This post is the second in a series about conducting human subjects research in emergencies. These posts are being written in response to a rapidly evolving situation and will reflect the state of knowledge at the time of writing.
In April 2020, Dr. Robin Armstrong, medical director of the Resort, a nursing home in Texas City, Texas, reported “signs of improvement” after he gave hydroxychloroquine, a drug approved by the FDA to treat malaria, to 39 of his nursing home patients who were diagnosed with COVID-19.
At about the same time, information was emerging that now represents the current understanding that hydoxychloroquine isn’t only ineffective in treating COVID-19, but also may cause serious harm to patients. Tensions were raised even higher by the seemingly inexplicable enthusiasm for this treatment by the President and some media outlets.
Almost immediately, there was a public outcry about the possibility that this was an illegal or unethical “research experiment” – perhaps even comparable to the U.S. Public Health Service’s shameful observational study of untreated syphilis among African American sharecroppers in Tuskegee, Alabama that began in the 1920’s and devolved into a decades long gruesome deprivation of a safe, effective, and inexpensive treatment.
But the current global effort to discover safe and effective treatments and vaccines for COVID-19 shines a light on the complexity caused by the division of powers between individual states and the federal government codified in the U.S. Constitution.
A current U.S. law protecting humans involved in federally funded or regulated research, the “Common Rule,” was intended to prevent something like Tuskegee from happening again. It does so by requiring an ethics committee, called an Institutional Review Board, to review all proposed studies in advance for compliance with its guidelines for protecting human subjects and then be continuously monitored by the same committee until the study’s conclusion.
There are lots of loopholes, however, and the Texas City Study falls through several of them.
First, the Common Rule doesn’t apply to the activities of treating physicians unless they are formally part of a federal research study. There are federally regulated studies of hydroxychloroquine conducted by the University of Minnesota or Columbia University, but Texas City isn’t a participating site.
So, if what happened wasn’t federally regulated research study, might it have violated federal law because hydroxychloroquine is not approved to treat COVID-19?
No again. Hydroxychloroquine is an FDA approved drug — for malaria. But with very, very few exceptions, any licensed physician in the U.S. can prescribe any drug approved by the FDA for any condition to any patient — for almost any purpose. This is called prescribing a drug “off-label.” Much of the scholarship explaining this authority is in the context of a different but related issue — the legality of pharmaceutical companies themselves promoting their drugs to prescribing physicians for off-label uses.
Further, the FDA has actually issued a form of emergency approval, called an Emergency Use Authorization, for hydroxychloroquine, allowing it to be considered as though it were approved for treating COVID-19. But the effect of doing that wasn’t to make it legal, the usual reason to get an EUA, which then allows use of an unapproved drug. It was to make it more available.
Under the terms of the Emergency Use Authorization, the FDA removed the drug from the normal chain of retail supply by allowing the use of hydroxychloroquine sulfate and chloroquine phosphate products donated to the Strategic National Stockpile (SNS), so it did not have to be ordered, or paid for, by a pharmacy.
Dr. Armstrong, however, reports that he got the hydroxychloroquine he administered to his patients directly from the manufacturer through a connection in the Republican Party. This connection circumvented another potential obstacle to administering hydroxychloroquine to his patients, the reluctance of Medicaid to pay for drugs prescribed off-label.
But are there no consequences to prescribing a drug that hasn’t been proven safe and effective to an elderly and vulnerable population? The short answer: it depends.
Dr. Phillip Keiser with the Galveston County Health Department was correct in explaining that, “You know from an ethical and legal point of view, I can prescribe any drug that’s licensed by the FDA and if I do a bad job of it… well there may be some civil consequences or the licensing boards may weigh in on that.”
As a matter of Constitutional law, when the 13 original colonies agreed to give up some of their individual powers to create a federal government, one of the most important powers they kept to themselves was the power to protect the health and safety of their citizens. Under these retained Police Powers, each state makes its own decisions about licensing doctors and passing laws governing the ability of patients to be compensated for professional negligence.
Medical negligence, malpractice, is triggered by an action performed by a health care provider that harms a patient and which is below the standard of care of a reasonable physician. In the case of a rapidly involving situation where medical knowledge changes quickly, the standard is at the time the care delivered. This is especially relevant here when many treatments are being used to treat critically ill patients at the same time the drugs are being studied for safety and effectiveness.
Is it likely for a physician to be held liable for acting below the standard of care for prescribing an FDA approved drug when it was being prescribed widely in the U.S. and abroad and when that agency itself had already created a pathway for no-cost distribution? Probably not and even more likely not when treating patients who were facing death with no other treatment available. In this case, even if there was a case for medical negligence it would be very difficult to bring in Texas, which has extremely tough procedural barriers for bringing a case. And if the risk of a medical negligence claim isn’t already quite low, Texas is one of many states now seeking even more protection from liability for harm caused by prescribing off-label drugs to COVID-19 patients. The only remaining legal issue would be around informed consent, and even then there would have to be direct proof of harm.
Future posts — Looking at the Constitutionality of state laws seeking to promote or restrict off-label prescribing, and highlighting more of the legal loopholes likely to affect the testing of unapproved drugs intended to prevent COVID-19, including those that encourage conducting “pilot” studies outside of the regulated research framework, including outside the U.S., in order to reduce the cost of getting data to submit to the FDA.
Many thanks to Pranav S. Patel, B.S., M.P.H., University of Florida J.D. Candidate 2022 for his excellent assistance with the research for this post.