Two right-to-try bills in the House of Representatives that would make it easier for terminally ill patients to use experimental drugs as a last resort have put the US Food and Drug Administration (FDA) on a hot seat.
The FDA’s predicament was evident yesterday as the agency announced two improvements to its “compassionate use” program that makes experimental drugs under FDA review available to seriously ill patients. Meanwhile, a House subcommittee weighed the pros and cons of right-to-try legislation that creates an alternative to the FDA process. Bill sponsors assert that the compassionate use program creates barriers for using experimental drugs, although lawmakers heard that more than 99% of applications get approved ― within minutes for emergencies.
The changes to the FDA program, also known as expanded access, are designed not to improve the approval rate but to pump up the number of successful applications, which amount to roughly 1000 per year. The first change would make it less of a hassle for a physician to win permission to treat a patient with an experimental drug. To do so, a physician must receive a green light from his or her organization’s institutional review board (IRB), there to ensure patient safety. That requirement can delay the patient’s receiving the drug, because the full IRB doesn’t meet at the drop of a hat.
In his agency blog, FDA Commissioner Scott Gottlieb, MD, said yesterday that only one designated member of the IRB needs to sign off on the use of an experimental drug, which should make the application process less daunting to physicians.
The other change addresses what Dr Gottlieb calls the biggest obstacle in the compassionate use program ― drugmakers declining to make their products available despite an okay from the FDA. One probable reason why is that pharmaceutical companies worry that any adverse events experienced by a compassionate-use patient may hurt their chances of FDA approval. And these companies aren’t exactly sure how regulators use that adverse-event data, according to a new report released yesterday by the Government Accountability Office (GAO).
The GAO recommended that the FDA provide more clarity on that matter, and Dr Gottlieb obliged in yesterday’s announcement. Repeating what he told the health subcommittee of the House Energy and Commerce Committee yesterday morning, Dr Gottlieb said it’s difficult to determine the cause of adverse events that happen to a compassionate-use patient, who are usually treated outside of a controlled, clinical trial. “They may have more advanced disease than clinical trial participants, be receiving other drugs at the same time, and have other diseases,” he said. Accordingly, the FDA has updated its compassionate-use guidance for industry to say that suspected adverse events must be reported “only if there is evidence to suggest a causal relationship.”
These modifications to compassionate use follow other recent tweaks, such as simplifying the physician application form so it takes only 45 minutes to complete, as opposed to 100 hours, as advertised before.
“The FDA Thinks It Knows Better Than the Doctor”
The occasion for yesterday’s House hearing ― and the seemly preemptive announcement by the FDA ― was a pair of bills that essentially allow an end run around federal regulators when it comes to the use of experimental drugs. They’re coast-to-coast versions of various right-to-try laws enacted by 37 states.
One of the bills, called the Right to Try Act, was passed unanimously by the Senate in August. Under this measure, a patient with a life-threatening disease who has exhausted approved treatments and can’t participate in a clinical trial for a drug under FDA consideration can use that drug if at least a phase 1 clinical trial of the drug has been completed. Dr Gottlieb advised lawmakers that patient eligibility ought to be narrowed down to terminal illness, because the broad category of life-threatening illness includes chronic conditions such as diabetes. A House version of the Senate bill that wasn’t up for discussion applies just to the terminally ill.
The other bill before the Energy and Commerce health subcommittee, called the Compassionate Freedom of Choice Act, resembles what the Senate passed, but with some significant differences. The bill applies to medical devices as well as drugs. Patient eligibility is limited to the terminally ill. And the requested drug needn’t have undergone a phase 1 clinical trial. It only needs to be, or have been, the subject of one or more clinical trials.
Significantly, neither bill obliges pharmaceutical companies to make experimental drugs available to patients. Dr Gottlieb noted that these companies tend to make just enough of them for clinical trials.
Backers of right-to-try legislation at the hearing framed the debate in small-government, libertarian terms. One such supporter was Naomi Lopez Bauman, healthcare policy director for the Goldwater Institute. “Who should ultimately decide what level of risk is acceptable to a dying patient ― federal officials or patients themselves, in consultant with their doctor?” Bauman said in written testimony.
Subcommittee member Rep. Joe Barton (R-TX) also championed the physician-patient relationship over FDA oversight. “It still seems to me the FDA thinks it knows better than the doctor,” Barton said.
However, right-to-try legislation has come under fire from physicians themselves. The American College of Clinical Oncology, for example, believes patients would miss out on FDA patient protections under right-to-try, and not necessarily gain better access to the drugs they want. Lawmakers heard similar criticisms from Alison Bateman-House, PhD, MPH, an assistant professor of medical ethics at NYU Langone Health, and Ellen Sigal, PhD, chair and founder of Friends of Cancer Research.
Several Democratic members of the health subcommittee suggested that the right-to-try bills were solutions in search of a problem at the FDA compassionate use program and its 99% approval rate.
“What I’m struggling to figure out is what’s broken,” said Rep. Anna Eshoo (D-CA). “The FDA has very good figures.”
Added Rep. Gene Green (D-TX): “I’m not convinced the FDA is a barrier to investigational treatments.”