Adequate Enrollment Research Articles

A Systematic Review of Worldwide Female Enrollment in Randomized Controlled Trials of Post-Stroke Lower Extremity Rehabilitation

Abstract This review systematically examined the reporting of sex and female participation in post-stroke lower extremity (LE) motor rehabilitation randomized controlled trials (RCTs) over time and identified differences in female participation across RCTs conducted in low-and-middle-income countries (LMICs), high-income-countries (HICs), and HIC-regions. Systematic searches were conducted of MEDLINE, Embase, CINAHL and PsycINFO from 1970 to May 2022. RCTs in English were included if they examined post-stroke LE motor rehabilitation interventions in adults diagnosed with stroke. A total of 1,285 RCTs were analyzed; 4.5% of RCTs did not report sex, and the overall female participation was 39.4%. The percentage of female participants did not significantly differ between HICs and LMICs. Within HICs, the percentage of female participants was significantly higher in European RCTs than RCTs in Asia & Oceania (P = 0.008). No significant changes in female participation were found for any of the countries or regions over the last two decades. Female participation was significantly higher in RCTs conducted in the acute phase compared to those in the chronic phase (p < 0.001). More research is needed to understand the reasons behind female under-enrollment and further efforts are required to ensure adequate enrollment of males and females.

Embracing the challenges of neonatal and paediatric pulmonary hypertension.

Paediatric pulmonary arterial hypertension (PAH) shares common features with adult disease, but is associated with several additional disorders and challenges that require unique approaches. This article discusses recent advances, ongoing challenges and distinct approaches for caring for infants and children with PAH, as presented by the paediatric task force of the 7th World Symposium on Pulmonary Hypertension. We provide updates on diagnosing, classifying, risk-stratifying and treating paediatric pulmonary hypertension (PH) and identify critical knowledge gaps. An updated risk stratification tool and treatment algorithm is provided, now also including strategies for patients with associated cardiopulmonary conditions. Treatment of paediatric PH continues to be hindered by the lack of randomised controlled clinical trials. The challenging management of children failing targeted PAH therapy is discussed, including balloon atrial septostomy, lung transplantation and pulmonary-to-systemic shunt (Potts). A novel strategy using a multimodal approach for the management of PAH associated with congenital heart diseases with borderline pulmonary vascular resistance is included. Advances in diagnosing neonatal PH, especially signs and interpretation of PH by echocardiography, are highlighted. A team approach to the rapidly changing physiology of neonatal PH is emphasised. Challenges in drug approval are discussed, particularly the challenges of designing accurate paediatric clinical trials with age-appropriate end-points and adequate enrolment.

Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies.

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.

Enrollment of Black, Indigenous and People of Color (BIPOC) and female participants in the US diabetes trials spanning 2000 to 2020: A chronological survey

AimsLittle is known about the enrollment practice of both Black, Indigenous and People of Color (BIPOC) and females in the US diabetes trials. We aimed to perform a chronological survey to evaluate the enrollment of BIPOC and female participants in the US diabetes randomized controlled trials (RCTs) over the past two decades. MethodsWe searched databases to systematically include the US diabetes RCTs from 2000 January 1st to 2020 December 31st. Primary outcome was the adequate enrollment of both BIPOC and females, defined by the participation to prevalence ratio (PPR) > 0.8. We tested the temporal trend in adequate enrollment over time and used logistic regression analysis to explore the relationship between adequate enrollment and trial characteristics. ResultsA total of 69 US diabetes trials were included for analyses, with a median BIPOC and female enrollment percentage of 29.0 % and 45.4 % respectively. There were 22 (31.9 %) trials with adequate enrollment of both BIPOC and females. No significant trend of adequate enrollment percentage of BIPOC and females over time was observed (P = 0.16). Of trial types, those with medication interventions were significantly related to decreased odds of adequate enrollment, when compared to trials with non-drug interventions (odds ratio = 0.29, 95 % confidence interval: 0.11–0.84). ConclusionsLess than one third of the US diabetes trials adequately enrolled both BIPOC and females over the past two decades, and no temporal improvement in BIPOC and female participant enrollment was observed. These results highlight the need for more endeavors to mitigate inadequate representation regarding BIPOC and female enrollment in diabetes trials.

Sex, racial, and ethnic disparities in motor neuron disease: clinical trial enrolment

Objective Motor neuron disease (MND) is a group of neurological diseases, the majority being amyotrophic lateral sclerosis (ALS), with varying clinical presentations across demographics. Clinical trial enrollment reflecting global disease burden improves understanding of diverse presentations and aids personalized therapy development. We assessed the sex, racial, and ethnic composition of MND/ALS clinical trial participants relative to global disease burdens. Methods We searched ‘motor neuron disease OR amyotrophic lateral sclerosis’ on ClinicalTrials.gov from 02/2000–04/2024. We extracted trial (start year, study site, sponsor location, phase, masking, intervention) and demographic data (sex, race, ethnicity) from randomized interventional studies. We obtained sex-based MND/ALS disease burden estimates from the Global Burden of Disease database. For females, we calculated pooled participation-to-prevalence ratio (PPR) with 95% confidence intervals (CIs), with PPR of 0.8–1.2 indicating adequate enrollment. We used Kruskal–Wallis tests to compare demographic groups across trial characteristics. Results Of 85 trials, females comprised 37.47% (n = 5011) of 13,372 participants; the pooled female PPR was 0.97 (95% CI: 0.77–1.16). Of 41 trials (9340 participants) reporting race, 121 (1.30%) participants were Black or African American, 16 (0.17%) American Indian or Alaskan Native, and 6 (0.06%) Native Hawaiian or Other Pacific Islander. 24 trials (595 participants) reported ethnicity, with a minority of Hispanic participants (n = 153; 2.57%). Conclusions MND/ALS clinical trials had adequate female enrollment relative to global disease burdens. Race and ethnicity data were underreported. However, there were enrollment disparities of racial and ethnic groups. Increased trial leadership diversity, equitable enrollment policies, and addressing barriers to participation could improve enrollment diversity.

Novel motivational interviewing-based intervention improves engagement in physical activity and readiness to change among adolescents with chronic pain.

Engaging adolescents with chronic pain in physical activities is challenging. Motivational interviewing (MI) combined with activity promotion may encourage teens to make behavioural changes. This research aimed to assess the feasibility and acceptability of our MI-based physical activity promotion programme, the M3 training. In our exploratory study with 35 adolescent-parent dyads, we evaluated the feasibility by enrolment, drop-out and retention rates. Acceptability of the M3 training was examined by adherence rates and participation experiences through open-ended questions. We also assessed changes in pain self-efficacy and readiness to change after the M3 training intervention. The M3 training was feasible with an adequate enrolment (77.8%) and retention (85.7%) rate. Both teens and parents found the M3 training acceptable and considered exercise and physical activity the most helpful elements of the programme (36% and 37%, respectively). While self-efficacy remained unchanged, we identified a significant increase in the readiness to change for adolescents and parents. M3 training improved physical activity engagement while prioritising adolescents' autonomy. Furthermore, it appears to be a clinically relevant approach and could result in a positive shift in readiness to change within a shorter timeframe. The preliminary version of the M3 training was reviewed and commented upon by the public (adolescents and adults). Adolescents who participated in this study were designing their own movement programme, considering their lived experiences. Participants' feedback was used to create the online version of the M3 training (which will be published elsewhere).

Feasibility and acceptability of an online parenting intervention to address behaviour problems in moderately to extremely preterm pre-school and school-age children.

Preterm birth is associated with adverse mental health outcomes, including internalizing problems, social difficulties and inattention. Interventions are needed beyond infancy and toddlerhood to support children and their families. We examined the feasibility and acceptability of the I-InTERACT Preterm pilot study, an online parenting intervention for preterm children ages 3-8. Families participated in a weekly intervention comprised of seven sessions with online modules followed by videoconference coaching sessions with a therapist. Following completion of the study, caregivers completed a survey to assess their satisfaction and were asked to participate in a voluntary semi-structured interview to provide feedback. We anticipated greater than a 50% participation rate (enrollment feasibility) and 75% completion rate (adherence feasibility). We also hypothesized that at least 80% of participants would be satisfied with the intervention (acceptability). Nineteen of 32 families (59%) enrolled in the study, suggesting adequate enrollment feasibility. Feasibility of programme completion (adherence) was lower than anticipated (59%). Regarding satisfaction, all caregivers agreed that the programme's information was relevant to them and their family. Nearly all participants (92%) indicated that they had a better understanding of the effects of preterm birth on behaviour, that they enjoyed the programme, that it met their expectations and that they recommend the programme to others. In qualitative interviews, caregivers expressed satisfaction with the content, skills they learned, and receiving direct coaching. Caregivers suggested improvements to increase intervention feasibility and skill implementation, including offering biweekly sessions and more hands-on coaching. Our largely satisfactory acceptability rates suggest the value of and need for a parenting intervention for children born preterm past the initial period of early development. Future directions include modifying the intervention in response to caregiver feedback to improve recruitment, engagement and adherence.

Representation of the population in need for pivotal clinical trials in lymphomas

AbstractDespite the advances in cancer outcomes, significant health disparities persist. Several new agents have been recently approved for treatment of lymphomas, leading to improved outcomes. Extending the benefits of these new agents starts by adequate enrollment of all affected patient populations. This study aimed to evaluate the extent to which randomized controlled trials (RCTs) match the demographic and geographic diversity of the population affected by lymphoma. Two Food and Drug Administration databases, clinicaltrials.gov, and relevant primary manuscripts were reviewed for drug approval data and demographic representation in RCTs for classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma. Maps showing the distribution and frequency of trial participation relative to disease burden, insurance status, and racial representation were created. Black, Hispanic, and female patients were significantly underrepresented in the RCTs for lymphoma compared with that for the disease burden (3.6% [95% confidence interval (CI), 2.8-5.4] vs 14.6% [95% CI, 13.8-15.3]; 6.7% [95% CI, 5.5-7.9] vs 16.3% [95% CI, 15.5-17.1]; and 39.1% [95% CI, 37.3-40.9] vs 42.7% [95% CI, 42.3-43.1], respectively). White and male patients were overrepresented. More counties with higher mortality rates and racial minority representation had low access to the trials, particularly for cHL in the southern region of the United States. There are significant racial misrepresentations in pivotal RCTs in the United States, and geographic distribution of these trials may not provide easy access to all patients in need. Disparities in enrollment should be corrected to make results applicable to all populations.

Hydroxyurea Dosing in Very Young Children (HUGKISS): Challenges of Study Design

Introduction: The acute and chronic complications of sickle cell anemia (SCA) are well-known, with many of them arising in the first few years of life. The BABY HUG trial showed that 20 mg/kg/day of hydroxyurea therapy is safe, blunts the decline of fetal hemoglobin (HbF), and is clinically beneficial for very young infants and children with SCA. Nevertheless, children treated with hydroxyurea continued to develop acute complications and acquire end organ damage. Although the BABY HUG trial established the safety and efficacy of fixed dose hydroxyurea in very young children with SCA, further study was needed to define the optimal dosing regimen to maximize benefit in this group. We describe our approach to designing and implementing the Hydroxyurea Management in Kids: Intensive versus Stable Dosage Strategies (HUGKISS) study, which assessed the feasibility of enrolling and randomizing very young children with SCA to intensified versus fixed doses of hydroxyurea. The hematologic and clinical effects of both doses were also monitored. Methods: The HUGKISS trial was designed as a single-blind, multicenter, randomized controlled pilot study. It was felt that the objectives of HUGKISS could be safely and more efficiently obtained with a single-blind design (with investigators blinded), because a double-blind design would be logistically challenging and would place significant burden on families and pharmacies. For example, in one double-blind design, caregivers would have to administer two aliquots of study drug (hydroxyurea + hydroxyurea or hydroxyurea + placebo), thereby providing a potential source for medication error. However, because the HUGKISS study required dosage adjustment of hydroxyurea based on complete blood count results, a HUGKISS Enabled Local Provider for Evaluating Response (HELPER) was utilized. Each HELPER was an unblinded local medical provider, unaffiliated with the steering committee or data analysis, who was knowledgeable about SCA. This individual monitored hydroxyurea concordance and toxicities in real time. All patients received hydroxyurea at 20 mg/kg/day for 8 weeks. If they were stable and adherent, they were randomized to either continued fixed dosing or intensified dosing, which involved escalation of hydroxyurea dosing every 8 weeks to a maximum of 35 mg/kg/day. While the primary endpoint was assessing feasibility of enrollment and randomization, the main secondary endpoint assessed was changes in HbF levels. This choice reflected the age of the patient population, which would be undergoing a physiologic decline in HbF during the study period. We monitored adherence via the Medication Adherence Measure (MAM) and measurement of remaining hydroxyurea suspension in the prescribed bottle. Both were performed every four weeks. A medication possession ratio was calculated using the results from both methods, and used to quantitate adherence. Enrollment screening logs were also maintained at all sites. The most common reason for declining participation in HUGKISS was that families desired more time to "think about" hydroxyurea and participation in a trial, followed by disinterest in using hydroxyurea, and a fear of participating in clinical trials. Conclusion: Important considerations when designing trials involving young children with SCA include choice of endpoints, obtaining adequate enrollment, maintaining blinding of a liquid formulation with dose adjustments, and assessment of medication adherence. The HUGKISS study employed a novel single-blind design to facilitate safe and efficient administration of hydroxyurea for families, while also ensuring close monitoring of toxicities through a HELPER.

Feasibility and Acceptability of Bright IDEAS-Young Adults: A Problem-Solving Skills Training Intervention.

Simple SummaryYoung adults with cancer face many different stressors due to a diagnosis of cancer during a unique developmental period. Interventions are needed to address their needs and help better manage distress. Bright IDEAS is a problem-solving skills-training program that has shown to improve people’s problem-solving abilities and reduce the negative affect on caregivers of children with cancer. This study aimed to evaluate if an adapted version of Bright IDEAS was feasible and acceptable to young adults with cancer. Forty young adults recently diagnosed with cancer were enrolled. The results suggested that young adults were satisfied with Bright IDEAS and supported the potential impact to improve problem-solving skills and reduce symptoms of depression and anxiety.Background: Young adults with cancer are a vulnerable group with unique emotional, social, and practical needs. There is a lack of evidence-based interventions to address their needs and to foster skills that could increase their capacity to cope. Bright IDEAS is a problem-solving skills training intervention that has demonstrated efficacy in improving people’s problem-solving ability and reducing distress among caregivers of children with cancer. This study evaluated the feasibility and acceptability of Bright IDEAS adapted for young adults (Bright IDEAS-YA). Methods: Forty young adults recently diagnosed with cancer were enrolled in a single arm feasibility study. Results: Feasibility was demonstrated by the adequate enrollment (67.8%), retention (80.0%), and participants’ adherence to the intervention (average of 5.2 out of 6 sessions completed). Participants reported satisfaction with the intervention. Qualitative feedback identified the systematic approach to problem-solving and interaction with the trainer as strengths of the intervention. Participants demonstrated improvements in problem-solving skills and symptoms of depression and anxiety. Conclusions: In conclusion, the results support the feasibility of the intervention and an adequately powered randomized controlled trial is needed to determine the efficacy of the intervention on psychosocial outcomes.

Adequate enrollment of women in cardiovascular drug trials and the need for sex-specific assessment and reporting

Cardiovascular disease (CVD) is the leading cause of death for women in the United States and globally. There is an abundance of evidence-based trials evaluating the efficacy of drug therapies to reduce morbidity and mortality in CVD. Additionally, there are well-established influences of sex, through a variety of mechanisms, on pharmacologic treatments in CVD. Despite this, the majority of drug trials are not powered to evaluate sex-specific outcomes, and much of the data that exists is gathered post hoc and through meta-analysis. The FDA established a committee in 1993 to increase the enrollment of women in clinical trials to improve this situation. Several authors, reviewing committees, and professional societies have highlighted the importance of sex-specific analysis and reporting. Despite these statements, there has not been a major improvement in representation or reporting. There are ongoing efforts to assess trial design, female representation on steering committees, and clinical trial processes to improve the representation of women.This review will describe the pharmacologic basis for the need for sex-specific assessment of cardiovascular drug therapies. It will also review the sex-specific reporting of landmark drug trials in hypertension, coronary artery disease (CAD), hyperlipidemia, and heart failure (HF). In reporting enrollment of women, several therapeutic areas like antihypertensives and newer anticoagulation trials fare better than therapeutics for HF and acute coronary syndromes. Further, drug trials and cardiometabolic or lifestyle intervention trials had a higher percentage of female participants than the device or procedural trials.

A viable MBA for BoP students: PiMS in rural Kasaragod, Kerala

Learning outcomes Participants will learn to analyze the basis of consumer segmentation in management education. It will specifically highlight the importance of positioning in influencing the marketing strategy of a firm and discuss the importance of a differentiated-low cost strategy to gain competitive advantage. The case will familiarize students with the business environment of rural India, and the applicability of the 4A’s and the 5D’s framework. Finally, the case will help participants understand the difference between a rural market and a Bottom-of-Pyramid (BoP) market. Case overview/synopsis A rural MBA institute for BoP students is grappling with the problem of low admissions, leading to an existential crisis. Two divergent options are presented to the protagonist. The first is to close down the B-school and use the infrastructure and facilities for a well-funded government skill development program which is vocational and intended for creating blue-collar workers. The second is to find ways to bolster the B-school to ensure that it gets adequate student enrollment, thereby leading to profitability. Complexity academic level This case is suitable for an undergraduate or MBA course in marketing management, rural marketing in India, South-Asian marketing or strategic marketing. Supplementary materials Teaching notes are available for educators only. Please contact your library to gain login details or e-mail support@emeraldinsight.com to request teaching notes. There is an accompanying spreadsheet with the case for studying the market. It contains relevant market data that would support analysis of the case. Comments are added for easy understanding. Instructors can access the separate spreadsheet that works out the break-even calculations for the fee structure of the institute. Instructions on calculations as well as comments are added for easy understanding. Subject code CSS 8: Marketing.

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation.

Content available: Audio Recording.

Racial and Ethnic Differences in Drug Disposition and Response: Review of New Molecular Entities Approved Between 2014 and 2019.

Race and ethnicity can contribute to differences in drug exposure and/or response. Here, we report that about 10% of the new molecular entities (NMEs) approved between 2014 and 2019 by the US Food and Drug Administration's Center for Drug Evaluation and Research showed differences in exposure and/or response based on race/ethnicity or pharmacogenetic factors known to vary in frequency across global populations. Fewer NMEs (10%) reported differences in the labeling in 2014 to 2019 when compared to about 21% of NMEs approved between 2008 and 2013 that had differences in pharmacokinetics, safety, response, and/or pharmacogenetics. Understanding the underlying mechanisms that lead to such differences and adequate enrollment of racial and ethnic subgroups is essential to obtain sufficient information on exposure and response. Though drug development is global, when heterogeneous populations are not adequately enrolled, the risk-benefit assessments can remain incomplete for certain subgroups. Consequently, this can result in regional differences in drug approval, population-specific prescribing recommendations, or need for additional postmarketing studies to address concerns related to exposure, response, or lack of representation that lead to gaps in information.

S346 Enrollment Rate of African Americans in a Colon Cancer Screening Trial at a Historically Black College and University Is Similar to Other Patient Populations

Introduction: Clinical trials often have low enrollment of minorities, particularly African-Americans (AAs), which may limit the generalizability of research findings. Previously identified barriers to AAs recruitment include historical abuses leading to mistrust, communication issues with providers, socio-economic factors, and a lack of access to clinical trials. In a Historically Black College and University (HBCU) serving a primarily AA population at a large safe-net hospital, we evaluated the enrollment of eligible AA patients for a colorectal cancer (CRC) screening clinical trial. This was compared to the enrollment rates across other study sites. Methods: A large, prospective, multi-centered clinical trial to validate a blood-based test for early detection of CRC (PREEMPT-CRC) was initiated at a HBCU, where 84% of patients are AAs. To maximize study recruitment, culturally sensitive methods were employed including racially congruent recruitment staff as well as synchronized timing of consent/study procedures with pre-endoscopy COVID testing/clinic visits. Detailed information for all eligible subjects was recorded. Demographic and socio-economic data including census information for enrolled and not enrolled subjects were compared. The enrollment rate (defined as enrolled/eligible patients) over the first 6 weeks at the HBCU and that of the other study sites providing screening logs was analyzed. Results: The enrollment rate at the HBCU was 55% (44 out of 80 eligible patients; 95% CI 43.5-66.2%), compared to 49.8% (258 out of 518 eligible patients; 95% CI 45.4- 54.2%) at the other 26 study sites. While age and gender of enrolled patients at the HBCU were comparable to other sites, the main difference was race: at the HBCU the study participants were 79.5% AAs and 9.1% whites, while at the other sites the participants were 11.5% AAs and 82.8% whites (p< 0.001). At the HBCU, the demographic characteristics and socio-demographic data including income, marital status, insurance status/type, and census tract median household income of the 44 enrolled and 36 not-enrolled subjects were similar (Table 1). Conclusion: Contrary to conventional belief that AAs do not want to be involved in clinical trials, we find their enrollment is similar to a predominant white study population when offered the opportunity in a culturally sensitive setting. Future trials should consider including HBCU sites in order to attain adequate AA enrollment to improve the generalizability of research findings.Table 1.: Baseline Patient Demographic and Sociodemographic Information

BLACK PATIENTS' REPRESENTATION IN MAJOR RANDOMIZED CONTROLLED TRIALS OF HEART FAILURE WITH PRESERVED EJECTION FRACTION

BACKGROUND The black population is generally underrepresented in randomized controlled trials (RCTs). The representation of black individuals in heart failure with preserved EF (HFpEF) RCTs has not been evaluated. We aim to characterize the representation of black patients in major RCTs of chronic HFpEF therapies. METHODS AND RESULTS We conducted a comprehensive database search of PubMed and EMBASE, using the search terms ‘African American’, ‘black’, ‘heart failure with preserved ejection fraction’, ‘heart failure’, ‘diastolic heart failure’, ‘treatment’, ‘therapy’, intervention’, ‘race’, ‘ethnicity’ and ‘randomized clinical trials’. Abstracts and conferences proceedings were excluded, and no language restriction was applied. Our search yielded 17 RCTs: 15 for pharmacotherapies, one evaluating lifestyle modification, and one evaluating diuretic therapy guided by a wireless pulmonary artery monitoring device. The trials enrolled a total of 19,458 patients. Only nine trials of the 17 trials (52.9%) explicitly reported enrollment of Blacks. There were 695 Blacks, accounting for 4.1% of the participants in these nine trials. The TOPCAT trial recruited the largest number of Blacks (302), accounting for 8.7% of the total enrolled participants. Only three out of the 17 RCTs (17.6%) reported outcomes for Blacks. There was no difference in outcomes among Blacks and non-blacks in these three RCTs. CONCLUSION Black patients are poorly represented in major HFpEF RCTs. Our systematic review reinforces the need for adequate enrollment of Blacks in future RCTs of HFpEF to ensure that the benefits and safety of future HFpEF therapies can be confirmed in this high-risk population. The black population is generally underrepresented in randomized controlled trials (RCTs). The representation of black individuals in heart failure with preserved EF (HFpEF) RCTs has not been evaluated. We aim to characterize the representation of black patients in major RCTs of chronic HFpEF therapies. We conducted a comprehensive database search of PubMed and EMBASE, using the search terms ‘African American’, ‘black’, ‘heart failure with preserved ejection fraction’, ‘heart failure’, ‘diastolic heart failure’, ‘treatment’, ‘therapy’, intervention’, ‘race’, ‘ethnicity’ and ‘randomized clinical trials’. Abstracts and conferences proceedings were excluded, and no language restriction was applied. Our search yielded 17 RCTs: 15 for pharmacotherapies, one evaluating lifestyle modification, and one evaluating diuretic therapy guided by a wireless pulmonary artery monitoring device. The trials enrolled a total of 19,458 patients. Only nine trials of the 17 trials (52.9%) explicitly reported enrollment of Blacks. There were 695 Blacks, accounting for 4.1% of the participants in these nine trials. The TOPCAT trial recruited the largest number of Blacks (302), accounting for 8.7% of the total enrolled participants. Only three out of the 17 RCTs (17.6%) reported outcomes for Blacks. There was no difference in outcomes among Blacks and non-blacks in these three RCTs. Black patients are poorly represented in major HFpEF RCTs. Our systematic review reinforces the need for adequate enrollment of Blacks in future RCTs of HFpEF to ensure that the benefits and safety of future HFpEF therapies can be confirmed in this high-risk population.

Management of Brain and Leptomeningeal Metastases from Breast Cancer.

The management of breast cancer (BC) has rapidly evolved in the last 20 years. The improvement of systemic therapy allows a remarkable control of extracranial disease. However, brain (BM) and leptomeningeal metastases (LM) are frequent complications of advanced BC and represent a challenging issue for clinicians. Some prognostic scales designed for metastatic BC have been employed to select fit patients for adequate therapy and enrollment in clinical trials. Different systemic drugs, such as targeted therapies with either monoclonal antibodies or small tyrosine kinase molecules, or modified chemotherapeutic agents are under investigation. Major aims are to improve the penetration of active drugs through the blood–brain barrier (BBB) or brain–tumor barrier (BTB), and establish the best sequence and timing of radiotherapy and systemic therapy to avoid neurocognitive impairment. Moreover, pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. This review aims to provide an overview of the clinical and molecular factors involved in the selection of patients for local and/or systemic therapy, as well as the results of clinical trials on advanced BC. Moreover, insight on promising therapeutic options and potential directions of future therapeutic targets against BBB and microenvironment are discussed.

Utilizing Medical Students As Patient Mentors: An Intervention to Improve Transition Readiness in Young Adults with Sickle Cell Disease

Background:Advances in medical care have resulted in nearly 95% of all children with sickle cell disease (SCD) living to adulthood. Standardized transition programming does not currently exist, resulting in high rates of mortality and morbidity among young adults (YA) during the transition period. Mentoring and social support have been used to impact health behavior change. Medical student mentors can serve as mentors offering specialized support for YA. This study examined the feasibility and preliminary efficacy of a medical student mentor intervention to improve transition outcomes for YAs with SCD. Methods:24 YA with sickle cell disease and 9 medical student mentors enrolled in the intervention. Feasibility and acceptability of the intervention was assessed through enrollment rates, reasons for refusal, retention rates, engagement with the intervention, satisfaction, and reasons for drop-out. The preliminary efficacy of the intervention among patient participants was assessed using dependent t-tests to evaluate changes in transition readiness, health related quality of life, self-efficacy, SCD knowledge medication adherence, and health literacy. Among medical student mentor participants, changes in attitudes towards chronic illness and SCD knowledge were explored. Results:Patient participants demonstrated adequate enrollment (63.2%), retention (75.0%), and adherence to the intervention (88.3%) and rated the intervention components highly. Patient participants demonstrated significant improvements in transition readiness (p= .001), self-efficacy (p= .002), medication adherence (p= .02), and health literacy (p= .05). Medical students also demonstrated significant improvements in SCD knowledge (p= .01). Discussion:A medical student mentor intervention to facilitate transition from pediatric to adult care for young adults with SCD is both feasible and acceptable to patients and medical students. Preliminary evidence suggests such an intervention may provide dual benefit for both patients and students. A randomized controlled trial is needed to evaluate efficacy. Disclosures No relevant conflicts of interest to declare.

El origen de la universidad Incluyente en México: Su evolución y retos

Desde el desarrollo de los tiempos, la educación ha ido evolucionando, ya que esto ha traído la inclusión de alumnos con diversas variantes en su desarrollo, y con esto podemos ver que en México, ha sido una continua inclusión dentro de las formas de educar. En la que hemos visto un crecimiento de matrícula muy adecuado y lo que nos indica un desarrollo continuo del proceso de crecimiento de la UACH. En el proceso de realización de esta investigación pudimos ver como se ha ido incrementando la matrícula y la aceptación de los alumnos con discapacidad, los cuales han ido ganando terreno en el ámbito educativo. Al final concluimos, que a pesar de todo, y pese a todos los altibajos que ha sufrido nuestra economía y sociedad, se acaba de dar un vuelco a ver las necesidades de este sector tan dañado, y tan frágil de nuestra sociedad, esos pequeños-grandes guerreros, que no importando su condición, luchan por seguir en esta tierra, por ganar un espacio y que quieren ser tratados, como lo que son Unos Seres Especiales, aquellos, que por naturaleza, por accidente o por enfermedad, dejaron de desarrollar algún sentido, o bien lo desarrollan poco, pero que al entrar al habito educativo pueden lograr sus metas y sus ideales.

Abstract A17: Predictions of comparative clinical outcomes for checkpoint inhibitor combo therapies and mechanistic targets in first-line NSCLC

Abstract The success of checkpoint inhibitors for immunotherapy has ushered in a new era of cancer treatment. While response rates of approximately 20% are observed with checkpoint monotherapy in NSCLC, it remains one of the most deadly forms of cancer. Combinatory therapy approaches have been rapidly implemented, with the selection of agents largely based on theoretical considerations (Kargl, 2017 #19227). The high number of new clinical trials of anti-PD1 with a combination therapy raises the concern that adequate patient enrollment may become a barrier to trial completion and approval. Hence, drug candidate selection and identification of patients most likely to benefit from treatment are emerging needs of the field. Further, irregularity in patient enrollment criteria and trial designs prevents the direct comparison of regimens, impeding clinical decision making. To address rationale immunotherapy decisions for first- line NSCLC patients, we developed a mechanistic, systems biology model to compare the efficacy of 4 candidate therapies in combinations with an anti-PD1 therapy. Our model captured mechanisms underlying the pro- and anti-inflammatory influences of the innate immune system on Tregs and T cell effector function. “Simulated patients” were then created based on patient level data of 30-60 baseline measurements from preclinical and clinical publications in squamous and nonsquamous NSCLC patients. The model permeated all vectors and combinations of data. Each unique set of permutations that fit within clinical monotherapy data from platinum doublet chemotherapy SOC, anti-PD1, anti-CTLA4, and EGFR inhibitor trials in NSCLC represented a simulated patient. Over 200 patients were simulated to create a virtual trial population. As a performance validation, our model blindly predicted the NSCLC results from published combination trials of anti-PD1 + CTLA4 and anti-PD1 + EGFR. The model then was used to predict results for an anti-PD1 + Lag3 and anti-PD1 + CCL2, for which no trial results are available. We conducted a direct comparison between the co-therapy regimens, controlling for trial design and using the same simulated patient population for each trial arm. The large and diverse simulated patient population allowed us to evaluate trends in the characteristics of the tumor microenvironment of differential responders/nonresponders on one regimen vs. another, such as the immune cell composition, biomarker levels, and cytokine levels. Citation Format: Kadie Vanderman, Andrew Stine, Steven Chang. Predictions of comparative clinical outcomes for checkpoint inhibitor combo therapies and mechanistic targets in first-line NSCLC [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A17.