Without older subjects, cancer drugs trials rely on atypical patients
(Reuters Health) – Patients selected to participate in studies of cancer drugs tend to be younger than most people with the disease in the general population, researchers say.
In one recent study, in fact, they were more than six years younger than the median age of patients with the same kind of cancer, researchers reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago.
The study was also published online in JAMA Oncology to coincide with the presentation at the ASCO meeting.
“We found that the age disparities in enrollment of elderly patients, which are pervasive in clinical trials in cancer, seem to be worsening,” said the study’s lead author, Dr. Ethan Ludmir, a resident physician in the department of radiation oncology at the University of Texas MD Anderson Cancer Center in Houston. “And these disparities are particularly pronounced among trials funded by industry.”
Why does that matter?
“Data from these clinical trials may not be as applicable to the general population as one would imagine,” said senior author Dr. Clifton David Fuller, an associate professor in the department of radiation oncology at MD Anderson. “And that’s because the results are based on a slightly different group of patients.”
Currently, clinical trials seem to look for the youngest and most fit patients to test therapies in, Fuller said.
“We found that anywhere from 10 to 20 percent of trials had a built-in age cutoff, which means that if you are older you can’t participate,” Ludmir said. “Sometimes that cutoff is the median age.”
Aside from when studies explicitly give an age cutoff, it’s not known exactly why there is a bias toward younger patients, Fuller said. The first step is to identify the reasons, he said, adding that this is a subject for future research by his team.
To determine the size of the age disparity, the researchers first analyzed information on clinical trials listed on the ClinicalTrials.gov website. To get a median age for various cancers, they turned to the National Cancer Institute’s Surveillance, Epidemiology, and End Results database.
The researchers focused on 302 clinical trials that collectively enrolled 262,354 patients between 1994 and 2015. They calculated the difference in median age in each trial versus the median age for patients with the same cancer as those in the trial.
Overall, the difference between the median age of trial participants and that of the general population was 6.49 years. The differences were wider in industry-funded trials compared to non-industry sponsored trials: 6.84 years versus 4.72 years.
While the government has pushed for clinical trials to achieve more equity in term of gender, race and ethnicity, it hasn’t addressed the age disparity, the researchers noted.
The new study highlights the age disparities present in clinical trials, said Dr. Annie Im, an assistant professor at the Hillman Cancer Center at the University of Pittsburgh Medical Center.
“This has been a pervasive problem for a long time,” Im said. “People are hesitant to enroll older patients based on the unfounded concern that these patients won’t do as well and will impact the results of the trial.”
But, Im said, “most of the people we see in practice are older. Age is one of the risk factors for cancer. Studies like this one are bringing awareness to the problem. I think the community as a whole has a responsibility to do something about it.”
That’s unlikely to happen, said Dr. Otis Brawley, Bloomberg Distinguished Professor at the Johns Hopkins Kimmel Cancer Center.
“It’s been long known by the people who design clinical trials that the group of people in the trials are different from the ones we are treating,” said Brawley, who designs clinical trials. “One of the biggest differences has led to the identification of the ‘healthy volunteer effect,’ which means that the people in the trial tend to be healthier than the general population, except that they have cancer. They are less likely to smoke, be overweight, to have hypertension and to have cardiovascular disease than the general population.”
That doesn’t mean the study isn’t important, Brawley said. It should remind oncologists to translate trial findings for “the patient in front of you.”
“What I’ve been doing for years is telling patients ‘for people in these studies, this is what the response rates were,” Brawley said. “‘For you, I don’t know exactly what it will be. But I know this is the best science.’”
SOURCE: bit.ly/2EMEREI JAMA Oncology, online June 3, 2019.