Imagine that you are dying of cancer — or worse, your child is — and you find out about an experimental drug that might, just might, be a lifeline.
Now you can understand why, over the last three years, 33 states have passed laws entitling terminally ill patients to try unapproved drugs that have completed preliminary safety testing. In many of the remaining states, including Pennsylvania and New Jersey, "right-to-try" bills have been proposed. And in February, federal legislation that would bolster state laws was introduced in the House and Senate. It is backed by President Trump and Vice President Pence, who as governor signed Indiana's statute.
"Americans – our constituents – should have every opportunity to fight for their life, or the life of their loved one," said Rep. Brian Fitzpatrick (R., Pa), a cosponsor of the House bill.
The right-to-try concept sounds like humane common sense. Advocates point to patients who were saved by "compassionate access" to unapproved drugs — and others who might have been.
But critics – physicians, scholars, the pharmaceutical industry – see the laws as misguided and misleading. They imply that eliminating the Food and Drug Administration's oversight will guarantee access to unapproved drugs — even though the laws don't obligate drug developers to provide an experimental therapy. If they do, they can charge patients for the costs, which can reach many thousands of dollars, and which health insurers don't have to cover. Insurers may not even have to cover complications from trying the drug.
New York University bioethicist Arthur Caplan says the laws are "utterly inadequate for helping the dying and the desperate."
"Politicians know a surefire winning issue when they see one," Caplan wrote in one of his many scathing critiques. "They would better be described as 'right to beg' laws — a right which, sadly, the terminally ill already have and already use in social media campaigns."
'Eager to help'
To get approved by the FDA, an experimental drug must go through a series of increasingly large and costly clinical trials – the first focused on safety, the second on effectiveness, the third a big, confirmatory study. For oncology drugs, the process typically takes a decade and costs about $70 million.
The FDA lets drug companies grant compassionate access to patients who don't qualify for clinical trials or live too far from a test site. First, the treating physician must submit a request to the company; if it says yes, the physician applies to the FDA for permission to proceed.
Why would a company deny a dying patient a chance for hope?
Lots of reasons. The company may be a tiny start-up with no system for managing requests. Or it may have no extra supply of the experimental drug. Or it may fear bad publicity — even an interruption of clinical trials — if a patient is harmed by compassionate use.
Despite these complexities, the Goldwater Institute, a Phoenix-based libertarian think tank that developed the template for right-to-try laws, suggests that regulators are the problem.
"Over one million Americans die from a terminal illness every year," the institute says on its website. "Many … struggle in vain to get accepted into a clinical trial. Unfortunately, FDA red tape and government regulations restrict access to promising new treatments, and for those who do get access, it's often too late."
In fact, the FDA approves almost all compassionate-use requests, typically in a matter of days – or immediately over the phone in urgent cases, associate commissioner Peter Lurie testified last year before a Senate committee. In the previous six years, the agency approved 99 percent of applications, an average of 1,200 a year.
The FDA acts as a safeguard, Lurie said, noting that the agency made safety tweaks such as changing dosing in 11 percent of applications.
"Even patients with life-threatening diseases and conditions require protection from unnecessary risks, particularly as … the products they are seeking through expanded access are unapproved – and may never be approved," Lurie said.
"The FDA's role is fairly minimal" in compassionate access, said Svetomir Markovic, a hematologist-oncologist at Mayo Clinic in Rochester, Minn. "They're usually extremely eager to help. I've dealt with them for 20 years, and they have never been the obstacle."
Still, the right-to-try movement has challenged the status quo.
In the face of criticism, the FDA has made its process less cumbersome than it once was. Last year, for example, the agency streamlined the application form, reducing it from an eight-hour time commitment to about 45 minutes, Lurie said.
What's more, the idea of companies' granting individual compassionate-use requests without regulatory oversight is not far-fetched. The European counterpart to the FDA, the European Medicines Agency, says on its website that when a doctor obtains access to an experimental drug for an individual patient "the agency does not need to be informed."
'They use good science'
Frank Burroughs of Lorton, Va., has a deep, wrenching understanding of the conflicting needs inherent in compassionate access.
His daughter, Abigail, was 21, a college honors student, when her head and neck cancer became life-threatening. They sought access to two experimental drugs that targeted a mutation driving her cancer, and thousands of people wrote letters to pressure the companies. But both ImClone and AstraZeneca refused, largely because their drugs were not being tested in head and neck cancer.
The ImClone drug, Erbitux, was approved to treat metastatic head and neck cancer in 2011 — a decade after Abigail's 2001 death became an impetus for the right-to-try movement.
Inspired by his daughter, Burroughs founded a nonprofit advocacy group, the Abigail Alliance for Better Access to Developmental Drugs. It unsuccessfully petitioned the FDA and then fought in court, arguing that terminally ill patients have a constitutional right to access experimental drugs. Ultimately, a federal appellate court rejected the argument, and the U.S. Supreme Court refused to hear an appeal.
Today, Burroughs talks about accelerating the whole clinical trials process, as well as creating a provisional approval mechanism to expand access to promising drugs. He sees right-to-try laws as "a step forward" — but not a solution.
"We need to get these drugs approved much earlier," he said in an interview. "But we don't want to dismantle the FDA. We agree they use good science."
The proposed federal legislation would limit the FDA's authority in unprecedented ways.
First, it would bar the FDA from interfering with state right-to-try laws. Right now, legal experts believe state measures are hollow because they are pre-empted by the federal law that empowers the FDA.
Second, the FDA would be forbidden from using "outcomes" of a drug taken under right-to-try laws — even deadly side effects — to delay or deny approval of the drug. Drug-safety experts say that would put the FDA in an impossible bind, because its job is to consider all safety data when deciding whether to prove a drug, and to add warnings about risks.
The federal bill also says doctors and drug companies would bear no liability for bad outcomes.
On Tuesday, the American Society of Clinical Oncology, with 40,000 cancer professionals worldwide, put its opposition on record. "We don't support right-to-try legislation because these laws ignore key patient protections without actually improving patient access to investigational drugs outside of clinical trials," said ASCO chief medical officer Richard L. Schilsky.
In a statement, PhRMA, the powerful pharmaceutical-industry lobby, sounded unsupportive: "The FDA plays a critical role in evaluating the safety and effectiveness of prescription drugs. … Any legislation should protect the integrity of clinical trials and the FDA oversight of expanded access to maintain the best interests of patients."
Merck, the pharmaceutical giant, has also taken a dim view: "While well-intentioned, current 'right-to-try' legislation is not in the best interest of patients and is unlikely to help us bring forward innovative, safe and effective medicines as quickly as possible. In addition, we remain supportive of the FDA having an oversight role in the process around expanded access to investigational medicines."