Characterization of Comorbidities Limiting the Recruitment of Patients in Early Phase Clinical Trials

Abstract

Background Early phase clinical trials evaluate the safety and efficacy of new treatments. The exclusion/inclusion criteria in these trials are usually rigorous and may exclude many patients seen in clinical practice. Our objective was to study the comorbidities limiting the participation of patients with breast, colorectal, or lung cancer in clinical trials. Materials and Methods We queried http://clinicaltrials.gov on December 31, 2016. We reviewed the eligibility criteria of 1,103 trials. Logistic regression analyses were completed, and exclusion was studied as a binary variable. Results Out of 1,103 trials, 70 trials (6%) excluded patients >75 years of age, and 45% made no reference to age. Eighty‐six percent of trials placed restrictions on patients with history of prior malignancies. Regarding central nervous system (CNS) metastasis, 416 trials (38%) excluded all patients with CNS metastasis, and 373 (34%) only allowed asymptomatic CNS metastasis. Regarding chronic viral infections, 347 trials (31%) excluded all patients with human immunodeficiency virus, and 228 trials (21%) excluded all patients with hepatitis B or C infection. On univariate analysis, chemotherapy trials were more likely to exclude patients with CNS metastasis and history of other malignancies than targeted therapy trials. Multivariate analysis demonstrated that industry‐sponsored trials had higher odds of excluding patients with compromised liver function. Conclusion Many clinical trials excluded large segments of the population of patients with cancer. Frequent exclusion criteria included patients with CNS metastasis, history of prior malignancies, and chronic viral infections. The criteria for participation in some clinical trials may be overly restrictive and limit enrollment. Implications for Practice The results of this study revealed that most early phase clinic trials contain strict exclusion criteria, potentially excluding the patients who may be more likely to represent the population treated in clinical settings, leaving patients susceptible to unintended harm from inappropriate generalization of trial results. Careful liberalization of the inclusion/exclusion criteria in clinical trials will allow investigators to understand the benefits and drawbacks of the experimental drug for a broader population, and possibly improve recruitment of patients with cancer into clinical trials.

Trial-level factors affecting accrual and completion of oncology clinical trials: A systematic review

“…Compared to targeted therapy clinical trials, chemotherapy clinical trials were more likely to have exclusion criteria pertaining to CNS metastasis and history of other malignancies. Industry-sponsored trials were more likely to have liver function exclusion criteria than those with other types of sponsors such as the NCI or universities [ 31 ].…”

“…Each eligibility criterion needs to be evaluated to ensure it is supported by the scientific literature and not included just because it was contained in previous protocols [ 34 ]. Duma et al [ 31 ] also recommends eligibility criteria to be relaxed once a drug's toxicity profile is better understood.…”

Inclusive Cancer Care: Rethinking Patients Living with HIV and Cancer

“…Specifically, future studies should evaluate patient-, provider-, and health system-level barriers that exist this population, as well as test solutions to mitigate these barriers. Additionally, clinical research must be more inclusive of PLHIV and cancer to study this population, which has increasing cancer incidence yet also high exclusion from participation in trials [24]. Inclusion of PLHIV in cancer clinical trials will additionally improve physician confidence that treatments are safe and efficacious and will enhance shared decision-making with patients [25].…”

The effect of prior cancer on non‐small cell lung cancer trial eligibility

“…1 This is despite estimates that up to 70% of patients are very willing to participate in trials, 2 suggesting that multiple barriers exist to enrollment. Prohibitive clinical trial eligibility criteria have been long cited as one of these barriers, [3][4][5] and have led to initiatives to make clinical trial eligibility criteria more inclusive. 6,7 Lung cancer is the leading cause of cancer-related death.…”