Right-to-try laws could curtail the development of innovative new therapies

Right-to-try legislation, enacted in 32 states and under consideration in the House of Representatives and the Senate, has a message aimed straight at the heart: let terminally ill Americans who have no other options try new medicines, even though these experimental agents haven’t been approved by the Food and Drug Administration.

But the deaths of four people in a clinical trial of a new cancer therapy called CAR-T underscore why the FDA should maintain its gatekeeper role in the drug development process, something right-to-try advocates fundamentally oppose. These deaths also highlight why right-to-try legislation could interfere with the development of innovative therapies.

CAR-T therapy essentially entails removing some immune cells from an individual, programming them to seek out cancer cells, and putting them back into the person. That allows the patient’s own immune system to destroy the cancer (albeit it with some outside help). CAR-T has created huge expectations, with the hype outpacing data. At least three companies have sought to make CAR-T a reality and are racing to secure FDA approval for their products.

This is exactly the environment in which you would expect patients to join clinical trials, hoping to be part of the next new thing. It is also the situation in which those patients who aren’t able to enroll in clinical trials may request access to the experimental treatment via compassionate use (also known as expanded access or pre-approval access).

One of the many lessons from clinical trials is that new therapies often have unforeseen side effects. In the case of the CAR-T leukemia trial sponsored by Juno Therapeutics, one of those “side effects” was the deaths of several study participants. That didn’t mean Juno’s approach was doomed — the trial has since resumed — but that adjustments were needed before any other individuals could be allowed to try the new treatment.

The author of the right-to-try concept, the libertarian Goldwater Institute, has been lobbying since 2014 for right-to-try laws, initially state by state and now on the federal level. These laws remove the FDA from decisions about which experimental drugs can be tried by dying patients unable to enroll in clinical trials. Right-to-try advocates seek unfettered freedom for patients to try whatever experimental drugs they can obtain.

However, because these laws don’t force pharmaceutical companies to provide experimental treatments or insurers to pay for this care, the only entity these laws affect is the FDA. This targeting is because right-to-try advocates accuse the FDA of limiting access to investigational drugs. Given that the FDA approves more than 99 percent of compassionate use requests, this is a faulty line of attack. Besides, access to investigational drugs is controlled by the companies developing those drugs, not the FDA, which becomes involved only after a company has agreed to make its experimental drug available.

Setting aside the possibility of individual harm, granting patients unfettered access to investigational drugs would harm the development of new drugs, mainly by hindering enrollment in clinical trials. If offered direct access to a desired experimental drug, why would anyone want to take part in a clinical trial in which the odds of getting a placebo or a different drug can be as high as 50-50?

But perhaps the impact on clinical trial enrollment wouldn’t be as bad as it seems. If that’s the case, could providing access to investigational drugs outside of clinical trials produce enough “real-world data” to permit us to determine whether the new drugs are safe and effective enough for the FDA to approve them for sale and use? A thought experiment in which three patients receive the same investigational therapy through right-to-try laws shows why an individualistic approach to access to experimental drugs is bad for patients, bad for innovative technologies, and bad for all of us.

Imagine that patients A, B, and, C receive the therapy via the right-to-try pathway rather than through a clinical trial. Each one dies. If A’s doctor in Seattle, B’s doctor in Atlanta, and C’s doctor in New York independently decide that their patient’s death is due to their underlying disease and not the experimental drug, they have no impetus to sound any sort of alarm. After all, when viewed in isolation, the death of a very sick patient is an unfortunate but not unexpected outcome. In contrast, the death of three patients in a small clinical trial would be instantly noted, recorded, and reviewed repeatedly over the development cycle of the experimental drug. In the case of the CAR-T trials, very small numbers of deaths have resulted in trials being stopped and thoroughly reviewed.

While the three doctors in my right-to-try thought experiment would be expected to report drug-related deaths or other serious adverse events to the company in return for their patients’ being granted access to the experimental drug, this is akin to an honor pledge. Doctors aren’t audited to see if they are reporting properly, and if a doctor decides the death was from something other than the investigational drug, she is not even required to report it except in an annual report.

But the company’s ability to spot trouble with its drug would be hindered by not learning promptly of such deaths. And with right-to-try laws removing the FDA from decisions about what experimental treatments people can try, it would be blind to the fact that three people died after receiving the same experimental treatment.

New therapies pose risks, not just to the patients who volunteer to test them but also to the advancement of science, the development of new areas of research, the financial wellbeing of companies pursuing innovative research and, eventually, to all of us who may someday benefit from those new therapies. Monitoring investigational drugs by some central body is essential.

When it comes to the development of new drugs, the FDA plays an essential role in protecting all of us. Thinking that individual patients and their doctors should be free of FDA oversight and be able to try any experimental therapy to which they can gain access is, at best, shortsighted. At worst, it sacrifices science, industry, and the well-being of others to the false idol of unregulated individual liberty.

Alison Bateman-House, PhD, is an assistant professor in the Division of Medical Ethics at NYU School of Medicine and co-chair of the school’s Working Group on Compassionate Use and Pre-Approval Access.