By ARTHUR CAPLAN, KELLY MCBRIDE FOLKERS, and ANDREW MCFADYEN
A patient with glioblastoma recently received an experimental cancer vaccine at the University of California, Irvine. Notably, this is being hailed as the first case of someone utilizing the Right to Try Act of 2017. ERC-USA, a U.S. subsidiary of the Brussels-based pharmaceutical company Epitopoietic Research Corporation, says it provided its product, Gliovac, to the patient at no cost. The vaccine is currently undergoing Phase II clinical trials. A handful of people in Europe have received access to it through “compassionate use.” This patient did not qualify for ongoing clinical trials in the U.S. The patient, who remains anonymous, is the first known individual to receive an experimental medicine that has not been approved by the FDA, as permitted under the federal right to try law.
Glioblastoma is a nasty cancer – John McCain and Ted Kennedy passed away after battling the disease for just over a year. We believe that patients with terminal illnesses, like those with glioblastoma, should have every reasonable tool at their disposal to treat their disease.
That being said, we’ve argued before that right to try laws are not the best way to help desperate patients. They still aren’t. The number of cases claimed to date is exactly one. And, further examination of what we know about this case does not make a strong argument for the widespread usage of the right to try pathway.
President Trump signed the Right to Try Act into law on May 30, 2018. 41 states have their own version of the law. According to the Goldwater Institute, a libertarian organization that crafted the model bill, right to try is based on the belief that the government should refrain from interfering in one’s ability to access experimental medical products. However, the FDA’s expanded access program, which has existed for over 30 years, facilitates access to experimental medicines for thousands and thousands of patients each year. Right to try proponents claim that the demand for experimental drugs is higher than the expanded access program can accommodate. Their solution was to pass a federal law that allows patients’ physicians to request from manufacturers the use of experimental drugs, biologics and vaccines that have completed Phase I testing without any prior review by the FDA or an institutional review board (IRB), both required by expanded access. By removing these two sources of “bureaucratic delay,” right to try advocates insist that patients can access experimental drugs more expediently. Thus far, the demand projected by Goldwater for drugs under right to try is nowhere to be seen. And despite some glowing media coverage, the speed promised under the right to try law was replaced by a lengthy delay between application and treatment.
A close look at the details of this “first” right to try case shows both the FDA and UC Irvine’s IRB were involved. So why did ERC-USA choose the right to try pathway over the expanded access program? UC Irvine’s IRB states that the institution follows the statutory requirements of California’s right to try law, which mandates more stringent reporting and informed consent requirements than the federal law.
ERC-USA notified the FDA that it planned to treat a patient under the Right to Try Act. The company received an acknowledgement from the FDA in July 2018—nearly six months before the patient started receiving treatment in late November. Right to try proponents have asserted that the FDA’s expanded access program contains unnecessary bureaucratic steps that discourage patients from seeking experimental therapies in the first place. But ERC-USA likely chose to involve the FDA and UC Irvine its IRB to ensure that any provision of an experimental agent to a patient outside of a clinical trial wouldn’t interfere with the product’s clinical development and to confirm that the patient was aware of possible risks and benefits.
Right to try advocates have long argued the expanded access program takes too much time from application to administration of drug for patients. However, the FDA allows over 99% of the applications it receives for compassionate use to proceed. The agency’s mean turnaround time for expanded access requests is between 8 and 26 days. In emergency situations, the FDA routinely approves EA requests within 24 hours. In this “first” case, it is highly likely that this patient would have received drug more rapidly had ERC-USA used the existing expanded access program over right to try.
Finally, it has been reported that ERC-USA has received several other right to try requests, but only one patient has been granted access to its experimental vaccine in the U.S. thus far, raising a host of questions. Why only this one patient? What mechanisms does ERC-USA have in place to ensure equity in granting requests? Who was in charge of adjudicating this request, and how was it prioritized over others? Was there undue influence for this particular patient over others by an outside group? Will safety data be collected and made available as part of their informed consent to future patients who may receive this investigational agent? And if the patient isn’t paying for the vaccine, who is?
Taken together, these factors reveal that this case is not a strong argument, either for the need for a right to try policy or even that a right to try pathway was utilized.
The FDA’s expanded access program isn’t perfect, but it’s improving. Late last year, the agency announced that it would be facilitating expanded access requests with the establishment of a centralized call center for patients and physicians. In an area of healthcare rife with confusion, more centralization means that patients can get their questions answered – and that they will be treated fairly. Under right to try, there’s no guarantee (and no mechanism to help ensure) that patient requests are reviewed equitably, and there is no transparency regarding how companies make decisions about who gets a treatment and who does not. Moreover, reporting requirements for safety and efficacy under right to try are much more lax and less transparent than they are under expanded access. Without such strict and open reporting, future patients will not be as informed as they should be when all seek access to the same investigational agent. For pharmaceutical companies seeking to rapidly bring their potentially life-saving drugs to market, such transparency is necessary to ensure the path to market for patients isn’t derailed.
Patients need pharmaceutical and biotechnology companies to work with the FDA when they provide their experimental products to patients. In addition to single patient access, the FDA can facilitate large cohort expanded access programs, in which multiple patients with the same condition receive early access to an investigational product that might help them. Ironically, the first claimed right to try case only reinforces the notion that the federal version of the law won’t work. Patients need institutions and regulators to work together to give them an equitable and informed choice if they wish to try unapproved treatments.
The authors are members of the Working Group on Compassionate Use and Preapproval Access (CUPA) at the Division of Medical Ethics at the NYU School of Medicine. CUPA members Kay Holcombe, Lisa Kearns, and Kenneth Moch contributed to this piece.