My sister Gale had exhausted every option. Metastatic cancer raged through her body, defeating all conventional treatments. She faced a final decision: succumb to the disease, or wage one last battle with an experimental bone marrow transplant known to kill 20 percent of patients. Gale chose to fight, opting to use the unproven therapy at a time when institutional review boards and scientific peer review regulated experimental therapies rather than the Food and Drug Administration (FDA). Now, three decades later, the FDA has an expanded access policy, also known as “compassionate use,” that seeks to ensure the quality of unproven therapies used by dying patients. In Gale’s case, the side effects of the treatment were swift and violent. Within two days, she was dead. Clinical trials have since demonstrated that the therapy had limited efficacy and a greater risk of lethality than reported at the time.

Legislation before Congress seeks to grant all terminally ill patients the “Right to Try” experimental therapies once approved alternatives have failed. Although the FDA authorizes 99.5 percent of compassionate use requests, advocates of Right to Try claim the process is too slow. The FDA has streamlined the current process so that requests are reviewed within 24 hours; filling out an application now takes less than an hour. And yet, Right-to-Try laws have been approved by more than 30 statehouses.

Unfortunately, the current federal legislation provides almost no protections for patients. Everyone with a late-stage terminal illness like my sister deserves the chance to try an experimental therapy. However, serious changes to today’s legislative proposal are needed before this law is safe for patients.

First, provisions for informed consent are essential. Most early-phase drugs are dangerous and ultimately proven ineffective, with upwards of 90 percent never brought to market. Right-to-Try laws allow patients to request from companies therapies that have passed a Phase I trial with the FDA. But this is only a preliminary step in which a small group of patients receive the experimental therapy under carefully controlled conditions. The trial is designed to detail obvious toxicities and identify a tolerable range of potentially effective doses before the drug advances to a larger, Phase II trial. Before the results of that second study, there is no reliable data on whether the therapy works.

Meanwhile, patients like Gale who receive the therapy may risk a sudden and painful death from unanticipated side effects, as early-phase trials rarely evaluate the risks of extended or repeated administration. Key information about the safety or efficacy of experimental therapies is typically not made public until after drug approval. Provisions insuring informed consent would guarantee that patients requesting expanded access can judge the magnitude of their decision.

Second, the limits of Right to Try must be clear. Even if patients receive the right to request an experimental therapy — under the current paradigm or a new Right-to-Try regime — the drug company developing the therapy is under no obligation to provide it.

There are legitimate reasons for this, including supply shortages, a lack of financial incentives, and concerns that negative “compassionate use” outcomes could be used by the FDA to delay or deny approval (which is protected against by the Right-to-Try legislation). Development roadblocks would stop therapies from reaching patients. However, the FDA cannot simply ignore expanded access outcomes. Patients petitioning for expanded access deserve accurate information about whether the potential benefits of an experimental treatment outweigh the risks. What are the side effects? What are the chances of success? This highly personal calculus is impossible if drug companies do not monitor and report side effects.

A key component is transparency. The Reagan-Udall Foundation for the FDA (RUF) is a nonprofit that seeks to enhance the safety and efficacy of new treatments. This year, RUF will launch an Expanded Access Navigator to raise awareness among doctors, and then patients and families, when it comes to the compassionate use of experimental therapies. The Navigator will be piloted in oncology with the goal of increasing the accessibility of information to patients and providers. Meanwhile, patient communities and advocacy groups must come together to help patients understand their options.

Everyone agrees that dying patients should have access to promising experimental therapies when all available options have been exhausted. Right to Try is a path to achieving that goal; in pursuing it, however, we must not subject patients to false hope or unacceptable side effects. Informed consent and transparency—currently lacking from the proposed legislation—are essential. With proper adjustments, federal Right-to-Try legislation could enable very sick patients to access otherwise unavailable drugs.

In its current form, however, Right to Try does nothing for patients other than allow them to request a drug they may never receive and that may be more likely to hurt them than to help them. Unless Right to Try is significantly revised, this law will be a threat to patient health and well-being.

http://healthaffairs.org/blog/2017/03/14/how-do-we-protect-patients-fro…