By Gary Evans, Medical Writer

Adding to the considerable confusion on Right to Try (RTT) laws, by which dying patients may seek access to experimental drugs, a legal expert tells IRB Advisor that the 41 RTT state laws may be found unconstitutional if they conflict with the federal law passed last year.

Others say the state laws would have faced a challenge of constitutionality even before the federal law was enacted, had that been invoked. The current RTT landscape is a thicket of ethical concerns and legal questions.

“At present, patients with life-threatening conditions have 43 different pathways — expanded access [through FDA], federal Right to Try, and the 41 state laws — through which they can access an experimental medical product,” Alison Bateman-House, PhD, MPH, MA, noted in a recent paper.1

An assistant professor in the Division of Medical Ethics at New York University Langone Medical Center, Bateman-House chairs the Group on Compassionate Use and Preapproval Access (CUPA). They have argued that the FDA’s established program for expanded access to experimental drugs remains the best way to deal with this issue because it requires IRB oversight. To this point, they have fought a losing battle against the expansion of state laws and the 2018 federal RTT law.

Both the state RTT law in California and the federal statute were cited in a recent decision by clinicians at the University of California, Irvine, to administer an experimental drug to a brain cancer patient. The university and ERC-USA initiated treatment with the company’s investigational compound ERC1671, which is known as Gliovac in Europe. The therapy was administered to a patient with aggressive brain cancer who did not qualify for an ongoing clinical trial of ERC1671 in the U.S. According to the company, the compound is a vaccine comprised in part of freshly extracted tumor cells and lysates designed to stimulate the immune system to target cancer cells.

The use of both the California RTT and the federal law facilitated the patient receiving treatment but also raised questions about how the state laws function now that a federal statute is on the books.

“If the drug the patient received was provided outside of the FDA’s expanded access program or an FDA-approved clinical trial, and if it was somehow legal, then it was because of the federal RTT law,” says Christopher Robertson, JD, PhD, a law professor at the University of Arizona. “That would be true even if the people also complied with the state RTT law. Saying that they went through the state RTT law does not conflict with the conclusion that the access was gained via the federal RTT law.”

State RTT laws, if invoked separately, could be challenged as unconstitutional, he says. “If a state RTT law was interfering with the federal RTT law, it could be pre-empted; for example, ruled null by the U.S. Constitution’s Supremacy Clause.”

The safest course for now is for physicians and other providers to try to comply with both state and federal RTT laws, he adds. Indeed, that is what Cal-Irvine did in the recent case, and in following the state RTT law actually invoked stronger requirements for informed consent and IRB review than federally required, says Lisa Kearns, MS, MA, senior research associate in the division of medical ethics and an expert on state RTT laws at CUPA.

“Importantly, the California law requires very strict informed consent — similar to the federal regulations in the FDA’s [expanded access] program — that are not stipulated in the federal RTT law,” she says. “That’s a huge thing. There are extensive requirements of what the consent form must contain.”

Also, California is the only state that requires IRB oversight in its RTT law. The federal law has no IRB review requirement, so the case is something of a hybrid, she says.

“This was one instance, and it didn’t seem to be a big deal to anybody, but what could happen is that a state RTT law might try to do something that the federal law prohibits,” Kearns says.

For example, the federal RTT law gives liability protection to the drug manufacturers providing the experimental products, she says.

“Most of the state laws [waive] liability provided that the company acted in good faith and with reasonable care,” Kearns says. “You could see somebody going after a company under a state law, and accusing them of acting in bad faith. Then you would have a conflict with the federal law, which says [drug companies] are protected. I think the safe conclusion, until any of this is tested in court, is that we are not sure [of the outcome].”

Though California is the only state that expressly includes an IRB provision, individual institutions could require this oversight even though it is not their state law, she emphasizes.

Perception and Reality

We asked Bateman-House to comment further on this complex issue in the following interview with IRB Advisor, which has been edited for length and clarity.

IRB Advisor: You note that, in theory, the state RTT laws could have been challenged as unconstitutional even before the federal law was passed.

Bateman-House: In theory, because you would not necessarily have had that determination made unless someone brought a case forward and a judge or a court decided it was unconstitutional. On its face, talking to lawyers, it was unconstitutional because states cannot take for themselves and govern something that has been under federal authority.

Since passage of the Food, Drug, and Cosmetic Act, the federal government has reserved for itself the ability to govern access to investigational drugs. These states were setting up laws involving powers that they did not actually have. The [state legislatures] understood this as well as anyone, but the fact of the matter is that these were technically laws that did not really have any legal “oomph.” So that led to the federal law. This particular case was handled in accordance with the California law, but that state law was likely unconstitutional without the federal law that gave it backing.

IRB Advisor: Who could have challenged a state law on this basis prior to the federal RTT law?

Bateman-House: The only people who could have brought up a court case against the state RTT laws were either a patient deemed terminally ill under these laws, or the companies that were being asked to provide [investigational drugs]. The companies were being asked, but they had no reason to want to go to court and fight for something that wasn’t even affecting them, and would make them look worse in the court of public opinion. These patients just can’t bring things to court — they are dying, and they don’t have the time or the money to do it. That is a pretty big step and nobody was going to bring a case like that.

IRB Advisor: There were concerns that FDA could be bypassed in RTT cases, but reports2 indicate in the Cal-Irvine case that the company notified the FDA six months before the procedure.

Bateman-House: The FDA notification had nothing to do with the California law. That was the company just doing what it thought was appropriate. It still was not as safe, in my opinion, as expanded access because FDA notification is not the same thing as FDA review of a protocol. Theoretically, the FDA could have done things to this protocol to make it safer or more likely to help the patent. We will never know because the FDA did not review the protocol. They were just informed that this was going to happen.

IRB Advisor: You and CUPA colleagues argue that the FDA expanded access is still the safest, most ethical pathway and that paperwork delays and other criticisms were largely overstated. If true, how did we get so far afield from a system that wasn’t broken?

Bateman-House: Because perception trumps reality sometimes. There was a perception that the system was not working well. There were some high-profile cases where patients were not getting [the investigational therapies] they wanted. When you look at those cases, you see across the board that it was the companies who were saying no.

The system that we have has no power to make a company provide something. Its products are its products, and it will decide when and where to give them to somebody. But the perception was that there was something wrong with the system. Bad actors came in to exploit that perception for their own ends, which was government deregulation.

REFERENCES

1. Folkers KB, Bateman-House A. Glioblastoma patient is first to receive treatment under Right to Try. Our question is Why? Cancer Letter Feb. 1, 2019. Available at: https://bit.ly/2DZAEO9.

2. Caplan A, Folkers KB, McFadyen A. A Bizarre Claim of Right to Try. The Health Care Blog, Jan. 18, 2019. Available at: https://bit.ly/2WNDywH.