Are Comorbid Conditions Excluding Otherwise Eligible Patients From Clinical Trial Enrollment?

The presence of comorbid conditions was associated with lower rates of clinical trial discussions between patients and their physicians, subsequently leading to decreased trial participation, according to an analysis performed by Southwest Oncology Group (SWOG).¹

Barriers to clinical trial enrollment are multifaceted, and the decision by a patient to participate does not guarantee involvement. Physical barriers to participation, like limited access to a cancer clinic, may preclude a patient from accessing an appropriate clinical trial for their disease.

It is well known that large academic institutions are better equipped to enroll clinical trial participants, and results from studies have shown they do so at a rate almost twice that of community-based centers.²

“Although most patients with cancer receive their care in community centers, patients receiving care at academic centers are more likely to participate in clinical trials,” said Joseph M. Unger, PhD, MS, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and lead author of the SWOG analysis, in an interview withTargeted Therapies in Oncology. “The main reason for nonparticipation in clinical trials is the lack of availability of a clinical trial for the patient’s histology and stage of disease. Community sites are generally less likely to have an available trial for a patient than academic sites.”

Adding to these physical barriers are clinical considerations in the form of comorbidities. Recent recommendations from the American Society of Clinical Oncology (ASCO), Friends of Cancer Research (Friends), and the FDA reconsider common eligibility criteria for clinical trials so that they may more accurately reflect real-world patient populations. The 4 areas outlined that were least likely to affect survival but commonly led to exclusion were the presence of brain metastases, a minimum patient age, HIV infection, and organ dysfunction and prior and concurrent malignancies.³

“The efforts of ASCO, Friends, and the FDA to establish recommendations for updating trial eligibility criteria were a long, complex process involving many stakeholders, although their adoption into trials has already begun,” Unger said. “Our hope is that physicians will see that trial eligibility can be expanded while still maintaining patient safety, and they will increasingly consider participation in trials as an option for their patients.”

Unger said that the SWOG analysis provides evidence that comorbidities are influential in driving decision making in cancer treatment and that modernizing criteria is essential for making trials available to more patients.

The survey on which the analysis is based included 5499 participants who had made a treatment decision within the prior 3 months. These participants responded to questions about whether they discussed clinical trial participation with their treating clinician, whether those conversations resulted in being offered enrollment, and whether they accepted or declined participation. Comorbidity data for 18 separate conditions were also collected based on the Charlson comorbidity index. The most commonly reported comorbidities were hypertension (1924 participants), vision loss (912), arthritis (841), asthma (630), and hearing loss (613). More than half of respondents (65.6%) reported ≥1 comorbidity (TABLE).

The presence of ≥1 comorbid condition decreased the likelihood of trial discussion between patients and their physician, with 37.2% of patients reporting that they had discussed the possibility compared with 44.1% of those who had not reported having a comorbid condition (odds ratio [OR], 0.86; 95% CI, 0.75-0.97;P= .02).

Similarly, patients in the comorbid group were less likely to be offered participation in a clinical trial (15.7% vs 21.7%; OR, 0.82; 95% CI, 0.70-0.96;P= .02) and were less likely to enroll at all (7.8% vs 11.3%; OR, 0.76; 95% CI, 0.61-0.94;P= .01).

Dawn L. Hershman, MD, MS, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center and professor of medicine and epidemiology at Columbia University Irving Medical Center in New York, said in an interview withJAMA Oncologythat physicians may be self-selecting patients based on these comorbid conditions.⁴

“We all come to the table with certain biases. When we see patients are on medications, [we may interpret that] as a level of frailty that is not necessarily captured by comorbidities alone. We make an assumption that the patient is not going to be interested or they are not going to be eligible without checking,” said Hershman. “That may be reflected in physician bias, and that is why trials are not discussed.”

Unger echoed Hershman’s concerns but was optimistic about the adoption of new guidelines.

“Updating trial eligibility will likely have an outsize impact on enrolling patients from community settings, simply because most patients receive their care in the community setting,” he said. “These changes are likely to provide many opportunities for patients from community sites to participate in trials.”

References:

1. Unger JM, Hershman DL, Fleury ME, Vaidya R. Association of patient comorbid conditions with cancer clinical trial participation [published online January 10, 2019].JAMA Oncol.doi: 10.1001/jamaoncol.2018.5953.
2. Unger JM, Cook E, Tai E, Bleyer A. The role of clinical trial participation in cancer research: barriers, evidence, and strategies.Am Soc Oncol Educ Book.2016;35:185-198. doi: 10.14694/EDBK_156686.
3. Kim ES, Bruinooge SS, Roberts S, et al. Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research joint research statement.J Clin Oncol.2017;35(33):3737-3744. doi: 10.1200/JCO.2017.73.7916.
4. West J. Association of patient comorbid conditions with cancer clinical trial participation [published online January 10, 2019].JAMA Oncol.edhub.ama-assn.org/jn-learning/audio-player/17138083. Accessed January 11, 2019.