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Healio – Modernized trial eligibility criteria aim to remove comorbidities as a barrier to enrollment

Healio – Modernized trial eligibility criteria aim to remove comorbidities as a barrier to enrollment

Patients with cancer and comorbidities are routinely left out of clinical trial discussions, offers and participation, according to results of a study published in JAMA Oncology.


At least 60% of trial eligibility exclusions are related to patient comorbidities or performance status, according to study background.


Those statistics could start to change because of the implementation of new eligibility guidelines for clinical trials, due in part to this and other studies.


“The movement to modernize eligibility criteria in trials has been led by both researchers and patient advocacy groups. The motivation has been in part scientific, as cancer researchers aim to recruit patients to trials who are more representative of the cancer population,” Joseph M. Unger, PhD, MS, health services researcher and biostatistician for SWOG Cancer Research Network at Fred Hutchinson Cancer Research Center, told HemOnc Today. “With these motivations in mind, ASCO partnered with Friends of Cancer Research and the FDA to establish working groups to examine common eligibility criteria in depth and to identify those criteria that were suitable to be redesigned in trials. The team of researchers and investigators then published their findings in Journal of Clinical Oncology. The findings have been widely disseminated and are being adopted by clinical trialists.”


In this study, Unger and colleagues sought to evaluate the relationship between comorbidities, clinical trial decision-making and trial participation, and they predicted the potential impact of reducing major comorbidity exclusion criteria in trials to provide a benchmark for evaluation of the ASCO recommendations.


The analysis included 5,499 patients (mean age, 56.63 years; 62.6% women; 94.4% white) with a diagnosis of breast, lung, colorectal or prostate cancer who participated in a national survey accessible at multiple cancer-oriented websites. The survey collected data on demographics, staging and 18 comorbidities, as well as treatment decisions made within the past 3 months.


Most patients (65.6%; n = 3,610) had one or more comorbidities, the most common being hypertension (n = 1,924), vision loss (n = 912), arthritis (n = 841), asthma (n = 630), hearing loss (n = 613) and previous cancer (n = 559).


Among all patients, 2,174 (39.5%) indicated they discussed a trial with their physician, 978 (17.8%) indicated they were offered trial participation, and 496 (9%) indicated they had participated in a trial.


Multivariable logistic regression showed that compared with having no comorbidities, the presence of one or more comorbidities led to a 7% decreased likelihood of trial discussions (44.1% vs. 37.2%; OR = 0.86; 95% CI, 0.75-0.97), a 7% decreased likelihood of trial offers (21.7% vs. 15.7%; OR = 0.82; 95% CI, 0.61-0.94), and a 4.5% decreased likelihood of trial participation (11.3% vs. 7.8%; OR = 0.76; 95% CI, 0.61-0.94).’


Researchers estimated that the removal of ASCO-recommended comorbidity restrictions could result in up to 6,317 additional patient trial registrations every year. Eliminating all comorbidity restrictions would enable up to 11,992 patients with cancer to join trials annually.


Unger said that, ideally, he would like to see clinical trials for each comorbidity but added that it isn’t feasible because of costs and time.


“A more optimal approach is to model the trial design to best reflect the cancer population for which the new treatment is targeted, although always keeping in mind the safety of the patient,” Unger said. “The effort to modernize these eligibility criteria is intended to strike the right balance between patient safety and patient access to trials.”


Limitations of this study included the fact that patients were mostly younger and white and had to self-report data, as well as a lack of data on the severity of morbidities.


Unger and colleagues wrote, however, that common disease conditions were represented in the cohort at expected rates.


“Additional research is required to further establish which comorbidities most strongly and negatively affect trial participation,” Unger and colleagues wrote. “This is particularly important in the era of biomarker-driven trials, which threaten to shrink eligible patient pools still further based on biomarker status. The modernization of trial eligibility criteria will benefit patients interested in participating by expanding their opportunities to receive care in trials.”


In an accompanying editorial, Grace Mishkin, MPH, and colleagues wrote that new eligibility criteria to discuss in the future include drug washout periods, number of prior therapies allowed based on the study phase, performance status, exclusion of concomitant medications without drug-interactions. And population-based laboratory reference ranges.


“Expanding clinical trial participation is a dynamic and continuous effort to seamlessly adapt clinical trial design to current knowledge and should not be a 1-time event,” Mishkin and colleagues wrote. “Upcoming discussions will encompass evaluation of other eligibility criteria where the potential for improvement exists.”…