Covid-19 Threatens Drug Evaluation Process: Researchers

Harvard Medical School researchers say the current search for treatments for Covid-19 “represent fundamental threats to the U.S. drug development process.” Writing in the New England Journal of Medicine, the researchers say it is a false dichotomy to suggest it is necessary to choose between rapid deployment of treatments and adequate scientific scrutiny of new or existing drugs.

“For the Covid-19 pandemic and other pressing medical challenges, the health of individual patients and the public at large will be best served by remaining true to our time-tested approach to clinical trial evidence and drug evaluation, rather than cutting corners and resorting to appealing yet risky quick fixes,” the article says.

The authors discuss how very limited observational and anecdotal evidence raised the possibility that chloroquine and hydroxychloroquine could have activity against SARS-CoV-2, leading to an FDA emergency use authorization (EUA) to use the drugs with Covid-19 patients. The paper says that although the EUA was limited, its issuance was widely and falsely reported by President Trump and others as meaning that FDA had approved the drugs for the indication. “Meanwhile,” the authors say, “serious concerns have been raised about the adequacy of the available studies of these drugs.”

The article says that advocating that FDA should quickly approve drugs without randomized trials runs counter to the idea of evidence-based medicine and risks further undermining the public’s understanding of and faith in the drug review process that requires substantial evidence of safety and efficacy based on adequate and well-controlled trials before a drug can be marketed.

“Though this unprecedented emergency provides a compelling reason for FDA to act as efficiently as possible, the agency and the medical community can still maintain the highest scientific standards while acting expeditiously,” the authors declare.

The paper suggests that widening access to experimental therapies that have not been fully evaluated is likely to have several unintended consequences:

·         benefits to patients are unknown and may be negligible, in which case expanded access undermines doctors’ attempts to practice evidence-based medicine;

·         medications such as hydroxychloroquine have well-documented risks and subjecting patients to such risks would be unjustifiable absent meaningful clinical benefit;

·         distributing unproven drugs under expanded access or an EUA may detract from the resources needed to carry out clinical trials, including the patient base and necessary funds; and

·         with drugs that are already approved and marketed for other conditions, widespread off-label use can limit access for patients who need them for their established use.

The authors note that at least 25 drugs are under investigation for use in Covid-19, with 10 in active clinical trials. If data emerge showing that any regimen is truly effective in treating Covid-19, the authors conclude, FDA should be able to review the data and provide an approval decision within days or weeks.

“Adequate clinical trials will soon confirm or refute the usefulness of several candidate drugs in treating Covid-19,” the authors conclude. “But the weeks leading up to provision of that evidence reveal a great deal about threats to our approach to evaluating medications. Issues such as inadequate trial design, overreaching public declarations, and widespread use of unproven treatments will continue to present themselves during the pandemic and beyond.”