Socioeconomic Deprivation and Health Care Use in Patients Enrolled in SWOG Cancer Clinical Trials.

Importance: Reducing acute care use is an important strategy for improving value. Patients with cancer are at risk for unplanned emergency department (ED) visits and hospital stays (HS). Clinical trial patients have homogeneous treatment; despite this, structural barriers to care may independently impact acute care use. Objective: To examine whether ED visits and HS within 12 months of trial enrollment are more common among Medicare enrollees who live in areas of socioeconomic deprivation or have Medicaid insurance. Design, Setting, and Participants: This cohort study included patients with cancer who were 65 years or older and treated in SWOG Cancer Research Network trials from 1999 to 2018 using data linked to Medicare claims. Data were collected from 1999 to 2019 and analyzed from 2022 to 2024. Main Outcomes and Measures: Outcomes were ED visits, HS, and costs in the first year following enrollment. Neighborhood socioeconomic deprivation was measured using patients' zip code linked to the Area Deprivation Index (ADI), measured on a 0 to 100 scale for increasing deprivation and categorized into tertiles (T1 to T3). Type of insurance was classified as Medicare with or without commercial insurance vs dual Medicare and Medicaid. Demographic, clinical, and prognostic factors were captured from trial records. Multivariable regression was used, and the association of ADI and insurance with each outcome was considered separately. Results: In total, 3027 trial participants were analyzed. The median (range) age was 71 (65-98) years, 1280 (32.3%) were female, 221 (7.3%) were Black patients, 2717 (89.8%) were White patients, 90 (3.0%) had Medicare and Medicaid insurance, and 660 (22.3%) were in the areas of highest deprivation (ADI-T3). In all, 1094 patients (36.1%) had an ED visit and 983 patients (32.4%) had an HS. In multivariable generalized estimating equation, patients living in areas categorized as ADI-T3 were more likely to have an ED visit (OR, 1.34; 95% CI, 1.10-1.62; P = .004). A similar but nonsignificant pattern was observed for HS (OR, 1.36; 95% CI, 0.96-1.93; P = .08). Patients from areas with the highest deprivation had a 62% increase in risk of either an ED visit or HS (OR, 1.62; 95% CI, 1.25-2.09; P < .001). Patients with Medicare and Medicaid were 96% more likely to have an ED visit (OR, 1.96; 95% CI, 1.56-2.46; P < .001). Conclusions and Relevance: In this cohort of older patients enrolled in clinical trials, neighborhood deprivation and economic disadvantage were associated with an increase in ED visits and HS. Efforts are needed to ensure adequate resources to prevent unplanned use of acute care in socioeconomically vulnerable populations.

Impact of Broadening Trial Eligibility Criteria on the Inclusion of Patients With Brain Metastases in Cancer Clinical Trials: Time Series Analyses for 2012-2022.

PURPOSE: In October 2017, an ASCO, Friends of Cancer Research (FoCR), and US Food and Drug Administration (ASCO/FoCR/FDA) task force recommended that common eligibility criteria be modified to make trials more inclusive. We examined whether patterns of exclusions regarding patients with brain metastases changed over time in relation to these recommendations. METHODS: Trial eligibility criteria were abstracted from ClinicalTrials.gov for phase I-III US-based interventional clinical trials for patients with advanced breast, colorectal, lung, or melanoma cancers from January 2012 to December 2022. Trials were examined to determine whether patients with brain metastases were not excluded, conditionally excluded (ie, excluded in some circumstances), or wholly excluded. An interrupted time series analysis with multinomial logistic regression was used to determine whether the ASCO/FoCR/FDA recommendations were associated with changes in brain metastases criteria. RESULTS: We evaluated N = 3,077 trials. Patients with brain metastases were not excluded in 506 trials (16.4%), conditionally excluded in 2,263 trials (73.5%), and wholly excluded in 308 trials (10.0%). In the postrecommendation period, we estimated a 68% increase in the odds of brain metastases not excluded compared with conditionally excluded (odds ratio, 1.68 [95% CI, 1.06 to 2.66], P = .03). The proportion of trials in which patients with brain metastases were not excluded increased (from 11.5% v 17.3%) and conditionally excluded decreased (from 82.3% to 75.2%, P = .03). We found no difference in the proportion of trials in which patients with brain metastases were wholly excluded (7.5% v 6.2%, P = .42). CONCLUSION: The ASCO/FoCR/FDA task force recommendations were associated with a shift in patterns of brain metastases exclusion criteria from conditionally excluded to not excluded. These findings demonstrate that the cancer clinical trial community has begun to change the way trials are written to be more inclusive.

Universal Viral Screening of Patients with Newly Diagnosed Cancer in the United States: A Cost-efficiency Evaluation.

Recommendations for universal screening of patients with cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are inconsistent. A recent multisite screening study (S1204) from the SWOG Cancer Research Network found that a substantial number of patients with newly diagnosed cancer had previously unknown viral infections. The objective of this study was to determine the cost-efficiency of universal screening of patients with newly diagnosed cancer. We estimated the cost-efficiency of universal screening of new cancer cases for HBV, HCV, or HIV, expressed as cost per virus detected, from the health care payer perspective. The prevalence of each virus among this cohort was derived from S1204. Direct medical expenditures included costs associated with laboratory screening tests. Costs per case detected were estimated for each screening strategy. Secondary analysis examined the cost-efficiency of screening patients whose viral status at cancer diagnosis was unknown. Among the possible options for universal screening, screening for HBV alone ($581), HCV alone ($782), HBV and HCV ($631) and HBV, HCV, and HIV ($841) were most efficient in terms of cost per case detected. When screening was restricted to patients with unknown viral status, screening for HBV alone ($684), HBV and HCV ($872), HBV and HIV ($1,157), and all three viruses ($1,291) were most efficient in terms of cost per newly detected case. Efficient viral testing strategies represent a relatively modest addition to the overall cost of managing a patient with cancer. Screening for HBV, HCV, and HIV infections may be reasonable from both a budget and clinical standpoint. SIGNIFICANCE: Screening patients with cancer for HBV, HCV, and HIV is inconsistent in clinical practice despite national recommendations and known risks of complications from viral infection. Our study shows that while costs of viral screening strategies vary by choice of tests, they present a modest addition to the cost of managing a patient with cancer.

Representativeness of Patients Enrolled in the Lung Cancer Master Protocol (Lung-MAP).

PURPOSE: Lung Cancer Master Protocol (Lung-MAP), a public-private partnership, established infrastructure for conducting a biomarker-driven master protocol in molecularly targeted therapies. We compared characteristics of patients enrolled in Lung-MAP with those of patients in advanced non-small-cell lung cancer (NSCLC) trials to examine if master protocols improve trial access. METHODS: We examined patients enrolled in Lung-MAP (2014-2020) according to sociodemographic characteristics. Proportions for characteristics were compared with those for a set of advanced NSCLC trials (2001-2020) and the US advanced NSCLC population using SEER registry data (2014-2018). Characteristics of patients enrolled in Lung-MAP treatment substudies were examined in subgroup analysis. Two-sided tests of proportions at an alpha of .01 were used for all comparisons. RESULTS: A total of 3,556 patients enrolled in Lung-MAP were compared with 2,215 patients enrolled in other NSCLC studies. Patients enrolled in Lung-MAP were more likely to be 65 years and older (57.2% v 46.3%; P < .0001), from rural areas (17.3% v 14.4%; P = .004), and from socioeconomically deprived neighborhoods (42.2% v 36.7%, P < .0001), but less likely to be female (38.6% v 47.2%; P < .0001), Asian (2.8% v 5.1%; P < .0001), or Hispanic (2.4% v 3.8%; P = .003). Among patients younger than 65 years, Lung-MAP enrolled more patients using Medicaid/no insurance (27.6% v 17.8%; P < .0001). Compared with the US advanced NSCLC population, Lung-MAP under represented patients 65 years and older (57.2% v 69.8%; P < .0001), females (38.6% v 46.0%; P < .0001), and racial or ethnic minorities (14.8% v 21.5%; P < .0001). CONCLUSION: Master protocols may improve access to trials using novel therapeutics for older patients and socioeconomically vulnerable patients compared with conventional trials, but specific patient exclusion criteria influenced demographic composition. Further research examining participation barriers for under represented racial or ethnic minorities in precision medicine clinical trials is warranted.

Medicaid Expansion of the Patient Protection and Affordable Care Act and Participation of Patients With Medicaid in Cancer Clinical Trials.

Importance: The Patient Protection and Affordable Care Act (ACA) Medicaid expansion resulted in increased use of Medicaid insurance nationwide. However, the association between Medicaid expansion and access to clinical trials has not been examined to date. Objective: To examine whether the implementation of ACA Medicaid expansion was associated with increased participation of patients with Medicaid insurance in cancer clinical trials. Design, Setting, and Participants: Data for this cohort study of 51 751 patients were from the SWOG Cancer Research Network. All patients aged 18 to 64 years and enrolled in treatment trials with Medicaid or private insurance between April 1, 1992, and February 29, 2020, were included. Interrupted time-series analysis with segmented logistic regression was used. The monthly unemployment rate and presidential administration were adjusted to reflect potential differences in Medicaid use associated with economic conditions and national administrative policies, respectively. Data analysis was conducted between June 22, 2021, and August 5, 2022. Exposure: Implementation of Medicaid expansion on January 1, 2014, was the independent exposure variable. Main Outcomes and Measures: The number and proportion of patients by insurance type enrolled in cancer clinical trials over time were analyzed. Results: Overall, data for 51 751 patients were analyzed. Mean (SD) age was 50.6 (9.8) years, 67.3% of patients were female, 41.1% were younger than 50 years, and 9.1% used Medicaid. A 19% annual increase (odds ratio [OR], 1.19; 95% CI, 1.11-1.28; P < .001) was identified in the odds of patients using Medicaid after the ACA Medicaid expansion, resulting in a 52% increase (OR, 1.52; 95% CI, 1.29-1.78; P < .001) compared with what was expected in the number of Medicaid patients enrolled over time. The association was greater in states that adopted Medicaid expansion in 2014 to 2015 (OR, 1.26; 95% CI, 1.15-1.38; P < .001) compared with other states (OR, 1.08; 95% CI, 0.96-1.21; P = .20; P = .04 for interaction). By February 2020, the proportion of patients with Medicaid insurance was 17.8% (95% CI, 15.0%-20.8%; P < .001), whereas the expected proportion had ACA Medicaid expansion not occurred was 6.9% (95% CI, 4.4%-10.3%; P < .001). Conclusions and Relevance: Findings suggest that implementation of ACA Medicaid expansion was associated with increased participation of patients using Medicaid in cancer clinical trials. Improved participation in clinical trials for Medicaid-insured patients is critical for socioeconomically vulnerable patients seeking access to the newest treatments available in trials and for improving confidence that trial findings apply to patients of all backgrounds.

Assessment of financial screening and navigation capabilities at National Cancer Institute community oncology clinics.

BACKGROUND: Cancer-related financial hardship is a side effect of cancer diagnosis and treatment, and affects both patients and caregivers. Although many oncology clinics have increased financial navigation services, few have resources to proactively provide financial counseling and assistance to families affected by cancer before financial hardship occurs. As part of an ongoing randomized study testing a proactive financial navigation intervention, S1912CD, among sites of the National Cancer Institute Community Oncology Research Program (NCORP), we conducted a baseline survey to learn more about existing financial resources available to patients and caregivers. METHODS: The NCORP sites participating in the S1912CD study completed a required 10-question survey about their available financial resources and an optional 5-question survey that focused on financial screening and navigation workflow and challenges prior to starting recruitment. The proportion of NCORP sites offering financial navigation services was calculated and responses to the optional survey were reviewed to determine current screening and navigation practices and identify any challenges. RESULTS: Most sites (96%) reported offering financial navigation for cancer patients. Sites primarily identified patients needing financial assistance through social work evaluations (78%) or distress screening tools (76%). Sites revealed challenges in addressing financial needs at the outset and through diagnosis, including lack of proactive screening and referral to financial navigation services as well as staffing challenges. CONCLUSIONS: Although most participating NCORP sites offer some form of financial assistance, the survey data enabled identification of gaps and challenges in providing services. Utilizing community partners to deliver comprehensive financial navigation guidance to cancer patients and caregivers may help meet needs while reducing site burden.

Novel Approaches for Dynamic Visualization of Adverse Event Data in Oncology Clinical Trials: A Case Study Using Immunotherapy Trial S1400-I (SWOG).

PURPOSE: Clinical trial adverse event (AE) data are increasingly complex and high-dimensional, especially for trials evaluating novel targeted agents and immunotherapies. Standard approaches to summarize and analyze AEs remain generally tabular, failing to describe the nature of AEs. Novel dynamic and data visualization methods are needed to enable a more comprehensive assessment of the overall toxicity profile of treatments. METHODS: We developed methods for visualizing the numerous categorizations and types of AEs along with a dynamic approach to better reflect its highly dimensional nature without sacrificing the reporting of rare events. Circular plots displaying the proportion of maximal-grade AEs by system organ classes (SOCs) and butterfly plots displaying the proportion of AEs by severity for each AE term were developed to enable comparisons of AE patterns by treatment arm. These approaches were applied to a randomized phase III trial (S1400I; ClinicalTrials.gov identifier: NCT02785952) comparing nivolumab with nivolumab plus ipilimumab in patients with stage IV squamous non-small-cell lung cancer. RESULTS: Our visualizations revealed that patients randomly assigned to nivolumab and ipilimumab had higher rates of grade 3 or higher AEs compared with nivolumab alone for several SOCs, including musculoskeletal (5.6% v 0.8%), skin (5.6% v 0.8%), vascular (5.6% v 1.6%), and cardiac (4% v 1.6%) toxicities. They also suggested a pattern of higher prevalence of moderate GI and endocrine toxicities and showed that although the rates of cardiac and neurologic toxicities were similar, the types of events were discordant. CONCLUSION: The graphical approaches we proposed enable a more comprehensive and intuitive evaluation of toxicity types by treatment groups, which is not apparent in tabular and descriptive reporting methods.

Racial and Ethnic Disparity in Preference-Weighted Quality of Life: Findings from the Selenium and Vitamin E Cancer Prevention Trial.

Differences in preference-weighted health-related quality of life (HRQOL) scores by race/ethnicity may be due to social factors. Here, Short-Form Six-Dimension (SF-6D) scores are analyzed among men in a prostate cancer prevention trial to explore such differences. Selenium and vitamin E cancer prevention trial participants who completed the SF-6D at baseline, and in at least 1 of follow-up years 1, 3, and 5 were included. This study compared mean SF-6D scores across race/ethnicity at each point using a linear mixed model controlling for demographic and clinical characteristics. At baseline, 9691 men were eligible for analysis, of whom 7556 (78%) were non-Hispanic White, 1592 (16.4%) were non-Hispanic Black, and 543 (5.6%) were Hispanic. Hispanic and White participants had higher unadjusted mean SF-6D scores than Black participants at every time point (P < 0.05), while white participants had lower mean scores than Hispanic participants at every time point after baseline (P < 0.05). After adjusting for covariates, statistically significant differences in HRQOL among the 3 groups persisted. Hispanic participants had higher preference scores than White participants by 0.073 (P < 0.001), 0.075 (P < 0.001), and 0.040 (P < 0.001) in follow-up years 1, 3, and 5, respectively. Black participants had lower scores than White participants by 0.009 (P = 0.004) and 0.008 (P = 0.02) in follow-up years 1 and 3, respectively. The results suggest there is a preference-weighted HRQOL difference by race/ethnicity that cannot be explained by social and clinical variables alone. Understanding how individuals belonging to different racial/ethnic categories view their own HRQOL is necessary for culturally competent care and cost-effectiveness analyses.

Population, Clinical, and Scientific Impact of National Cancer Institute's National Clinical Trials Network Treatment Studies.

PURPOSE: In the United States, the National Cancer Institute National Cancer Clinical Trials Network (NCTN) groups have conducted publicly funded oncology research for 50 years. The combined impact of all adult network group trials has never been systematically examined. METHODS: We identified randomized, phase III trials from the adult NCTN groups, reported from 1980 onward, with statistically significant findings for ≥ 1 clinical, time-dependent outcomes. In the subset of trials in which the experimental arm improved overall survival, gains in population life-years were estimated by deriving trial-specific hazard functions and hazard ratios to estimate the experimental treatment benefit and then mapping this trial-level benefit onto the US cancer population using registry and life-table data. Scientific impact was based on citation data from Google Scholar. Federal investment costs per life-year gained were estimated. The results were derived through December 31, 2020. RESULTS: One hundred sixty-two trials comprised of 108,334 patients were analyzed, representing 29.8% (162/544) of trials conducted. The most common cancers included breast (34), gynecologic (28), and lung (14). The trials were cited 165,336 times (mean, 62.2 citations/trial/year); 87.7% of trials were cited in cancer care guidelines in favor of the recommended treatment. These studies were estimated to have generated 14.2 million (95% CI, 11.5 to 16.5 million) additional life-years to patients with cancer, with projected gains of 24.1 million (95% CI, 19.7 to 28.2 million) life-years by 2030. The federal investment cost per life-year gained through 2020 was $326 in US dollars. CONCLUSION: NCTN randomized trials have been widely cited and are routinely included in clinical guidelines. Moreover, their conduct has predicted substantial improvements in overall survival in the United States for patients with oncologic disease, suggesting they have contributed meaningfully to this nation's health. These findings demonstrate the critical role of government-sponsored research in extending the lives of patients with cancer.

Sex, Racial, and Ethnic Representation in COVID-19 Clinical Trials: A Systematic Review and Meta-analysis.

Importance: Since the onset of the COVID-19 pandemic, there have been calls for COVID-19 clinical trials to be fully representative of all demographic groups. However, limited evidence is available about the sex, racial, and ethnic representation among COVID-19 prevention and treatment trials. Objective: To investigate whether female participants and racial and ethnic minority individuals are adequately represented in COVID-19 prevention and treatment trials in the US. Data Sources: Identified studies were registered on ClinicalTrials.gov or published in the PubMed database from October 2019 to February 2022. Study Selection: Included studies must have provided the number of enrolled participants by sex, race, or ethnicity. Only interventional studies conducted in the US for the primary purpose of the diagnosis, prevention, or treatment of (or supportive care for) COVID-19 conditions were included. Data Extraction and Synthesis: Data on counts of enrollments by demographic variables (sex, race, and ethnicity) and location (country and state) were abstracted. Studies were broadly categorized by primary purpose as prevention (including vaccine and diagnosis studies) vs treatment (including supportive care studies). A random effects model for single proportions was used. Trial estimates were compared with corresponding estimates of representation in the US population with COVID-19. Main Outcomes and Measures: Sex, racial, and ethnic representation in COVID-19 clinical trials compared with their representation in the US population with COVID-19. Results: Overall, 122 US-based COVID-19 clinical trials comprising 176 654 participants were analyzed. Studies were predominantly randomized trials (n = 95) for treatment of COVID-19 (n = 103). Sex, race, and ethnicity were reported in 109 (89.3%), 95 (77.9%), and 87 (71.3%) trials, respectively. Estimated representation in prevention and treatment trials vs the US population with COVID-19 was 48.9% and 44.6% vs 52.4% for female participants; 23.0% and 36.6% vs 17.7% for Hispanic or Latino participants; 7.2% and 16.5% vs 14.1% for Black participants; 3.8% and 4.6% vs 3.7% for Asian participants; 0.2% and 0.9% vs 0.2% for Native Hawaiian or Other Pacific Islander participants; and 1.3% and 1.4% vs 1.1% for American Indian or Alaska Native participants. Compared with expected rates in the COVID-19 reference population, female participants were underrepresented in treatment trials (85.1% of expected; P < .001), Black participants (53.7% of expected; P = .003) and Asian participants (64.4% of expected; P = .003) were underrepresented in prevention trials, and Hispanic or Latino participants were overrepresented in treatment trials (206.8% of expected; P < .001). Conclusions and Relevance: In this systematic review and meta-analysis, aggregate differences in representation for several demographic groups in COVID-19 prevention and treatment trials in the US were found. Strategies to better ensure diverse representation in COVID-19 studies are needed, especially for prevention trials.

Trends in Obesity Prevalence Among Patients Enrolled in Clinical Trials for Obesity-Related Cancers, 1986 to 2016.

Importance: Obesity rates have risen in the United States since the 1980s. Several studies have shown links between obesity and the incidence of specific cancer types, but none have systematically examined obesity prevalence at the time of cancer diagnosis, or among clinical trial participants, all of which may affect clinical outcomes. Objective: To examine the prevalence of obesity and, separately, overweight and obesity over 30 years among patients with cancer enrolled in clinical treatment trials for obesity-related cancers; and to compare trends with corresponding trends in the US. Design, Setting, and Participants: This cohort study examined clinical treatment trials for obesity-related cancers conducted by the SWOG Cancer Research Network at community and academic sites. Participants included adult patients enrolled in phase 2 or phase 3 clinical treatment trials in obesity-related cancers between 1986 and 2016. Statistical analysis was performed from June 2020 to July 2022. Exposures: Year of enrollment to a clinical trial. Main Outcomes and Measures: Prevalence of obesity (body mass index [BMI] ≥ 30) and overweight or obesity (BMI > 25) at the time of clinical trial enrollment. Multivariable logistic regression analysis, adjusted for demographic and clinical factors, was used to analyze patient height and weight collected at clinical trial enrollment. Results: Among 23 926 patients (median [IQR] age, 58 [51-66] years; 17 594 [73.5%] female; 969 [4.0%] Hispanic, 2173 [9.1%] non-Hispanic Black, 19 890 [83.1%] non-Hispanic White) enrolled between 1986 and 2016, unadjusted obesity rates increased from 23.5% (in 1986 to 1990 [n = 657]) to 42.3% (in 2011 to 2016 [n = 836]). There was an increasing linear trend in obesity (odds ratio [OR], 1.23 for each 5-year increase; 95% CI, 1.21-1.26; P < .001), which persisted after covariate adjustment for demographic and clinical characteristics. Findings were consistent for the combined prevalence of overweight and obesity. The observed overall increasing trend in obesity prevalence from 1999-2000 to 2015-2016 was greater in trial patients (21.3% [SE = 0.7] to 49.1% [SE = 1.6]) than in US adults (30.5% [SE = 1.5] to 39.6% [SE = 1.6]) (P for trend = .03), but was similar to US cancer survivors (18.9% [SE = 1.9] to 42.2% [SE = 2.1]; P for trend = .31). Conclusions and Relevance: This cohort study found that patients with cancer and obesity are currently well-represented in cancer clinical trials, increasing confidence that trial findings are generalizable to patients with obesity in clinical practice. Availability of data on height and weight at diagnosis through cancer registries will enable a more rigorous analysis of obesity prevalence among patients with cancer.

Access to urologists for participation in research: An analysis of NCI's Community Oncology Research Program landscape survey.

Purpose: Urological cancer clinical trials face accrual challenges, which may stem from structural barriers within cancer programs. We sought to describe the extent to which urology cancer care providers are available within community cancer research programs and explore the role of oncology practice group ownership in their access to urology practices to participate in research. Materials and methods: We conducted secondary analysis of organizational survey data collected in 2017 among National Cancer Institute Community Oncology Research Program practice groups. We used logistic regression to assess the association of self-reported access to urologists to participate in research and oncology practice group ownership type: independent, payor-provider, health-system, or public ownership. Results: Of the 209 community oncology practice groups in the analysis sample, 133 (63.6%) had access to urologists for research participation. Ownership was not statistically significantly associated with access to urology practices after controlling for other covariates (p = 0.4). Instead, having a hospital outpatient clinic (p = 0.008) and identifying as a safety-net hospital (p = 0.035) were both positively significantly associated with access to urologists to participate in research. Conclusions: Two-thirds of community cancer research groups have access to urology. Oncology ownership status was not associated with access to urologists for research. Research groups may need support to increase their capacity to engage non-oncology cancer care providers in research.

Sex Differences in Risk of Severe Adverse Events in Patients Receiving Immunotherapy, Targeted Therapy, or Chemotherapy in Cancer Clinical Trials.

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.

"When Offered to Participate": A Systematic Review and Meta-Analysis of Patient Agreement to Participate in Cancer Clinical Trials.

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 January 1, 2000, to January 1, 2020, that examined clinical trial participation in the United States. 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 2-sided. RESULTS: We identified 35 studies (30 about treatment trials and 5 about cancer control trials) among which 9759 patients were offered trial participation. Overall, 55.0% (95% confidence interval [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 with White patients (55.1%, 95% CI = 44.3% to 65.6%; P = .88). The main reasons for nonparticipation 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.

Economic Evaluations in National Cancer Institute-Sponsored Network Cancer Clinical Trials.

OBJECTIVES: Amid a rapid increase in cancer care costs, we examined the extent to which economic evaluations (EEs) were conducted for new treatments evaluated in clinical trials at SWOG, a large National Cancer Institute-sponsored cancer research network. METHODS: We investigated phase III cancer treatment clinical trials activated from 1980 onward with primary articles reporting the protocol-designated endpoints published in scientific journals by 2017. Using PubMed, Web of Science, and EconLit, we searched for EEs using trial name, cancer type, information on the comparison arms, and refined keywords for EE designs. We reported the overall proportion of trials with associated EEs and trends of this proportion over time. We synthesized and analyzed information on funding sources, health outcomes, and sources of quality-of-life and cost data from the EEs. RESULTS: Among 182 examined trials, 15 EEs were associated with 13 (7.1%) trials. Among the EEs, almost half (7 of 15) were either unfunded or did not report funding information, whereas nearly half (7 of 15) were funded by pharmaceutical companies and 2 (2 of 15, 13.3%) were supported by federal funding. All EEs reported a healthcare payer perspective. The proportion of trials with an associated EE increased from 1980 to 1989 and 2000 to 2009, but never exceeded 11%. Sources for cost and quality-of-life data for the EEs primarily came from outside the clinical trials. CONCLUSIONS: Few economic studies of treatments evaluated in National Cancer Institute-sponsored clinical trials have been conducted. Policymakers, payers, and patients lack economic evidence to consider newly evaluated cancer treatments, despite an urgent need to control healthcare costs.

Association of Patient Demographic Characteristics and Insurance Status With Survival in Cancer Randomized Clinical Trials With Positive Findings.

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 (≥65 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; P = .09) compared with those with private insurance (HR, 1.66; 95% CI, 1.44-1.92; P < .001; P = .03 for interaction). Receipt of experimental treatment was associated with reduced added overall survival benefits in patients 65 years or older (HR, 1.21; 95% CI, 1.11-1.32; P < .001) compared with patients younger than 65 years (HR, 1.41; 95% CI, 1.30-1.53; P < .001; P = .01 for interaction), although both older and younger patients appeared to strongly benefit from receipt of experimental treatment. The progression- or relapse-free survival HRs did not differ by age, sex, or race/ethnicity but differed between patients with Medicaid or no insurance (HR, 1.32; 95% CI, 1.06-1.64; P = .01) vs private insurance (HR, 1.74; 95% CI, 1.54-1.97; P < .001; P = .03 for interaction). Conclusions and Relevance: Patients with Medicaid or no insurance may have smaller added benefits from experimental therapies compared with standard treatments in clinical trials. A better understanding of the quality of survivorship care that patients with suboptimal insurance receive, including supportive care and posttreatment care, could help establish how external factors may affect outcomes for these patients.

Healthcare utilization and cost of care in elderly breast cancer patients enrolled in SWOG clinical trials.

IMPORTANCE: Patients with cancer are at risk for unplanned hospitalizations during treatment which can increase the cost of care. OBJECTIVES: To determine demographic and clinical factors associated with healthcare utilization and costs among clinical trial participants. DESIGN, SETTING, AND PATIENTS: We conducted a retrospective analysis among breast cancer patients over the age of 65 treated on SWOG clinical trials from 1999 to 2011 with trial data linked to Medicare claims. MAIN OUTCOMES AND MEASURES: The outcomes were healthcare utilization (emergency room visits (ER), hospitalizations) and costs from Medicare Claims. Demographic, clinical, and prognostic factors were captured from clinical trial records. We identified cardiovascular comorbidities/risk factors (CVD-RFs) of diabetes, hypertension, hypercholesterolemia, and coronary artery disease (CAD) from Medicare claims. Multivariable logistic and linear regression were used to assess the association between CVD-RFs and outcomes. RESULTS: Among the 708 patients included in the analysis, 160 (22.6%) experienced 234 separate hospitalizations, and 193 (27.3%) experienced 311 separate ER visits. Black race was associated with an increase in hospitalizations (OR [95% CI], 2.52 [1.10-5.79], p = 0.03), but not emergency room visits compared to white race. Diabetes, hypertension, hypercholesterolemia, and CAD were all independently associated with increased risk of both hospitalizations and ER visit. Hypertension had the strongest association, with more than a threefold risk of hospitalization for those with hypertension compared to those without (OR [95% CI], 3.16 [1.85-5.40], p < 0.001). For those with ≥ 3 RFs, the risk of hospitalization was nearly 3 times greater compared to 0 or 1 CVD-RFs (OR [95% CI], 2.74 [1.71-4.38], p < 0.001). Similar results were seen for ER visits. In the first 12 months after trial registration, patients with diabetes ($38,324 vs $30,923, 23.9% increase, p = 0.05), hypercholesterolemia ($34,168 vs $30,661, 11.4% increase, p = 0.02), and CAD ($37,781 vs $31,698, 19.2% increase, p = 0.04) had statistically significantly higher total healthcare costs. Additionally, those with ≥ 2 significant CVD-RFs ($35,353 vs. $28,899, 22.3% increase, p = 0.005) had statistically significantly higher total healthcare costs. CONCLUSIONS: Among participants treated on clinical trials, black race and presence of multiple cardiovascular comorbidities was associated with a substantial increase in ER visits, hospitalizations and healthcare costs. Efforts to reduce unplanned hospitalizations should focus on this high-risk group.

Association of National Cancer Institute-Sponsored Clinical Trial Network Group Studies With Guideline Care and New Drug Indications.

Importance: National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying effective new antineoplastic regimens. However, the downstream clinical effect of their trials has not been systematically examined. Objective: To examine the association of NCTN trials with guideline care and new drug indications. Design, Setting, and Participants: This retrospective cohort study evaluated phase 3 SWOG Cancer Research Network clinical trials from January 1, 1980, through June 30, 2017. Only completed trials with published results were included. To be considered practice influential (PI), a trial must have been associated with guideline care through its inclusion in National Comprehensive Cancer Network (NCCN) clinical guidelines or US Food and Drug Administration (FDA) new drug approvals in favor of a recommended treatment. Data were analyzed from June 15, 2018, through March 29, 2019. Main Outcomes and Measures: Estimated overall rate of PI trials, as well as trends over time. The total federal investment supporting the set of trials was also determined. Results: In total, 182 trials consisting of 148 028 patients were studied. Eighty-two studies (45.1%; 95% CI, 37.7%-52.6%) were PI, of which 70 (38.5%) influenced NCCN guidelines, 6 (3.3%) influenced FDA new drug approvals, and 6 (3.3%) influenced both. The number of PI trials was 47 of 65 (72.3%) among those with positive findings and 35 of 117 (29.9%) among those with negative findings. Thus, 35 of 82 PI trials (42.7%) were based on studies with negative findings, with nearly half of these studies (17 of 35 [48.6%]) reaffirming standard of care compared with experimental therapy. The total federal investment spent in conducting the trials was $1.36 billion (2017 US dollars), a rate of $7.5 million per study or $16.6 million per PI trial. Conclusions and Relevance: Nearly half of all phase 3 trials by one of the NCTN's largest groups were associated with guideline care or new drug indications, including those with positive and negative findings. Compared with the costs of a new drug approval in pharmaceutical companies, typically estimated at more than $1 billion, the amount of federal funds invested to provide this valuable evidence was modest. These results suggest that the NCTN program contributes clinically meaningful, cost-efficient evidence to guide patient care.

Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation.

BACKGROUND: Barriers 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: These 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.