A systematic review and meta-analysis of enrollment into ARDS and sepsis trials published between 2009 and 2019 in major journals

Background Enrollment problems are common among randomized controlled trials conducted in the ICU. However, little is known about actual trial enrollment rates and influential factors. We set out to determine the overall enrollment rate in recent randomized controlled trials (RCTs) of patients with acute respiratory distress syndrome (ARDS), acute lung injury (ALI), or sepsis, and which factors influenced enrollment rate. Methods We conducted a systematic review by searching Pubmed using predefined terms for ARDS/ALI and sepsis to identify individually RCTs published among the seven highest impact general medicine and seven highest impact critical care journals between 2009 and 2019. Cluster randomized trials were excluded. Data were extracted by two independent reviewers using an electronic database management system. We conducted a random-effects meta-analysis of the eligible trials for the primary outcome of enrollment rate by time and site. Results Out of 457 articles identified, 94 trials met inclusion criteria. Trials most commonly evaluated pharmaceutical interventions (53%), were non-industry funded (78%), and required prospective informed consent (81%). The overall mean enrollment rate was 0.83 (95% confidence interval: 0.57–1.21) participants per month per site. Enrollment in ARDS/ALI and sepsis trials were 0.48 (95% CI 0.32–0.70) and 0.98 (95% CI 0.62–1.56) respectively. The enrollment rate was significantly higher for single-center trials (4.86; 95% CI 2.49–9.51) than multicenter trials (0.52; 95% CI 0.41–0.66). Of the 36 trials that enrolled < 95% of the target sample size, 8 (22%) reported slow enrollment as the reason. Conclusions In this systematic review and meta-analysis, recent ARDS/ALI and sepsis clinical trials had an overall enrollment rate of less than 1 participant per site per month. Novel approaches to improve critical care trial enrollment efficiency are needed to facilitate the translation of best evidence into practice.

P.020 The North American AED Pregnancy Registry: A Canadian Subgroup Analysis (1997-2019)

Background: This study aims to provide data on the care of pregnant women with epilepsy (pWWE) that is directly applicable to the Canadian context. Methods: Between 1997 and 2019, pWWE from Canada and the USA who enrolled into the North American AED Pregnancy Registry (NAARP) completed a questionnaire on their AED (anti-epileptic drug) usage. Enrollment rates to NAARP were compared between the two countries, and between the different Canadian provinces using population-based enrollment rate ratios (PERR). The AED prescription pattern among Canadian pWWE was analysed and compared with the USA. Results: During the study period, 10,215 women enrolled into NAARP : 4.1% (n=419) were Canadian, below the expected population-based contribution (PERR=0.42; p<0.01). Within Canada, the three northern territories (PERR=0; p<0.01), Prince-Edward Island (PERR=0; p<0.01), and Quebec (PERR=0.41; p<0.01) had the lowest enrollment rate ratios. Lamotrigine was the most commonly prescribed AED among canadian pWWE; they were, however, more likely to be on polytherapy (25%; p=0.13), on Carbamazepine (24%; p<0.01) or valproic acid (21%; p<0.01) than their American counterparts. Conclusions: Greater enrollment of Canadian women to NAARP, through enhanced clinician referrals, in particular from underrepresented provinces/territories, could lead to more accurate population-specific data and help identify gaps in the care of this vulnerable patient population.

Face-to-Face Nursing Promotion of Cardiac Rehabilitation

Practice Problem: The burden of cardiovascular disease is rising at global and national levels, and cardiac rehabilitation is recognized as one of the most beneficial and cost-effective strategies to manage it. One significant problem globally, nationally, and locally is the low numbers of eligible patients who enroll in cardiac rehabilitation. PICOT: In patients with isolated coronary artery bypass graft (CABG) (P), how does face-to-face nursing promotion of cardiac rehabilitation (I) compared to the patients who do not have face-to-face nursing promotion (C), affect the percentage of patients enrolling in cardiac rehabilitation after discharge (O) within 8 weeks (T)? Evidence: The evidence used to guide this project included the need for a healthcare organization to have a systematic process for cardiac rehabilitation enrollment, face-to-face nursing promotion, improvement of the healthcare team’s knowledge about cardiac rehabilitation, and identification of patient barriers that hinder cardiac rehabilitation enrollment. Intervention: A systematic approach for cardiac rehabilitation was developed using the interprofessional team. After the healthcare team received standardized education, nurses in various roles provided face-to-face promotion, the ARNPs endorsed cardiac rehabilitation, and the care managers addressed barriers. Outcome: The cardiac rehabilitation enrollment rate increased by 16% among all patients admitted with an isolated CABG on the pilot unit. Conclusion: Implementation of face-to-face nursing promotion, ARNP endorsement, and reducing barriers were clinically significant in increasing the cardiac rehabilitation enrollment rate.

Face-to-Face Nursing Promotion of Cardiac Rehabilitation

Practice Problem: The burden of cardiovascular disease is rising at global and national levels, and cardiac rehabilitation is recognized as one of the most beneficial and cost-effective strategies to manage it. One significant problem globally, nationally, and locally is the low numbers of eligible patients who enroll in cardiac rehabilitation. PICOT: In patients with isolated coronary artery bypass graft (CABG) (P), how does face-to-face nursing promotion of cardiac rehabilitation (I) compared to the patients who do not have face-to-face nursing promotion (C), affect the percentage of patients enrolling in cardiac rehabilitation after discharge (O) within 8 weeks (T)? Evidence: The evidence used to guide this project included the need for a healthcare organization to have a systematic process for cardiac rehabilitation enrollment, face-to-face nursing promotion, improvement of the healthcare team’s knowledge about cardiac rehabilitation, and identification of patient barriers that hinder cardiac rehabilitation enrollment. Intervention: A systematic approach for cardiac rehabilitation was developed using the interprofessional team. After the healthcare team received standardized education, nurses in various roles provided face-to-face promotion, the ARNPs endorsed cardiac rehabilitation, and the care managers addressed barriers. Outcome: The cardiac rehabilitation enrollment rate increased by 16% among all patients admitted with an isolated CABG on the pilot unit. Conclusion: Implementation of face-to-face nursing promotion, ARNP endorsement, and reducing barriers were clinically significant in increasing the cardiac rehabilitation enrollment rate.

Overcoming Barriers to Clinical Trial Participation: Outcomes of a National Clinical Trial Matching and Navigation Service for Patients With a Blood Cancer

PURPOSE: There are numerous barriers to cancer clinical trial participation in the United States. This paper describes the approach and outcomes of The Leukemia & Lymphoma Society's Clinical Trial Support Center (CTSC), whose nurse navigators assist patients with a blood cancer and their oncologists by identifying all appropriate trials based on clinical data and patient preference, facilitating informed and shared decision making, and minimizing enrollment barriers. METHODS: Data on patients served from October 2017 to October 2019 were analyzed using bivariate and multivariate analyses to determine demographic and clinical characteristics associated with enrollment. Reasons for nonenrollment were examined. RESULTS: The CTSC opened 906 patient cases during this time frame. Among all US patients with a closed case (n = 750), the clinical trial enrollment rate was 16.1%. Among those with a known enrollment outcome after a trial search (n = 537), the enrollment rate was 22.5%. Multivariate analysis controlling for variables significant in bivariate analyses (insurance, treatment status, Eastern Cooperative Oncology Group performance status, and urban or rural residence) revealed that patients with Medicaid were less likely to enroll than those with private or commercial insurance (adjusted odds ratio, 0.054; CI, 0.003 to 0.899), and patients in treatment or maintenance were less likely to enroll than those relapsed or refractory to most recent therapy (adjusted odds ratio, 0.312; CI, 0.139 to 0.702). Primary reasons for nonenrollment were preference for standard of care (66.3%) and patient passed away (16.1%). CONCLUSION: The CTSC is an effective, replicable model for addressing multilevel barriers to clinical trial participation. The findings highlight the need to increase opportunities for trial participation sooner after diagnosis and among patients with Medicaid.

Factors impacting enrollment on NCI-COG Pediatric MATCH trial treatment protocols.

10007 Background: The NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial assigns patients age 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on the genetic alterations detected in their tumor. Treatment arm assignments and enrollment decisions have now been made for 1000 study participants: we report here match and enrollment data and factors affecting treatment protocol enrollment. Methods: Patients enrolled in the Pediatric MATCH screening protocol were assigned to an open treatment protocol if an actionable mutation (aMOI) was detected by tumor DNA and RNA-based cancer gene panel sequencing. After a match, treatment protocol enrollment must occur within 8-12 weeks. Patient demographic data, reasons for not enrolling on treatment protocol (if applicable), and prior history of molecular testing were reported by study sites. The Fisher exact test was used to compare protocol enrollment rates between groups. Results: Results were analyzed for the first 1000 patients with testing completed (enrolled between July 2017 and October 2020). At least one tumor aMOI was detected in 310 (31%) patients and treatment protocol slots were available for 284 patients (28%). A total of 131 patients (46% of those matched) enrolled on a treatment arm. No difference in treatment protocol match or enrollment rate was observed for gender, race, or ethnicity. Both treatment protocol match rate (105/275, 38% vs 86/394, 22%) and enrollment rate (56/275, 20% vs 33/394, 8%) were significantly more frequent in patients with a reported history of prior molecular testing (p<0.0001). The most common reasons provided for not enrolling on a treatment protocol were: patient receiving other treatment (32% of responses), poor clinical status (16%), lack of measurable disease (11%), or ineligible diagnosis for that treatment arm (10%). Ineligibility due to history of excluded prior targeted therapy (6%) or inability to swallow capsules (4%) was less frequent. Conclusions: The rate of Pediatric MATCH treatment protocol enrollment has exceeded pre-study projections, due to more frequent actionable mutation detection and treatment assignment than anticipated (28% observed, 10% projected). This may in part reflect an increased number of targetable events in recurrent or refractory pediatric cancers. Correlative studies analyzing pre-treatment tumors from MATCH study patients are underway and will address this hypothesis. Prior history of molecular testing was associated with higher match and enrollment rate and poor clinical status was a common reason for not enrolling on a treatment protocol, suggesting that early molecular screening of children with solid malignancies may facilitate enrollment to biomarker-selected trials of targeted therapies. Clinical trial information: NCT03155620.

Improving the inclusion rate in clinical trials of bladder cancer despite COVID-19 pandemic by using ASCO quality training program.

e18674 Background: In 2019, we used the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP) as an instrument to improve the inclusion rate in clinical trials (CTs) for bladder cancer patients from 24% in 2018 to 43,75% in 2019. CTs play an important role in developing new treatments, expanding or refining treatments that are already available, and/or identifying behavioral changes that can prolong or improve the lives of subjects. Therefore, we believe it is important for patients and for society to maintain the inclusion rate in clinical trials despite COVID-19 pandemic. Methods: We collected the number of bladder cancer patients evaluated for the first time in the Oncology department, the number of patients who were offered a clinical trial, the screen failures and the number of patients enrolled in CTs. Results: In 2019, we were able to increase the enrollment rate in CTs for bladder cancer patients to from 24% to 43,75% thanks to the ASCO-QTP. With this program we created a list of measures and identified the ones that would have a greater impact. The one that seems to have had the highest impact is the diffusion of CTs in the Investigation Unit and the Genitourinary (GU) board. In 2020, thanks to this measure and despite the COVID-19 pandemic, we were able to maintain a 40,81% enrollment rate. When analyzing the patients evaluated for the first time in the Oncology department, 48 in 2019 and 49 in 2020, there were some interesting differences. In 2020, 42,86% had stage IV disease with respect to 39,6% in 2019, and only 22,44% had non-muscle invasive disease (NMIBC) versus 33,33% in 2019. However, thanks to the diffusion of CTs in the Investigation Unit and in the GU-board, which translates in an early derivation of patients to Medical Oncology and an increase in the number of available CTs, we were able to offer a CT to 73,5% of patients in 2020 against 60,4% in 2019. Although there was an increase of screen failures in 2020 (32,65% vs. 16,66%), 50% of them were due to the absence of a biomarker in a biomarker driven CT, with respect to 25% in 2019. Conclusions: Using ASCO-QTP as an instrument, we identified the importance of the diffusion of CTs and the close collaboration between departments. Maintaining these measures, we were able to uphold the inclusion rate in CTs for bladder cancer patients in 40,81% despite the later diagnosis of patients due to COVID-19 pandemic.

THE ROLE OF GENDER-TARGETED CASH TRANSFERS IN INCREASING SCHOOL ENROLLMENT IN PUNJAB, PAKISTAN

Purpose of the study: This study is conducted to assess the success of the Female Stipend Program (FSP), started in the province Punjab, Pakistan under the Punjab Education Sector Reform Program in 2003. Methodology: Panel data on household-level collected from years 2016 to 2018 is used for the analysis. The impact of cash transfers (directed towards female students in selected districts of the province) on female school enrollment in public (elementary and high) schools is measured. Enrollment growth in public schools is used as a dependent variable whereas female stipend, the number of schools, student to teacher ratio, the population of the districts, and basic facilities available in public schools are taken as independent variables. The results are obtained by employing Linear Mixed Multilevel Modeling. Main findings: All the variables, except the population of districts, are having a highly significant impact on the enrollment rate in Punjab. Female school's stipend, number of schools in the district, and the accessibility to basic infrastructural facilities have an important impact on female enrollment rate while a high student to teacher ratio negatively contributes to female enrollment rate. Furthermore, districts, where a stipend program is implemented, have higher enrollments as compared to other districts in the province. Application of the study: Outcomes of the study indicate that cash transfer programs directed towards female school enrollment are very fruitful in the case of Punjab. Therefore, such programs should be started in other provinces of the country as well. Novelty/ Originality of the study: The present study contributes to the research gap by using the largest data set available for all 36 districts of the province. To further highlight major factors contributing to high female school enrollments, the study includes school infrastructure, the population of districts, student-teacher ratio, and availability of schools in the model.