‘Right to try’ should focus on regulatory changes that embrace the fast pace of precision medicine

The “right to try” bill (S. 204), which suddenly resurfaced when the House scheduled it for committee meetings this week, was designed to allow patients with a terminal diagnosis — who have run out of effective treatment options — access to try a drug that just might help, even without Food and Drug Administration approval. This legislation — a priority for President Trump — sounds like a no-brainer. As the clock runs out, with a patient facing hospice as the next and last step, what could be wrong with giving an unproven drug a chance?

Nothing, if it’s done right. What’s wrong is the proposed legislative approach – which is why the right to try bill has been so contentious (a House version, H.R. 5247, passed in March with too many differences from the Senate-approved version to reconcile).

{mosads}The proposed legislation would be bypassing the FDA while failing to address the real roadblocks that exist when desperate patients and families attempt to access potentially life-saving drugs. The bill would remove all doctor and pharmaceutical accountability while increasing patient risk.

Knowing the glacial timelines often required for passing legislative changes in health care, we were hoping to see something more innovative that kept pace with exciting scientific advances — specifically those in precision medicine. right to try is veering off in the wrong direction because the FDA isn’t the problem.

Terminally ill patients already have the ability to apply for access to unproven therapies by filing a request for compassionate use, and the FDA approves 99 percent of those requests. However, pharmaceutical companies are reluctant to provide the drugs fearing negative publicity or lawsuits should a patient suffer a poor outcome. Therefore, even when requests for compassionate use are approved, the road to hope often ends there.

Right to try legislation — which continued to gain ground at the state level even as it has started and stopped its way through Washington — reduces risk to pharmas by removing the FDA from the equation. Poor outcomes wouldn’t be reported and pharmas would have protection against legal liability, while patients — and science itself, would suffer unintended consequences.

Many of these consequences would affect children with brain tumors, a population that has much to gain from precision medicine — high-tech genomic testing that can rapidly inform customized treatment decisions based on an individual’s genetic makeup. The potential to match children with promising drugs would seem to argue for right to try laws. Yet the impact of such legislation is negligible compared to what the real unmet needs are.

These children need access to treatment options that keep up with science. Brain tumors in children are the number one cause of pediatric cancer-related deaths. For sixty years, children have been treated for the “type” of brain tumor they are diagnosed with, based on location and what it looks like under a microscope, resulting in minimal improvement in overall survival for the deadliest brain tumor types. Meanwhile, research has shown that tumors of the same type and location may be vastly different molecularly in different patients, and therefore responsive to an entirely different treatment approach.

So instead of the right to try bill, we suggest regulatory changes that embrace the fast pace of precision medicine. In lieu of large clinical trials that take years to develop, complete, and analyze, we advocate for “n of 1” trials (frontline therapy designed for just one patient). These new clinical trials provide customized treatment protocols based on genetic analysis. Children should not have to wait until they are considered terminal in order to apply for this kind of access.

All stakeholders involved in this process, including the FDA, pharmaceuticals, biotechs, researchers, and oncologists, should also consider re-thinking what “unproven” means. Data collected from sequencing thousands of tumors are analyzed for commonalities — not necessarily among tumor types, but among specific mutations and other genetic information that can be matched with combinations of drugs that have shown efficacy under similar circumstances. Patient A may have a brain tumor that’s more similar to Patient B’s liver tumor than it is to any other brain tumor. Why would a brain tumor oncologist be stopped from trying a drug that is known to be efficacious against the genomically similar liver tumor?

We need more progressive legislation that minimizes risk and incentivizes drug manufacturers to allow for timely execution of a customized “n of 1” trial design in pediatrics, where patient response to treatment varies tremendously, large-scale enrollment is very limited, and evidence is therefore hard to come by.

New legislation could force the hand of drug companies into participating in these “n of 1” trials, providing drugs quickly on a case-by-case basis if potential is demonstrated via precision medicine, a new era of biology-focused clinical trials will come to fruition. How much longer can we possibly wait before we allow breakthrough science to help children? We need the right to try something completely innovative in pediatric oncology — not a right to try bill that fails to meet the real needs of our precious children.

Dr. Mark M. Souweidane and Dr. Jeffrey P. Greenfield are pediatric neurosurgeons and the co-directors of the Children’s Brain Tumor Project at Weill Cornell Medicine.