Trial Sites Research Articles

Agronomic performance and consumer acceptability of improved water yam (Dioscorea alata L.) varieties in the Republic of Benin

White yam (Dioscorea rotundata L.) is widely cultivated, and is a staple food in the Republic of Benin. However, its production is highly sensitive to soil infertility, leading to low yields over the years. In order to address the challenges of land reduction and climate change, it is crucial to introduce more adapted yam varieties to traditional Beninese agriculture. Water yam (Dioscorea alata L.) varieties are viable options, as they need less soil fertility and yield more than D. rotundata, but have a poor culinary performance. The aim of this study is to assess the agronomic and culinary performance of 15 improved water yam genotypes developed by the International Institute of Tropical Agriculture (IITA) compared to local cultivars. In 2022 and 2023, multilocal trials (4 sites) were performed in the yam-growing areas, and nine villages were selected for culinary evaluation. Linear mixed-effects models and generalized mixed-effects models showed significant differences (p < 0.05) in location, year of experimentation, and certain evaluated agronomic parameters. The improved varieties had a strong likelihood of producing small tubers that could be used as seeds. The agronomic and culinary performance of local water yam accessions has been superior to that of improved varieties. Due to its numerous medium tubers, TDa_1508044 could be introduced for production of yam chips. TDa_1510080, which showed a stable high yield throughout the trial sites, and TDa_1510119, which gave a great number of marketable large-size tubers, showed the best agronomic performance with a yield of more than 25 t/ha. TDa_1510043, TDa_0000194, and TDa_1515030 improved varieties that performed well in both culinary and agronomic ways could be widely adopted by farmers in the yam-growing areas of Benin.

Interactive Media-Based Approach for an Exception From Informed Consent Trial Involving Patients With Trauma

Exception From Informed Consent (EFIC) research requires community consultation (CC) and public disclosure (PD). Traditional methods of conducting CC and PD are slow, expensive, and labor intensive. To describe the feasibility and reach of a novel interactive, media-based approach to CC and PD and to identify the similarities and differences between trial sites in website views, survey responses, online community forum attendance, and opt-out requests. This survey study analyzed the CC and PD campaigns conducted for the TAP trial (Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival), an EFIC trial of the early administration of prothrombin complex concentrate in patients with trauma. The CC and PD campaigns consisted of social media advertisements, linked websites, community surveys, and online community forums. These activities were coordinated from a central site and approved by a central institutional review board. This study focused on the first 52 of 91 TAP trial sites (level I trauma centers) in the US to have completed their CC and PD campaigns. Community members in the catchment areas of the participating trauma centers were targeted. Data analysis was conducted between October 2023 and February 2024. Social media advertisements, surveys, and online community meetings conducted as part of the CC and PD campaign for the TAP trial. Social media campaign reach and engagement, web page views, survey results, online community forum attendance, and opt-out requests. Fifty-two trial sites were approved for participant enrollment. Social media advertisements were displayed 92 million times, reaching 11.8 million individuals. The median (IQR) number of people reached in each location was 210 317 (172 068-276 968). Site-specific websites were viewed 144 197 times (median [IQR] viewings per site, 2984 [1267-4038]). A total of 17 206 fully or partly completed surveys were received, and survey respondents had a median (IQR) age of 40.1 (15-65) years and included 10 444 females (60.7%). Overall, 60.6% survey respondents said they would want to be entered into the trial even if they could not give consent, 87.7% agreed that emergency care research was necessary, and 88.0% agreed that the TAP trial should be conducted in their community. Online community forums were attended by a median (IQR) number of 38 (20-63) people. Four opt-out requests were received. The interactive media-based approach to CC and PD for the ongoing TAP trial showed the feasibility and benefits of executing an efficient, coordinated, centrally run series of locally branded and geographically targeted CC and PD campaigns for a large EFIC study.

Genetic Structure of Ganoderma boninense Populations Associated with Oil Palm at Neighboring Fields with Different Planting Ages in Malaysia.

Ganoderma boninense is a basidiomycete pathogen of African oil palm (Elaeis guineensis) and the causal agent of basal stem rot (BSR) disease, which is the most destructive fungal disease of oil palm in Southeast Asia. The disease is fatal for infected palms and can result in 50 to 80% losses in oil yields because of a reduction in productive life span and a yield decline of infected oil palms. In this study, G. boninense isolates collected from different locations and planting blocks with different palm ages were molecularly characterized using microsatellite genotyping. Results showed high pathogen genetic diversity (He = 0.67 to 0.74) among planting blocks and between oil palm estates. Two nearby planting blocks with similar planting ages (i.e., 1999 and 2001) had a similar percentage of BSR incidence (>20%) but showed distinct Ganoderma genetic structure as detected using STRUCTURE. Similar results were obtained from another trial site where planting blocks differing in planting age but located only less than 1 km apart showed a diverse genetic background. The pathogen genetic admixture of the oldest planting (>30% BSR incidence) differed significantly from the younger planting (1.8 to 2.8% BSR incidence, breeding trial block), suggesting that the host-pathogen genotype interaction may impact the Ganoderma genetic variation over time. The genetic structure of G. boninense, as revealed in this study, implies positive selection resulting from the pathogen genetic variation, host-pathogen interaction, and possible introductions of novel genetic variants (through spores) from adjacent plantings. These findings offer new insights into the genetic changes of G. boninense over time. The information is essential to design disease management strategies and breeding for BSR resistance in oil palm.

Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial

Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1-3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1-7), and prednisone (40 mg/m2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503). Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24-42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65-0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45-0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6-96·1) for BrECADD and 90·9% (88·7-93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7-99·5) and 98·2% (97·2-99·3), respectively. BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma. Takeda Oncology.

Vertical Distribution Patterns of Nitrogen and Phosphorus in Soil Solution: Insights from a Wetland Trial Site in the Li River Basin

Vertical Distribution Patterns of Nitrogen and Phosphorus in Soil Solution: Insights from a Wetland Trial Site in the Li River Basin

Insecticide applications with trunk injection method for reducing the damage level of Leptoglossus occidentalis (Heidemann, 1910) in stone pine stands

Leptoglossus occidentalis was first detected in Türkiye in 2009. The pest's damage to stone pine trees and its effects on seeds cause economic losses. In recent years, observations and predictions show that there is a significant threat not only to stone pine but also to other coniferous forests throughout country. In this study, pesticides were applied by trunk injection method in the experiment areas taken in stone pine stands of Bergama - Kozak region. In the systemic application carried out in 2020 and 2021, the Arborjet system was used and the insecticide with the active ingredient Azadirachtin (0.3 g/Lt) was used as an organic insecticide, as well as pesticide with the active ingredient Imidacloprid (200 g/Lt). In 2020, the highest seed filling rate was achieved after systemic Imidacloprid insecticide application with the Arborjet system. As a result of this application, the full seed rate reached 70.7% in Asagicuma, while this rate was 63.6% in the Karaveliler. The seed occupancy rate obtained from control trees in the Asagicuma was 37.96% and this rate reached 70.7% after systemic Imidacloprid application in the same field. Similarly, in the studies carried out in Asagicuma and Yukaribey experiment sites in 2021, only 35% of the seeds were filled in the cones taken from control trees, while the occupancy rate in the cones without insecticide application in the Yukaribey was determined to be 32.76%. In both trial sites, the highest seed fill rate was achieved after systemic Imidacloprid insecticide application with the Arborjet system. As a result of this application, the filled seed rate reached 67.89% in the Asagicuma and 69.86% in Yukaribey experiment sites.

Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review.

There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.

Project PRIME: road markings for motorcycle casualty reduction (an overview of findings from 2020 to 2022)

Pioneering road markings for motorcyclists, designed as Perceptual Rider Information for Maximising Expertise and Enjoyment (PRIMEs) were installed on approach to demanding bends at 22 trial sites and two comparison sites across the West Highlands of Scotland. The markings provided a series of ‘gateways’ to encourage safer riding. With 32,213 motorcyclists observed, the following statistically significant results were observed: speed reductions at 10 trial sites; positive changes in lateral position at the final PRIME gateway marking at 15 trial sites and positive changes in lateral position at the apex of the bend at 13 trial sites; reductions in braking at nine trial sites; increases use of PRIME road markings across 18 of the 22 trial sites. No statistically significant effects were observed at the comparison sites. These findings are discussed in relation to the ‘Road Safety Framework to 2030’ and the ‘Safe System’ approach to reducing motorcycle casualties.

The Impact of Planting Technology on the Maize Yield

The three–year trials of the impact of the planting technology on the maize yield were carried out at the trial sites Jakšić and Tenja. The KWS Intelligens and KWS Kollegas hybrids were used in the research, planted at a standard row spacing of 70 cm, and in the twin rows with a spacing of 48 × 22 cm. In 2020, the highest average grain yield at the site Jakšić in standard planting, with the KWS Intelligens hybrid, was 12.064 t ha–1, and in the twin row planting an increase in yield of +4.17% was recorded. The KWS Kollegas hybrid had the highest difference in grain yield between a standard and twin row planting in 2021 of +7.52%, in favor of the twin row. At the site Tenja, slightly higher grain yields were recorded in all three years of research. The major difference in yield was recorded in 2020 with the hybrid KWS Kollegas, of +8.22%, or 1.115 t more grain, when planting in the twin rows in comparison with a standard planting. The statistical tests indicate that planting in the twin rows at both trial sites obtained statistically significant results in all three years of research concerning the grain yield ha–1, grain weight per ear, and grain moisture content.

Rapid Development of a Registry to Accelerate COVID-19 Vaccine Clinical Trials.

The unprecedented scientific response to the SARS-Cov-2 pandemic in 2020 required the rapid development and activation of extensive clinical trial networks to study vaccines and therapeutics. The COVID-19 Prevention Network (CoVPN) coordinated hundreds of sites conducting phase 2 and 3 clinical trials of vaccines and antibody therapeutics. To facilitate these clinical trials, the CoVPN Volunteer Screening Registry (VSR) was created to collect volunteer information at scale, identify volunteers at risk of COVID-19 who met enrollment criteria, distribute candidates across clinical trial sites, and enable monitoring of volunteering and enrollment progress. We developed a secure database to support three primary web-based interfaces: a national volunteer questionnaire intake form, a clinical trial site portal, and an Administrative Portal. The Site Portal supported filters based on volunteer attributes, visual analytics, enrollment status tracking, geographic search, and clinical risk prediction. The Administrative Portal supported oversight and development with pre-specified reports aggregated by geography, trial, and trial site; charts of volunteer rates over time; volunteer risk score calculation; and dynamic, user-defined reports. Over 650,000 volunteers joined the VSR, and 1094 users were trained to utilize the system. The VSR played a key role in recruitment for the Moderna, Oxford-AstraZeneca, Janssen, and Novavax vaccine clinical trials, provided support to the Pfizer and Sanofi vaccine and prophylactic antibody clinical trials, and enhanced the diversity of trial participants. Clinical trial sites selected 166,729 volunteer records for follow-up screening, and of these 47·7% represented groups prioritized for increased enrollment. Despite the unprecedented urgency of its development, the system maintained 99·99% uptime. The success of the VSR demonstrates that information tools can be rapidly yet safely developed through a public-private partnership and integrated into a distributed and accelerated clinical trial setting. We further summarize the requirements, design, and development of the system, and discuss lessons learned for future pandemic preparedness.

Natural history of acid sphingomyelinase deficiency among European patients during childhood and adolescence: A retrospective observational study

Acid sphingomyelinase deficiency (ASMD) is a rare, lysosomal storage disease with limited evidence on its natural history. This retrospective, medical record abstraction study aimed to characterize the natural history of ASMD (types B and A/B) during childhood and adolescence. Recruiting sites were European centers (i.e., France, Germany, Italy, and the United Kingdom) from the ASCEND-Peds trial (NCT02292654); these sites were targeted because of the rarity of ASMD and specialized care provided at these centers. The study population comprised ASMD trial patients (before exposure to treatment) and ASMD non-trial participants who were managed at the same trial sites. Overall, 18 patients were included (11 trials; 7 non-trials; median [Q1; Q3] age at ASMD diagnosis: 2.5 [1.0; 4.0] years). Median follow-up duration was 10.0 years. Frequently reported medical conditions were hepatobiliary (17 [94.4%]) and blood and lymphatic system disorders (16 [88.9%]). Adenoidectomy (3 [16.7%]) was the most commonly reported surgical procedure; gastroenteritis (5 [27.8%]) was the most frequently reported infection, and epistaxis (6 [33.3%]) was the most commonly reported bleeding event. Abnormal spleen (16 [88.9%]) and liver (15 [83.3%]) size and respiratory function (8 [44.4%]) were commonly reported during physical examination. Overall, 11 (61.1%) patients were hospitalized; 6 (33.3%) patients had emergency room visits. Findings were consistent with published literature and support the current understanding of natural history of ASMD.

The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer’s Disease Trials

BackgroundAdvances in plasma biomarkers to detect Alzheimer’s disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer’s Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD.ObjectivesThe AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based phlebotomy centers and plasma biomarker quantification to assess an individual’s eligibility for AD preclinical trials.DesignPilot feasibility study with co-primary outcomes.SettingThis pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic consent, use of community laboratories for plasma collection, mass spectrometry-based biomarker assay, and telephone communication of plasma biomarker screening eligibility.ParticipantsParticipants invited to the AlzMatch pilot feasibility study were active in the APT Webstudy, 50 years of age or older, resided within 50 miles of both a Quest Diagnostics Patient Services Center (a national diagnostic laboratory with convenient locations for sample collection and processing) and one of six TRC-PAD vanguard clinical trial sites, had no self-reported dementia diagnosis, were able to communicate in English and engaged with the APT Webstudy within the prior 6 months.MeasurementsPrimary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate, plasma biomarker eligibility status (based on amyloid beta-42/40 [Aβ42/40] concentration ratio), ApoE proteotype, and trial inclusion criterion), and completion of telephone contact to learn eligibility to screen for a study.Results300 APT Webstudy participants were invited to consent to the AlzMatch study. The AlzMatch e-consent rate was 39% (n=117) (95% CI of 33.5%–44.5%) overall, which was higher than the expected rate of 25%. Similar consent rates were observed across participants based on self-defined sex (41% Female (n=75), 37% Male (n=42)) and race and ethnicity (37% from underrepresented groups (URG) (n=36), 40% not from URG (n=79)). Among those that consented (n=117), plasma was successfully collected from 74% (n=87) (95% CI of 66%–82%), with similar rates across sex (76% Female (n=57), 71% Male (n=30)) and race and ethnicity (75% URG (n=27) and 75% not from URG (n=59)). 60% (n=51) of participants with plasma biomarker results were eligible to screen for future preclinical AD trials.ConclusionElectronic consent of participants through an online registry, blood sample collection at community-based centers, plasma biomarker quantification and reporting, and biomarker assessments for study eligibility were all feasible with similar engagement rates across demographic groups. Although this pilot was a small and selective sample, participants engaged and consented at higher than expected rates. We conclude that collecting blood at community laboratories for biomarker analyses may improve accessibility beyond research, and may facilitate broader access for clinical use of AD plasma biomarkers. Based on our results, an expanded version of the AlzMatch study is underway, which involves expanding invitations to additional APT Webstudy participants and clinical trial sites.

Limitations and solutions for developing a grain yield and protein content forecasting model based on vegetation indices in organic wheat production – on-farm experimentation

ABSTRACT Multispectral imaging has gained increased attention in recent years for monitoring and predicting crop-related characteristics. Vegetation indices can provide valuable insight into crop health and growth, especially in conventional agriculture and small-sized experimental plots. However, the effectiveness of such methods in non-conventional agricultural systems still needs to be clarified. This study was the first to test three vegetation indices (NDVI, GNDVI, NDRE) for grain yield and protein content prediction in organic farming under real-life farm management practices. Using two small-plot and one on-farm organic wheat variety trial sites, unmanned aerial vehicle-based remote sensing data was compared with physical sampling results in 2 years to assess the potential of agricultural remote sensing to predict yield and protein content on small- and medium-sized plots of organic winter wheat (Triticum aestivum L.). The correlations between vegetation indices and crop traits were stronger in small- than in medium-sized plots (r max = 0.85 and 0.75, respectively, for grain yield), probably due to increased heterogeneity of the larger plots, due to differences in weed cover, soil nutrient supply, etc., and it was strongly affected by the time of measurement. Linear equation for yield and protein content prediction was not sufficiently precise; the machine learning algorithms improved the accuracy of yield estimation. Both methods considered NDRE with a higher weight than NDVI when modelling grain yield and protein content based on the vegetation index values, which suggested that NDRE was more suitable for prediction. Small-plot-based predictions over-estimated grain yield and under-estimated grain protein content in medium-sized plots.

Geographic Distribution of Clinical Trials for Advanced-Stage Cancer

This quality improvement study evaluates the geographic distribution of clinical trials and assesses the distances patients with cancer must travel to access a clinical trial site.

Improving ethnic and racial diversity within clinical trial populations through community recruitment and inclusion initiatives: Experience from MyTACTIC.

e13679 Background: Clinical trial populations are not typically ethnically diverse, restricting healthcare equity and the generalizability of clinical trial data to real-world populations. Moreover, mostpatients (pts) with cancer in the US receive treatment in the more diverse community setting, where minority groups are usually better represented but with lower trial enrollment rates than academic centers. MyTACTIC (NCT04632992) is a phase II, non-randomized basket trial evaluating targeted therapies in pts with advanced solid tumors with specific biomarkers. Inclusive research practices, including mostly community recruitment, were implemented in MyTACTIC to improve access for patients who may otherwise not have been able to enroll. This retrospective analysis presents their impact on the diversity of the trial population. Methods: Adult pts with advanced solid tumors were enrolled from community cancer clinics (private practices and community hospitals) or large academic centers, into 1 of 15 arms based on biomarker alterations. Inclusive research practices implemented to diversify pt recruitment included: revision of eligibility requirements to be more inclusive for minorities; language simplification and streamlining of study protocol; training activities; free transportation. We compared race and ethnicity data between the study population and trial sites’ catchment area (geographical area of pts around the clinical site). Results: Forty pts, all of White race, were initially enrolled across 14 sites, which prompted additional focus on diversity efforts. The trial was expanded to 45 sites across 21 states: 252 pts were enrolled (83% of White race) (Table). Most (96%) selected sites (n=249 pts) were community clinics. The proportion of pts from racial minorities was generally higher in study centers from ethnically diverse catchment areas. Protocol streamlining and staff training were also beneficial to pt recruitment. Free-ride transportation removed the barrier of access to clinical trial sites. The impact of other initiatives will be presented. Conclusions: Running clinical trials at community oncology sites does not, in itself, equal increased diversity of study populations: other efforts, including but not limited to free transportation and community site selection, are also needed. Here we share some learnings from the MyTACTIC study, based on outcomes from the various inclusive research practices implemented in this trial. Clinical trial information: NCT04632992 . [Table: see text]

Geographic distribution and accessibility of clinic trials for advanced-stage pancreatic cancer in the United States: A focus on rural and minority health disparities.

11048 Background: Our research delves into the geographical distribution and accessibility of clinical trials for metastatic pancreatic cancer patients in the U.S., spotlighting the challenges faced by rural communities and minority groups. Prior research indicated nearly half of these patients would have to commute over an hour to reach a trial site. [1] Our study provides a refreshed perspective on this issue, offering a more comprehensive analysis. Methods: Utilizing the ClinicalTrials.gov portal, we identified active interventional clinical trials for metastatic pancreatic cancer patients as of November 25, 2022. We obtained distinct zip codes linked to these trials and, using 2020 census data, gauged the proportion of the U.S. populace residing within specific distances from these sites. Our analysis encompassed factors like urbanity, ethnicity, and other socio-economic parameters. We also developed illustrative maps to visually represent the U.S. clinical trial accessibility landscape. Results: The majority of Americans diagnosed with metastatic pancreatic cancer have clinical trials within their reach. A significant 65.7% of the U.S. populace resides within a 30-mile radius of a relevant clinical trial site. However, a closer look reveals pronounced disparities based on urban-rural demarcations and racial lines, with American Indians facing the most pronounced accessibility challenges. Conclusions: Our data underscores the uneven geographical spread of these trials. This skewed distribution poses accessibility hurdles for specific demographics, especially those in rural areas and certain racial groups. Our findings underscore the pressing need for strategic initiatives to rectify these disparities, ensuring clinical trials are within reach for every individual, irrespective of their location or background.

NCI MATCH (EAY131) arm Z1D: Retrospective evaluation of attributions of adverse events experienced on nivolumab in patients with MSI-high tumors.

e14711 Background: Machine learning algorithms for prediction of Adverse Events (AEs) due to immune checkpoint inhibitors (ICIs) rely on clinically annotated data to serve as gold standards. Clinical trials are the best sources of such data, but audits to assess validity are rare, compromising future machine learning efforts. We reviewed AEs reported on the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) EAY-131 Arm Z1D. Patients matched to Arm Z1D due to MSI-high status were treated with nivolumab. Routine and serious AEs were reported to NCI. Attribution data from AEs on 29 patients with tumor genomics suitable for machine learning approaches were obtained and reviewed retrospectively. Methods: Documented AEs were sorted by grade via the Common Terminology for Adverse Events (CTCAE) system and categorized as related or unrelated to ICIs. Primary source data reported to NCI were reviewed. If any ambiguity was found, trial sites were queried to provide additional information and documentation. Decisions were made by an experienced NCI medical officer with the benefit of additional data and site responses. All serious AEs and a subset of ambiguous routine AEs were assessed to determine if attribution conformed to expected attribution per the nivolumab package insert. Uncertain attribution required additional queries, including email or phone correspondence. Grade 1 or 2 events were only evaluated to determine if any attribution to ICIs was possible. If a higher grade event was attributed to ICIs, there was no further query for lower grade events on the same patient. Results: A total of 639 Grade 1, 152 Grade 2, 75 Grade 3, 10 Grade 4, and 5 Grade 5 events were reported among the 29 patients. One Grade 5 event, 5 Grade 4 events, 13 Grade 3 Events, 9 Grade 2 events, and 6 Grade 1 events were considered less likely to be attributed to ICIs compared with the initial sponsor or site investigator assessment of possibly, probably, or definitely related. Two Grade 4 events, 1 Grade 2 event, and 8 Grade 1 events were considered to be possibly, probably, or definitely due to ICIs compared with the initial sponsor or site assessment of less likely or unrelated. Site responsiveness to retrospective queries from the sponsor varied. Additional lab values, primary source documentation, and communication with site investigators were necessary to make modifications. A total of 11 AEs required additional queries to site investigators. Conclusions: Retrospective reviews of real-time site and sponsor assessments of attribution exhibit significant modification of initial attribution to ICIs in this review of 29 patients on Arm Z1D of the NCI MATCH trial. Machine learning approaches for prediction of AEs on patients treated with ICIs may require careful assessments of primary source data to develop adequate training sets, given the paucity of gold standard data available.

An ancillary care policy in a vaccine trial conducted in a resource-constrained setting: evaluation and policy recommendations

IntroductionClear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic...

Decentralized trial recruitment methods to facilitate broad coverage across urban and rural counties for a blood-based test in early colorectal cancer detection.

1607 Background: Based on the 2022 census, 20% of the U.S. population lives in rural areas. Recent literature suggests that individuals in these areas may encounter health disparities, potentially leading to higher mortality from colorectal cancer (CRC) when compared to their urban counterparts. The PREEMPT CRC is a prospective, multicenter clinical study designed to validate an investigational blood test (MyTectCRC) intended to provide a convenient and accessible option for CRC screening. PREEMPT CRC included a decentralized clinical trial (DCT) site to broaden enrollment from a wider range of geographical areas, including traditionally underrepresented rural regions. This analysis evaluates demographic characteristics of participants from rural and urban areas enrolled in two distinct strategies within the DCT sites. Methods: Eligibility criteria for PREEMPT CRC have been previously described (NCT04369053). All DCT activities occurred under one clinical study ‘Metasite’, enabled by a multichannel recruitment strategy that included 1) Direct-to-Participant (DTP) via digital enrollment and 2) Site-Based (SB) partners who supported the principal investigator by identifying participants scheduled to receive a screening colonoscopy. Participant zip codes were mapped to local counties and aligned with either 1) Metropolitan (Urban) or 2) non-Metropolitan (Rural) counties. Enrolled participants were analyzed for demographics and lifestyle behaviors such as tobacco, alcohol, and drug use. Results: The DCT site enrolled 12,137 participants, where 7,634 used DTP and 4,503 used SB. Of all DCT participants, 24.4% resided in rural areas. DTP's rural population recruitment (27.8%) was double that of the SB (13.5%). The female and male distribution was similar across the groups. A larger percentage of participants from underrepresented races overall were enrolled from urban areas; however, there were some noticeable trends in the rural population. For participants who resided in rural areas and reported their race, 12.5% of DTP participants were Black and 1.2% were Asian, compared to 9.6% and 1.2%, respectively, in SB. For participants in rural areas who reported ethnicity, within DTP, 5.1% identified as Hispanic/Latinx, compared to 14.3% Hispanic/Latinx in SB. Lifestyle behavior factors were similar between DTP and SB participants who resided in rural and urban areas. Conclusions: Through the use of a DCT, the PREEMPT CRC study reached rural areas especially through DTP methodology. Furthermore, the use of SB versus DTP showed certain shifts in demographics, these differences highlight the effectiveness of targeted outreach strategies and reflect the importance for integration of multiple methods and tools to enhance essential population characteristics across geographical locations. Clinical trial information: NCT04369053 .

Development and preliminary validation of a platform for systematic, unbiased pre-screening of non-small cell lung cancer (NSCLC) across three community oncology practices.

e23230 Background: With a rapidly increasing number of candidate drugs and clinical trials in oncology, efficiency in clinical trial execution has become a primary focus area for innovation. Currently, fewer than 5% of oncology patients enroll in clinical trials, and data suggests a lack of diversity in clinical trial patient populations compared to the broader patient demographic. To address these issues, we developed a systematic unbiased pre-screening platform for all patients. This approach holds the promise of hastening clinical trials by enhancing the identification of eligible patients and concurrently promoting diversity among those invited to participate in these trials. Methods: A framework for use of EMR ingested data and standardized abstraction of select 160 variables was developed for patients with NSCLC. An algorithm based on 7 key eligibility criteria was developed to generate an automated assessment of eligibility for a presumed trial. Abstracted data was compared to a medical oncologist’s assessment (gold standard) and the automated tool was validated by comparing eligibility assessment before each visit with that of a medical oncologist. Results: Three community oncology practices in the US participated. Source data-verified values for histology, ECOG PS, treatment history, line of therapy, and current metastatic status were available for &gt; 90% of patients in real-time. Tumor NGS testing rates for actionable alterations exceeded 75%. From Oct 23, 2023 to Jan 14, 2024, 786 NSCLC pts had MD visits. Preliminary validation of the automated tool in 79 patients revealed concordant classification in 76/79 pts (96.2%). Sensitivity, specificity, PPV and NPV were &gt; 90%. Concordance for all variables was 98% between the abstractor and medical oncologist. Conclusions: A platform for systematic, unbiased pre-screening of patients for clinical trials in NSCLC has been developed to support and facilitate oncology sites without imposing financial or resource burdens or affecting routine clinical workflow. Preliminary validation supports high performance. Updated validation data will be presented in the meeting. The high levels of data completeness and quality, including NGS testing rates that are substantially higher than what has previously been reported in community centers, underscore their suitability as clinical trial sites.