Unnecessarily restrictive criteria for clinical trial participation excluding those with comorbidities excludes many “real-world” cancer patients and prevents them from potentially benefiting from new treatments, say cancer researchers.
Modernizing clinical trial eligibility criteria would significantly expand the pool of patients who could participate in such trials across a variety of cancers, they suggest.
These comments come from an article published online January 10 in JAMA Oncology.
“Comorbidities have a clear negative impact on both trial decision-making and participation,” says lead author Joseph Unger, PhD, health services researcher at the Fred Hutchinson Cancer Research Center, in Seattle, Washington.
“Allowing people with manageable comorbidities to join trials would increase treatment opportunities for several thousand patients,” he adds in a statement.
Unger is also a biostatistician for SWOG Cancer Research Network, the National Cancer Institute-sponsored network cooperative research group.
In their article, Unger and colleagues report results from a national survey that they conducted among cancer patients, which collected data on 18 different comorbid conditions.
The researchers embedded the survey within a web-based cancer treatment-decision tool available on multiple cancer-oriented websites.
All participants had to have been diagnosed with breast, lung, colorectal, or prostate cancer.
In total, 5499 respondents were included in the analysis, almost 88% of whom had made a decision about their treatment within the past 3 months.
Almost two thirds (65.6%) of survey participants had at least one comorbidity.
“The most prevalent disease condition was hypertension [reported by 35.0% of participants],” the authors report.
Vision loss was also relatively common at 16.6%, as was arthritis at 15.3%, asthma at 11.5%, and hearing loss at 11.2%. Some 10.2% of participants also reported having a prior cancer.
Further analyses revealed that 39.5% of survey participants had discussed a clinical trial with their physician and 17.8% indicated they had been offered a chance to participate in a clinical trial.
However, only 9% of the group overall reported actually taking part in a clinical trial.
“In almost all cases, the presence of a comorbid condition was associated with lower observed rates of trial discussion…trial offer…and trial participation,” the researchers report.
Specifically, those who reported having one or more comorbidities were 14% less likely to have discussed participating in a clinical trial with their physician than patients with no comorbidities (37.2% vs 44.1%, respectively; P = .02).
Similarly, those with one or more comorbidities were 16% less likely to be offered a chance to participate in a clinical trial compared to those with no comorbidities (15.7% vs 21.7%; P = .02).
Actual participation in a trial was also 24% lower for those with comorbidities, at 7.8%, compared with 11.3% for participants with no comorbidities (P = .01).
“The most common comorbidities most strongly associated with each of the three outcomes included hypertension, prior cancer, and hearing loss,” researchers note.
Trial Participation Rate
Investigators then used a simulation model to assess how the rate of trial participation would change if the presence of comorbidities did not exclude patients from such trials.
An earlier effort by the American Society of Clinical Oncology (ASCO), Friends of Cancer Research, and the US Food and Drug Administration recommended modernization of certain criteria currently used to exclude patients from trials, including the presence of brain metastases, age limits, HIV infection, organ dysfunction, and prior cancer.
If patients with any of these comorbidities were allowed to enroll in clinical trials, the removal of all restrictions on the ASCO-recommended categories would have allowed up to 6317 additional patients to participate in cancer trials in 2018, the investigators state.
As the authors point out, one of the reasons a history of prior cancer might have been chosen as an exclusion criterion is that its presence might confound interpretation of outcomes for the cancer under current treatment.
“However, recent evidence suggests that the existence of prior cancers has limited or no impact on outcomes for new diagnoses,” the authors insist.
Similarly, about half of all older adults with hypertension have well-controlled blood pressure and, as such, hypertension should not interfere with the treatment under investigation.
Furthermore, this group represents a “large pool” of potential trial participants, as investigators point out.
In the end, modernization of trial eligibility criteria will benefit not only patients themselves who might be interested in pursuing expanded treatment options but hasten the rate at which clinical trials can be carried out along with the rate at which new treatments are identified, the authors suggest.
An Important Step
In an accompanying editorial, lead author S. Percy Ivy, MD, National Cancer Institute, Bethesda, Maryland, and colleagues suggest that oncologists are already aware of how removing unnecessarily restrictive criteria to clinical trial participation to enroll in exploratory studies would encourage participants who are more representative of the cancer population as a whole.
“Modernizing eligibility criteria by removing restrictions on comorbid conditions represents an important step forward in our efforts to enhance clinical trial participation across the population,” Ivy and colleagues state.
However, the editorialists caution that eligibility criteria are just one of many possible barriers to clinical trial participation.
“Continued efforts to address these barriers will allow oncology practitioners to discuss clinical trial enrollment with their patients in a more realistic environment and to guide and support them through the decision-making process, with the hope of new and more effective therapies,” they conclude.