Cancer Researchers Urge Rule Relax for Clinical Trials
Concerningly, 20% of publicly funded cancer clinical trials in the United States fail because investigators are unable to enroll enough participants. Yet, patients and their physicians are left frustrated when they encounter the sometimes insurmountable requirements to join a study.
In a bid to change this for good, researchers are pruning the list of eligibility criteria, writes Nature. On 16 April, representatives of the US Food and Drug Administration (FDA) will meet stakeholders in Washington DC to discuss how restrictive eligibility criteria for clinical trials could be limiting patients’ ability to access experimental treatments, as well as the quality of the data generated by the studies. The agency plans to use the information it gathers to develop guidelines for drug makers.
“You can have the greatest ideas and the greatest science,” explained Stuart Lichtman, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. “But if no one goes on the study, what good is it?”
More often than not, eligibility requirements are intended to protect either the participant or the study. For example, participants with a degree of liver failure might not be allowed to take part in a trial of a drug thought to pose a risk to that organ. In addition, criteria might exclude people with conditions that could confound the results of a study.
However, some researchers believe that a ‘cut-and-paste’ mentality has increased clinical-trial requirements over time, as scientists have used previous trial protocols as templates for their next studies. Therefore, this might restrict participation in a specific trial.
David Gerber, a lung-cancer specialist at the University of Texas Southwestern Medical Center in Dallas, and his collaborators found that 80% of clinical trials sponsored by the US National Cancer Institute excluded people with previous cancer diagnoses. Although, in many cases, previous cancer might have been caught early and removed successfully before the person developed lung cancer.
“What really frustrates me are instances when, in my mind and in my heart, it really seemed that the patients should be eligible,” noted Gerber. “If I had the exact same treatment outside of a clinical trial, I would give it to them without a concern.”
For example, people with HIV were once excluded from trials because of their poor prognosis. But now, with treatment, they often live as long as people without the virus and should be included in many cancer trials, the group concluded.
The team even recommended that in some cases, researchers should ease restrictions on people with organ dysfunction. This could be important, specifically in light of the ageing populations in some countries, like the United States, said Lichtman. The restrictions were implemented when cancer treatments were more broadly, and therefore might not be necessary for the more targeted drugs available today.
However, one particular recommendation that could generate some controversy, is to lower the age of eligibility for many adult cancer trials from 18 to 12. This is in line with the understanding of basic drug metabolism, explained Edward Kim, an oncologist at Atrium Health in Charlotte, North Carolina, who chaired the ASCO effort. “There is nothing magical about 18,” he noted. “Your body pharmacologically metabolizes drugs the same way at 12 as it does at age 18.”
Despite this, it’s important to bear in mind that some adult-cancer physicians might feel uncomfortable treating younger people, and often that treatment takes place in specialised children’s hospitals, unlike adult clinical trials. Also, most adolescent cancers are rare and can differ from adult cancer, even when they start in the same organ. This might mean that the change will have little impact on research overall, suggested pediatric oncologist Peter Adamson of the Children’s Hospital of Philadelphia in Pennsylvania. but there is still a chance that it could still help individual adolescents who might otherwise have been excluded from trials. “It’s the right thing to do,” he added.
Kim is currently attempting to get their changes implemented, and have submitted their suggestions to an influential programme that coordinates clinical development of new therapies at the US National Cancer Institute. The team revealed that they have been contacted by researchers at large pharmaceutical companies who are eager to make the changes in their upcoming trials. Gerber has even been asked to give talks on his analyses around the world, highlighting how countries with aging populations would do well to reevaluate their own clinical trial criteria.
The eventual result could be data that is more relevant to the people whom Kim and his colleagues treat every day. “These patients have these characteristics and they’re going to be treated eventually by their doctors,” he concluded. “This is the real world.”