Craig Klugman criticizes medical autonomy and Right to Try, that is, laws that protect the right of terminally ill patients to try, with the recommendation of their physician, treatments that have passed Phase 1 of an FDA clinical trial and are being administered in clinical trials but haven’t yet been fully FDA-approved. Why, when patients, doctors, and lawmakers on both sides of the political aisle have supported Right to Try, does Klugman balk?
One answer he gives is that, in his view, the current drug approval system “has saved millions of lives and billions of dollars.” But he provides no evidence that the current system is superior to alternatives. In fact, despite the fact that the current system makes the FDA risk-averse and more focused on preventing unsafe or ineffective drugs from getting to market than focused on empowering patients to make informed decisions, “unsafe” drugs nevertheless routinely get FDA approval. In 1997, for instance, the FDA removed fenfluramine after 25 years on the market when reports associated it with heart conditions. In fact, almost one-third of FDA-approved drugs were later flagged or removed from the market due to safety concerns. The FDA itself recognizes that “there is never 100% certainty when determining reasonable assurance of safety and effectiveness.”
But how many patients have suffered – how many have died – because of today’s paternalistic system – one that rewards delay, reduces incentives to innovate, and takes life-and-death decisions away from patients? Our regulatory system can’t ensure safety and efficacy perfectly (no system can), but its extreme attempts to do so reduce people to the helplessness of knowing that promising treatments might exist just out of reach. Well, out of reach of those unable to afford to travel to another country, that is. The ethical conclusion here should be clear: as bioethicist Julian Savulescu writes, “[t]o delay by 1 year the development of a treatment that cures a lethal disease that kills 100,000 people per year is to be responsible for the deaths of those 100,000 people, even if you never see them.”
As for costs, report after report has exposed the expense – both financial and otherwise – that the FDA imposes on patients. The current system in fact costs lives and money that could be saved.
Klugman invokes the thalidomide example – of course; they always do – for why we need to keep the current paternalistic system. But the thalidomide incident actually teaches a different lesson. In 1962, in response to thalidomide, Congress passed the Kefauver-Harris Drug Amendments, which required manufacturers to “provide substantial evidence of effectiveness,” not just safety, for their products. As a result, drugs are now kept out of patients’ reach on grounds not just of safety, but also of efficacy. But thalidomide posed a safety problem, not an efficacy problem. A safety concern was used as an excuse to change the law from one that focused on empowering patients to make safe choices, to a slower, more costly, paternalistic approach that delays availability and erects roadblocks rather than alleviating suffering.
Now, as to Right to Try: when real-life examples of its early success are reported, Klugman’s response is to deny that they are true—and this is frankly bizarre. Dr. Delpassand has testified to Congress that within a year of his state’s enacting Right to Try, he successfully treated 78 terminally ill cancer patients using LU-177, a drug that had successfully completed its three phases of the FDA-approved clinical trials and has been available in European countries for years, but has still not received final FDA approval for sale. I should know, since I’m his lawyer: Dr. Delpassand had administered a successful FDA-approved clinical trial for LU-177 therapy for five years, but was then told by the FDA that he could not add more patients to the trial. Right to Try enabled him to continue administering LU-177 to patients suffering from neuroendocrine cancer after the FDA blocked the trial’s expansion. His patients were exceedingly grateful. One said that without Right to Try, he “would have had to go on disability to make trips to Switzerland.” Another said he “would have traveled to Switzerland for this same treatment and follow-up appointments every three months,” but thanks to Right to Try and Dr. Delplassand, he was able to stay in the United States and spend the time with his wife and kids. “This law,” he told me, “has been a life saver!”
Who is the FDA, Klugman, or anyone else to deny these patients their choice?
Supporters of the status quo often answer that the FDA already provides alternative paths to access: specifically, its clinical trial or expanded access programs. But the sickest patients often don’t qualify to participate in clinical trials, and those lucky enough to be granted admission may be given a placebo.
Even the FDA implicitly recognizes the inhumanity of its own system – after all, it calls the exception to the system “compassionate use.” Klugman repeats the FDA’s common refrain that it approves 99% of all “compassionate use” requests – and that may be true, but this statistic is an illusion, because it ignores how many patients don’t submit compassionate use requests because the approval process is so cumbersome. By the FDA’s own admission, the initial paperwork takes a doctor 100 hours to complete.[i] To administer treatment under this exception, the doctor must abide by burdensome protocols and data-reporting requirements, essentially making him responsible for overseeing a mini clinical trial for that one patient. Then an Institutional Review Board (a separate committee at a medical facility) must weigh the ethical considerations associated with the patient’s use of the treatment – and many meet infrequently. There are other restrictions, too, so that in practice, “compassionate use” is so tangled in red tape that only about 1,200 patients per year are even able to submit compassionate use requests to the FDA – even though over half a million Americans die annually of cancer alone. Razelle Kurzrock, who directs clinical trials at U.C. San Diego says that “it’s almost a self-fulfilling prophecy for the FDA to say they approve everything, because you don’t even put in the application before you sort of get a verbal approval from the FDA that it’s worth doing.” The bottom line is clear: “compassionate use” is false hope.
Nevertheless, Klugman claims that drug makers are the real barriers to access, not the regulatory system. No doubt companies play a role in curbing access, but as I discussed in my last post, companies’ hesitancy to provide treatments is exacerbated by a regulatory system that provides little incentive to help patients in need.
For example, companies fear that the FDA will delay or deny approval of their treatments if they offer treatments outside a clinical trial. And these fears are not unfounded. In 2014, the FDA put a partial hold on clinical trials run by the company CytRx after a patient received treatment through compassionate use and died. As a result of that hold, CytRx stock plunged. Under this system, why would pharmaceutical companies ever provide a drug to a patient outside of clinical trials? Even Dr. Arthur Caplan, director of medical ethics at New York University and critic of Right to Try, has called on the FDA to “put their approach to interpreting adverse events when they occur in the context of compassionate use in writing.” But they won’t.
Klugman says pharmaceutical executives he’s spoken with prefer a system of regulation. Ask yourself why that’s so. For starters, established businesses often support regulation, not in the name of the “public good,” but because it keeps out competition. The current clinical trial system benefits drug companies by letting them hide behind the FDA as a gatekeeper when making decisions about whether or not to provide treatments to patients. This lack of transparency allows the FDA to blame the manufacturers, and manufacturers to blame the FDA. As a result, nothing changes, and it’s the patients who suffer.
Klugman also opposes measures like Right to Try on the grounds that investigational treatments may be prohibitively expensive, so not everyone can afford them. That’s why charities – like that founded by Overstock CEO Jonathan Johnson – are already being formed to help patients pay for treatments.
But aside from that, does it make any sense to address this perceived disparity by denying access to all? Our current system caters to the wealthy and well connected – they have the means to travel overseas to get treatments that poorer patients can’t get in the United States, or the political or economic influence to get treatment prior to full FDA approval. Right to Try simply extends that option to everyone.
I think it’s strange that Klugman and Alison Bateman-House are so vehemently opposed to Right to Try. After all, in one sense Right to Try isn’t very radical – it doesn’t even permit self-medication, the topic of this month’s discussion. And far from seeking to “dismantle the FDA,” it’s designed to work alongside the existing clinical trial process. It only applies to drugs that have received FDA phase 1 approval, and are currently being given to patients by the FDA itself. Nor does it disrupt the process whereby the FDA reviews investigational medicines. And it only applies to terminally ill patients who’ve exhausted government-approved options and have the support of their doctors. It just affords these people the same access that the FDA is now allowing clinical trial patients. It’s certainly no cure-all. It’s not even particularly libertarian. It’s just one important step in the right direction.
But Right to Try’s greatest success has been to shine a light on patient autonomy. Suffering patients have been yearning for FDA reform for decades, but it wasn’t until the Right to Try movement that the FDA was forced to acknowledge the difficulty patients face in securing treatments. Last April, the FDA announced it was establishing a new position called a “compassionate use navigator” – a person who will guide patients through the FDA’s labyrinthine application process (the Agency is only now, over a year later, rolling out its website). Also in 2016, the Agency announced that it had streamlined its compassionate use process – again, nearly a year and a half after it had first publicized its intention to do so – purportedly reducing the paperwork burden of filing a compassionate use petition.
These improvements are welcome, and they’re a clear indication that Right to Try has transformed the national conversation about the rights of patients. But shorter forms and hand-holding bureaucrats don’t fix the system’s fundamental flaw, one Jessica Flanigan has highlighted this month: it requires patients to get the government’s permission slip to obtain treatment to save their lives. Lives that are theirs. Not the government’s. Not yours or mine. But theirs.
I emphasize this point for a simple reason. In all this talk of scientific protocols and administrative agencies, the one thing we must never lose sight of is that the life – the suffering and the joy – belongs to the patient, not to anyone else. If we can’t experience the consequences of those choices the way she can, what right have we to dictate her choices? What right have we to control such a fundamental aspect of another person’s being? The answer is: we have none. The life is the patient’s – the consequences of choices are the patient’s, and the decision is therefore the patient’s. Our drug approval system should teach, aid, and empower patients, not dictate to them the terms on which they will live, or not live, their lives.