Speeding COVID-19 drug approval will increase risks
The U.S. Food and Drug Administration last week announced relaxation of certain requirements in order to speed new potential remedies for the coronavirus to market. That sounds like a great idea. Right?
A common assumption is that powerful new treatments and tests are withheld from the public because they are tied up in red tape. That really smart basic scientists and physicians could solve our current crisis if the government would just get off their backs.
Unfortunately, we cannot speed new drugs or vaccines for coronavirus through the approval process without increasing the risk of harm. To be sure, we are all at risk and we don’t want medicines that could rescue us parked on the laboratory bench. But the drug discovery process is difficult and precise.
In one of his first blog posts, Francis Collins, the director of the National Institutes of Health, noted that for each 10,000 new molecular entities that might evolve into an Fda-approved medication, only about 250 showed enough promise to be tested in preclinical studies, usually with animal models.
Of these 250, most fail to produce results and only about 2% or five potential new drugs were promising enough to be evaluated in large human trials. And among these five, only one was shown to be effective enough and safe enough to be approved. In other words, only about 1 in 10,000 great ideas make it through the rigorous process.
It could be worse than that. That became apparent when the FDA cranked up standards for transparent reporting. The FDA Modernization Act of 1997 created a service called clinicaltrials.gov, which requires all studies to be prospectively registered. Scientists are now required to declare what they were looking for.
From a scientific perspective, this reduces the chances that pharmaceutical companies can selectively report results or spin the interpretation of lackluster findings. After the creation of the service, the number of positive studies declined dramatically.
By 2017, investigators were required to not only register but to also disclose the results from all of their studies, not just the ones that support their products, though the most recent evidence suggests that few are adhering to this policy. Among all studies evaluating new products, results are made public in less than half of the cases. Presumably, companies are less likely to report results that are not favorable to their products or disclose evidence of potential harm.
To be sure, we need great ideas and better medicines. The sad news is that the evaluation and licensing of new medications is a slow process. And while the public expects that new drugs are dramatic novel cures, many diseases are chronic and not cured, but only controlled, by medicines. And how about innovation? Many newly approved drugs are given the nod on the basis of “noninferiority,” which means they work about as well as another drug that is already on the market.
When the FDA denies approval, there are usually very good reasons. Those include higher death rates among those taking the active drug in comparison to those taking a comparison medication or placebo, inconsistent results across multiple studies, uncertainty about the correct dose, or focus on an outcome that may not be clinically meaningful.
What should we do about the coronavirus? There are no therapeutic agents or vaccines that can immediately come to the rescue. We may need to acknowledge that social distancing has great potential, albeit torturous and expensive. New drugs and vaccines are coming. It will just take some time.
Robert M. Kaplan is a faculty member at Stanford University’s Clinical Excellence Research Center, a former associate director of the National Institutes of Health, former chief science officer for the U.S. Agency for Health Care Research and Quality, and author of “More Than Medicine: The Broken Promise of American Health” (Harvard University Press, 2019).