Ethical concerns persist regarding seriously ill patients who want the chance to try unproven, unapproved drugs.

“‘Right to try’ refers to the ethical intuition that persons should be free to access pharmaceuticals, just as they should be free to refuse medical interventions of all kinds,” says Michael Brodrick, PhD, a philosopher at the Institute for Humane Studies at George Mason University in Fairfax, VA. “The freedom to choose an intervention is just the reciprocal of the freedom to refuse it. The right to refuse medical treatment arguably includes the right to access pharmaceuticals.”

However, the right to refuse treatment is firmly established in U.S. law. In contrast, an array of laws and regulations prohibit persons from accessing pharmaceuticals. “Those laws and regulations, therefore, raise ethical concerns,” Brodrick notes. On the other hand, legislation purporting to create a legal right to access pharmaceuticals whose safety and efficacy has not been established raises other ethical concerns. A proposed rule would require companies to report serious adverse effects annually under the 2018 Right to Try Act.1

However, there is no enforcement mechanism for reporting the serious adverse events, and there is no guarantee manufacturers will be compliant, says Lisa Kearns, MS, MA, a senior research associate in the division of medical ethics at NYU School of Medicine and a member of its Working Group on Compassionate Use and Pre-approval Access.

Although FDA approval is not needed under the right to try requirements, the treating physician still has to secure approval from the drug manufacturer. “The manufacturer won’t be excited about doing that, for several reasons,” says Gail Van Norman, MD, adjunct professor in the University of Washington Medicine’s department of bioethics and humanities. First, the drug manufacturer has to complete certain studies to receive market approval. “Typically, they start with healthy people as opposed to seriously ill people who are more likely to have adverse outcomes,” Van Norman observes. “There are also concerns about liability if there are unexpected serious outcomes.”2

One ethical concern is that most people overestimate the odds researchers will determine an experimental drug is safe and effective. “When a drug is in its early investigational phase, the odds that it will ever be approved are very small, about one in 10,” Van Norman says.3

Manufacturers could unintentionally exploit or mislead vulnerable people desperate for cures. “It can be easy to overplay the potential efficacy of your drug,” Van Norman says. “There’s an element of bias and wishful thinking.”

Individuals looking for cures do not automatically become incompetent to make risky decisions on their own behalf. “People taking on personal risks in their own self-interest is a balancing act, ethically. It is very situational-dependent,” Van Norman explains.

Individual rights to try an unproven drug must be balanced with the public good. “Enough people seeking right to try could potentially deplete supplies of the drug meant for studies,” Norman offers. Also, if an adverse event occurs in a patient who took the drug outside a clinical trial, it could lead to negative repercussions for eventual drug availability. “Investors funding that trial might get nervous and stop supporting that drug in development,” Kearns explains.

Right to try also could divert patients away from participating in clinical trials. “That could slow the careful vetting process that must be completed before a new drug can be approved for sale,” Brodrick says.

The Right to Try Act was “unnecessary in the first place,” according to Kearns. Terminally or seriously ill patients have had the ability to access investigational drugs via the FDA Expanded Access (EA) pathway for decades.4 “The Right to Try Act, in a sense, amended the FDA program by eliminating crucial patient safeguards,” Kearns argues.

FDA’s experienced, expert reviewers are best positioned to know whether an investigational drug could cause harm to patients because they can access confidential information about the drug (and similar drugs in development) that no one else can. “Right to try also eliminates institutional review board oversight of both the treatment protocol and — so important — informed consent,” Kearns says.

Although right to try does require informed consent, it does not specify what consent must include. In contrast, the FDA EA pathway mandates that consent align with Code of Federal Regulations requirements.

Additionally, while right to try prohibits charging more than direct costs for investigational products, it provides no enforcement mechanism for this. In contrast, the FDA program requires documentation of charges to ensure drug manufacturers are not profiting from providing preapproval access.

“Without an oversight body monitoring charging, right to try leaves the door wide open to unscrupulous actors. Patients could be charged anything at all,” Kearns warns.

Truly informed consent is difficult to achieve for terminally ill patients seeking access to drugs that have only completed the first phase of clinical trials. Little data on safety (and almost none on efficacy) are available. “According to some experts, consent forms should, among other things, state that the drug is experimental and has not been approved by the FDA,” Brodrick says.5

Safety and efficacy information, if available, and any potential risks and benefits should be disclosed. Alternative options, including palliative care, should be mentioned. Patients who might be eligible for clinical trials should be informed of them. “Finally, consent forms should disclose the cost of the drug and any financial risks to the patient,” Brodrick adds.

Right to try “intentionally errs on the side of removing potential access barriers while allowing patients to assume greater risk of being harmed by unapproved drugs,” Brodrick explains. However, state laws that do not conflict with federal law could provide for third-party oversight of right to try requests.

Drug companies and medical institutions also are adding oversight requirements to the right to try pathway. “Given the coexistence of these two pathways and the different ethical tradeoffs they present, medical institutions and drug companies will have to decide which pathway they should require, or whether they should offer both options,” Brodrick says.

REFERENCES

  1. U.S. Food & Drug Administration. FDA proposes new rule on reporting requirements. July 23, 2020.
  2. Van Norman GA. Expanding patient access to investigational drugs: Single patient investigational new drug and the “right to try.” JACC Basic Transl Sci 2018;3:280-293.
  3. Van Norman GA. Drugs, devices, and the FDA: Part 1: An overview of approval processes for drugs. JACC Basic Transl Sci 2016;1:170-179.
  4. U.S. Food & Drug Administration. Expanded access. Content current as of April 27, 2020.
  5. Chapman CR, Eckman J, Bateman-House AS. Oversight of right-to-try and expanded access requests for off-trial access to investigational drugs. Ethics Hum Res 2020;42:2-13.