While the federal Right to Try law enacted last year essentially bypassed IRB oversight of patients seeking investigational drugs, research ethics panels and their institutions can codify a requirement for local oversight into their policies and procedures, says Alison Bateman-House, PhD, MPH, MA, assistant professor in the Division of Medical Ethics at New York University Langone Medical Center.

Bateman-House and her colleagues at the NYU School of Medicine Working Group on Compassionate Use and Preapproval Access (CUPA) have been following Right to Try closely.

“IRBs are cut out. There is no need for a [Right to Try] proposal to go through an IRB, which is one of the reasons that I’m not in favor of it,” she tells IRB Advisor.

However, IRBs can make review required at the local level simply by mandating oversight in their institution’s standard operating procedures (SOPs) for investigational new drugs sought through the Right to Try pathway.

“Just because the law does not say that an IRB is required, does not mean that you can’t put in your own SOP that says it must be [reviewed by the IRB],” Bateman-House says. “I actually think that would alleviate some of my concerns about Right to Try.”

Despite the hue and cry accompanying its passage on May 30, 2018, the federal Right to Try Act seems to have had little impact thus far. The Right to Try law is aimed at increasing access to investigational products for those with life-threatening illness who have no other medical options and are unable to join a clinical trial. However, the general consensus after the bill was passed was that the expanded access pathway to experimental drugs currently in place at the FDA will continue to be the preferred method. (See IRB Advisor, July 2018.)

In addition to the federal law, 41 states have enacted Right to Try laws. Both the state law in California and the federal Right to Try 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.

“UCI worked to meet the regulatory and compliance requirements of both the state and federal Right to Try laws before starting treatment,” John Murray, a public information officer for UCI Health, told IRB Advisor.

The university and ERC-USA initiated treatment with the company’s investigational compound ERC1671, which is known as Gliovac in Europe. The therapy is being 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.

Daniela Bota, MD, PhD, medical director of the UCI Health Comprehensive Brain Tumor Program, issued the following statement: “We are gratified to have the opportunity to offer options for this aggressive cancer, as current treatment modalities have proven unsuccessful,” she said. “The Right to Try laws may be the only alternative for many patients who may not qualify for clinical trials based on a variety of factors, including progression of disease, comorbidities, existing medications, physical limitations, and others.”

In a recently updated Question and Answer section on its website, CUPA states that “as with expanded access, Right to Try does not require companies to grant patients’ requests for their investigational products. Furthermore, companies that are willing to provide nontrial preapproval access are able to choose whether to do so via Right to Try, expanded access, or both. … At present, CUPA is unaware of any patients who have accessed investigational medical products through the federal Right to Try pathway.”1

The law also requires companies to submit annual reports on Right to Try usage to the FDA, and for participating physicians to have liability insurance, CUPA notes.

“We are trying to give a little bit of guidance based on the drips and drabs that have come out from either FDA or from lawyers,” Bateman-House says. “We are still waiting to find out exactly how it would work. But patients have been desperately clamoring, so we tried to update it, explain what it was, and to the small extent that we can, fill in some of the questions.”

For example, on a question on whether Right to Try or expanded access would provide faster access to investigational drugs, CUPA answered:

“It is CUPA’s assessment that the slowest part of nontrial preapproval access likely occurs at the company level. Because both Right to Try and expanded access entail waiting for a response from the company developing the investigational product, both pathways will be affected by this time lag. FDA review, which is required for expanded access but not Right to Try, is quick: same day for emergencies and, on average, within four days for nonemergencies. … Regardless of whether Right to Try eventually proves to be a fast pathway, CUPA does not believe that any gain in speed is worth the loss of oversight by independent, expert third parties (the FDA and an IRB).”

To press the point home, CUPA answered a question about the importance of FDA oversight by citing the infamous thalidomide birth defects in the 1960s. The incident “spurred FDA regulations requiring drug companies to prove that their products are both safe and effective before they would be approved. The thalidomide tragedy demonstrated the unexpected yet devastating potential toxicities associated with drug treatment.”

For its part, the FDA, which was essentially cut out of the Right to Try Act as well, is providing information on a recently posted webpage.2 The FDA cites three decades of helping patients through its expanded access program and provides basic information on patient eligibility for Right to Try.

The FDA cites the following criteria for patient eligibility:

• diagnosed with a life-threatening disease or condition;

• exhausted approved treatment options and is unable to participate in a clinical trial involving the drug;

• provided, or their legally authorized representative has provided, written informed consent regarding the eligible investigational drug to the treating physician.

However, the FDA ultimately refers patients to their physicians and to the drug companies.

“If you are interested in Right to Try, you should discuss this pathway with your licensed physician,” the FDA states. “Companies who develop and make drugs and biologics, also known as sponsors, can provide information about whether their drug/biologic is considered an eligible investigational drug under Right to Try and if they are able to provide the drug/biologic under the act.”

Thus, FDA Commissioner Scott Gottlieb, MD, seems to be trying to finesse the issue to some extent, providing information on Right to Try but referring patients to doctors and drug companies if they want to pursue the path.

“The FDA is a political organization, and it has to do what it is told to do by the president or the legislative branch,” Bateman-House says. “When the whole Right to Try thing was going down, Gottlieb told the House of Representatives — I was there testifying as well — that it was not a good idea and that he personally didn’t think that the FDA was the holdup in people getting access.”

Indeed, Bateman-House says both she and Gottlieb advised that pharmaceutical companies were the key stakeholders and control the supply of investigational drugs to patients. Expanding on this point, CUPA’s recently updated answer on this question points to what may be the Achilles’ heel of Right to Try.

“Many companies see no upside to providing their investigational products through Right to Try,” CUPA states on its website. “If a product appears to be safe and/or effective in the expanded access setting, a company may wish to include that information in the paperwork submitted when it seeks marketing approval from the FDA. If a product appears to cause harm in the expanded access setting, a company will want to be able to say that there was FDA oversight of the product’s use outside of clinical trials.”

REFERENCES

1. Working Group on Compassionate Use and Pre-Approval Access. Available at: https://bit.ly/2Qzc6ys.

2. FDA. Right to Try. Nov. 20, 2018. Available at: https://bit.ly/2TIKBVc.