Skip to content

Journal of Clinical Pathways – Comorbidity exclusion criteria impair participation in cancer trials

Journal of Clinical Pathways – Comorbidity exclusion criteria impair participation in cancer trials

Easing comorbid-condition exclusion criteria could significantly increase participation in clinical trials for cancer, researchers report.


“Some eligibility exclusions for comorbid conditions will always remain for the sake of patient safety,” Dr. Joseph M. Unger from Fred Hutchinson Cancer Research Center, in Seattle, told Reuters Health by email. “But others should be modified or removed if evidence shows that patients with those conditions can be safely enrolled.”


Most clinical-trial exclusion criteria involve patient comorbidities or performance status. Recently, the American Society of Clinical Oncology (ASCO), Friends of Cancer Research and the U.S. Food and Drug Administration (FDA) recommended modernization of some of these exclusion criteria, including the presence of brain metastases, age limits, HIV infection, organ dysfunction and prior cancer.


Whether such changes would improve trial participation remains unclear. To investigate, Dr. Unger’s team used data from a large, national, web-based survey of 5,499 cancer patients who had made a treatment decision within the past three months to examine the relationship between comorbidities, clinical-trial decision-making and trial participation.


The most prevalent comorbidities were hypertension (35%), vision loss (16.6%), arthritis (15.3%), asthma (11.5%), hearing loss (11.2%) and previous cancer (10.2%).


Just under 40% of patients reported discussing a trial with their physician, the researchers report in JAMA Oncology, online January 10. But only 17.8% were offered trial participation and only 9.0% actually participated in a trial.


Among the 18 separate comorbid conditions included in the survey, almost all were associated with lower observed rates of trial discussion (16/18), trial offer (17/18) and trial participation (16/18), with hypertension, prior cancer and hearing loss most commonly associated with each of the three outcomes.


After adjusting for other factors, the presence of one or more comorbidities was associated with 14% lower odds (P=0.02) of trial discussions (37.2% vs. 44.1% for no comorbidities); 18% lower odds (P=0.02) of trial offers (15.7% vs. 21.7%); and 24% lower odds (P=0.01) of trial participation (7.8% vs. 11.3%).


Based on these findings, the removal of all restrictions on the ASCO-recommended categories would allow up to 6,317 additional patients to participate in clinical trials. If all 18 comorbidities were removed, up to 11,992 additional patients could participate, according to the researchers.


“I was encouraged to find that the changes to the ASCO-recommended criteria alone would account for more than half of the potential benefits of removing all comorbidity criteria,” Dr. Unger said. “This showed that the ASCO-recommended criteria were both targeted and clinically meaningful for patients.”


“Eligibility criteria have grown dated and will benefit from some updating,” he said. “Both patients and researchers will benefit from the modernization of trial eligibility criteria. Patients will benefit by improved access to clinical trials for their cancer care. Research will benefit by clinical trials that can be conducted more quickly, with results that are more widely applicable. Ultimately new treatments will be identified faster, benefiting all patients with cancer.”


“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,” write Dr. S. Percy Ivy and colleagues from the National Cancer Institute, in Bethesda, Maryland, in a linked editorial. “However, eligibility criteria represent just 1 of many potential barriers to clinical trial enrollment.”


“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.


Beth Zaharoff, senior director of patient-focused engagement and partnerships at TESARO, an oncology-focused biotech company in Waltham, Massachusetts, recently reported results of focus groups of patients who had participated in breast- and ovarian-cancer trials to identify concerns regarding their experiences.


“A bane of our existence for years in oncology has been the low number of people who choose to participate in clinical trials,” she told Reuters Health by email. “The 5% hasn’t changed considerably and as such, new ways of thinking should be instituted. We are getting better at bringing the patient voice into the development of our clinical trials. More closely analyzing our enrollment criteria could be another tool for drug developers to use.”


She stressed “the importance of thinking critically about how necessary and/or stringent each of the enrollment criteria needs to be. Spending a little extra time during protocol development can potentially increase enrollment down the road. Wanting to be in a clinical trial but not qualifying is a tremendous (and frequent) frustration for cancer patients.”


“In order to save precious time and resources, allocating more time at the outset to develop a protocol that will allow for the greatest number of participants and will be relevant, interesting, and feasible for them could pay dividends,” said Zaharoff, who was not involved in the new study.…