Community-based Clinical Trial Research Articles

Experience of participating in community-based clinical trials from rural Maharashtra: Analysis of over 4000 participant feedback forms

Experience of participating in community-based clinical trials from rural Maharashtra: Analysis of over 4000 participant feedback forms

More than Just a Number: Perspectives from Black Male Participants on Community-Based Interventions and Clinical Trials to Address Cardiovascular Health Disparities.

Black Americans remain significantly underrepresented and understudied in research. Community-based interventions have been increasingly recognized as an effective model for reckoning with clinical trial participation challenges amongst underrepresented groups, yet a paucity of studies implement this approach. The present study sought to gain insight into Black male participants' perception of clinical trials before and after participating in a community-based team lifestyle intervention in the United States. Black Impact, a 24-week community-based lifestyle intervention, applied the American Heart Association's Life's Simple 7 (LS7) framework to assess changes in the cardiovascular health of seventy-four Black male participants partaking in weekly team-based physical activities and LS7-themed education and having their social needs addressed. A subset of twenty participants completed an exit survey via one of three semi-structured focus groups aimed at understanding the feasibility of interventions, including their perceptions of participating in clinical trials. Data were transcribed verbatim and analyzed using a content analysis, which involved systematically identifying, coding, categorizing, and interpreting the primary patterns of the data. The participants reported a positive change in their perceptions of clinical trials based on their experience with a community-based lifestyle intervention. Three prominent themes regarding their perceptions of clinical trials prior to the intervention were as follows: (1) History of medical abuse; (2) Lack of diversity amongst research teams and participants; and (3) A positive experience with racially concordant research teams. Three themes noted to influence changes in their perception of clinical trials based on their participation in Black Impact were as follows: (1) Building trust with the research team; (2) Increasing awareness about clinical trials; and (3) Motivating participation through community engagement efforts. Improved perceptions of participating in clinical trials were achieved after participation in a community-based intervention. This intervention may provide a framework by which to facilitate clinical trial participation among Black men, which must be made a priority so that Black men are "more than just a number" and no longer "receiving the short end of the stick".

Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19.

Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls. Interferon- and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0. A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.

Risky Alcohol Consumption in the Elderly: Screening and Brief Intervention from Primary Care. The ALANE Study, a Randomized Clinical Trial

Background: Risky alcohol consumption (RAC) can lead to alcohol-related liver disease (ALD). Liver cirrhosis caused by ALD continues to increase as alcohol consumption continues unabated. In turn, the elderly are more sensitive to alcohol. Population ageing calls for preventive activities to improve their health. Brief interventions have proven to be cost-effective in addressing risk behaviours. Aim: We aimed to analyse the prevalence of RAC in people > 64 years and to assess the effect of a brief intervention in the subgroup of risky consumers. Methods: population-based study in two phases: (1) Phase I: Cross-sectional, descriptive multicentre study of prevalence of RAC in people > 64 years. (2) Phase II: Cluster randomized, controlled, single-blind, community-based clinical trial with two comparison groups of subjects with RAC, to assess the effectiveness of a brief intervention compared to standard practice in reducing alcohol consumption in primary care. Results: Out of the 932 subjects, 455 (49%) (268 men (64%) and 187 women (36%)) had an alcohol consumption that was considered to be risky. Overall, the brief intervention was effective in reducing alcohol consumption showing 1.8 OR (p = 0.030). That effect was caused by women whose group showed 3.3 OR (p = 0.009). There was no effect on men (p = 0.468). Conclusions: RAC in the elderly is very high, far more in men than in women. A brief intervention was successful in reducing alcohol consumption but not below risk levels. Further research is needed to determine which types of interventions are most effective in this population subgroup.

Family-Centered Prevention to Reduce Discrimination-Related Depressive Symptoms Among Black Adolescents

Racial discrimination undermines the mental health of Black adolescents. Preventive interventions that can attenuate the effects of exposure to racial discrimination are needed. To investigate whether participation in the Strong African American Families (SAAF) program moderates Black adolescents' depressive symptoms associated with experience of racial discrimination. This secondary analysis used data from a community-based randomized clinical trial of SAAF (SAAF vs no treatment control). Participants were followed up at 10, 22, and 34 months after the baseline assessment. Assessment staff were blind to participant condition. Participants in this trial lived in 7 rural counties in Georgia. SAAF was delivered at local community centers. Eligible families had a child aged 11 to 12 years who self-identified as African American or Black. The joint influence of random assignment to SAAF and exposure to racial discrimination was investigated. Data were analyzed from September 2022 to March 2023. SAAF is a 7-session (14 hours) family skills training intervention that occurs over 7 weeks. Small groups of caregivers and their adolescents participate in a structured curriculum targeting effective parenting behavior, adolescent self-regulation, and Black pride. The main outcome was adolescent-reported depressive symptoms, assessed at 34 months via the 20-item Center for Epidemiologic Studies Depression Scale for Children. Of 825 families screened randomly from public school lists, 472 adolescents (mean [SD] age, 11.6 years; 240 [50.8%] female) were enrolled and randomized to SAAF (252 participants) or a no treatment control (220 participants). Exposure to racial discrimination at age 13 years was associated with increased depressive symptoms at age 14 years (β = 0.23; 95% CI, 0.13 to 0.34; P < .001). Interaction analyses indicated that the experimental condition significantly moderated the association of racial discrimination with depressive symptoms: (β = -0.27; 95% CI, -0.47 to -0.08; P = .005). Probing the interaction with simple slopes at ±SD revealed that for the control group, racial discrimination was significantly associated with depressive symptoms (β = 0.39; 95% CI, 0.23 to 0.54; P < .001), while for the SAAF group, there was no association between racial discrimination and depressive symptoms (β = 0.12; P = .09). This randomized clinical trial found that the SAAF intervention reduced the incidence of racism-associated mental health symptoms among Black adolescents. SAAF is recommended for dissemination to health care practitioners working with rural Black adolescents. ClinicalTrials.gov Identifier: NCT03590132.

72 Bringing Neuropsychology to the Community: Adaptation of a Rey Osterreith Complex Figure Scoring System for Use in Large-Scale Community-Based Clinical Trials

Objective:The Rey Osterreith Complex Figure (ROCF) is a neuropsychological task used to measure visual-motor integration, visual memory, and executive functioning (EF) in autistic youth. The ROCF is a valued clinical tool because it provides an insight into the way an individual approaches and organizes complex visual stimuli. The constructs measured by the ROCF such as planning, organization, and working memory are highly relevant for research in, but the standardized procedures for scoring the ROCF can be challenging to implement in large scale clinical trials due to complex and lengthy scoring rubrics. We present preliminary data on an adaptation to an existing scoring system that provides quantifiable scores, can be implemented with reliability, and reduces scoring time.Participants and Methods:Data was taken from two large-scale clinical trials focusing on EF in autistic youth. All participants completed the ROCF following standard administration guidelines. The research team reviewed commonly used scoring systems and determined that the Boston Qualitative Scoring System (BQSS) was the best fit due to its strengths in measuring EF, the process-related variables generated, and the available normative data. Initially, the BQSS full scoring system was used, which resulted in comprehensive scores but was not feasible due to the time required (approximately 1-1.5 hours per figure for research assistants to complete scoring). Then, the BQSS short form was used, which was successful at solving the timing problem, but resulted in greater subjectivity in the scores impacting the team’s ability to become reliable. Independent reliability could not be calculated for this version because of the large number of discrepancies among scorers which included 2 neuropsychologists and 4 research assistants. A novel checklist was then developed that combined aspects of both scoring systems to help promote objectivity and reliability. In combination with this checklist the team created weekly check in meetings where challenging figures could be brought to discuss. Independent reliability was calculated amongst all research assistant team members (n=4) for the short form and novel checklist. Reliability was calculated based on (1) if the drawing qualified for being brought to the whole team and (2) individual scores on the checklist.Results:Independent reliability was calculated for 10 figures scored utilizing the novel checklist by a team of 4 trained research assistants. All scorers were able to achieve 80% reliability with a high average (80-86%). Study team members reported that scoring took less time taking on average 30-45 minutes per figure.Conclusions:Inter-rater reliability was strong on the checklist the study team created, indicating its potential as a useful adaptation to the BQSS scoring system that reduces time demands, making the tool feasible for use in large-scale clinical research studies with initially positive reliability factors. The checklist was easy to use, required little training and could be completed quickly. Future research should continue to examine the reliability of the checklist and the time it takes to complete. Additionally, the ROCF should be studied more broadly in research and examined as a potential outcome measure for large scale research studies.

Evaluation of an active focused intervention on the quality of life among elderly individuals in the slum areas of Thane district in India: An experimental field-based randomized clinical trial

Care-giving to elderly population is challenging impacting their quality of life (QoL). We carried out the present study evaluating the influence of an intervention targeting this population in improving their QoL. A community-based randomized clinical trial was undertaken targeting the elderly population residing in an urban slum area after evaluating the baseline QoL using pre-validated questionnaire from World Health Organization (WHO QOL-BREF). Intervention involving mainly the interaction with elderly population in facilitating their interaction with the health care providers, and social clubs was carried out in the intervention group. Control group of participants was provided the usual standard of care without any active intervention.: Eight-hundred and fifty-two were included (study group: 426 and control group: 426) with a large-majority in the age range of 60-69 years. Most of the participants were educated, housewives, economically dependent on their family members, with a monthly income ranging between 5001 and 10000 rupees. The demographic characteristics were comparable between the intervention and control groups except for the concomitant diseases that were significantly more in the intervention group. Baseline mean WHO QOL-BREF scores were 40.04 and 45.2 in the intervention and control groups, respectively. Post-intervention, the QoL scores were significantly (p &amp;#60; 0.05) greater in the intervention group. Those between 60 and 69 years, male gender, those independant on their family members, and healthy individuals had significantly greater QoL scores post-intervention.We observed that our intervention had significant beneficial effects in improving the QoL among the elderly individuals residing in an urban slum area. We have also identified certain sub-groups of individuals with a greater response. There is an urgent need for evaluating the utility of our intervention using a randomized study.

Abstract P570: The Association of Ideal Cardiovascular Health With Self-Reported Health in Black American Women

Introduction: Black American women suffer disproportionately from an increased burden of cardiovascular health (CVH) risk factors, earlier onset of cardiovascular disease (CVD), and higher CVD mortality when compared to their White women. The Partnering in Negating Statistics (P.I.N.S.) for Black Women Initiative is an academic-community-government partnership aimed at uplifting Black women to achieve total health and wellness through the provision of education, access to resources, and partnership in science. Women’s community wellness events have operationalized the P.I.N.S. Initiative mission since 2021, drawing Black women and their families to take part in resources like cardiovascular disease screenings (AHA’s Life’s Simple 7 [LS7] and Life’s Essential 8 [LE8]) and education. The study presented herein examined the association of ideal cardiovascular health (ICH) with self-reported health among Black American women who attended the community wellness events. Methods: Community wellness events focusing on Black women occurred in 2021 and 2022. At these events, a battery of measurements including CVH metrics (blood pressure, glucose, cholesterol, body mass index [BMI], physical activity, smoking, diet and sleep duration) and self-reported health(poor, fair, good, excellent) were collected from participants who chose to participate in biometric screening. The associations between LS7 (range 0-14)/LE8 (range 0-100) with self-reported health were tested using multinomial logistic regression controlling for age, income, and education. Results: One-hundred and twenty-three Black American women with complete LS7 and self-reported health data were included in the analysis 2021 and 2022, of those 63 of participants in 2022 had LE8 data. The mean age of participants was 50 (SD 14), 66%, 23%, 7% and 2% were employed, retired, unemployed and students, 76% and 15%, were enrolled in private insurance, Medicaid/Medicare and 15% had no insurance. Sixty-nine percent had educational attainment ≥ college. In fully adjusted analyses, a 1-unit increase (range 4-13) in LS7 was associated with a 34% lower odds of fair vs. excellent self-reported health (OR 0.66, 95%CI: 0.46, 0.96,p=0.0281). A 1-unit increase in LE8 (range 38-91) was associated with a 13% lower odds of fair vs. excellent self-reported health (OR 0.87, 95%CI: 0.78, 0.98, p=0.0258). Conclusion: Attainment of higher ICH was associated with lower odds of fair vs. excellent self-reported health among Black American women. This finding is important in community-based health interventions and clinical trial recruitment in historically underrepresented populations including Black women, as individuals who appropriately recognize their health status may be more likely to engage in clinical and community-based research to improve health.

Abstract B120: Identifying cancer disparities research gaps in NCORP: A pilot portfolio analysis

Abstract Background/Purpose: Clinical trials offer an underutilized platform to address health disparities. Most disparities-related work in clinical trials has focused on improving patient diversity, rather than on the research questions to reduce disparities. Within the NCI Community Oncology Research Program (NCORP), a large community-based clinical trials network, cancer disparities research incorporates the needs of diverse populations across its scientific portfolio of cancer control, symptom science, prevention, and care delivery studies. The objective of this portfolio analysis was to pilot a process to identify disparities-focused studies and related research gaps. Methods: We identified NCORP studies approved between August 2014-April 2021 with a focus on NIH health disparity and NCORP populations of interest (e.g., racial/ethnic minorities, rural residents, older adults, adolescent/young adults). After screening study titles and aims, studies were included if they focused exclusively on cancer disparities (primary aim) or had a disparities-related aim in studies with a broader focus (secondary aim). Coders abstracted study protocols across NCORP research areas, study-, cancer- and disparities-related characteristics. Coding disagreements were discussed until agreement. Descriptive statistics are reported. Results: The search identified 101 NCORP approved studies, of which 31% (n=31) were deemed disparities-focused. Most disparities-focused studies had primary disparities aims (n=26); fewer had secondary disparities aims (n=5). Sixty-five percent focused on populations underrepresented in clinical trials (9 older adults, 8 AYAs, and 3 other underserved), and 35% focused on health disparity populations (7 racial/ethnic minorities, 2 rural, and 2 socioeconomically disadvantaged). Most studies were available to English-speaking patients only (n=17), with Spanish the most common language accommodation (n=9). By NCORP scientific scope, 20 studies assessed patients’ quality of life, cancer-related or treatment-related symptoms; fewer addressed care delivery (n=8), prevention (n=1), or other topics (n=2). The most common outcome was adverse events or toxicity (n=6) and studies mostly included patients in active (n=19) versus post-treatment (n=10). Study designs were observational (n=15) or interventional (n=16) and examined individual (n=14), interpersonal (n=15) or multiple domains of influence (n=2). Conclusion: Through this pilot we defined a process to identify and describe NCORP disparities focused research and assessed related gaps. Over 30% of studies in the pilot had a primary disparities aim and focused on several populations of interest. Preliminary recommendations based on this pilot include strategies to increase secondary disparities approaches, disparities focused cancer prevention and care delivery research, studies examining multiple domains of influence, and expansion of language availability. NCORP’s strong infrastructure will build on this work to enhance the portfolio of disparities research in the community setting. Citation Format: Brenda A. Adjei, Manami Bhattacharya, Diane St. Germain, Alexis Bakos, Worta McCaskill-Stevens. Identifying cancer disparities research gaps in NCORP: A pilot portfolio analysis [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B120.

INTEGRATION OF DIGITAL TECHNOLOGY IN RESEARCH INVOLVING OLDER ADULTS: LESSONS FROM COMMUNITY-BASED TRIALS

Abstract Working with study participants in community-based clinical trials during COVID-19 pandemic has created diverse challenges to study teams. Globally, COVID-related restrictions were implemented including country-wide lockdowns and social distancing, and study teams had to quickly adjust their study protocols to work in a virtual environment. Meeting virtually for recruitment activities or intervention delivery may be particularly challenging when the target group is older adults—one of the vulnerable populations to experience the digital divide due to limited digital access and limited digital literacyThis symposium covers the lessons learned related to use of digital technology in participant recruitment and intervention delivery across a range of populations, including community-dwelling Korean American older adults to African American older women living with pain and low mood, caregivers of persons living with heart failure, and low-income cancer survivors with multiple chronic conditions. The discussion will include 1) findings from screening over 1,000 older Korean Americans to enroll them into a multi-site community-based trial, 2) lessons in diversifying intervention delivery methods to African American older women, 3) the integration of virtual modality into a self-care and social support intervention for caregivers of persons with heart failure, and 4) the deployment of mHealth to deliver a home-based exercise program to ethnically diverse low-income cancer survivors with co-morbid conditions in the setting of the COVID-19 pandemic. This symposium seeks to build the evidence related to recruitment and intervention delivery targeting diverse groups of older adults in community settings using technology by sharing common challenges, experiences, and opportunities.

235. Tracking Invasive Extraintestinal Pathogenic Escherichia coli Disease in Older Adults in a Community-Based Clinical Trial Setting

Abstract Background A vaccine developed to prevent invasive extraintestinal pathogenic Escherichia coli disease (IED) is being evaluated in a phase 3 clinical trial (NCT04899336). However, historical performance of similar clinical trials has been challenged by inefficient endpoint catchment. Here we report the EXPECT-1 (NCT04087681) study findings on the capture techniques for IED and hospital admissions in a community-based setting. Methods EXPECT-1 was a prospective, observational study conducted in networks of 8 hospitals with surrounding primary care centers in North America, Europe, and Asia. Participants were followed for 1 year to track hospital admissions and occurrence of IED as reported by the primary care physician (PCP) or the participant. In 151 US participants, a geofence technology was used to track admissions to hospital areas. Participants were eligible if aged ≥ 60 years and if they did not have severe chronic conditions. Data were collected from October 24, 2019 until January 28, 2021. Study outcomes included incidence of IED and the rate of hospital admission. Results In total, 4470 participants were enrolled: 68% were female, 74.4% were white, median age was 70 years, and 59.4% had a urinary tract infection (UTI) in the past 10 years. Four IED events were captured with a cumulative incidence (95% CI) of 0.09% (0.024–0.229%) and an incidence rate of 98.6 cases (25.6–248.4) per 100,000 person-years. The incidence increased to 0.15% (0.041–0.385%) and 164.4 (43.8–420) per 100,000 person-years among participants with a history of UTI. Of the 4 IED events, 2 were participant self-reports, 1 PCP report, and 1 report via follow-up phone call. Of all hospital admissions, 56.6% were captured by PCPs and 48.7% by participants’ self-reports. The Kappa statistic varied from 0.31–0.65, indicating fair to moderate agreement between PCP reports and participant self-reports. Geofencing captured 99% of &amp;gt; 800 entries and exits from hospital areas. Conclusion The findings suggest that older adults with a history of UTI in the past 10 years may be a good target population for an efficacy clinical investigation on IED. PCP reports, participant self-reports, and geofencing can be promoted to track study endpoints in a community-based clinical trial setting. Disclosures Joachim Doua, MD, MPH, Janssen: Employee|Janssen: Stocks/Bonds Stephen Ruhmel, MPH, Janssen: Employee Oscar Go, PhD, Janssen: Employee of Janssen Research &amp; Development LLC. Ranee Chatterjee, MD, MPH, Bristol Myers Squibb: Grant/Research Support|Epigenomics: Grant/Research Support|Verily: Grant/Research Support Michal Sarnecki, MD, Janssen: Employee|Janssen: Stocks/Bonds Jan Poolman, PhD, Janssen: Janssen Vaccines &amp; Prevention B.V.|Janssen: Stocks/Bonds Marc Bonten, MD, PhD, Astra-Zeneca: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Novartis: Advisor/Consultant.

Community-based participatory research application of an artificial intelligence-enhanced electrocardiogram for cardiovascular disease screening: A FAITH! Trial ancillary study

ObjectiveWith the emergence of artificial intelligence (AI)-based health interventions, systemic racism remains a concern as these advancements are frequently developed without race-specific data analysis or validation. To evaluate the potential utility of an AI-based cardiovascular diseases (CVD) screening tool in an under-resourced African-American cohort, we reviewed the AI-enhanced electrocardiogram (ECG) data of participants enrolled in a community-based clinical trial as a proof-of-concept ancillary study for community-based screening. MethodsEnrollees completed cardiovascular testing including standard 12-lead ECG and a limited echocardiogram (TTE). All ECGs were analyzed using previously published institution-based AI algorithms. AI-ECG predictions were generated for age, sex, and decreased left ventricular ejection fraction (LVEF). Diagnostic accuracy of the AI-ECG for decreased LVEF and sex was quantified using area under the receiver operating characteristic curve (AUC). Correlation between actual age and AI-ECG predicted age was assessed using Pearson correlation coefficients. ResultsFifty-four participants completed both an ECG and TTE (mean age 55 years [range 31-87 years]; 66.7% female). All participants were in sinus rhythm, and the median LVEF of the cohort was 60-65%. The AI-ECG for decreased LVEF demonstrated excellent performance with an AUC of 0.892 (95% confidence interval [CI] 0.708-1); sensitivity=50% (95% CI 9.5-90.5%; n=1/2) and specificity=96% (95% CI 86.8-98.9%; n=49/51). The AI-ECG for participant sex demonstrated similar performance with AUC of 0.944 (95% CI 0.891-0.998); sensitivity=100% (95% CI 82.4-100.0%; n=18/18) and specificity=77.8% (95% CI 61.9-88.3%; n=28/36). The AI-ECG predicted mean age was 55 years (range 26.9-72.6 years) with a strong correlation to actual age (R=0.769; p<0.001). ConclusionOur analyses of previously developed AI-ECG algorithms for prediction of age, sex, and decreased LVEF demonstrated reliable performance in this community-based, African-American cohort. This novel, community-centric delivery of AI could provide valuable screening resources and appropriate referrals for early detection of highly-morbid CVD for under-resourced patient populations.

Examining evidence of time-dependent treatment effects: an illustration using regression methods

BackgroundFor the design and analysis of clinical trials with time-to-event outcomes, the Cox proportional hazards model and the logrank test have been the cornerstone methods for many decades. Increasingly, the key assumption of proportionality—or time-fixed effects—that underpins these methods has been called into question. The availability of novel therapies with new mechanisms of action and clinical trials of longer duration mean that non-proportional hazards are now more frequently encountered.MethodsWe compared several regression-based methods to model time-dependent treatment effects. For illustration purposes, we used selected endpoints from a large, community-based clinical trial of low dose daily aspirin in older persons. Relative and absolute estimands were defined, and analyses were conducted in all participants. Additional exploratory analyses were undertaken by selected subgroups of interest using interaction terms in the regression models.DiscussionIn the trial with median 4.7 years follow-up, we found evidence for non-proportionality and a time-dependent treatment effect of aspirin on cancer mortality not previously reported in trial findings. We also found some evidence of time-dependence to an aspirin by age interaction for major adverse cardiovascular events. For other endpoints, time-fixed treatment effect estimates were confirmed as appropriate.ConclusionsThe consideration of treatment effects using both absolute and relative estimands enhanced clinical insights into potential dynamic treatment effects. We recommend these analytical approaches as an adjunct to primary analyses to fully explore findings from clinical trials.

Increasing research to address cancer care disparities in an NCI-sponsored community oncology network.

176 Background: Improving the delivery and outcomes of cancer care should be informed by research that aims to reduce disparities among underserved populations and those underrepresented in clinical studies. The NCI Community Oncology Research Program (NCORP), a community-based clinical trials network, conducts such research. In this analysis, we aimed to identify opportunities to develop a robust program of disparities-relevant cancer care delivery research (CCDR). Methods: We reviewed NCORP CCDR studies approved between August 2014-May 2022. Any study with at least one aim addressing care delivery in NIH-health disparity or underrepresented populations was deemed disparities-relevant. Studies were categorized as: primary if they were focused exclusively on cancer disparities within populations of interest; secondary if they had a disparities-related aim in a broader study; and exploratory if the aim assessed differences by race, ethnicity, income, insurance status, or practice-level characteristics. For each CCDR protocol, study and disparities-related characteristics were abstracted by two reviewers, who resolved any disagreements by discussion. Descriptive statistics are summarized. Results: Of 23 CCDR studies, a majority had at least one disparities-relevant aim: 4 primary, 3 secondary, and 10 exploratory. Studies with primary and secondary aims focused on racial/ethnic minorities, rural residents, older adults, adolescent/young adults and socioeconomically disadvantaged populations. Cancer care delivery gaps addressed by these studies included shared decision making, guideline adherence, case management, healthcare expenditures, and healthcare accessibility. Most studies focused on patients undergoing active treatment and included multilevel interventions. Only one of the disparities-relevant studies was available to non-English speaking patients. Conclusions: The inclusion of disparities-relevant aims in most of the care delivery studies is encouraging. The fact that most studies with a primary or secondary aim included an intervention demonstrates strong interest in generating evidence that will support improved cancer care delivery. Studies also addressed several distinct disparity populations across a range of care delivery gaps. These results represent opportunities for targeted network efforts to increase the disparities research portfolio and may inform strategies to optimize equitable care delivery that meets the needs of diverse cancer patient/survivor populations.

Effect of Graphic Warning Labels on Cigarette Pack–Hiding Behavior Among Smokers

The inclusion of graphic warning labels (GWLs) on cigarette packs is recommended for tobacco control but has not yet been implemented in the US. It is unknown whether and to what extent the inclusion of GWLs on cigarette packs affects smokers' willingness to display the packs in public. To determine whether the inclusion of GWLs on cigarette packs affects pack-hiding behavior among smokers in social settings. This community-based randomized clinical trial assessed smokers' real-world experience of using cigarettes repackaged to include GWLs (GWL packs) compared with standard US packs and blank packs over a 3-month intervention period with 12 months of follow-up between September 6, 2016, and December 3, 2019. The study included 357 participants aged 21 to 65 years from San Diego County, California, who smoked 5 or more cigarettes per day, were not actively planning to quit smoking, were not pregnant, and had no unstable medical conditions. Participants purchased and received cigarette packs through the study website. During the 1-month run-in period, participants received their usual US cigarette packs. During the 3-month intervention period, participants were randomized to receive GWL packs (study-manufactured packs with 3 rotating images under license from the Commonwealth of Australia; GWL pack group), blank packs (study-manufactured packs devoid of industry marketing imagery; blank pack group), or standard US packs (US pack group). Pack hiding was queried daily (with participants reporting behavior within the last 4 hours) and weekly via interactive text messages during the 1-month run-in and intervention periods. Self-reported smoking behavior was biochemically validated. Among 357 enrolled participants, the mean (SD) age was 39.3 (11.8) years; 195 participants (54.6%) were female, 40 (11.2%) were Hispanic, 243 (68.1%) were non-Hispanic White, and 74 (20.7%) were of other non-Hispanic races (including American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, or multiracial). A total of 18 987 cigarette packs were purchased and delivered during the run-in and intervention periods. Daily querying showed that the inclusion of GWLs on cigarette packs increased the percentage of smokers who hid their packs at least some of the time from 41.3% (95% CI, 39.6%-43.0%) during the run-in period to 57.1% (95% CI, 55.9%-58.1%) by the end of the intervention period. In the postintervention period, returning to standard US packs reduced pack-hiding behavior to the levels observed during the run-in period. Pack hiding remained at run-in levels for both the blank pack group (35.2%; 95% CI, 33.6%-36.8%) and the US pack group (41.4%; 95% CI, 39.7%-43.1%]) throughout the study. Although even participants in the GWL group with the lowest prestudy tendency to conceal score (ie, 1) had a mean (SE) probability of pack hiding during the intervention of 0.84 (0.02), this group's probability of pack hiding decreased to a mean (SE) of 0.43 (0.03) after intervention. When social reactions to packs were queried at the end of the study, the modal response from participants in the GWL pack group was observers' aversive reactions to the packs, whereas the modal response from participants in the blank pack group was observers' positive interest in the study. Neither smoking prevalence nor consumption differed by group at any point in the study. In this randomized clinical trial, receiving cigarettes in GWL packs vs blank packs increased pack-hiding behavior in social settings, which may be associated with aversive reactions from observers. However, 12-month smoking behavior did not change. ClinicalTrials.gov Identifier: NCT02676193.

Early Th2 inflammation in the upper respiratory mucosa as a predictor of severe COVID-19 and modulation by early treatment with inhaled corticosteroids: a mechanistic analysis

BackgroundCommunity-based clinical trials of the inhaled corticosteroid budesonide in early COVID-19 have shown improved patient outcomes. We aimed to understand the inflammatory mechanism of budesonide in the treatment of early COVID-19.MethodsThe STOIC trial was a randomised, open label, parallel group, phase 2 clinical intervention trial where patients were randomly assigned (1:1) to receive usual care (as needed antipyretics were only available treatment) or inhaled budesonide at a dose of 800 μg twice a day plus usual care. For this experimental analysis, we investigated the nasal mucosal inflammatory response in patients recruited to the STOIC trial and in a cohort of SARS-CoV-2-negative healthy controls, recruited from a long-term observational data collection study at the University of Oxford. In patients with SARS-CoV-2 who entered the STOIC study, nasal epithelial lining fluid was sampled at day of randomisation (day 0) and at day 14 following randomisation, blood samples were also collected at day 28 after randomisation. Nasal epithelial lining fluid and blood samples were collected from the SARS-CoV-2 negative control cohort. Inflammatory mediators in the nasal epithelial lining fluid and blood were assessed for a range of viral response proteins, and innate and adaptive response markers using Meso Scale Discovery enzyme linked immunoassay panels. These samples were used to investigate the evolution of inflammation in the early COVID-19 disease course and assess the effect of budesonide on inflammation.Findings146 participants were recruited in the STOIC trial (n=73 in the usual care group; n=73 in the budesonide group). 140 nasal mucosal samples were available at day 0 (randomisation) and 122 samples at day 14. At day 28, whole blood was collected from 123 participants (62 in the budesonide group and 61 in the usual care group). 20 blood or nasal samples were collected from healthy controls. In early COVID-19 disease, there was an enhanced inflammatory airway response with the induction of an anti-viral and T-helper 1 and 2 (Th1/2) inflammatory response compared with healthy individuals. Individuals with COVID-19 who clinically deteriorated (ie, who met the primary outcome) showed an early blunted respiratory interferon response and pronounced and persistent Th2 inflammation, mediated by CC chemokine ligand (CCL)-24, compared with those with COVID-19 who did not clinically deteriorate. Over time, the natural course of COVID-19 showed persistently high respiratory interferon concentrations and elevated concentrations of the eosinophil chemokine, CCL-11, despite clinical symptom improvement. There was persistent systemic inflammation after 28 days following COVID-19, including elevated concentrations of interleukin (IL)-6, tumour necrosis factor-α, and CCL-11. Budesonide treatment modulated inflammation in the nose and blood and was shown to decrease IL-33 and increase CCL17. The STOIC trial was registered with ClinicalTrials.gov, NCT04416399.InterpretationAn initial blunted interferon response and heightened T-helper 2 inflammatory response in the respiratory tract following SARS-CoV-2 infection could be a biomarker for predicting the development of severe COVID-19 disease. The clinical benefit of inhaled budesonide in early COVID-19 is likely to be as a consequence of its inflammatory modulatory effect, suggesting efficacy by reducing epithelial damage and an improved T-cell response.FundingOxford National Institute of Health Research Biomedical Research Centre and AstraZeneca.

Child and parent secondary outcomes in stepped care versus standard care treatment for childhood trauma

IntroductionStepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT) is comparable in efficacy to standard TF-CBT for child posttraumatic stress symptoms (PTSS), but less is known about the effectiveness of SC-TF-CBT on child and parent secondary outcomes. The aim of this community-based randomized clinical trial was to compare child- and caregiver-secondary outcomes among SC-TF-CBT versus TF-CBT participants. MethodsChildren (ages 4 to 12) with PTSS and their caregivers were randomly assigned to either SC-TF-CBT (n = 91) or TF-CBT (n = 92). Secondary child (internalizing and externalizing behavior problems, anger outburst and sleep disturbances) and parent outcomes (PTSS, depression symptoms, and parenting stress) were measured at baseline, post-treatment and 6- and 12-month follow-up. ResultsThere were comparable changes at all-time points in child and caregiver secondary outcomes. Non-inferiority tests indicated that for completers and intent-to-treat samples, SC-TF-CBT was non-inferior to TF-CBT for all outcomes except parenting stress at 6-months. The analysis with completers did not support non-inferiority at post-treatment for internalizing and externalizing problems and at 6- and 12-month follow-up assessments for externalizing problems, but the intent-to-treat analysis did support non-inferiority. LimitationsLimitations included modest rates of attrition, excluding in vivo component for standard TF-CBT, parent-only assessments, and no control condition. ConclusionsSC-TF-CBT is an effective alternative treatment method although parents with high stress may need more support and children with externalizing problems may need more standard TF-CBT sessions.

Prophylactic efficacy of Unani herbal and herbo-mineral preparations in population at risk of COVID-19 – A randomised controlled prospective field trial

Present study was aimed to evaluate the efficacy of Unani poly-herbal decoction and Khamira Marvareed (herbo-mineral preparation) in COVID-19 susceptible population. This study was conducted as prospective, open label, randomized Controlled, prophylactic Community-based clinical trial. Four thousand five hundred healthy adults from containment zone were allocated randomly into intervention (n=2250) and control group (n=2250). The intervention group was given a combination of herbal drugs namely Unnab ( Zizyphus jujube Mill.), 5 pieces; Sapistan ( Cordia myxa L . ), 9 pieces; Behidana ( Cydonia oblonga Mill.), 3gms in decoction form and Khameera Marwareed , 5gms as semisolid preparation, orally once daily in the morning for 20 days. No drug was given in the control group. The subjects were assessed on 0, 20 th and 35 th day. The prophylactic effect of the Unani intervention was evaluated on the basis of difference of COVID-19 incidence between the groups, COVID-19 like symptoms, scores of immunity status questionnaire and WHOQOL-BREF scale after completion of 35 th day of study. The study remained inconclusive to find any difference in COVID-19 incidence, but showed highly significant result (p&lt;0.001) in favour of Unani intervention in containing all COVID-19 like symptoms except cough; highly significant results (p&lt;0.001) in score of immunity status questionnaire and highly significant results (p&lt;0.001) in scores of physical and psychological domains of WHOQOL-BREF scale. The highly significant results in almost all secondary outcomes suggest the efficacy of the Unani intervention in control of COVID-19 like symptoms and may be beneficial in prevention of COVID-19 infection.

Predictors of suicidal ideation trajectories in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study

A better understanding of suicidal ideation (SI), including patterns of SI, may help elucidate links between depression, SI, and suicidal behavior. This study sought to identify trajectories of SI in a large, community-based clinical trial of participants with major depressive disorder (MDD) and to investigate the relationships between these trajectories and predictors of interest, including anxiety and anhedonia. A longitudinal latent class analysis was conducted in 3923 participants enrolled in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study of citalopram for the treatment of MDD. An unconditional latent class analysis was conducted using SI at study weeks 0, 2, 4, 6, and 9 as the indicators. A multinomial regression was then conducted with SI trajectory as the outcome and anhedonia, severity of depressive symptoms, atypical depression, anxiety, history of suicide attempt, history of substance abuse, history of trauma, and other covariates as the predictors. Four SI trajectories were identified: 1) variable SI; 2) little-to-no SI; 3) persistent SI; and 4) improving SI. Compared to the little-to-no SI trajectory, those with more severe anhedonia were more likely to experience persistent SI, while those with more severe anxiety were more likely to experience improving SI. Factors that distinguish SI trajectories, such as anxiety and anhedonia, may be critical targets for intervention or profiles for prognosis.

The role of community advisory boards in community-based HIV clinical trials: a qualitative study from Tanzania

BackgroundCommunity Advisory Boards (CAB) have become essential organs of involving communities in HIV clinical trials especially in developing countries. However, limited empirical evidence exists on the role of CABs in low and middle-income countries including Tanzania. This study aims at exploring the role of CABs in community-based HIV clinical trials conducted in Tanzania.MethodologyWe adopted a phenomenological approach to purposefully select HIV clinical trial stakeholders. These included CAB members, researchers and Institutional Review Board (IRB) members in Tanzania. We conducted In-depth Interviews (IDIs) with ten participants and three Focus Group Discussions (FGDs) with eighteen participants. The data were thematically analyzed with the aid of MAXQDA software version 20.2.1.ResultsThe findings indicate that at every stage of implementation of a community-based HIV clinical trial, a functioning CAB is important for its success. This importance is based on contextualization of the informed consent process and protocol, managing rumours in the community, weighing trial risks and benefits, sensitizing the community, assisting participant recruitment, tracing and retention. However, being perceived as financial beneficiaries than community representatives emerged as a challenge to CAB members.ConclusionThe study empirically indicates the need for functioning CABs in every stage of implementation of community-based HIV clinical trials. The roles of which are interwoven in serving research goals and protecting the interests of the community and that of trial participants.