As the COVID-19 drug pipeline explodes, a fragmented approach to coronavirus drug development risks compromising the potential evidence base.
Researchers have already opened over 180 clinical trials of potential COVID-19 treatments for recruitment, and nearly 150 could start soon. An analysis of some of these trials by The Centre for Evidence-Based Medicine shows that interventional products span everything from repurposed antivirals and anti-inflammatory agents to cell therapies and traditional Chinese medicines. And a systematic review of the currently ongoing trials, published on medRχiv, cautions that the poor methodological quality, small sample sizes and long execution time of currently registered trials could compromise the collection of high-quality clinical evidence.
Zhi Hong, CEO of Brii Biosciences and former head of infectious disease research at GlaxoSmithKline, is amongst those who has raised concerns. The fragmentation of the field could make it hard to enrol patients into trials of the most promising agents, he cautioned in a commentary in Biocentury.
In an attempt to coordinate the COVID-19 clinical trial landscape, the WHO has now launched the Solidarity Master Protocol. By establishing consistent end points, control arms and inclusion–exclusion criteria, this umbrella trial — in hospitalized patients with COVID-19 infection — could increase the value of the emerging trial data set.
The first four arms of the Solidarity trial will test: Gilead’s RNA polymerase inhibitor remdesivir, first developed for the treatment of Ebola; chloroquine or hydroxychloroquine, anti-malarial drugs that were only included in the trial after public interest in these agents picked up; ritonavir plus lopinavir, a combination of anti-retroviral drugs that did not improve COVID outcomes in preliminary trial results published in the NEJM; and ritonavir plus lopinavir in combination with IFNβ, an immunomodulatory agent that may boost the efficacy of the anti-retroviral agents.
Solidarity investigators can add other arms to the adaptive trial as necessary.
Nature Reviews Drug Discovery 19, 298 (2020)