By Jennifer Paul Cohen, M.S. Candidate in Bioethics, Columbia University
There is a determined and thus far extremely successful effort in this country, endorsed by both the FDA and the pharmaceutical industry, to enable terminally ill patients to obtain drugs which have not been approved by the FDA. A recent development in this trend is right-to-try laws passed by state legislatures that are designed to provide patients access to nonapproved drugs directly from drug manufacturers.
The first right-to-try law passed in 2014 in Colorado, and since then 32 states have passed one. These laws reflect the perception that the FDA is holding back both innovation and life-giving drugs from people facing a terminal illness who are desperate to try them.
Contrary to the promise contained in their names, right-to-try laws do not establish any rights for or impose any obligations on patients, physicians, pharmaceutical companies, or the FDA. But they have three extremely problematical features:
- These laws are redundant, as the FDA already has a process that allows terminally ill patients to obtain these drugs. Consequently, these laws are most likely unconstitutional, as they violate the Supremacy Clause of the U.S. Constitution, therefore placing at risk patients who are obtaining drugs as a result of these laws. This violates the ethical duty of beneficence and nonmaleficence, as well as the duty of truth-telling, which respects the patient’s autonomy.
- Secondly, by skirting the FDA’s regulatory authority, these laws diminish the requirement that medicines be safe and effective and undermine the authority and legitimacy of the FDA.
- Finally, these laws, which indemnify the doctor, the pharmaceutical manufacturer, and the insurance company from claims of mistreatment, increase the danger of unnecessary overtreatment at the end of life. In the name of providing hope to the terminally ill, they promote unproven therapies with very little chance of therapeutic benefit.
WHAT ABOUT THE EXPANDED ACCESS PROGRAMS?
Right-to-try laws give the impression that no other mechanism allowing access to experimental drugs exists. To the contrary, the FDA has had a mechanism for obtaining such drugs for nearly 30 years. The FDA’s expanded access programs include multiple categories ranging from individual patients asking for an investigational new drug (IND) application that has a 30-day waiting period, or requesting inclusion in an existing IND that does not have a 30-day waiting period, or applications for an emergency IND where treatment can be authorized by telephone prior to written submission. In February 2015, in response to pressure from the right-to-try movement and high-profile cases in the media, the FDA streamlined its policies for obtaining drugs through what the industry refers to as “compassionate use.” The FDA estimates that the revised, one-page form the agency requires should take approximately 45 minutes for a physician to complete. The FDA approves 99 percent of the expanded access requests it receives, and it receives roughly 1,000 requests per year. While this approval percentage rate is high, the argument proponents of state right-to-try laws make is that the numbers of patients applying to the FDA for investigational drugs represent “infinitesimally small numbers of requests.” Darcy Olsen, author of The Right to Try: How the Federal Government Prevents Americans from Getting the Lifesaving Treatments They Need, compares the number of people dying from cancer in 2015 (1,615 per day) to the number of requests the FDA receives (1,200 per year) and concludes that the FDA’s expanded access model is a failure, causing patients to die prematurely. However, the reason for the discrepancy is unclear. We will have to see if the increased publicity around expanded access and the streamlined FDA approval process results in more people applying for experimental drugs.
Another argument against the FDA’s expanded access program is that it slows down the general approval process for a drug. However, the FDA estimates that out of the roughly 10,000 approvals granted under the expanded access program, two drug applications were delayed as a result.
THE FDA NEEDS MORE OVERSIGHT, DATA COLLECTION
The right-to-try laws are an attempt to use state law to nullify the federal law that outlines the FDA’s expanded access programs. The Supremacy Clause of the U.S. Constitution provides that states are bound by federal law. This means that state laws such as right-to-try laws that are designed to evade federal regulations should be unconstitutional. In addition, federal case law does not recognize the right of terminally ill patients to access investigational drugs.
By skirting the FDA’s regulatory authority, these laws diminish the requirement that medicines be safe and effective and undermine the authority and legitimacy of the FDA, whose mandate is to protect and advance public health. A critical function of the FDA is its oversight of the pharmaceutical industry. Rather than reduce the role of the FDA in the expanded access program, the public should be pushing for the FDA to take on more oversight and data collection. The FDA does not know how many of the 10,000 requests for drugs over the last 10 years under the expanded access program have resulted in any therapeutic benefit. A requirement that data from expanded access be reported to the FDA so that safety and efficacy could be optimized would aid in assessing the therapeutic value of the program. Simply assuming that terminally ill patients are facing no meaningful additional risks when they take an unapproved drug is an abdication of the ethical imperative of nonmaleficence and respect for patient autonomy. As Arthur Caplan writes, the perception that drugs that are out of Phase 1 testing are safe is misleading. Phase 1 testing is done on healthy people. He warns:
“Trying an experimental drug on sick people who are already significantly compromised in their health status, and who are receiving myriad other medications, may well kill them more quickly or more painfully.”
GO BEYOND SATISFYING THE DEFINITION OF “LEGAL”
The compassionate use or expanded access systems in place now to make drugs available to terminally ill patients are already ethically problematical, and state right-to-try laws have the unfortunate result of further muddying the waters. The constitutional and misleading aspects of the right-to-try laws are the most troublesome, but the larger issue is the statement they make about the ethical treatment of the terminally ill. By removing the requirement that the FDA approve a request, the laws imply that there is less need for an unbiased, oversight authority to agree that a drug is safe and effective for use. Under the right-to-try paradigm, as long as the company that makes the drug (hardly an unbiased actor) agrees to allow the patient access to the drug (after being indemnified against legal redress) the transaction is legal.
It is critical that a program based on giving investigational drugs to dying patients be one that goes beyond satisfying the low bar of “legal.” Such a program should aim to provide a therapeutic benefit to patients beyond that of hope. The right-to-try movement as well as social media pressure on drug manufacturers has begun an important dialogue on the ethical treatment of terminally ill patients. Drug manufacturers have responded with more transparency and codification of their policies on their websites and, in the case of Johnson & Johnson, the establishment of an outside Compassionate-Use Advisory Committee (CompAC).
The larger ethical dilemma is how far physicians, the FDA, and drug manufacturers want to go in privileging hope for individual patients over proven therapeutic benefit. Olsen admits that we are discussing a system of extremely long odds designed to give patients hope: “Dying patients are not looking for a 100 percent guarantee the drug is effective. They are looking for hope. They are looking for a fighting chance.” The truth is that dying patients will have nowhere near a 100 percent chance that investigational drugs will produce a therapeutic benefit. Without solid data on the patients who have benefited from expanded access and those who have not, it is simply a roll of the dice. The FDA should be collecting such data and continuing its oversight of the expanded access process. Right-to-try laws that remove the FDA as a participant in this ethically challenging area do not represent a step forward.