Weighing the Merits of Right-to-Try Laws and FDA's Expanded Access Program
Alison Rodriguez and Mary Caffrey
Just a month before attendees gathered in Philadelphia, Pennsylvania, for the annual meeting of Patient-Centered Oncology Care®, legislators in the state’s capital of Harrisburg made it the 38th to pass a right-to-try law. That was 6 states in 2017 alone.1 Championed by conservative groups like the Goldwater Institute as well as Vice President Mike Pence,2 the laws sound good on their face: they can connect terminally ill patients with experimental treatments; even opponents say the idea of giving dying patients “one last chance” is hard to oppose.
But as panelists discussed during the session presented by The American Journal of Managed Care®, these state laws are not necessarily good for patients or long-term drug development, and there is a better alternative: the FDA’s newly streamlined Expanded Access program, which allows patients to gain access to investigational therapies in a more regulated way, with greater accountability. Thus, there is great concern about a proposed federal right-to-try legislation, including a version that has passed the United States Senate.
The panel featured W. Kevin Kelly, DO, director of the Division of Solid Tumor Oncology at the Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia; Marjorie A. Speers, PhD, executive director for the WCG Foundation; and Diana Zuckerman, PhD, president of the National Center for Health Research, board member of the Reagan-Udall Foundation.
As Speers explained, the Expanded Access program began decades ago during the AIDS crisis, when patients demanded protocols be established for those not enrolled in a clinical trial who wanted to try a potentially life-saving medication when nothing else was available. Once FDA approves a request, the patient’s doctor supervises administration of the drug as an extension of an ongoing clinical trial, with significant reporting requirements. The modern proliferation of right-to-try laws has occurred even though FDA has streamlined its process and increased its approval of individual Expanded Access applications, from 1200 to 1500 in recent years, she said. “There has been a lot of attention and pressure on the FDA to make more of these drugs available,” Speers said. “And much of that has been through social media.”
Zuckerman said that so far, state-level right-to-try laws have not had a significant effect, but the proposed version of a federal law could do harm by letting patients obtain drugs independent of the FDA. The Senate version was amended so that drug makers are not required to sell investigational drugs to patients outside of clinical trials, but if they do, they must report adverse events to the FDA.2 Typically, patients receiving investigational drugs while they are going through FDA approval can only be charged for the drug’s manufacturing cost, and patients usually receive them for free. Zimmerman said an early version of the bill did not cap sale prices, but the bill that passed the Senate only allows pharmaceutical companies to charge manufacturing costs.2 Still, if patients obtain drugs this way, there are far fewer requirements than there are currently under the FDA’s Expanded Access program.3
And this appears to be central to the appeal: Right-to-try laws purport to cut the FDA out of the picture, connecting patients directly with pharmaceutical companies to reduce burdens on patients and physicians, if drugs have cleared phase 1 safety hurdles. But some see this as a threat to the drug development process; FDA’s Expanded Access requires at least some evidence of efficacy in addition to phase 1 results.
Speers discussed the 3 categories of use under the FDA’s Expanded Access program. Applications can be submitted for (1) individual patients, (2) intermediate-size patient populations, (3) wider treatment use ahead of distribution after approval.
Because this process includes patients with life-threatening diseases, Speers noted that the FDA has ensured transparency in the process of
accessing the necessary experimental drugs. Therefore, a patient must complete an application, and a specific judgment about the individual patient is made by the FDA. The agency also can also review the requests with a clinical trial’s Institutional Review Board.
Speers also discussed the accessibility of experimental medications for patients through the Expanded Access program. Some of the issues raised through the expansion of right-to-try laws concern the low number of patients who take part in clinical trials—it’s only about 10%.
“There are things that we can do to move trials along more quickly, and it’s across a whole range of things: recruitment, data, and design, and what’s required as a standard to make the decision. That’s I think where we want our emphasis to be, and for this to be a smaller program but remove those barriers that can be removed from it,” she said.
Kelly, a clinician, emphasized the importance of safety when evaluating patients for investigational drugs, considering that many clinicians would not have experience in administering these drugs.
“Can we get more expansion protocols to expand to more patients, [and] decrease the eligibility criteria, so we can treat these patients on a study [by] physicians who actually know how to use the drugs?” Kelly asked.
Still, he has seen both sides of the issue. “I spent several years at the FDA on the advisory committee, so I know the safety issue that they grapple with,” he said. “But being on the front line, it’s a lot different. I have patients coming to me to all the time asking me about investigational drugs. Some are appropriate, some are not ... And it’s a lot of education that the patients actually need to understand what is their disease, what are the treatments, and what is a reality.”
The rise of checkpoint inhibitors offers a great example, he said, in that there are significant toxicities involved—if a physician has never seen them he or she might not know how to handle them. To expand access and knowledge among clinicians, collaborative databases should be developed so data can be shared among a large range of individuals.
Zuckerman also noted the importance of physicians and patients report- ing the serious adverse events from individual patient uses of investigational drugs. In the Expanded Access program, physicians administer the drugs on behalf of the FDA and there are significant reporting requirements, which demands accountability, according to Zuckerman.
“I think we really should focus on education for physicians who want to use an investigational drug through Expanded Access,” she said.
Despite the risks and challenges involved in administering these inves- tigational drugs, Zuckerman said there are ways to streamline the application and monitoring process, so that safety can still be the highest priority while making it easier for patients and physicians to participate.
Each panelist expressed the issues and potentially negative effects of the federal right-to-try laws. Each concluded by offering an ideal system that would address the different concerns. Zuckerman proposed a simpler system that makes it easier for patients, Speers proposed limiting the use of expanded access until after a drug has been approved by the FDA but before it is on the market, and Kelly proposed a patient-centric system that provides patients with a direct source for information.