Commentary outlines “best practices” for studies looking into possible treatments, vaccine.
Everyone wants a treatment or cure for COVID-19.
A viable vaccine against SARS-CoV-2 wouldn’t be bad either.
However, it’s important that researchers pursuing these vital innovations don’t cut corners in design, protocols, and ethics to achieve these Holy Grails. That’s the take-home message of a commentary published on April 23rd in Science, in which the authors argue against the idea that “crisis situations demand exceptions to high standards for quality” in research.
“For years, I’ve worked on the issue of ethics in clinical research and I’ve covered problems and inefficiencies we see under normal circumstances, like issues of bias, etc,” Jonathan Kimmelman, PhD, James McGill Professor in the Biomedical Ethics Unit/Social Studies of Medicine Department at McGill University in Montreal, told Contagion®. “And so, I expected that the same problems we see under normal circumstances would be amplified in the pandemic. But what we’re seeing here is more excuses being made for these problems, and a willingness to overlook them.”
Hence, Kimmelman added, the title of the commentary—“Against Pandemic Research Exceptionalism.”
He and his colleague Alex John London, PhD, Clara L. West Professor of Ethics and Philosophy at Carnegie Mellon University in Pittsburgh, argue that for research into, among other things, drug treatments and vaccines against the new coronavirus to “fulfill their social responsibilities,” it must meet 5 essential conditions.
The first is importance—in other words, like any new research, studies centered on COVID-19 should “address key evidence gaps,” and evaluate interventions that are “the most promising therapeutic and prophylactic alternatives as judged from reviews of existing evidence and trials.” They note that there are, as of their writing, 18 clinical trials of various hydroxychloroquine-based regimens enrolling more than 75,000 patients, just in North America alone. This despite limited evidence supporting the efficacy of the anti-malaria drug in the treatment of a coronavirus.
“Testing different regimens derived from a common clinical hypothesis in uncoordinated protocols increases the probability of false-positive findings due to chance (and)… also frustrates cross-comparisons and squanders opportunities to evaluate regimens side by side,” the write.
Not surprisingly Drs. Kimmelman and London also advocate that all pandemic-related research studies should have “rigorous design”—with valid comparators, where appropriate—and “analytical integrity.” In addition, they note, all trials should be reported completely, promptly, and consistently with prespecified analyses, as well as sufficient “quality control” (eg, peer review). Many studies have been posted to preprint web sites with an idea to getting the information out to the public—and the medical and scientific communities—faster, perhaps at the expense of accuracy.
Finally, newly launched studies must have a realistic opportunity to reach their recruitment targets and be completed "within a time frame where the evidence is still actionable.” This is “in tension,” Kimmelman and London write, given the need for speed brought forth by the pandemic, but no less important—even now.
“One of the things we highlight in our paper is the huge amount of duplication in the testing of hydroxychloroquine, for example—and that’s just in North America,” Kimmelman said. “Normally, when you are trying to get a drug approved by the FDA, you try to do one or two high-quality pivotal trials. I’m not sure why individual countries feel the need to conduct multiple clinical trials, but that seems to be the climate we’re in.”