EPID-11. A POPULATION STUDY OF CLINICAL TRIAL ACCRUAL FOR WOMEN AND MINORITIES IN NEURO-ONCOLOGY FOLLOWING THE NIH REVITALIZATION ACT

INTRODUCTION The NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate the progress made in neuro-oncology in all phase therapeutic clinical trials for neuro-epithelial central nervous system tumors in comparison to their demographic-specific age-adjusted disease incidence and mortality. METHODS Registry study of all published clinical trials for World Health Organization (WHO) defined neuro-epithelial CNS tumors between January 2000 and December 2019. Study participants for trials were obtained from PubMed and ClinicalTrials.gov. Population-based data from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and c2 tests were used to analyze the data. RESULTS Among 662 published clinical trial articles representing 49, 907 accrued participants, 62.5% of study participants were men and 37.5% were women (P< 0.0001) representing a mortality specific over-accrual for men (P= 0.001) and under-accrual for women (P= 0.001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with their US cancer mortality, Blacks (47% of expected mortality, P=.008), Hispanics (17% of expected mortality, P< .001) and Asians (33% of expected mortality, P< .001) were underrepresented compared with Whites (114% of expected mortality, P< .001). CONCLUSIONS Nearly 30 years since the Revitalization Act, minorities and women are consistently underrepresented when compared with their demographic-specific incidence and mortality in therapeutic clinical trials for neuroepithelial tumors. This study provides a framework for investigating cancer clinical trial accrual and offers guidance regarding workforce factors associated with enrollment of vulnerable patients.

A Population Study of Clinical Trial Accrual for Women and Minorities in Neuro-Oncology Following the NIH Revitalization Act

BACKGROUND The NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate progress made in all phase therapeutic clinical trials for neuro-epithelial CNS tumors stratified by demographic-specific age-adjusted disease incidence and mortality. Additionally, we identify workforce characteristics associated with clinical trials meeting established accrual benchmarks. METHODS Registry study of published clinical trials for World Health Organization defined neuro-epithelial CNS tumors between January 2000 and December 2019. Study participants were obtained from PubMed and ClinicalTrials.gov. Population-based data originated from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and Chi2 tests were used for data analysis. RESULTS Among 662 published clinical trials representing 49,907 participants, 62.5% of study participants were men and 37.5% were women (P<0.0001) representing a mortality specific over-accrual for men (P=0.001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with mortality, Blacks (47% of expected mortality, P=0.008), Hispanics (17% of expected mortality, P<0.001) and Asians (33% of expected mortality, P<.001) were underrepresented compared with Whites (114% of expected mortality, P<0.001). Clinical trials meeting accrual benchmarks for race included minority authorship. CONCLUSIONS Following the Revitalization Act, minorities and women remain underrepresented when compared with their demographic-specific incidence and mortality in therapeutic clinical trials for neuroepithelial tumors. This study provides a framework for clinical trial accrual efforts and offers guidance regarding workforce considerations associated with enrollment of vulnerable patients.

Growth in eligibility criteria content and failure to accrue among National Cancer Institute (NCI)-affiliated clinical trials.

1515 Background: Cancer clinical trial accrual across diverse socioeconomic and demographic groups is a national priority, yet up to 20% of trials fail due to poor accrual. Eligibility criteria content may contribute to poor accrual, but effects are challenging to measure. We sought to evaluate growth of eligibility criteria within NCI-affiliated cancer trials and the impact on trial accrual over the past decade. Methods: We conducted a retrospective study with the Aggregate Analysis of ClinicalTrials.gov (AACT) (abstracted: 02/02/2021). We included NCI-affiliated, interventional Phase II or III trials that initiated between 01/01/2008 and 12/13/2018. We excluded active and recruiting trials that lacked accrual data on the Cancer Trials Support Unit website. Trials whose status was “Withdrawn”, “Terminated”, or “Suspended” due to low accrual, or had less than 50% target accrual after two years active were deemed accrual failures. Eligibility criteria were extracted from inclusion and exclusion criteria and complexity was estimated by the number of unique content words, calculated by removing duplicates and stop words from the word count. Association of unique word count with accrual failure was evaluated by univariable and multivariable logistic regressions, adjusting for other predictors of low accrual identified in earlier research. Results: Of 1197 trials included, 231 (19.3%) failed due to low accrual. Eligibility criteria increased in length from a median of 214 (IQR [23, 282]) unique content words in 2008 to 417 (IQR [289, 514]) in 2018. The rate of trial accrual failure increased with unique word count decile from 11.8% in the first decile (12 to 112 words) to 29.4% in the tenth decile (445 to 750 words) (P = 0.004). On multivariable analysis, unique word count remained independently associated with low accrual (OR: 1.07 per decile, 95%CI [1.01-1.13], P = 0.02), as did Phase III and metastatic disease settings (Table). Conclusions: Eligibility criteria content has increased dramatically in the last decade in NCI-affiliated trials. Increasing eligibility criteria content associates strongly with accrual failure, even after adjusting for multiple known predictors of accrual. These findings underscore the need for efforts to simplify eligibility criteria to improve trial accrual. Further investigation is ongoing to determine specific criteria qualities that portend accrual failure.[Table: see text]

The role of experience and clinical decision support in clinical trial accrual within oncology.

1527 Background: Patient accrual for cancer clinical trials is suboptimal. The complexity of applying eligibility criteria and enrolling patients may deter oncologists from recommending patients for a trial. As such, there is a need to understand how experience, training, and clinical decision support impact physician practices and intentions related to trial accrual. Methods: From May to September 2017, we conducted a survey on clinical trial accrual in a national sample of medical, surgical, and radiation oncologists. The 20-minute survey assessed barriers and facilitators to clinical trial accrual, including experience (e.g., “In the past 5 years, have you been a study or site PI of a trial?”), training (e.g., “Did you receive training about trial design and recruitment as part of medical school, residency, or fellowship? After fellowship?”), and clinical decision support (e.g., “What kind of clinical decision support has your practice implemented?). We used logistic regression to identify factors associated with frequency of discussing trials (with ≥25% of patients) and likelihood of recommending a trial to a patient (likely or very likely) in the future. Results: Survey respondents (n = 1,030) were mostly medical oncologists (59%), age 35-54 years (67%), male (74%), and not in academic practice (58%). About 18% of respondents (n = 183) reported discussing trials with ≥25% of their patients, and 80% reported being likely or very likely to recommend a trial to a patient in the future. Prior experience as principal investigator of a trial was associated with both frequency of discussing trials (OR 3.27, 95% CI 2.25, 4.75) and likelihood of recommending a trial in the future (OR 5.22, 95% CI 3.71, 7.34), as was receiving additional training in clinical trials after fellowship (discussion with patients: OR 2.48, 95% CI 1.80, 3.42; recommend in future: OR 1.92, 95% CI 1.37, 2.69). Implementing clinical decision support was not associated with discussing trials with ≥25% of patients (OR 1.12, 95% CI 0.76, 1.67), but was associated with being likely to recommend a trial in the future (OR 1.73, 95% CI 1.11, 2.71). Conclusions: In a national survey of oncologists, we observed differences in physician practices and intention related to clinical trial accrual. Whereas the vast majority (80%) reported being likely or very likely to recommend trials in the future, far fewer (20%) reported discussing trials with their patients within the past 5 years. Implementation of clinical decision support – electronic tools intended to optimize patient care and identification of patient eligibility – was not associated with frequency of past discussion of clinical trials but was associated with recommending a trial in the future. Given the stronger association between experience as a site Principal Investigator and recommending a trial, future research should explore how improving opportunities to lead a clinical trial impact trial accrual.

Accrual of Black participants to cancer clinical trials following a five-year prospective initiative of community outreach and engagement.

100 Background: Accrual of Black participants to cancer clinical trials remains a major challenge across the country. Here, we report the outcomes of a five-year initiative of community outreach and engagement to improve enrollment of adult Black participants to clinical trials at the Abramson Cancer Center (ACC) at the University of Pennsylvania. Methods: Primary metrics were the percentage of Black patients among all cancer cases in our catchment area, the percentage of adult Black patients cared for at the ACC, and the percentage of adult Black participants enrolled on the three types of NCI-defined clinical trials. Results: In 2014, at baseline, Black residents comprised 19% of the population and 16.5% of cancer cases in our catchment area surrounding Philadelphia, but only 11.1% of ACC patients were Black. The percentages of Black participants accrued onto treatment, non-therapeutic interventional, and non-interventional trials were 12.2%, 8.3%, and 13.0%, respectively. We then established a center-wide program with community guidance to address these gaps. Key elements of the program included: 1) culturally tailored marketing strategies for cancer clinical trials; 2) plans for each protocol to facilitate Black participant enrollment; 3) new partnerships with faith-based organizations serving Black communities to conduct educational events about clinical trials; 4) pilot programs with Lyft and Ride Health to address transportation barriers; 5) patient education by nurse navigators regarding cancer and clinical trials; and 6) an improved informed consent process. These efforts reached more than 10,000 individuals in venues including churches, neighborhoods, community parks and centers, and health centers with formats ranging from educational forums to wellness fairs. Reassessing metrics in 2018, we found that the percentage of Black patients seen at ACC had increased to 16.2%, matching the percentage of Black cancer patients among all cancer cases in our catchment area (16.5%). Total cancer clinical trial accrual had increased from 9,308 participants in 2014 to 13,170 in 2018 (41.5% increase). The percentages of Black participants accrued onto treatment, non-therapeutic interventional, and non-interventional trials were 23.9%, 33.1%, and 22.5%, respectively – a 1.7- to 4.0-fold increase in five years and higher than the percentage of Black patients seen at the ACC. Conclusions: Our multifaceted, community-based engagement initiative to encourage clinical trial enrollment was associated with improved accrual of Black participants to cancer clinical trials. These findings also suggest that gaps in access to cancer centers are a key factor driving access to clinical trials. Medicaid expansion occurred concurrently in all states in our catchment area and its impact on accrual merits further research.

A provider-focused, point-of-care technology to improve clinical trial accrual.

309 Background: Low accrual to clinical trials is a significant burden to advancing research efforts, particularly detrimental to patients who may benefit clinically from enrollment in a promising trial. Low accrual has been linked to a lack of provider awareness of clinical trials at the point of care and current technology solutions have not adequately addressed this important issue. Methods: We aimed to develop a system to improve clinical trial access for patients throughout UCLA Hematology-Oncology through the development of a point of care web-based tool to allow providers to easily identify available clinical trials for their patients. First, we built a comprehensive database of current clinical trials at UCLA, with special emphasis on streamlined exclusion/inclusion criteria. We incorporated this database into a front-end web and mobile-responsive tool with a user-friendly interface allowing users to rapidly identify patients eligible for clinical trial enrollment. We launched this tool 1/15/2019 to 56 oncologists at UCLA Health. Results: From 1/15/19 to 6/14/19 we had had a total of 713 unique logins to the clinical trials website. This included “academic oncologists,” those oncologists specializing in a particular disease sub-type and often a ‘hub’ for clinical trials, with an average of 6.4 logins per oncologist, and “community oncologists” with an average of 18.8 logins per oncologist over that time frame. A brief survey of users who logged in over 4 times during that time revealed that on average, 4-5 additional patients per user were screened for clinical trials not previously identified. Conclusions: Clinical trial accrual can be enhanced through improved provider awareness of available trials at the point-of-care. A well-designed user interface with features to help facilitate provider navigation to available trials and quick inclusion and exclusion criteria were critical to the success of the tool. Although the web-based tool achieved its primary purpose in improving clinical trial awareness, its utility diminished over time due to the lack of real-time updates of trial data. Based on provider feedback, if the available trial data can be updated and maintained on a regular basis, this can be a valuable tool to improve clinical trial awareness and subsequently, accrual.

Assessing Genitourinary Cancer Clinical Trial Accrual Sufficiency Using Archived Trial Data

PURPOSE Clinical trials often fail to reach their anticipated end points, most frequently because of poor accrual. Prior studies have analyzed trial termination, but it has not been easy to assess accrual estimates using international databases such as ClinicalTrials.gov because of limitations in accessing accrual information. Specifically, it is not easy to extract both anticipated and actual accrual of clinical trials. We designed a new algorithmic approach to extracting trial accrual data from ClinicalTrials.gov and used it to estimate the sufficiency of patient accrual onto genitourinary (GU) cancer trials. METHODS We queried ClinicalTrials.gov for completed/terminated phase II and III clinical trials for prostate, bladder, kidney, testicular, and ureteral cancers registered after 2007. We extracted trial characteristics from available XML files. We then used a Python algorithm to access prior trial registrations on the ClinicalTrials.gov archive site and extract both anticipated and actual accrual numbers. We then compared the actual accrual of each trial to its anticipated accrual and defined sufficient accrual as 85% of anticipated accrual. RESULTS The algorithm was 100% accurate compared with hand extraction in a small validation subset. A total of 925 trials were included, of which 840 (91%) had both anticipated and actual accrual. Only 418 (50%) trials had sufficient accrual (≥ 85% of anticipated). Considering only trials marked as successfully completed, 395/597 (66%) reached sufficient accrual. CONCLUSION GU cancer trials often do not meet their anticipated accrual goals. New approaches to trial conduct are direly needed. Our reproducible and scalable approach to extracting accrual information can be applied to analysis of ClinicalTrials.gov in future analyses in the hope of improving the efficiency of the clinical trials enterprise.