Update on Enrollment of Older Adults Onto National Cancer Institute National Clinical Trials Network Trials.

BACKGROUND: Older adults are a large and growing proportion of cancer cases in the United States, but concerns persist about whether older adults are adequately represented in the cancer clinical trials that test new options for treatment and cancer care. METHODS: This paper describes adult patient enrollments by age group to the National Cancer Institute's National Clinical Trials Network (NCTN) from 2016 to 2021, compares patient enrollment by age with the estimated incident cancer population across cancer types, and explores possible associations between patient age and patient race, ethnicity, and sex. RESULTS: This analysis found that patients aged 18 to 69 years were overrepresented in NCTN trials, whereas patients aged 70 years and older were underrepresented compared with the estimated incident cancer population. Underrepresentation of older patients was seen across cancer types. Older patients who enrolled to NCTN trials were more likely to be non-Hispanic White than the estimated incident cancer population. CONCLUSIONS: Compared with earlier analyses, NCTN trials are enrolling greater proportions of older adults, primarily driven by higher enrollment among patients aged 65 to 74 years. There is still significant room for improvement, however, especially among patients aged 75 years and older. Additionally, patient demographics should not be viewed in isolation: older Hispanic patients, for instance, were particularly underrepresented among patients enrolled to NCTN trials. The intersection between trial enrollment and age, race, and ethnicity warrants further study so that more targeted enrollment enhancement efforts can be developed that enhance trial diversity across demographic groups.

Implementing Modernized Eligibility Criteria in US National Cancer Institute Clinical Trials.

In 2018, the Cancer Therapy Evaluation Program (CTEP) at the US National Cancer Institute published new protocol template language that focused on organ function and prior and concurrent cancers in an effort to modernize eligibility criteria for cancer treatment trials. We conducted an analysis of CTEP-supported trials to evaluate the uptake and incorporation of the new language. The analysis included evaluation of 122 protocols approved in the years 2018-2020 for inclusion of the modernized eligibility criteria and consistency with new protocol template language related to 7 major eligibility criteria. These were cardiac function, liver function, kidney function, HIV status, prior and/or concurrent malignancies, treated and/or stable brain metastasis, and new and/or progressive brain metastases. Overall, CTEP trials evaluated in this period demonstrated that eligibility criteria were implemented to a relatively high degree ranging from a low of 54.1% for prior and/or concurrent malignancies to a high of 93.4% for eligibility criteria related to HIV infection. The findings demonstrate that modernized eligibility criteria can be successfully implemented but that consistent implementation requires sustained focused effort. As a result of these findings, CTEP began a new initiative in January 2022 that incorporates a specific review of eligibility criteria for new protocols to promote and improve consistency with the modernization effort.

Continuing to Broaden Eligibility Criteria to Make Clinical Trials More Representative and Inclusive: ASCO-Friends of Cancer Research Joint Research Statement.

PURPOSE: Restrictive clinical trial eligibility criteria (EC) limit the number of patients who can enroll and potentially benefit from protocol-driven, investigational treatment plans and reduce the generalizability of trial results to the broader population. Following publication of expert stakeholder recommendations for broadening EC in 2017, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) convened working groups to produce additional recommendations and analyze the potential impact on clinical trials using real-world data. EXPERIMENTAL DESIGN: Multistakeholder working groups were appointed by an ASCO-Friends leadership group to propose recommendations for more inclusive EC related to: washout periods, concomitant medications, prior therapies, laboratory reference ranges and test intervals, and performance status. RESULTS: The four working groups, ASCO Board of Directors, and Friends leadership support the recommendations included in this statement to modernize EC related to washout periods, concomitant medications, prior therapies, laboratory references ranges and test intervals, and performance status to make trial populations more inclusive and representative of cancer patient populations. CONCLUSIONS: Implementation of the recommendations is intended to result in greater ease of determining patient eligibility. Increased opportunities for patient participation in research will help address longstanding underrepresentation of certain groups in clinical trials and produce evidence that is more informative for a broader patient population. More patients eligible will also likely speed clinical trial accrual.See related commentary by Giantonio, p. 2369.

The National Cancer Institute and Department of Veterans Affairs Interagency Group to Accelerate Trials Enrollment (NAVIGATE): A federal collaboration to improve cancer care.

Cancer clinical trials represent an important option for patients with a diagnosis of cancer and the clinician-investigators involved in their care who seek options for their disease. For all who are impacted by cancer, these studies offer opportunities for greater learning. Conducting these important studies involves several challenges, including recruiting eligible participants. To address barriers that arise over the course of these activities, the Department of Veterans Affairs (VA) and National Cancer Institute (NCI) have partnered to increase Veteran participation in oncology clinical trials. This initiative, the NCI And VA Interagency Group to Accelerate Trials Enrollment, or NAVIGATE, is focused on addressing recruitment across the VA healthcare system and finding systematic solutions related to activating, recruiting for and conducting oncology clinical trials at VA Medical Centers. Additional goals include (1) establishing a sustainable network that can serve as a model for other VA sites interested in doing cancer clinical trials, (2) recruitment of minority patients, and (3) developing best practices and policies that can be deployed across the VA healthcare system. In this manuscript, we describe the scope, organization, activities, and future directions of NAVIGATE while also highlighting key needs for successfully conducting cancer clinical trials within the VA system. This partnership between 2 large federal agencies with a shared commitment to improving cancer care may provide lessons to others who are also dedicated to helping those affected by the disease.

Feasibility of Implementing the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events in a Multicenter Trial: NCCTG N1048.

Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute-sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.

Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement.

Purpose The primary purposes of eligibility criteria are to protect the safety of trial participants and define the trial population. Excessive or overly restrictive eligibility criteria can slow trial accrual, jeopardize the generalizability of results, and limit understanding of the intervention's benefit-risk profile. Methods ASCO, Friends of Cancer Research, and the US Food and Drug Administration examined specific eligibility criteria (ie, brain metastases, minimum age, HIV infection, and organ dysfunction and prior and concurrent malignancies) to determine whether to modify definitions to extend trials to a broader population. Working groups developed consensus recommendations based on review of evidence, consideration of the patient population, and consultation with the research community. Results Patients with treated or clinically stable brain metastases should be routinely included in trials and only excluded if there is compelling rationale. In initial dose-finding trials, pediatric-specific cohorts should be included based on strong scientific rationale for benefit. Later phase trials in diseases that span adult and pediatric populations should include patients older than age 12 years. HIV-infected patients who are healthy and have low risk of AIDS-related outcomes should be included absent specific rationale for exclusion. Renal function criteria should enable liberal creatinine clearance, unless the investigational agent involves renal excretion. Patients with prior or concurrent malignancies should be included, especially when the risk of the malignancy interfering with either safety or efficacy endpoints is very low. Conclusion To maximize generalizability of results, trial enrollment criteria should strive for inclusiveness. Rationale for excluding patients should be clearly articulated and reflect expected toxicities associated with the therapy under investigation.

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

PURPOSE: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS AND MATERIALS: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. RESULTS: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." CONCLUSIONS: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.

Feasibility Assessment of Patient Reporting of Symptomatic Adverse Events in Multicenter Cancer Clinical Trials.

IMPORTANCE: In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials. OBJECTIVE: To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials. DESIGN, SETTING, AND PARTICIPANTS: A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted κ statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014. RESULTS: Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling "too ill" in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most κ < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 [93.2%]) and useful (230 [93.1%]), and investigators thought that the patient-reported AEs were useful (133 [94.3%]) and accurate (119 [83.2%]). CONCLUSIONS AND RELEVANCE: Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials.

A Randomized Controlled Study Comparing the National Cancer Institute's Original and Revised Consent Form Templates.

Since 1998, the National Cancer Institute (NCI) has mandated that researchers use its consent form template in developing consent forms for their NCI-funded clinical trials. The template was substantially revised in 2013 to aid in the development of simpler, more concise consent forms. The NCI conducted a randomized controlled trial with cancer survivors (N = 153) to assess the revised template's effect on individuals' knowledge, satisfaction, clarity, and likelihood of joining a trial in the future. We found that the revised template resulted in equally high knowledge and satisfaction scores as the original template, but with fewer words and pages. The likelihood that an individual would participate in a trial diminished after he or she reviewed either the original or revised consent form, yet having knowledge about trials before reviewing the consent forms resulted in increased satisfaction. To ensure an informed decision-making process, we recommend using the revised NCI consent form template along with using educational interventions aimed at increasing the understanding potential participants have of a trial before they receive a consent form.

Clinical Trial Assessment of Infrastructure Matrix Tool to Improve the Quality of Research Conduct in the Community.

PURPOSE: Several publications have described minimum standards and exemplary attributes for clinical trial sites to improve research quality. The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) developed the clinical trial Best Practice Matrix tool to facilitate research program improvements through annual self-assessments and benchmarking. The tool identified nine attributes, each with three progressive levels, to score clinical trial infrastructural elements from less to more exemplary. The NCCCP sites correlated tool use with research program improvements, and the NCI pursued a formative evaluation to refine the interpretability and measurability of the tool. METHODS: From 2011 to 2013, 21 NCCCP sites self-assessed their programs with the tool annually. During 2013 to 2014, NCI collaborators conducted a five-step formative evaluation of the matrix tool. RESULTS: Sites reported significant increases in level-three scores across the original nine attributes combined (P<.001). Two specific attributes exhibited significant change: clinical trial portfolio diversity and management (P=.0228) and clinical trial communication (P=.0281). The formative evaluation led to revisions, including renaming the Best Practice Matrix as the Clinical Trial Assessment of Infrastructure Matrix (CT AIM), expanding infrastructural attributes from nine to 11, clarifying metrics, and developing a new scoring tool. CONCLUSION: Broad community input, cognitive interviews, and pilot testing improved the usability and functionality of the tool. Research programs are encouraged to use the CT AIM to assess and improve site infrastructure. Experience within the NCCCP suggests that the CT AIM is useful for improving quality, benchmarking research performance, reporting progress, and communicating program needs with institutional leaders. The tool model may also be useful in disciplines beyond oncology.

Validity and Reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

IMPORTANCE: To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). OBJECTIVE: To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items. DESIGN, SETTING, AND PARTICIPANTS: A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit. MAIN OUTCOMES AND MEASURES: Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). RESULTS: A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P≤.006). CONCLUSIONS AND RELEVANCE: Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.

Creating a "culture of research" in a community hospital: Strategies and tools from the National Cancer Institute Community Cancer Centers Program.

BACKGROUND: The value of community-based cancer research has long been recognized. In addition to the National Cancer Institute's Community Clinical and Minority-Based Oncology Programs established in 1983, and 1991 respectively, the National Cancer Institute established the National Cancer Institute Community Cancer Centers Program in 2007 with an aim of enhancing access to high-quality cancer care and clinical research in the community setting where most cancer patients receive their treatment. This article discusses strategies utilized by the National Cancer Institute Community Cancer Centers Program to build research capacity and create a more entrenched culture of research at the community hospitals participating in the program over a 7-year period. METHODS: To facilitate development of a research culture at the community hospitals, the National Cancer Institute Community Cancer Centers Program required leadership or chief executive officer engagement; utilized a collaborative learning structure where best practices, successes, and challenges could be shared; promoted site-to-site mentoring to foster faster learning within and between sites; required research program assessments that spanned clinical trial portfolio, accrual barriers, and outreach; increased identification and use of metrics; and, finally, encouraged research team engagement across hospital departments (navigation, multidisciplinary care, pathology, and disparities) to replace the traditionally siloed approach to clinical trials. LIMITATIONS: The health-care environment is rapidly changing while complexity in research increases. Successful research efforts are impacted by numerous factors (e.g. institutional review board reviews, physician interest, and trial availability). The National Cancer Institute Community Cancer Centers Program sites, as program participants, had access to the required resources and support to develop and implement the strategies described. Metrics are an important component yet often challenging to identify and collect. The model requires a strong emphasis on outreach that challenges hospitals to improve and expand their reach, particularly into underrepresented populations and catchment areas. These efforts build on trust and a referral pipeline within the community which take time and significant commitment to establish. CONCLUSION: The National Cancer Institute Community Cancer Centers Program experience provides a relevant model to broadly address creating a culture of research in community hospitals that are increasingly networked via systems and consortiums. The strategies used align well with the National Cancer Institute-American Society of Clinical Oncology Accrual Symposium recommendations for patient-/community-, physician-/provider-, and site-/organizational-level approaches to clinical trials; they helped sites achieve organizational culture shifts that enhanced their cancer research programs. The National Cancer Institute Community Cancer Centers Program hospitals reported that the strategies were challenging to implement yet proved valuable as they provided useful metrics for programmatic assessment, planning, reporting, and growth. While focused on oncology trials, these concepts may be useful within other disease-focused research as well.

Recommended patient-reported core set of symptoms to measure in adult cancer treatment trials.

BACKGROUND: The National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO). METHODS: We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001-2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment. RESULTS: We recommend that a core set of 12 symptoms--specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea--be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients. CONCLUSIONS: This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies.

Use of the National Cancer Institute Community Cancer Centers Program screening and accrual log to address cancer clinical trial accrual.

PURPOSE: Screening logs have the potential to help oncology clinical trial programs at the site level, as well as trial leaders, address enrollment in real time. Such an approach could be especially helpful in improving representation of racial/ethnic minority and other underrepresented populations in clinical trials. METHODS: The National Cancer Institute Community Cancer Centers Program (NCCCP) developed a screening log. Log data collected from March 2009 through May 2012 were analyzed for number of patients screened versus enrolled, including for demographic subgroups; screening methods; and enrollment barriers, including reasons for ineligibility and provider and patient reasons for declining to offer or participate in a trial. User feedback was obtained to better understand perceptions of log utility. RESULTS: Of 4,483 patients screened, 18.4% enrolled onto NCCCP log trials. Reasons for nonenrollment were ineligibility (51.6%), patient declined (25.8%), physician declined (15.6%), urgent need for treatment (6.6%), and trial suspension (0.4%). Major reasons for patients declining were no desire to participate in trials (43.2%) and preference for standard of care (39%). Major reasons for physicians declining to offer trials were preference for standard of care (53%) and concerns about tolerability (29.3%). Enrollment rates onto log trials did not differ between white and black (P = .15) or between Hispanic and non-Hispanic patients (P = .73). Other races had lower enrollment rates than whites and blacks. Sites valued the ready access to log data on enrollment barriers, with some sites changing practices to address those barriers. CONCLUSION: Use of screening logs to document enrollment barriers at the local level can facilitate development of strategies to enhance clinical trial accrual.

Racial/ethnic differences in clinical trial enrollment, refusal rates, ineligibility, and reasons for decline among patients at sites in the National Cancer Institute's Community Cancer Centers Program.

BACKGROUND: This study examined racial/ethnic differences among patients in clinical trial (CT) enrollment, refusal rates, ineligibility, and desire to participate in research within the National Cancer Institute's Community Cancer Centers Program (NCCCP) Clinical Trial Screening and Accrual Log. METHODS: Data from 4509 log entries were evaluated in this study. Four logistic regression models were run using physical/medical conditions, enrollment into a CT, patient eligible but declined a CT, and no desire to participate in research as dependent variables. RESULTS: Age ≥ 65 years (OR = 1.51, 95% CI = 1.28-1.79), males (OR = 2.28, 95% CI = 1.92-2.71), and non-Hispanic black race (OR = 1.53, 95% CI = 1.2-1.96) were significantly associated with more physical/medical conditions. Age ≥ 65 years was significantly associated with lower CT enrollment (OR = 0.83, 95% CI = 0.7-0.98). Males (OR = 0.78, 95% CI = 0.65-0.94) and a higher grade level score for consent form readability (OR = 0.9, 95% CI = 0.83-0.97) were significantly associated with lower refusal rates. Consent page length ≥ 20 was significantly associated with lower odds of "no desire to participate in research" among CT decliners (OR = 0.75, 95% CI = 0.58-0.98). CONCLUSIONS: There were no racial/ethnic differences in CT enrollment, refusal rates, or "no desire to participate in research" as the reason given for CT refusal. Higher odds of physical/medical conditions were associated with older age, males, and non-Hispanic blacks. Better management of physical/medical conditions before and during treatment may increase the pool of eligible patients for CTs. Future work should examine the role of comorbidities, sex, age, and consent form characteristics on CT participation.

The National Cancer Institute-American Society of Clinical Oncology Cancer Trial Accrual Symposium: summary and recommendations.

INTRODUCTION: Many challenges to clinical trial accrual exist, resulting in studies with inadequate enrollment and potentially delaying answers to important scientific and clinical questions. METHODS: The National Cancer Institute (NCI) and the American Society of Clinical Oncology (ASCO) cosponsored the Cancer Trial Accrual Symposium: Science and Solutions on April 29-30, 2010 to examine the state of accrual science related to patient/community, physician/provider, and site/organizational influences, and identify new interventions to facilitate clinical trial enrollment. The symposium featured breakout sessions, plenary sessions, and a poster session including 100 abstracts. Among the 358 attendees were clinical investigators, researchers of accrual strategies, research administrators, nurses, research coordinators, patient advocates, and educators. A bibliography of the accrual literature in these three major areas was provided to participants in advance of the meeting. After the symposium, the literature in these areas was revisited to determine if the symposium recommendations remained relevant within the context of the current literature. RESULTS: Few rigorously conducted studies have tested interventions to address challenges to clinical trials accrual. Attendees developed recommendations for improving accrual and identified priority areas for future accrual research at the patient/community, physician/provider, and site/organizational levels. Current literature continues to support the symposium recommendations. CONCLUSIONS: A combination of approaches addressing both the multifactorial nature of accrual challenges and the characteristics of the target population may be needed to improve accrual to cancer clinical trials. Recommendations for best practices and for future research developed from the symposium are provided.

Early-phase clinical trials in the community: results from the national cancer institute community cancer centers program early-phase working group baseline assessment.

PURPOSE: The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) formed an Early-Phase Working Group to facilitate site participation in early-phase (EP) trials. The Working Group conducted a baseline assessment (BA) to describe the sites' EP trial infrastructure and its association with accrual. METHODS: EP accrual and infrastructure data for the sites were obtained for July 2010-June 2011 and 2010, respectively. Sites with EP accrual rates at or above the median were considered high-accruing sites. Analyses were performed to identify site characteristics associated with higher accrual onto EP trials. RESULTS: Twenty-seven of the 30 NCCCP sites participated. The median number of EP trials open per site over the course of July 2010-June 2011 was 19. Median EP accrual per site was 14 patients in 1 year. Approximately half of the EP trials were Cooperative Group; most were phase II. Except for having a higher number of EP trials open (P = .04), high-accruing sites (n = 14) did not differ significantly from low-accruing sites (n = 13) in terms of any single site characteristic. High-accruing sites did have shorter institutional review board (IRB) turnaround time by 20 days, and were almost three times as likely to be a lead Community Clinical Oncology Program site (small sample size may have prevented statistical significance). Most sites had at least basic EP trial infrastructure. CONCLUSION: Community cancer centers are capable of conducting EP trials. Infrastructure and collaborations are critical components of success. This assessment provides useful information for implementing EP trials in the community.

Implementation of timeline reforms speeds initiation of National Cancer Institute-sponsored trials.

BACKGROUND: The National Cancer Institute (NCI) organized the Operational Efficiency Working Group in 2008 to develop recommendations for improving the speed with which NCI-sponsored clinical trials move from the idea stage to a protocol open to patient enrollment. METHODS: Given the many stakeholders involved, the Operational Efficiency Working Group advised a multifaceted approach to mobilize the entire research community to improve their business processes. New staff positions to monitor progress, protocol-tracking Web sites, and strategically planned conference calls were implemented. NCI staff and clinical teams at Cooperative Groups and Cancer Centers strived to achieve new target timelines but, most important, agreed to abide by absolute deadlines. For phase I-II studies and phase III studies, the target timelines are 7 months and 10 months, whereas the absolute deadlines were set at 18 and 24 months, respectively. Trials not activated by the absolute deadline are automatically disapproved. RESULTS: The initial experience is encouraging and indicates a reduction in development times for phase I-II studies from the historical median of 541 days to a median of 442 days, an 18.3% decrease. The experience with phase III studies to date, although more limited (n = 25), demonstrates a 45.7% decrease in median days. CONCLUSIONS: Based upon this progress, the NCI and the investigator community have agreed to reduce the absolute deadlines to 15 and 18 months for phase I-II and III trials, respectively. Emphasis on initiating trials rapidly is likely to help reduce the time it takes for clinical trial results to reach patients in need of new treatments.

Stakeholder perspectives on implementing the National Cancer Institute's patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty-eight percent felt that patients in clinical trials would be willing to self-report adverse symptoms at clinic visits via computer, and 68% felt patients would self-report weekly from home via the internet or an automated telephone system. Lack of computers and limited space and personnel were seen as potential barriers to in-clinic self-reporting, but these were judged to be surmountable with adequate funding. The PRO-CTCAE items and software are viewed by a majority of survey respondents as a means to improve adverse event data quality and comprehensiveness, enhance clinical decision-making, and foster patient-clinician communication. Research is ongoing to assess the measurement properties and feasibility of implementing this measure in cancer clinical trials.