The clamor reveals the misperception over the power that the Food and Drug Administration has over doctors’ clinical decisions. And though the FDA last weekend granted emergency authorization for the drugs to be added to the Strategic National Stockpile for use in treating hospitalized COVID-19 patients, the agency does not have the final say over how doctors use drugs that it’s approved. What it can do is prevent or delay urgently needed drugs from getting to patients through its approval process.
At a previous Coronavirus Task Force briefing, President Trump incorrectly told the press that the antimalarial drug chloroquine had already gone through the FDA’s approval process for the treatment of COVID-19 infection. He was later corrected by the FDA commissioner, who said the approval process had not and will not be completed until controlled clinical trials have convinced the agency. People might therefore conclude that doctors are not legally permitted to prescribe chloroquine, or its analog hydroxychloroquine, to treat COVID-19 infections. In fact, doctors around the globe, including in the U.S., are already using these and other drugs to treat their patients, and reporting on their findings in the peer‐reviewed medical literature.
In the March issue of the International Journal of Antimicrobial Agents, a group of French medical researchers reported on chloroquine’s potential based on their experience with a small group of patients. A Chinese medical team reported similar encouraging results in early February. Researchers at the University of Washington in Seattle are using chloroquine to treat their COVID-19 patients, with one of its research associates calling the results thus far “very promising.” And a report in the Wall Street Journal by two physicians, including the director of the Division of Infectious Disease at the University of Kansas Medical Center, also touts the drug’s potential.
The use of chloroquine, hydroxychloroquine, and other drugs (such as azithromycin and antiviral drugs used against HIV) to treat COVID-19 are examples of “off‐label” prescribing. Ironically, once a drug is approved for the treatment of the condition for which it was initially intended, the FDA does not restrict its use in other situations. This is called “off‐label,” because the label is only allowed to state the condition for which its use was FDA‐approved.
The possible coronavirus cure is said to be pending government approval. But physicians have a way around that.
Clinicians use drugs “off‐label” very frequently. In fact, according to the Agency for Healthcare Research and Quality, “one in five prescriptions written today are for off‐label use.” An example of this in my specialty of general surgery is the antibiotic erythromycin to treat paralyzed intrinsic muscles of the stomach, a condition called gastric atony.
The public misperception over the FDA’s control of clinicians derives from “mission creep” in the drug approval process. Prior to 1962, drug makers had to convince the FDA their product was safe to consume and had proper information about use and dosage on their labels. The 1962 Kefauver‐Harris Amendments to the Food Drug and Cosmetic Act of 1938 added the burden of proving the drug’s efficacy in treating the condition for which it was developed.
Efficacy requirements add years to the approval process. It is reasonable to wonder why, after doctors wait all this time to get permission to treat their patients with a drug for condition A, the FDA in principle then trusts them to use their clinical judgment to treat conditions B through Z. Why not skip the efficacy component of the approval process altogether and speed things up? Most of what clinicians read in journals or observe at conferences deal with the efficacy and comparative effectiveness of various medications and procedures to treat health conditions. This informs their off‐label prescribing.
Many years often pass before clinical trials convince the FDA to update its approved use of a drug to include what had been an off‐label use. Aspirin had been used off‐label to prevent recurrent strokes and heart attacks for many years before the FDA approved it for that purpose.
The FDA may eventually approve chloroquine, hydroxychloroquine, and other drugs for the treatment of the coronavirus. But that could be a long while off. In the meantime, it is important for people to know that clinicians are not prohibited from prescribing these drugs now.