The Parochial School Of Medicine

photo by Marco Verch, licensed under Creative Commons

Whenever I hear journalists or public health officials dismiss a potential treatment for COVID-19 as “not proven,” I wonder: What would they say if a doctor proposed using one of these medications to save them or their loved one?

I can’t picture anyone replying “Don’t bother. Since we have not seen results from any double-blind clinical trials, it is not worth raising false hopes or wasting medication on my spouse (or parent or child) on a therapy that is not proven.”

Right now there is only one proven method to defeat the coronavirus causing the current pandemic. That method is not to catch it in the first place. Most of us have huddled in our homes for weeks now, toward exactly that end. But this technique is irrelevant to the hundreds of thousands of Americans diagnosed with COVID-19, or to the millions more here and abroad who have been infected (many without ever being tested). It’s also no use to practitioners and other front-line personnel who cannot stay at home. They are either treating the sick or making it possible for the rest of us to stay isolated.

Although many existing and new drugs are being investigated as possible COVID-19 therapies, most of the public’s attention currently rests on two long-established anti-malarial medications: chloroquine phosphate and hydroxychloroquine sulfate. There is reason to believe they can be effective, particularly when used in combination with an antibiotic, azithromycin. There is also reason to be skeptical. Some studies have shown promising results; other studies have not. All these studies have been too small to consider their results conclusive. Until researchers can reliably collect and evaluate more data, we don’t know how this coin-toss will land.

I have personal experience with these drugs. They were prescribed for me and my family (I don’t recall which of us got which) ahead of a vacation trip to the Amazon region of Brazil in 2010. We began taking them several weeks ahead of our departure and continued for some weeks after we returned, as a prophylactic. Nobody got malaria, and nobody suffered serious side effects.

Does that mean I would take one of those medications right now, if offered? Of course not. I am not sick and I have the option to stay home. There is no reason for me to do anything else.

If one of my daughters were working in an emergency room in New York City, would I want her to take these medications? I probably would – especially if she told me that there was inadequate personal protective gear to assure her safety. Not only would I worry about her health, but potentially protecting her also could provide protection for her co-workers, the patients they treat, and everyone they encounter outside the ER. These drugs’ side effects, while potentially dangerous, are also relatively rare.

You can bet your last dollar that if I were seriously ill with COVID-19 and deteriorating in intensive care right now, my wife would insist that medical staff apply one of these therapies. The risk-reward trade-off of using a drug whose safety, if not efficacy, is well-documented to counter a life-threatening illness in an otherwise healthy, 60-something man is crystal clear. In the absence of a better option, you try the drug and hope for the best.

Malaria is caused by a blood-borne parasite that is transmitted by mosquitoes in tropical regions. We would not ordinarily assume that a virus would respond to anti-malarials, nor to an antibiotic designed to fight bacteria. But the doctors in China and France who first resorted to chloroquine and hydroxychloroquine were aware of the drugs’ history of anti-viral applications. Chloroquine had shown some promise in laboratory tests against other viruses, including the coronavirus that produced the SARS outbreak in 2003. (That SARS test was conducted in vitro – in other words, in cells, not live animals.) The added antibiotic provides some ammunition against secondary infections. This may account for the anecdotal reports that patients do better when it is added to the anti-malarials than when they are used alone, though widespread use of antibiotics among those not known to have bacterial infections involves its own potential downside. The skeptics of these treatments are right to observe that we don’t know whether these drugs really work, let alone how.

President Trump has been the most vocal and visible advocate of using the anti-malarials to fight what he calls “the invisible enemy.” The president is hardly shy about using hyperbole, now as ever. This has led much of the press to highlight a supposed conflict between his enthusiasm and the caution of Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases.

There is actually not much conflict between their statements, however, because they are usually saying two different things. Fauci has noted that until we have reliable data collected under known conditions, we don’t know whether or to what extent the off-label use of the anti-malarials is effective against COVID-19. This is true. Trump has highlighted reports by some practitioners who have tried the drugs on real-world patients, who then improved. We know for a fact that some practitioners have made such reports. We can accept on reasonable faith that they really did have patients who got better. We do not know whether the patients got better as a result of the drug. Trump is optimistic that they did; he may or may not be right.

Many of the same news outlets emphasizing the “not proven” aspect of this story are often quick to report that something or someone is “under investigation.” So let’s agree that hydroxychloroquine and chloroquine are under investigation for being effective against COVID-19. Then, if one of these journalists happens to become ill – and although I would not wish it for anyone, some already have – they will not look as hypocritical should they make the reasonable choice to try these medications themselves, if their doctors offer them.

A joint statement on March 25 by the American Medical Association, American Pharmacists Association and American Society of Health-System Pharmacists noted that some medical professionals were using the anti-malarial drugs to protect themselves and their families, while some hospital systems were stocking up as potential treatment for COVID-19 patients. The three groups declared that they “strongly oppose these actions.”

“We collectively support state and federal requirements that direct a prescription must be written only for a legitimate medical purpose,” the three organizations said. “We also strongly support a pharmacist’s professional responsibility to make reasonable inquiries to a prescriber to resolve any questions about a prescription. If a prescription is not for a legitimate medical purpose, it should not be written, and it should not be dispensed. That determination can and should be made on a case-by-case basis, and physicians, pharmacists and other members of the healthcare team are more than capable of working together and resolving questions.

“At the same time, we caution hospitals, health systems, and individual practitioners that no medication has been FDA-approved for use in COVID-19 patients, and there is no incontrovertible evidence to support off-label use of medications for COVID-19. Stockpiling these medications—or depleting supplies with excessive, anticipatory orders—can have grave consequences for patients with conditions such as lupus or rheumatoid arthritis if the drugs are not available in the community. The health care community must collectively balance the needs of patients taking medications on a regular basis for an existing condition with new prescriptions that may be needed for patients diagnosed with COVID-19. Being just stewards of limited resources is essential.”

Nobody wants to see patients with other conditions go without their medications. But rheumatoid arthritis and lupus are autoimmune conditions that are not as acutely and imminently life-threatening as COVID-19, though some clinicians have noted that an acute lupus flare-up or withdrawal symptoms could send patients to hospitals already overburdened with COVID-19 patients. Still, any shortage of these long-established drugs can be met relatively quickly. Manufacturers already have provided millions of new doses. The humanitarian priorities of the three naysaying organizations were misplaced. The idea that pharmacists should withhold medications prescribed by doctors in the absence of “incontrovertible evidence” in the middle of a pandemic is barely short of bizarre.

Call it the parochial school of medicine. Would the authors of that statement turn down the anti-malarials if they had to go into an ER filled with COVID-19, either as practitioners or patients?

Since that statement was issued, the Food and Drug Administration has approved an emergency use application for these drugs to be prescribed against COVID-19. This was not strictly necessary. Doctors are authorized to prescribe any approved drug for “off-label” use against other conditions. Yet it does provide some encouragement, and perhaps some liability protection for the wrongful death lawsuits that will follow the pandemic as surely as lawyers working on contingent fees follow ambulances after traffic accidents. It also allowed the government to distribute millions of doses that drug companies had donated.

Even this FDA approval was not enough to stop the naysaying. Scott Gottlieb, who was FDA commissioner in the Trump administration until April 2019, and Margaret Hamburg, FDA commissioner under former President Barack Obama, both decried the emergency authorization in the absence of clinical studies.

I hope Gottlieb and Hamburg never need to ask for one of these drugs to treat somebody close to them. Those two former officials are exactly where we need them to be in the middle of this crisis – on the sidelines, where they can Monday-morning quarterback to their hearts’ content. Meanwhile, the people in charge today fight the battle at hand with the only weapons they have.