To Try or Not to Try: The Impact of Right-to-Try Laws
Melissa Gamble, BA
PharmD student, Skaggs School of Pharmacy and Pharmaceutical Sciences
University of Colorado Anschutz Medical Campus
Right-to-try laws, currently approved in 37 states, allow terminally ill patients who have exhausted all other options to try experimental agents that have successfully passed phase 1 drug trials.1 In oncology, phase 1 trials generally test novel therapies in patients with cancer who have exhausted standard-of-care treatment options in order to gather data on general safety and toxicity and recommended drug dosing for phase 2 studies. Efficacy is not a focus of phase 1 studies. Right-to-try legislation bypasses important government safety measures, including the Food and Drug Administration (FDA) expanded-access application process and institutional review board (IRB) review. Reporting of adverse drug events and evaluating use in patients is not mandatory, according to these laws. The laws restrict liability to the patients alone and do not require manufacturers to provide access to drugs. At most, they can shorten the time to drug acquisition in exchange for reduced patient protection and a disregard of societal well-being. In short, right-to-try laws, including the recently proposed federal legislation, the Trickett Wendler Right to Try Act (H.R. 878/S. 204), do not add any new material to the FDA’s expanded-access program already in place for these patients (Table 1 – see this article in the PDF). (See also the update in "Legislative News." )
Impact on Patients
The right-to-try laws provide little benefit to patients for whom experimental agents are warranted. Proponents of these laws, citing the need for greater patient autonomy, do not believe that patients should need government permission for access to drugs that may save their lives. Though respect for patient autonomy is a fundamental concept of medicine, it is not as simple as allowing patients to make their own decisions. Autonomy should also include the provision of medical guidance for patients so that they understand the situation adequately for informed decision making.3 Physicians must provide this autonomy in balance with their duty to do no harm. If a physician determines that treatment with an experimental agent is appropriate and applies for the FDA's expanded-access program, two safety measures are in place. Also, the denial of experimental agents by the FDA is rare, with more than 99% of patients getting approved.4 However, if the benefit of an experimental drug does not outweigh the calculated risk, a physician may deny the patient’s request to use it. Patients have the right to seek out a physician willing to provide them the opportunity, even if it is not in their best interest. With FDA regulatory processes in place, an unethical request would be denied. Elimination of these processes could lead to an increased risk of harm to the patient.
Supporters of right-to-try laws argue that bypassing government approval reduces the patient’s time to drug acquisition. Though the process was cumbersome when these laws were first suggested, the FDA recently sped up the processing of expanded-access applications with a new form (FDA form 3926) to an average time of 4 days in non-emergent cases and within hours for emergent cases.5 The second component of government approval includes the IRB review, which can take longer for non-emergent cases but can be circumvented in emergent cases.6 Still, the reality is that the drug manufacturer approval is what lengthens the time to experimental treatment after the expanded-access application has been approved. Right-to-try laws do nothing to shorten this amount of time. The benefit of reducing days to treatment by 2 days may not outweigh the risks associated with a lack of patient protection normally provided by FDA oversight, especially in emergent situations.
Access to experimental drugs remains a major barrier for patients, even with right-to-try laws. First, the laws do not guarantee that the manufacturer will provide the drug to the patient. Therefore, these laws do not ensure the right to try but instead allow the right to petition. In the current FDA regulatory process, patients are already allowed the right to petition with oversight. Laws are already in place to help patients gain access to medications. The 21st Century Cures Act, a federal law enacted in December 2016, requires drug companies to be more transparent about how they decide which patients get access and the approximate time needed before attaining the investigational agent.7 The right-to-try laws are not set up to augment access from the drug manufacturers regarding time or cost. Also, these laws do not require health insurance providers to cover the cost or provide assistance for experimental agents.5 Without the means to afford or reduce the inevitably high drug cost, most patients cannot access these medications anyway. In fact, an unintended consequence of right-to-try laws could include a disparity between those who can and those who cannot afford experimental agents. Therefore, right-to-try laws do not introduce any new component to compensate for the lack of access or the affordability of drugs and could potentially increase the inequality between the wealthy and the poor.
Impact on Providers
Providers are also affected by proposed right-to-try laws. Currently, physicians must take the time to apply on behalf of the patient to the FDA and IRB. Right-to-try laws aim to reduce physicians’ effort, time, and liability by eliminating the need to report to the FDA and IRB. They allow a physician in good standing to request access to experimental medications, assuming all other options have been exhausted, without government intervention or follow-up. The belief is that physicians will be able to recommend experimental treatments for patients without fear of repercussions from the state medical board if complications occur.8 However, this freedom and lack of liability are not harmless. Although advocates for these laws view the regulatory processes that physicians must adhere to as obstacles, those against the laws consider them safety measures. Providers, whether unintentionally or not, may not be as rigorous in their efforts to provide the safest care to their patient. Their integrity may falter if they do not have to answer to anyone.
In addition to FDA and IRB approval, physicians must inform these entities about adverse drug reactions that a patient may experience while on the medication. According to the right-to-try laws, physicians would no longer have to follow up on the adverse effects that a patient may experience because of experimental agents.5 This could have major implications for future patients. Reporting of adverse drug events is a major way to gather safety information that would otherwise not be available for informed decision making. Pertinent information could be excluded from discussions surrounding the use of a drug that could cause avoidable harm. Providers would have to make recommendations in the absence of more complete safety data that could affect their decision to treat a patient or not. Right-to-try laws may claim to improve patient autonomy, but they certainly can interfere with providers’ foremost goal of beneficence.
Impact on Society
Right-to-try laws may be detrimental to society as well. Although these laws attempt to foster individual patient autonomy, they pose an indirect threat to randomized controlled trials. Patients may choose to obtain an investigational drug directly from the drug company without enrolling in clinical trials in order to avoid receiving a placebo and to reduce the time commitment. This choice could slow down the clinical trial process, especially for diseases or conditions that affect a small patient population.6 The progress of phase 2 and 3 clinical trials that will show proof of efficacy and safety for these drugs will be compromised. It will take longer to develop products that could benefit larger patient populations and may even cost more in the end to produce effective agents. Such a result would have a large impact on public health, effectively undermining future medical developments.
Right-to-try laws were not created to balance individual risk with societal risks. Supporters argue that certain individuals may be excluded from randomized controlled trials, which prohibits them from receiving a drug that could save their life. If patients can get the medication directly from the drug company, they will not have to waste time trying to enroll in clinical trials that the FDA may recommend prior to using the expanded-access program. As previously stated, bypassing the FDA program means that reports of adverse drug events will not be available. The gathering of important safety and efficacy data is not guaranteed. These laws allow potentially harmful events that occur when an individual uses an investigational drug to go unreported. Proponents argue that representatives of drug companies worry that reporting adverse events associated with their experimental agents will diminish use by other patients or even lead to denial of the agent for the market.5 Yet these drugs have very serious side effects that should be made known to the public. Permitting vital knowledge to go unreported neglects public well-being. The advocates of right-to-try laws do not account for actions that put the rest of society at risk.
The FDA’s current expanded-access program is still the most appropriate available option for patients seeking investigational agents. The FDA considers the likelihood of effectiveness and risk of harm on an individual basis without compromising public health. It requires reporting of adverse drug events to consolidate safety data on the experimental agents. The application process has been expedited to simplify the form and reduce the time burden. Furthermore, more than 99% of patients are given permission to proceed with investigational drug use.4 The current process preserves the progression of investigational agents within clinical trials and the quality of medical care. The FDA prohibits drug companies from charging more than the manufacturing cost, and manufacturers rarely charge for compassionate-use medications under the expanded-access programs for fear of criticism. In conclusion, right-to-try laws do not break down the main barrier to access from the drug manufacturers, may impede medical progress, and raise concerns about proper oversight. The Trickett Wendler Right to Try Act would offer no added benefit to patients in comparison with the FDA’s expanded-access program.
1. FAQ—Right to Try National Movement for Terminal Patients. Available from http://righttotry.org/faq/
2. Holbein, ME, Berglund JP, Weatherwax K, Gerber DE, Adamo JE. Access to investigational drugs: FDA expanded access programs or “right-to-try” legislation? Clin Transl Sci. 2015;8(5):526-32.
3. Newman E, Kaloupek D. Overview of research addressing ethical dimensions of participation in traumatic stress studies: autonomy and beneficence. J Trauma Stress. 2009;22(6):595-602.
4. Expanded Access to Investigational Drugs for Treatment Use—Questions and Answers: Guidance for Industry. Available from www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM351261.pdf
5. Yang YT, Chen B, Bennett C. “Right-to-try” legislation: progress or peril? J Clin Oncol. 2015;33(24):2597-99.
6. Lurie P. 2016. Committee on Homeland Security and Government Affairs Hearing Testimony, US Food and Drug Administration. Available from https://www.fda.gov/NewsEvents/Testimony/ucm522044.htm
7. Hudson KL, Collins FS. The 21st Century Cures Act—a view from the NIH. New Engl J Med. 2017;376(2):111-13.
8. Feibel C. 2017. Patients demand the ‘right to try’ experimental drugs, but costs can be steep. Available from www.npr.org/sections/health-shots/2017/03/03/517796956/patients-demand-the-right-to-try-experimental-drugs-but-costs-can-be-steep