House Republicans passed a “right-to-try” bill late last week after failing to gather the necessary votes a week earlier. The legislation, which expands patients’ ability to seek experimental treatments, now heads to the Senate, which passed its own, looser version of a right-to-try bill last summer. Politico has a rundown of the back and forth, including some oddly vague positioning by Sen. Chuck Schumer (D–N.Y.). I would bet that some version of a right-to-try bill makes its way to President Donald Trump’s desk eventually, and that when it does he’ll sign it.
But the politics of the bill aren’t as interesting to me as what happens once we do have a federal right-to-try law.
In the best-case scenario, the law saves lives that would otherwise be lost. Doctors whose patients are terminally ill and incapable of benefitting from currently approved therapies or participating in a clinical trial would be able to request experimental drugs from pharmaceutical companies and then administer them, all without seeking approval from the Food and Drug Administration (FDA). In this scenario, pharmaceutical companies would be willing to sell (or donate) these investigational drugs, which, by law, would need to have passed only the first safety stage (“Phase I”) of clinical trials. Ideally, some number of people would receive a treatment years before the FDA approves it, the treatment would work in a way that no other treatment has, and the patients would outlive their current prognosis.
This scenario relies on some assumptions that we cannot currently test.
The first assumption is that there is a large pool of people who would benefit from right-to-try who are not benefitting from the FDA’s existing Expanded Access/Compassionate Use program. When patients have exhausted all approved treatment options and failed to gain admission to a clinical trial, doctors can apply for the FDA’s permission to use an investigational drug. The approval rate for Expanded Access is 99 percent and the agency recently simplified the application process, but we don’t know much about the one percent who are rejected, or how many doctors and patients feel overwhelmed by the application process, or whether the application process is structured in such a way as to discourage certain types of doctors and patients from ever applying. In 2017, 1,143 Expanded Access applicants were allowed to proceed, while only eight were not. I have seen no estimates of the number of people likely to seek access under right-to-try; it could be dozens or thousands or zero.
The second assumption is that drug developers are willing to participate in this partially deregulated market. The legislation, after all, does not require manufacturers and developers to provide drugs to a doctor; it only gives them the legal option to do so, and some protection from civil liability. But it is far from clear that any established drug maker wants to test those waters. Every calculation that drug developers make is aimed at increasing the odds of obtaining FDA approval and the subsequent period of monopoly. When they cut corners, it is to maximize profits. When they exercise an abundance of caution, it is to maximize profits. When they mess around with patent laws and voluntarily impose restricted distribution and make side deals with generic companies, they do all of that to maximize profits (which makes even more sense when you consider that the U.S. is where most drug makers can turn the biggest profit).
How does right-to-try maximize a drug developer’s profits? Under the House version, adverse events that reflect a drug’s safety profile must be reported to the FDA. That adverse event could extend the length of the developer’s clinical trial. It could even cause the FDA to issue a hold. What drug developer wants to trust that risk with a third party whose primary interest is not maximizing the drug company’s profits?
While I think right-to-try would better position patients and their doctors to demand access to unapproved drugs (and to use public opinion as leverage), I’m not sure protection from lawsuits is adequate incentive for drug developers to operate without preauthorization from the FDA. Sabotaging a trial, or irritating an FDA reviewer by breaking ranks, would likely outweigh the signalling benefits of having helped a desperate patient, or even dozens of desperate patients. Anything bad that happens on the alternative pathway—some weird or awful side effect, a terminally ill patient dying before she was expected to, or even a patient dying right when he would’ve under the existing standard of care—is going to look worse for a drug developer than if the same events had occurred under FDA’s Expanded Access program. Drug companies may not love the FDA, but they love FDA approval. Without it, insurance companies will not pay for a drug, hospital pharmacies will not stock it, and doctors will not prescribe it.
My colleague Ron Bailey sees right-to-try as a baby step toward a more widely deregulated drug development market. Along with former FDA Commissioner Andrew von Eschenbach, he’d like to see therapies approved for market after Phase II safety testing. Whether they work, and what they work for—currently the role of Phase III trials—could be determined on the open market and tracked with patient registries and post-marketing studies.
If a federal right-to-try law unleashes a torrent of applicants or emboldens drug makers to operate outside the FDA’s purview, that would be evidence that the FDA is, in fact, holding up the process. It could be that step toward the regulatory environment Bailey and von Eschenbach envision. My suspicion, though, is that the FDA has exerted just enough influence over the House right-to-try bill that its scope and scale will be severely limited—especially since the Senate seldom produces less onerous legislation. If so, whatever bill Trump signs will likely make things only slightly easier for doctors and patients and a lot riskier for drug developers. And that is the perfect combination of tweaks to give people the impression that the Expanded Access program is all we need.
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