President Donald J. Trump raised the national profile of controversial “right-to-try” legislation by throwing his support behind it during his recent State of the Union Address.
The legislation would let dying patients access experimental therapies with minimal US Food and Drug Administration (FDA) involvement, and with the president’s backing supporters are hopeful that their time has come.
But opponents say it would set a dangerous precedent — opening vulnerable patients up to financial exploitation and barely proven therapies — and they note that even industry might not want to see such a bill signed into law.
The battle lines have been drawn, even as FDA officials are reportedly negotiating with congressional sponsors of right-to-try bills to strike a balance.
Patient advocates — starting with the AIDS epidemic in the late 1980s — have long said that the FDA is a bureaucratic logjam that prevents access to potentially life-saving products. One group, the Abigail Alliance for Better Access to Developmental Drugs, sued the FDA in 2003, saying that it had breached patients’ constitutional right to try a dozen investigational cancer drugs. An appeals court ruling against the Abigail Alliance was eventually upheld by the Supreme Court of the United States.
But those who believe in the “right to try” have never given up — even if the effort has largely been driven more recently by libertarian-leaning think tanks, and not physicians or patients. The Phoenix-based Goldwater Institute wrote a model state law that has been adopted by 38 states since the first one — Colorado — did so in 2014. However, the state laws have no real standing because the federal Food, Drug, and Cosmetic Act governs the use of medical therapies. Supporters have been seeking an overarching federal law — and got one in August 2017, when the Senate passed the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 (S.204).
House leaders have said they want to bring that bill to the floor soon.
A letter spearheaded by the Goldwater Institute and signed by 20 other health organizations — including the Abigail Alliance — was sent to the House last September seeking its support of the Senate bill.
Patient Self-determination
Salvatore J. Giorgianni Jr, PharmD, a scientific adviser to the nonprofit Men’s Health Network, said his organization supports right-to-try efforts, with caveats. Patients’ rights to self-determination have been minimized, Giorgianni told Medscape Medical News. “The patient should be more front and center in this process,” he said.
Under the FDA’s current rules, a patient with a serious or life-threatening condition requires a physician to guide the process. The physician determines whether the risk from the investigational therapy outweighs the risk from the patient’s disease. The clinician then approaches the manufacturer to obtain the drug; the company is not required to acquiesce. If the company does agree, the physician then submits the request to the FDA, using a single-page form. Once approved by the FDA, a single institutional review board member has to sign off on the clinician’s request.
The agency says it approves 99% of the requests in hours, if not days. About 11% of the requests are modified, usually in favor of protecting the patient. The agency requires clear labeling on the investigational therapies, prohibits promoting or commercializing investigational products, and limits how much patients can be charged.
But the process is not without flaws, says Giorgianni. “The treating physician has to agree to engage in what can be a long and bureaucratic process,” he said, adding that they can also be uncertain about the liability they face. It takes time to fill out the paperwork and then engage with the manufacturer. And the FDA approval is not always quick. “It sometimes can be rapid and sometimes can be slow,” he said.
The Senate bill would exempt from the FDA Act those who provide unapproved, investigational drugs to a patient who has been diagnosed with a life-threatening disease or condition “who has exhausted approved treatment options and is unable to participate in a clinical trial involving the drugs,” according to a bill summary. Patients could seek any therapies that had completed at least a phase 1 study.
The manufacturer must report annually to the FDA on safety issues encountered with right-to-try users. The agency is required to post an annual summary of that data.
Manufacturers, prescribers, and pharmacists would be indemnified from legal action.
If it sounds similar to the current FDA process, that’s because it largely is — with the exception that the FDA would not be involved in approving the application to use an investigational therapy.
The Men’s Health Network was not among the cosigners of the Goldwater Institute letter that urged the House last September to approve the Senate right-to-try bill. The network does not endorse any specific legislation, said Giorgianni. It has outlined some principles that need to be followed — and that includes protecting the integrity of the FDA approval process and preventing financial exploitation of vulnerable patients; all of this could be accomplished through legislation that adjusts the FDA expanded access program, he said.
“If we called this ‘compassionate protocol enhancement,’ it might be viewed differently,” he said, adding that perhaps “right to try” was a misnomer that put off organizations that might otherwise support the effort.
First, Do No Harm, Say Opponents
The National Organization for Rare Disorders (NORD) is not convinced, and said it would not support the federal legislation as written. NORD recently joined several dozen other patient advocacy and medical organizations — including the American Society of Clinical Oncology, Friends of Cancer Research, The Leukemia & Lymphoma Society, the Myotonic Dystrophy Foundation, and the United Mitochondrial Disease Foundation — in urging against passage of any federal right-to-try bills.
Not only would the bill not do what it purports to do — increase access to investigational therapies — but, “we believe actually it could harm our patients if enacted,” Paul Melmeyer, NORD director of federal policy, told Medscape Medical News.
The FDA plays an important role in protecting patients by helping to determine if the benefits of the therapy outweigh the risks, if clinical trials would be harmed, and if the proposed dosing and administration are appropriate for that patient, Melmeyer said.
Melmeyer, like other critics of the effort, said that manufacturers are in the driver’s seat in the current process and would be under proposed legislation too. They can refuse to grant access to an investigational therapy for any reason: if they think they can’t make enough to meet demand or are concerned about liability or how the FDA might weigh adverse events that occur when it comes to considering final approval.
The drug industry as a whole has not actively spoken up about right to try. Alison Bateman-House, PhD, MPH, an assistant professor of medical ethics at NYU Langone Health, said the companies she works with as an ethics consultant — including Johnson & Johnson’s Janssen unit and Cytokinetics — are not interested in a process that would exclude the FDA or minimize its involvement.
One executive, Kenneth I. Moch, president and CEO of Cognition Therapeutics, publicly expressed his opposition at an October 2017 House Energy and Commerce Health Subcommittee hearing. “While I am a strong supporter of expanded access programs, I am NOT a supporter of Right-to-Try legislation,” he said, calling it “feel-good legislation which gives false hope to patients in need, without actually helping them.”
Moch, who is on the board of directors for BIO, the biotechnology industry trade association, agreed that manufacturers, not the FDA, were the obstacle.”The decision as to whether or not to grant an expanded access request falls to the leadership of the company developing the new medicine, not the FDA,” he said.
FDA as Scapegoat?
Those who are against right to try say that the FDA is at the center of a problem it has not created. “The FDA is not the obstacle,” said Bateman-House, in a recent briefing sponsored by the advocacy group Breast Cancer Action. “The obstacle, as far as we can tell, is the actual companies.”
Erica Lessem, MPH, deputy executive director with the Treatment Action Group, a New York-based patient advocacy nonprofit, agreed that it is usually the manufacturers who do not want to give access to their experimental therapies.
“Right to try not only addresses the wrong problem but is completely misleading,” said Lessem, at the same briefing. “It confers no rights to patients. It does confer some rights to drug companies,” she said.
Bateman-House was recently joined by more than 300 other ethicists who urged the House Energy and Commerce Committee to vote against the Senate right-to-try proposal and several other House proposals under consideration.
Even opponents like Bateman-House and Lessem agree with right-to-try advocates that the FDA’s expanded access process could use a number of tweaks. It is still largely invisible to physicians and patients, and can be cumbersome, even with the agency’s recent efforts to streamline the process, they say.
“There’s still plenty we can be doing to actually increase the visibility of expanded access opportunities,” said Melmeyer.
Bateman-House agreed that the program is a black box. “That’s the biggest problem,” she told Medscape Medical News. Physicians and patients are unfamiliar with the program and have not been taught how to apply and go through the process, she said.
The FDA received about 1500 requests for expanded access in 2017, with about half of those from individual patients and half from protocols that covered anywhere from two to 50 patients each, said Bateman-House.
But those numbers don’t tell the whole story. That’s something both sides agree on.
“We have no idea how many people ask their doctors to help them get access to investigational drugs,” said Bateman-House. No one knows how many times those requests were turned down by doctors or how many times drug companies accepted or rejected physicians’ requests, she said.
It is only known how many requests go into the FDA, and how many make it out.
And even if the FDA approves the request, it isn’t always used, as the patient could have died or changed their mind about using the experimental product, she said.
Supporters of the right to try contend that thousands of patients die waiting for a drug or vaccine that could have saved them, if only the FDA had approved it more quickly.
“The need is real,” said Lessem, who cautioned against creating a sense of false hope. “But it’s not like there are all of these drugs that could magically cure everybody, and we just need to get the FDA out of the way,” she said.
