A joint effort to relax or ‘modernize’ eligibility criteria for participation in cancer clinical trials has recently been undertaken by a group of national organizations, including the American Society of Clinical Oncology, Friends of Cancer Research, and the U.S. Food and Drug Administration. Ensuring patient safety is one of the top priorities when clinical trial inclusion and exclusion criteria are determined. However, overly strict eligibility criteria limit patient participation and the generalizability of clinical trial results to the greater population. One recommendation to increase trial participation is to relax restrictions on patients with comorbidities. Although comorbidities are believed to be a significant determinant of trial participation, the role of this specific factor in clinical trial decision-making outcomes had not been examined using patient-level data. To address this gap, Dr. Joseph Unger in the Public Health Sciences Division and colleagues conducted a study to determine whether comorbidities are associated with lower rates of clinical trial participation; the results of this study were recently published in JAMA Oncology.
Data collected from an online national survey completed by patients with a recent breast, colorectal, lung, or prostate cancer diagnosis were used for the study. The survey was accessible to patients through various websites that had a cancer treatment decision-making tool. Patients who opted in to the study were surveyed three months after they registered to use the online treatment tool. Approximately 5,500 patients made a treatment decision in the three-month window and completed the survey. Patients were asked about current and previous diagnoses of eighteen comorbidities, including cardiovascular, liver, lung, kidney diseases, as well as previous cancer and other diseases such as diabetes or Alzheimer’s, among others. Three questions assessed patient clinical trial decision-making and participation: whether the patient had discussed trial participation with a physician, whether participation in a trial was offered, and whether the patient participated in a trial.
The age-adjusted prevalence of comorbidities in the surveyed population was representative of that in the general U.S. adult population. Overall, 65.5% of patients indicated they had at least one comorbidity. When each comorbidity was analyzed individually, nearly all were associated with either a significant reduction in trial discussion, offer for trial participation, or trial participation. Similar results were found when the authors assessed the overall presence of one or more comorbidities (see figure).
The authors then performed simulation analyses to estimate how trial participation rates might change if enrollment restrictions due to the presence of comorbidities were eliminated. The elimination of the different categories of comorbidities as recommended by the ASCO working groups was estimated to provide a relative increase in the overall trial participation rate of 7.3%.. Such an increase translates to thousands of additional patients becoming eligible to participate in cancer clinical trials each year.
This study clearly demonstrates the adverse impact of the presence of comorbidities on cancer clinical trial participation rates. Nearly all comorbidities were associated with a reduction in at least one component related to trial participation. These results strongly suggest that modification of clinical trial exclusion criteria would be met with increased trial participation and generalizability of trial results to a greater proportion of cancer patients.
“The reaction to the study has been quite positive as it affirms the work of several key organizations involved in a large effort to help redesign clinical trials,” Dr. Unger said. “These changes are currently being implemented across a broad spectrum of cancer studies in the U.S.”
Dr. Unger indicated that changes to eligibility criteria are important to both patients and researchers. “These changes benefit patients by providing more opportunities to receive their care in trials. And the participation of more patients will speed the conduct of trials, and thus the rate at which new beneficial treatments are identified, which ultimately benefits all cancer patients.”
Fred Hutch/UW Cancer Consortium member Joseph Unger contributed to this research.
This research was supported by the National Cancer Institute.
Unger JM, Hershman DL, Fleury ME, Vaidya R. 2019. Association of patient comorbid conditions with cancer clinical trial participation. JAMA Oncology. doi: 10.1001/jamaoncol.2018.5953.
Basic Sciences Division
Human Biology Division
Maggie Burhans, Ph.D.
Public Health Sciences Division
Vaccine and Infectious Disease Division
Clinical Research Division
Julian Simon, Ph.D.
Clinical Research Division
and Human Biology Division
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