BackgroundBarriers to cancer clinical trial participation have been the subject of frequent study, but the rate of trial participation has not changed substantially over time. Studies often emphasize patient-related barriers, but other types of barriers may have greater impact on trial participation. Our goal was to examine the magnitude of different domains of trial barriers by synthesizing prior research.MethodsWe conducted a systematic review and meta-analysis of studies that examined the trial decision-making pathway using a uniform framework to characterize and quantify structural (trial availability), clinical (eligibility), and patient/physician barrier domains. The systematic review utilized the PubMed, Google Scholar, Web of Science, and Ovid Medline search engines. We used random effects to estimate rates of different domains across studies, adjusting for academic vs community care settings.ResultsWe identified 13 studies (nine in academic and four in community settings) with 8883 patients. A trial was unavailable for patients at their institution 55.6% of the time (95% confidence interval [CI] = 43.7% to 67.3%). Further, 21.5% (95% CI = 10.9% to 34.6%) of patients were ineligible for an available trial, 14.8% (95% CI = 9.0% to 21.7%) did not enroll, and 8.1% (95% CI = 6.3% to 10.0%) enrolled. Rates of trial enrollment in academic (15.9% [95% CI = 13.8% to 18.2%]) vs community (7.0% [95% CI = 5.1% to 9.1%]) settings differed, but not rates of trial unavailability, ineligibility, or non-enrollment.ConclusionsThese findings emphasize the enormous need to address structural and clinical barriers to trial participation, which combined make trial participation unachievable for more than three of four cancer patients.

Background Patient participation in clinical trials is vital for knowledge advancement and outcomes improvement. Few adult cancer patients participate in trials. Although patient decision-making about trial participation has been frequently examined, the participation rate for patients actually offered a trial is unknown. Methods A systematic review and meta-analysis using 3 major search engines was undertaken. We identified studies from 1/1/2000-1/1/2020 that examined clinical trial participation in the U.S. Studies must have specified the numbers of patients offered a trial and the number enrolled. A random effects model of proportions was used. All statistical tests were two-sided. Results We identified 35 studies (30 about treatment trials and 5 about cancer control trials) among which 9,759 patients were offered trial participation. Overall, 55.0% (95% CI: 49.4% to 60.5%) of patients agreed to enroll. Participation rates did not differ between treatment (55.0%, 95% CI: 48.9% to 60.9%) and cancer control trials (55.3%, 95% CI: 38.9% to 71.1%, p=.98). Black patients participated at similar rates (58.4%, 95% CI: 46.8% to 69.7%) compared to White patients (55.1%, 95% CI: 44.3% to 65.6%, p=.88). The main reasons for non-participation were treatment choice or lack of interest. Conclusions More than half of all cancer patients offered a clinical trial do participate. These findings upend several conventional beliefs about cancer clinical trial participation, including that Black patients are less likely to agree to participate and that patient decision-making is the primary barrier to participation. Policies and interventions to improve clinical trial participation should focus more on modifiable systemic structural and clinical barriers, such as improving access to available trials and broadening eligibility criteria.

the US Food and Drug Administration recently recommended modernizing criteria related to comorbidities routinely used to exclude patients from cancer clinical trials. The goal was to design clinical trial eligibility such that trial results better reflect real-world cancer patient populations, to improve clinical trial participation, and to increase patient access to new treatments in trials. Yet despite the assumed influence of comorbidities on trial participation, the relationship between patients' comorbidity profile at diagnosis and trial participation has not been explicitly examined using patient-level data.OBJECTIVES To investigate the association between comorbidities, clinical trial decision-making, and clinical trial participation; and to estimate the potential impact of reducing comorbidity exclusion criteria on trial participation, to provide a benchmark for changing criteria. DESIGN, SETTING, AND PARTICIPANTSA national survey was embedded within a web-based cancer treatment-decision tool accessible on multiple cancer-oriented websites. Participants must have received a diagnosis of breast, lung, colorectal, or prostate cancer. In total, 5499 surveyed patients who made a treatment decision within the past 3 months were analyzed using logistic regression analysis and simulations.EXPOSURES Cancer diagnosis and 1 or more of 18 comorbidities. MAIN OUTCOMES AND MEASURESPatient discussion of a clinical trial with their physician (yes vs no); if a trial was discussed, the offer of trial participation (yes vs no); and, if trial participation was offered, trial participation (yes vs no). RESULTSOf the 5499 patients who participated in the survey, 3420 (62.6%) were women and 2079 (37.8%) were men (mean [SD] age, 56.63 [10.05] years). Most patients (65.6%; n = 3610) had 1 or more comorbidities. The most common comorbid condition was hypertension (35.0%; n = 1924). Compared with the absence of comorbidities, the presence of 1 or more comorbidities was associated with a decreased risk of trial discussions (44.1% vs 37.2%; OR, 0.86; 95% CI, 0.75-0.97; P = .02), trial offers (21.7% vs 15.7%; OR, 0.82; 95% CI, 0.70-0.96; P = .02), and trial participation (11.3% vs 7.8%; OR, 0.76; 95% CI, 0.61-0.94; P = .01). The removal of the ASCO-recommended comorbidity restrictions could generate up to 6317 additional patient trial registrations every year.CONCLUSIONS AND RELEVANCE Independent of sociodemographic variables, the presence of comorbidities is adversely associated with trial discussions, trial offers, and trial participation itself. Updating trial eligibility criteria could provide an opportunity for several thousand more patients with well-managed comorbidities to participate in clinical trials each year.

PURPOSE Women have more adverse events (AEs) from chemotherapy than men, but few studies have investigated sex differences in immune or targeted therapies. We examined AEs by sex across different treatment domains. METHODS We analyzed treatment-related AEs by sex in SWOG phase II and III clinical trials conducted between 1980 and 2019, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events. Symptomatic AEs were defined as those aligned with the National Cancer Institute's Patient-Reported Outcome–Common Terminology Criteria for Adverse Events; laboratory-based or observable/measurable AEs were designated as objective (hematologic v nonhematologic). Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 14 objective AE categories were examined. RESULTS In total, N = 23,296 patients (women, 8,838 [37.9%]; men, 14,458 [62.1%]) from 202 trials experiencing 274,688 AEs were analyzed; 17,417 received chemotherapy, 2,319 received immunotherapy, and 3,560 received targeted therapy. Overall, 64.6% (n = 15,051) experienced one or more severe (grade ≥ 3) AEs. Women had a 34% increased risk of severe AEs compared with men (odds ratio [OR] = 1.34; 95% CI, 1.27 to 1.42; P < .001), including a 49% increased risk among those receiving immunotherapy (OR = 1.49; 95% CI, 1.24 to 1.78; P < .001). Women experienced an increased risk of severe symptomatic AEs among all treatments, especially immunotherapy (OR = 1.66; 95% CI, 1.37 to 2.01; P < .001). Women receiving chemotherapy or immunotherapy experienced increased severe hematologic AE. No statistically significant sex differences in risk of nonhematologic AEs were found. CONCLUSION The greater severity of both symptomatic AEs and hematologic AEs in women across multiple treatment modalities indicates that broad-based sex differences exist. This could be due to differences in AE reported, pharmacogenomics of drug metabolism/disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving immunotherapy, suggesting that studying AEs from these agents is a priority.

IMPORTANCE Few new treatments tested in phase 3 cancer randomized clinical trials show an overall survival benefit. Although understanding whether the benefits are consistent among all patient groups is critical for informing guideline care, individual trials are designed to assess the benefits of experimental treatments among all patients and are too small to reliably determine whether treatment benefits apply to demographic or insurance subgroups. OBJECTIVE To systematically examine whether positive treatment effects in cancer randomized clinical trials apply to specific demographic or insurance subgroups. DESIGN, SETTING, AND PARTICIPANTS Cohort study of pooled patient-level data from 10 804 patients in SWOG Cancer Research Network clinical treatment trials reported from 1985 onward with superior overall survival for those receiving experimental treatment. Patients were enrolled from 1984 to 2012. Maximum follow-up was 5 years. MAIN OUTCOMES AND MEASURES Interaction tests were used to assess whether hazard ratios (HRs) for death comparing standard group vs experimental group treatments were associated with age (Ն65 vs <65 years), race/ethnicity (minority vs nonminority populations), sex, or insurance status among patients younger than 65 years (Medicaid or no insurance vs private insurance) in multivariable Cox regression frailty models. Progression-or relapse-free survival was also examined. Data analyses were conducted from August 2019 to February 2020. RESULTS In total, 19 trials including 10 804 patients were identified that reported superior overall survival for patients randomized to experimental treatment. Patients were predominantly younger than 65 years (67.3%) and female (66.3%); 11.4% were black patients, and 5.7% were Hispanic patients. There was evidence of added survival benefits associated with receipt of experimental therapy for all groups except for patients with Medicaid or no insurance (HR, 1.23; 95% CI, 0.97-1.56;