‘Right to try’ unapproved drugs advances personal freedom -- but risks must be taken into account

Several times recently, President Trump endorsed terminally ill patients’ “right to try” drugs not approved by the FDA: “Patients with terminal conditions, terminal illness, should have access to experimental treatment immediately that could potentially save their lives,” he said in the State of the Union speech.

More than three dozen states and the U.S. Senate have passed laws aimed at providing easier access to experimental treatments that have undergone only the most minimal human testing, and the House will vote on a bill this week.  The concept is a worthy one, but the congressional bills need modification before becoming law.

The “right to try” website, operated by the libertarian Goldwater Institute, promotes allowing “terminally ill Americans to try medicines that have passed Phase 1 of the FDA approval process and remain in clinical trials but are not yet on pharmacy shelves. . . [and] expands access to potentially life-saving treatments years before patients would normally be able to access them.” 

But there’s the rub: About three-quarters of drugs that pass Phase 1 will ultimately fail to be approved and never be accessible because they founder on the grounds of safety or lack of efficacy. And of those that do ultimately gain approval, often the use for which the FDA approves them will be very different from the expectations during Phase 1 testing.

The right to try unapproved drugs has the potential to be compassionate and sound public policy, as well as an important statement about individuals’ free will, but as the saying goes, the devil is in the details. The most worrisome detail is that most—perhaps all—of the proposals, including the one introduced last year by Republican U.S. Senator Ron Johnson of Wisconsin, would enable patients to request the drugs after only the most meager safety testing. But safety should be a concern even for terminally ill patients.

Federal regulators are already implementing a version of “right to try.” From 2010-2015, the FDA approved more than 99 percent of applications for “compassionate use” applications, and since then has worked to simplify the process.

Phase 1 testing under the aegis of FDA, often the first time a new drug has been administered to humans, amounts to practically no testing at all. Those trials are performed for a short time on a very small number of subjects, typically 20-80 (paid) healthy volunteers, who often do not provide a good representation of how the drug will affect terminal patients. Those studies are intended to determine what doses of the drug are tolerated (in healthy volunteers) without obvious adverse effects, such as sudden death, seizures, or rapid failure of organ systems. Efficacy testing occurs only in the later stages of drug development.

Some people might say that terminal patients should be allowed to access these drugs because things cannot possibly get worse for people who are dying anyway. Not so. They can get worse. Adverse reactions can make the last days or weeks far more miserable if the drug causes a stroke, liver or kidney failure, neuralgia, or the agonizing Stevens-Johnson syndrome, a reaction to certain drugs marked by an excruciatingly painful rash that spreads and blisters.

Moreover, appropriate dosing schedules, precautions and contraindications are typically discovered only during post-Phase 1 clinical trials, or even after a drug has been on the market.  An example of the latter was the discovery last year that the drug Viberzi, which was approved in 2015 to treat inflammatory bowel disease, can cause a serious and painful condition called pancreatitis in patients who do not have a gallbladder.  That drug had undergone extensive pre-approval testing on more than 2,600 patients during the pivotal clinical trials.

A Wall Street Journal article on this subject elicited a number of angry responses to the assertion that although individuals’ “right to make choices based on their own judgments about risk and benefit” is important, “[s]ociety also has a role in preventing desperation-driven coercion of patients and their exposure to unacceptable risks.”

One letter-writer to the Journal caviled that, “society most certainly does not have a role in telling terminally ill patients that it knows better about analyzing risks and benefits and denying them choice.” Another commenter offered, “If a patient is terminal and legally competent, why should disapproval by you, or society, or fear of liability (which should be able to be neutralized) rob that patient of a humane, possibly life-extending option?”

They raise legitimate issues but ignore that society frequently intervenes to protect consumers from risks considered unreasonable—for example, by not affording them the freedom to experience the exhilaration of riding a motorcycle without a helmet. And in the pharmaceutical realm, the government polices and interdicts drugs bought via the internet from certain offshore pharmacies known to pose a significant risk because its products are often counterfeit, contaminated or otherwise substandard.

Federal regulators are already implementing a version of “right to try.” From 2010-2015, the FDA approved more than 99 percent of applications for “compassionate use” applications, and since then has worked to simplify the process.  

Right to try is a compassionate and worthy concept, but it needs thought and refinement based on an understanding of the drug approval process and of physicians’ commitment to primum non nocere--first, do no harm.

Thus, to invoke the right to try there should be some actual evidence of efficacy, beyond just speculation derived from computer simulations, cell culture or animal experiments. I suggest as an appropriate minimum threshold at least one Phase 2 trial (in which the drug has been administered to patients with the disease or symptom it is ultimately intended for) whose results provide a reasonable expectation of effectiveness. And, of course, the manufacturer of the medicine (most often a drug company, but sometimes a university research laboratory) should have to provide a statement that conveys the uncertainty about the likelihood of a positive response and of the known and possible side effects.

We need to prevent well-intended treatments from being worse than the disease. As one of my medical school professors admonished us, there is a difference between patients actually living longer and interventions that make them so miserable that it just seems like longer. 

Henry I. Miller, a physician, molecular biologist and former flu virus researcher, is the Robert Wesson fellow in scientific philosophy and public policy at Stanford University’s Hoover Institution. He was the founding director of the Food and Drug Administration’s Office of Biotechnology. Twitter: @henryimiller