergency nature of the pandemic, many of the initial trials were developed hastily and implemented quickly. This has led to trials that do not provide definitive answers to important biomedical questions, particularly those concerning the treatment of COVID-19.
A team of scientists at Johns Hopkins University has reviewed 201 COVID-19 clinical trials that were planned or implemented in the first three months of the pandemic. They found that many trials “lacked features to optimize their scientific value.” Specifically, they noted the following:
“Because one-third of trials exclude clinical endpoints, nearly one half are designed to enrol fewer than 100 patients and two-thirds are open label, many of these studies are likely to yield only preliminary evidence of a given treatment’s safety and effectiveness against COVID-19.”
The scientists further stated:
“Our findings provide reason for both optimism and caution. Many registered COVID-19 trials have been designed expediently, and while case series and single-arm trials have value and may provide early signals, randomised study designs provide higher quality evidence and will maximise chances for finding effective and safe treatments during this wave of the pandemic. These trial designs, however, need adequate funding as well as scientific leadership, especially as frontline clinicians are tasked with saving lives. In addition, it is important that surrogate outcomes, biomarkers or clinical scales are strongly and directly linked to what matters most for providers and patients—improved chances of recovery from COVID-19.”
Due to these and other issues, while there are many potential treatments for COVID-19 in clinical trials, it may take some time before definitive results about such therapies emerge. In this issue of TreatmentUpdate we review several leading potential treatments. A future issue will review other potential interventions for COVID-19, including ones that affect the immune system.
—Sean R. Hosein
REFERENCES:
- Mehta HB, Ehrhardt S, Moore TJ, et al. Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis. BMJ Open. 2020;10(6):e039978.
- Hwang TJ, Carpenter D, Lauffenburger JC, et al. Failure of investigational drugs in late-stage clinical development and publication of trial results. JAMA Internal Medicine. 2016;176(12):1826-1833.
- Parks JM and Smith JC. How to discover antiviral drugs quickly. New England Journal of Medicine. 2020;382(23):2261-2264.
- Bauchner H, Fontanarosa PB. Randomized clinical trials and COVID-19: Managing expectations. Editorial. JAMA. 2020; in press.