The President is getting a lot of flak for basically telling COVID-19 patients to try Hydroxychloroquine or as he has put it, “What do you have to lose.”
The criticism from the medical establishment is that the drug is not proven safe or effective for COVID-19. That is true, but it’s not the whole story.
Most people are or have recently become familiar with the concept of “off label” use, but I suspect few really understand some important aspects of the concept and how widespread it is in medical therapeutics.
A couple of basic points and the economics of the FDA approval process.
Drugs are almost always initially approved for a single use/disease/medical condition. After a drug is approved for one use, it is not uncommon for the drug manufacturer to seek approval for additional indications. Hydroxychloroquine was originally approved in 1955. I do not know what the initial indication was but now it is FDA approved for some kinds of malaria cases, lupus, rheumatoid arthritis and a couple other less common indications.
However, the FDA approval process is very expensive, and there are many reasons which cause a drug company not to seek to obtain additional indication approval from the FDA. These factors have led to many drugs being used off-label. Off-label use of FDA approved drugs is extremely common. For example, it is estimated that 30 to 50 percent of cancer patients receive chemotherapeutic agents not approved for the specific cancer for which it is given. In many to most other areas of medicine, off-label use is also quite common. Oftentimes, off-label use is eventually considered the standard of care.
The legal Status of Off Label Use
Here like in many cases, it is necessary to separate federal versus state law.
Under federal law, off-label use of almost all drugs is legal, and up to the discretion of the physician. (The exception being HGH (Human Growth Hormone) because there is a federal statute which limits its use to a few specific conditions). Drug companies are not allowed to advertise or promote the off-label use of their products, but physicians can use them off-label to their heart’s desire, (at least in the absence of some federal emergency regulation or rule). Therefore, general federal law does not bar a physician from using Hydroxychloroquine off-label.
In fact, on March 28, 2020 the FDA issued an emergency use authorization (EUA) to allow Hydroxychloroquine (and chloroquine phosphate products) donated to the Strategic National Stockpile (SNS) to be distributed and used for certain people who are hospitalized with COVID-19. So in some cases now, under federal law, it is no longer even considered off-label use. So arguably, whatever problems there are in using the drug, legally anyway, it is not with the Feds, technically at least.
Prescribing drugs constitutes the practice of medicine and is governed by state law. That means state can have different laws. The state medical boards are the primary enforcers of the practice of medicine. Off-label use is generally allowed under the laws of most states, at least so long as the off-label use has acquired standard of care status. I have spent a good chunk of my career fighting with medical boards about non-standard of care off-label use of FDA drugs, and honestly, it is a hit-or-miss proposition.
Besides the physician, the other major player in the Hydroxychloroquine scenario are the private pharmacists who dispense the medications to patients outside of a hospital setting.
So far, the states have adopted three positions on the use of these drugs for COVID-19.
Some states have said nothing.
At the other extreme, Michigan’s Governor banned off-label use of Hydroxychloroquine and threatened providers and pharmacists with board action if they did not comply. That initial ban may have been walked back by her, and in any event, some Michigan hospitals are using the drug to treat the disease regardless of the Michigan Governor’s ill-advised edict.
The third and most reasonable approach has been taken by states like Texas, Idaho and Ohio, which set some preconditions for off-label use of the drug.
The clearest regulation is Ohio’s which requires a positive Covid-19 test result, limits the prescription to a 14-day supply, and requires a new prescription (instead of a refill of an existing prescription) for additional use. Ohio also specifically bars its use prophylactically, which is perhaps implicit in the fact that a prescription requires a positive test result). Nevada limits the drug to a hospital setting, so if you are not sick enough to be a Nevada hospital, you’re out of luck.
Let’s Go Sideways for some perspective
It is now legal to use unapproved drugs which are in clinical trials
Over forty states and federal law now recognizes a “right to try” drugs which are in FDA approved clinical trials, but have not yet completed the FDA approval process establishing safety and efficacy.
In contrast, Hydroxychloroquine was first approved in the U.S. 1955. In 2017, there were five million prescriptions for the drug written in the U.S.
To be fair, advanced Covid-19 patients are far sicker than the average Hydroxychloroquine on-label user. A small Brazilian study released just today indicated that high doses (650 mg) were associated with increased risk of death and were not more effective than a smaller dose (450 mg). So, for sure, the jury is still out on the drug in terms of its safety for this use as well as its efficacy.
But we are in a pandemic which is now killing 2,000 US residents each day, and there is no proven effective treatment or preventative for the disease.
Equally disturbing is the seemingly extremely high mortality rate of patients who are intubated. I’ve heard death rates as high as 60-80 percent. One NY ER doctor (and perhaps others and in other countries) are starting to question whether intubation is appropriate for these patients. This seems like an additional reason why patients ought to be given the choice to try Hydroxychloroquine, since if they progress in the disease and need intubation, the odds of surviving are not good.
Personally, I would probably start with IV Vitamin C treatments, but if that did not work, I have to agree with President Trump in his common sense view since there is no approved treatment, why not try something with some “anecdotal” support, and do it early since the whole intubation/ventilator thing may prove to be exacerbating the problem. The use of this drug on a widespread scale “off-label” during a pandemic is going to present some challenges in terms of data collection and analysis, but I have some ideas about that which I will discuss in the my next post.
Rick Jaffe, Esq