Clinical Trial Sites Research Articles

The combination of transcatheter arterial chemoembolisation (TACE) and thermal ablation versus TACE alone for hepatocellular carcinoma.

Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking. To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma. We performed searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We endeavoured to identify relevant randomised clinical trials also in the China National Knowledge Infrastructure (CNKI) and Wanfang databases. We searched trial registration websites for ongoing studies. We also handsearched grey literature sources. The date of last search was 22 December 2020. We planned to include all randomised clinical trials comparing the combination of TACE plus thermal ablation versus TACE alone for hepatocellular carcinoma, no matter the language, year of publication, publication status, and reported outcomes. We planned to use standard methodological procedures expected by Cochrane. We planned to calculate risk ratios (RRs) with the corresponding 95% confidence intervals (CIs). For time-to-event variables, we planned to use the methods of survival analysis and express the intervention effect as a hazard ratio (HR) with 95% Cl. If the log HR and the variance were not directly reported in reports, we planned to calculate them indirectly, following methods for incorporating summary time-to-event data into meta-analysis. We planned to assess the risk of bias of the included studies using the RoB 2 tool. We planned to assess the certainty of evidence with GRADE and present the evidence in a summary of findings table. Out of 2224 records retrieved with the searches, we considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies. Accordingly, we found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review. We identified five ongoing trials, by handsearching in clinical trial websites. We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma. We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.

Abstract PO-105: Improving cancer care through inclusive clinical trials: An online collaborative community to improve representation in cancer clinical trials

Abstract Background: Diverse enrollment in clinical trials is a challenge for study sponsors, sites and patients. Non-Caucasians are underrepresented in cancer clinical trials relative to the burden of cancer they experience (1). Clinical trial participation disparities indicate inequities in current treatment options, impede advancements in medical research and drug development and perpetuate inequities in care to tomorrow's patients. Patients, providers, community leaders and researchers must work together to ensure all populations are included in clinical trials in order to produce comprehensive safety and efficacy profiles for potentially life-saving treatments. In a survey by LUNGevity, industry sposors reported having metrics for diversity and inclusion as well as a commitment to expanding site selection to include more minority-servicing sites with trusted community insights and engagement practices (2). A variety of independent resources exists to guide stakeholders and increase the representation in clincal trials; however, there is no common repository for accessing resources, reviewing opportunities for improvment and learning how to implement best practices. A dedicated platform helps researchers and patients answer common questions, such as: 1. Where are clinical trial sites with diverse patient populations? 2. How can community influence research? 3. How can sites, sponsors, CROs and patient advocates address barriers to participation? Methods: The National Minority Quality Forum (NMQF), through its Diverse Cancer Communities Working group, partnered with Medidata's Social Innovation Lab to build a virtual "Collaborative Community" - a moderated, web-based platform to share resources, best practices, and to crowd source solutions for inclusive clinical trial development. The pilot (July 2021) links to NMQF's Lung Cancer Index (3) to help stakeholders visualize lung cancer Medicare claims and other data in the United States by patient demographics and geography, with an overlay of clinical trial sites to help stakeholders find the best collaborators. Results: 20 stakeholders participating in the platform each with roles in clinical trial operations representative of sponsors, CROs, sites and patient advocacy. The pilot is evaluating engagement engagement metrics, including actie views, content sharing, discussion frequency and user-reported impact. Conclusions: Participating stakeholders from multiple areas of clinical development contribute to building capacity and experience within and across organizations that deliver representative clinical trials. Citation Format: Erin Fenske Williams, Mary Stober Murray, Victoria Rollins, Anupama Santhosh, Jeanne Regnante. Improving cancer care through inclusive clinical trials: An online collaborative community to improve representation in cancer clinical trials [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-105.

Alzheimer's disease drug development pipeline: 2022.

IntroductionAlzheimer's disease (AD) represents a global health crisis. Treatments are needed to prevent, delay the onset, slow the progression, improve cognition, and reduce behavioral disturbances of AD. We review the current clinical trials and drugs in development for the treatment of AD.MethodsWe searched the governmental website clinicaltrials.gov where are all clinical trials conducted in the United States must be registered. We used artificial intelligence (AI) and machine learning (ML) approaches to ensure comprehensive detection and characterization of trials and drugs in development. We use the Common Alzheimer's Disease Research Ontology (CADRO) to classify drug targets and mechanisms of action of drugs in the pipeline.ResultsAs of January 25, 2022 (index date for this study) there were 143 agents in 172 clinical trials for AD. The pipeline included 31 agents in 47 trials in Phase 3, 82 agents in 94 trials in Phase 2, and 30 agents in 31 trials in Phase 1. Disease‐modifying therapies represent 83.2% of the total number of agents in trials; symptomatic cognitive enhancing treatments represent 9.8% of agents in trials; and drugs for the treatment of neuropsychiatric symptoms comprise 6.9%. There is a diverse array of drug targets represented by agents in trials including nearly all CADRO categories. Thirty‐seven percent of the candidate agents in the pipeline are repurposed drugs approved for other indications. A total of 50,575 participants are needed to fulfill recruitment requirements for all currently active clinical trials.DiscussionThe AD drug development pipeline has agents representing a substantial array of treatment mechanisms and targets. Advances in drug design, outcome measures, use of biomarkers, and trial conduct promise to accelerate the delivery of new and better treatments for patients with AD.Highlights There are 143 drugs in the current Alzheimer's disease (AD) drug development pipeline.Disease‐modifying therapies represent 83.2% of the candidate treatments.Current trials require 50,575 participants who will donate 3,878,843 participant‐weeks to clinical trials.The biopharmaceutical industry sponsors 50% of all clinical trials including 68% of Phase 3 trials.Sixty‐three percent of Phase 3 trials and 46% of Phase 2 trials include non–North American clinical trial site locations indicating the global ecosystem required for AD drug development.

Abstract PO-006: Building a new clinical trial diversity alliance to transform our ability to reach understudied and underserved patients

Abstract Not all segments of the population have benefited equally from advances in science and medicine. Distinct populations continue to be understudied in science, underrepresented in research, and underserved by medicine. Multiple complex factors, including the lack of diverse representation in research, are contributing to disparate health outcomes. For instance, among both men and women, Black patients have the highest cancer death rates. Without intervention, future medical innovations will not broadly benefit all patients and society. Genentech, a member of the Roche Group, believes data representative of real-world patient populations is required to optimize clinical outcomes for all patients. To make meaningful progress toward this goal, we created a system-level strategy. Last year, we began building a network of clinical trial sites to advance the representation of diverse patient populations in the company's oncology clinical trials, test recruitment and retention approaches, and establish best practices that can be leveraged across the industry to help achieve health equity for people with cancer. The first step in identifying potential partners for this alliance was to develop site criteria. We considered numerous attributes including: operational capabilities and performance in enrolling underrepresented patient populations, D&I reputation and community involvement with these patient populations, attitude and commitment to inclusive research, and scientific reputation. We used both internal and external data sources to stratify sites based on two key attributes. First, we compared sites' historical enrollment of Black, Latinx and other underrepresented patients in oncology trials. Second, we evaluated the size of the Black and Latinx populations within the catchment area of sites. Included in the data analysis were about 20,000 potential oncology sites. Within those sites that had a large number of underrepresented patient populations, we used enrollment and experience with Genentech oncology trials to further refine our search. We refined our list based on study teams' experience with site capability to conduct phase I-IV trials. We then conducted in-depth site interviews to identify those sites that were aligned with our mission and were making significant efforts to reach patients of color. After the interview process was completed, four inaugural sites were selected for the launch of the Advancing Inclusive Research Site Alliance. Each of the centers will focus on enabling historically underrepresented patient groups to participate in Genentech's oncology trials and work collaboratively to share key learnings and explore innovative ways of increasing clinical trial access for every patient who might benefit. The AIR Site Alliance plans to expand to more research centers and broaden its focus into additional disease areas in the future. Together, we will work to enrich science, eliminate disparity in outcomes and provide equitable access to innovative therapies for all patients. Citation Format: Ruma Bhagat, Meghan McKenzie, Melissa Gonzales, Gerren Wilson, Nicole Richie, Quita Highsmith. Building a new clinical trial diversity alliance to transform our ability to reach understudied and underserved patients [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-006.

POSC429 Clinical Trial Site Attitudes and Experiences in Managing BYOD ePRO: Results of a Qualitative Study

Using bring-your-own-device (BYOD) to collect patient-reported outcomes (PRO) data is thought to improve convenience for trial participants. Seldom considered is the impact of BYOD on site workflow and activities, in comparison to using dedicated provisioned devices (PDs) provided to each participant. This qualitative study investigated the attitudes and experiences of site personnel involved in two global studies using BYOD ePRO, with an aim of understanding and alleviating potential pain points (Study 1: age 50+, Study 2: 18+).

Abstract IA-53: A multi-pronged approach to driving diversity in clinical trials: Bristol Myers Squibb & Bristol Myers Squibb Foundation efforts

Abstract Achieving diversity in clinical trials that reflects the epidemiology of the people and populations affected by diseases and conditions requires an integrated multi-pronged, multi-sector approach and one that is community-informed. This includes among other components community outreach and engagement, patient voice in study design, a culturally competent workforce of clinical trial investigators and team members who are committed to serving URM, and locating clinical trial sites in heavily diverse communities. Bristol Myers Squibb is taking steps and the Bristol Myers Squibb Foundation is making important philanthropic investments on these fronts to drive diversity in clinical trials. The presentation will provide an overview of these efforts, their specific interventions and lessons learned. Citation Format: Patricia M. Doykos. A multi-pronged approach to driving diversity in clinical trials: Bristol Myers Squibb & Bristol Myers Squibb Foundation efforts [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA-53.

Disparity in the rural‐urban distribution of clinical trial sites used in studies cited by diabetes treatment guidelines

Disparity in the rural‐urban distribution of clinical trial sites used in studies cited by diabetes treatment guidelines

Comprehensive Analysis of Adverse Events Associated With SGLT2is: A Meta-Analysis Involving Nine Large Randomized Trials.

Recently, Lin and colleagues assessed the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2is) by a meta-analysis [1], in which the authors assessed 16 kinds of adverse events (AE) reported in the published articles based on 10 randomized controlled trials. We conducted a further meta-analysis and targeted the association between use of SGLT2is and occurrences of various kinds of serious AE published in the Clinical Trials website (clinicaltrials.gov). Our meta-analysis revealed that use of SGLT2is was not significantly associated with occurrences of 980 kinds of serious AE but was significantly associated with lower risks of 29 kinds of serious AE, especially including several important respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease, sleep apnoea syndrome, and pneumonia). These findings may cause more studies to evaluate the possibilities of gliflozins being used for prevention of these specific diseases.

The effect of wheat germ-enriched enteral formula on clinical and anthropometric factors in mechanically ventilated patients admitted to the intensive care unit.

Nutritional support is considered as an important therapeutic strategy among critically ill patients. To evaluate the effect of a wheat germ-enriched formula in patients admitted to the intensive care unit (ICU). This randomized controlled clinical trial study was conducted on 100 patients admitted to the ICU. Patients randomly received a wheat germ-enriched formula or a standard formula from the first day of admission until weaning from the ventilator. Then, the duration of mechanical ventilation, the length of ICU, hospital admission, body composition and mortality rate were compared between the two groups. Based on the results, wheat germ-enriched formula caused a significant reduction in the length of mechanical ventilation (29.80±21.99 days vs. 36.48±8.78 days, P<0.001), the ICU length of stay (32.92±21.04 days vs. 37.70±8.76, P<0.001), and the SOFA score (4.60±1.28 vs. 5.68±1.25, P<0.001) compared to the control group. However, the intervention group demonstrated a significant increase in the basal metabolic rate, mid upper arm circumference, skeletal muscle mass, body cell mass, and GCS score compared to the control group (P<0.05). Finally, no significant difference was observed between the two groups in terms of the hospital length of stay, ICU mortality, and body fat percentage (P>0.05). In general, wheat germ enriched formula may exert beneficial effect on clinical and anthropomorphic variables in patients admitted to the ICU. The study was approved by the Ethics Committee of the Urmia University of Medical Sciences under number IR.umsu.rec.1396.88 and registered at the Iranian Registry of Clinical Trials Website as IRCT20171221037983N3.

EHR-based cohort assessment for multicenter RCTs: a fast and flexible model for identifying potential study sites.

ObjectiveThe Recruitment Innovation Center (RIC), partnering with the Trial Innovation Network and institutions in the National Institutes of Health-sponsored Clinical and Translational Science Awards (CTSA) Program, aimed to develop a service line to retrieve study population estimates from electronic health record (EHR) systems for use in selecting enrollment sites for multicenter clinical trials. Our goal was to create and field-test a low burden, low tech, and high-yield method.Materials and MethodsIn building this service line, the RIC strove to complement, rather than replace, CTSA hubs’ existing cohort assessment tools. For each new EHR cohort request, we work with the investigator to develop a computable phenotype algorithm that targets the desired population. CTSA hubs run the phenotype query and return results using a standardized survey. We provide a comprehensive report to the investigator to assist in study site selection.ResultsFrom 2017 to 2020, the RIC developed and socialized 36 phenotype-dependent cohort requests on behalf of investigators. The average response rate to these requests was 73%.DiscussionAchieving enrollment goals in a multicenter clinical trial requires that researchers identify study sites that will provide sufficient enrollment. The fast and flexible method the RIC has developed, with CTSA feedback, allows hubs to query their EHR using a generalizable, vetted phenotype algorithm to produce reliable counts of potentially eligible study participants.ConclusionThe RIC’s EHR cohort assessment process for evaluating sites for multicenter trials has been shown to be efficient and helpful. The model may be replicated for use by other programs.

Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis.

Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85–2.96), rash (RR: 1.53, 95% CI: 1.25–1.87), ALT elevation (RR 1.54, 95% CI 1.23–1.92), AST elevation (AST: RR 1.49, 95% CI 1.20–1.85), hepatitis (RR: 3.54, 95% CI: 1.96–6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00–6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21–1.48), dyspnea (RR:1.23, 95% CI: 1.12–1.35) and chest pain (RR: 1.26, 95% CI: 1.07–1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13–2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10–1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45–0.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.

Landscape of Carbon Ion Radiotherapy in Prostate Cancer: Clinical Application and Translational Research.

Carbon ion radiotherapy (CIRT) is a useful and advanced technique for prostate cancer. This study sought to investigate the clinical efficacy and translational research for prostate cancer with carbon ion radiotherapy. We integrated the data from published articles, clinical trials websites, and our data. The efficacy of CIRT for prostate cancer was assessed in terms of overall survival, biochemical recurrence-free survival, and toxicity response. Up to now, clinical treatment of carbon ion radiotherapy has been carried in only five countries. We found that carbon ion radiotherapy induced little genitourinary and gastrointestinal toxicity when used for prostate cancer treatment. To some extent, it led to improved outcomes in overall survival, biochemical recurrence-free survival than conventional radiotherapy, especially for high-risk prostate cancer. Carbon ion radiotherapy brought clinical benefits for prostate cancer patients, and quality of life assessment indicated that CIRT affected patients to a lesser extent. Potential biomarkers from our omics-based study could be used to predict the efficacy of prostate cancer with CIRT. Carbon ion radiotherapy brought clinical benefits for prostate cancer patients. The omics-based translational research may provide insights into individualized therapy.

Enhancing Diversity in Oncology Clinical Trials: Findings of a Case Study in Improving Black Patient Representation in a Multiple Myeloma Trial

Background:Black patients are underrepresented in multiple myeloma (MM) clinical trials. Despite the promise of Real-World Data (RWD), little research exists on RWD's usage to address this health disparity. In collaboration with a large pharmaceutical partner, we used RWD from commercial datasets (ConcertAI's Electronic Medical Record and claims datasets) aimed at identifying sites with a large Black patient population. We recommended including these sites in a recent clinical trial of Chimeric Antigen Receptor T cell (CAR-T) therapy for MM patients.Methods:We used the following criteria to identify promising sites: (1) high Black patient density, (2) access to a CAR-T accredited parent organization within 100 miles, (3) a hematologist/oncologist who treats MM patients, and (4) a history of treating MM patients with a Proteasome Inhibitor (PI) and Lenalidomide (Len) in the first line of therapy. For (1), sites were ranked using the lower 95% confidence interval for the percent of Black MM patients at the site. For (4), only sites with at least five MM patients who received PI and Len were included.Our data sources were: ConcertAI's Electronic Medical Record (EMR) and claims datasets to link each patient to a site, and Google maps API to identify the CAR-T center nearest each oncology site. The patients in our data sets were not identifiable, and our research was conducted in compliance with the Health Insurance Portability and Accountability Act.After having identified and filtered promising sites, we curated individual candidates in the order of Black patient density. The purpose of curation was to validate a final list of sites.Results:We identified 17 promising clinical trial sites affiliated with 16 healthcare systems in the mid-west, mid-Atlantic, southeastern, and southwestern regions of the United States (table 1). Our RWD captured an average of 141 MM patients (range: 6-791) who were treated at the 17 sites from 2015-2020. Thirty-nine percent of the patients were Black (range: 13-67%). This percentage was three times the recruitment rate of black patients in MM trials in the US (13%). On average, the sites were 44 miles driving distance (range: 0.8-96 miles) from the closest CAR-T center, had eight hematology/medical oncology specialists on staff (range: 1-17), and had previous interventional trial experience (13 sites had experience with MM trials). All of the identified sites were community-based sites, and none of the sites were previously identified by our pharmaceutical partner.Conclusions:We demonstrated that RWD can be leveraged to identify clinical trial sites with a high potential for Black patient recruitment, thereby addressing a known health disparity problem within multiple myeloma (MM) clinical trials. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Assessment of Healthcare Resource Utilization and Costs in Patients with Relapsed or Refractory Follicular Lymphoma Undergoing CAR-T Cell Therapy with Tisagenlecleucel: Results from the Elara Study

Assessment of Healthcare Resource Utilization and Costs in Patients with Relapsed or Refractory Follicular Lymphoma Undergoing CAR-T Cell Therapy with Tisagenlecleucel: Results from the Elara Study

GEOGRAPHIC ACCESS DISPARITIES TO CLINICAL TRIALS IN RETINOPATHY OF PREMATURITY IN THE UNITED STATES.

To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations. This cross-sectional epidemiological study used census tract-level data from three national public data sets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial site. Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial site if they lived in census tracts that were rural (adjusted odds ratio 1.20, P = 0.0002), had higher percentages of the population living ≤ federal poverty level (fourth quartile vs. first quartile, adjusted odds ratio 1.19, P < 0.0001), or had less education (associate vs. bachelor's degree, adjusted odds ratio 1.01, P <0.007). By contrast, counties with higher percentages of births with birth weight <1500 g (adjusted odds ratio 0.88, P = 0.0062) were less likely to travel >60 minutes. Similar variables predicted travel distance. Although counties with higher incidences of very low-birth-weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.

The effects of antifungal therapy on the recurrence of aspergillus infection after pulmonary aspergilloma resection: a study protocol for a single-center, prospective, non-blind, randomized, 24-month, parallel group study

BackgroundIn recent years, the incidence of pulmonary aspergilloma has increased. The harm of aspergilloma is life-threatening massive hemoptysis, and the conventional treatment is surgical treatment. However, whether the antifungal treatment after surgery is required and the course of treatment before and after surgery are still unclear.MethodsIn this study, patients with pulmonary aspergilloma confirmed pathologically after surgery will be selected as subjects to conduct a single-center, randomized, parallel grouping, prospective, 2-year clinical study. Through regular visits, the recurrence of aspergillus infection, quality of life, lung function indicators, safety of antifungal therapy and other indicators were recorded to evaluate the recurrence risk of aspergillus infection and safety of antifungal agents. Cox proportional risk regression model was used to analyze the influencing factors of antifungal therapy on aspergillus infection recurrence after aspergillus bulbectomy. Cox multiple regression model was used for optimal model fitting, and regression coefficient (β), relative risk (RR) and 95% confidence interval of RR were calculated.DiscussionThe study will explore whether antifungal therapy could improve the quality of life, reduce the recurrence of aspergillus infection, and ultimately improve the prognosis of patients with aspergilloma. The study results will provide high-quality evidence-based medical evidence for the formulation, revision and optimization of international and domestic clinical guidelines and expert consensus on chronic aspergillus lung disease, effectively improve the clinical treatment effect of aspergilloma, and form the latest concept of diagnosis and treatment of aspergilloma.Trial registration: The trial was registered on the Chinese Clinical Trial Registry website (https://www.chictr.org.cn/showprojen.aspx?proj=33231). Registration number: ChiCTR1800019990.

PL02.09 International Association for the Study of Lung Cancer (IASLC) Study of the Impacts of COVID-19 on International Lung Cancer Clinical Trials

In 2020, the global COVID-19 pandemic created major barriers to enrollment and completion of clinical trials. We surveyed investigators and collected aggregate enrollment data for lung cancer trials across the world before (2019) and during (2020-2021) the COVID-19 pandemic. This study consisted of two components. The 64-question Action Survey, distributed by email to select international clinical trial sites, assessed the impact of COVID-19 on the conduct of clinical trials at 173 sites in 2019-2021 and identified mitigation strategies used to combat these impacts. The Data Collection Survey collected aggregate enrollment numbers monthly from 171 lung cancer trials for 2019-2020. Data sources included government or regulatory agencies, industry sponsors, and Principal Investigators from 45 countries. We evaluated enrollment monthly and estimated Incidence Rate Ratios (IRR) with 95% confidence intervals (CI) by Generalized Estimating Equations. Aims of the study include: a) results from the Action Survey will be summarized to help understand the details of the impact COVID-19 had on clinical trials for lung cancer. We will report and evaluate mitigation strategies by region, economic status, trial type and COVID-19 burden; b) we will evaluate trial enrollment data from the Data Collection Survey over time by global region, trial type, and regional COVID-19 burden in simple analysis and with longitudinal statistical models; c) we will combine information from the Action Survey and Data Collection Survey to quantitatively evaluate the impact of mitigation strategies on clinical trial enrollment for trials open at the respective institutions. These results will be stratified by region, economic status, trial type, and regional COVID-19 burden. Additional analysis on how these strategies may impact patients will be included. Clinical trial enrollment declined by 43% from 2019 to 2020 (IRR: 0.57 [CI: 0.37, 0.88]) p=0.0115), with the most dramatic decrease April-August (Figure 1). Although monthly COVID-19 cases increased consistently for all of 2020, the impact on trial enrollment was significantly less in October-December compared to April-June of 2020 (p=0.0160, Figure 1). The most frequent challenges identified by the Action Survey (N=173) were fewer eligible patients (67%), suspension of trials (60%), institutional closures (39%), research staff availability (48%), and protocol compliance (61%). Overall 26% of sites reported disruptions from trial participants COVID-19 infection and 40% from exposure-related quarantine. Patient-specific challenges included access to trial site (52%), ability to travel (60%), and willingness to visit site (63%). Patient concerns included fear of COVID-19 infection (83%), securing transportation (38%), travel restrictions (47%), and lab/radiology access (14%). The Action Survey identified the most frequent mitigation strategies sites employed, which included modified monitoring requirements (44%), telehealth visits (43%), modified required visits (25%), mail-order medications (24%), and altered trial schedules (19%). Some sites allowed labs (27%) and radiology (20%) at non-study facilities and a few implemented altered (7%) or electronic (10%) consent processes. Sites felt the most effective mitigation strategies were delayed visits (65%), remote monitoring (64%), delayed assessment (62%), IRB changes (62%), remote symptom monitoring (59%) or diagnostics (59%), and telehealth visits (59%). The COVID-19 pandemic created many challenges causing reductions in lung cancer clinical trial enrollment. Mitigation strategies were employed and, even though the pandemic worsened, trial enrollment began to improve. A more flexible approach -removing unnecessary barriers- may improve enrollment and access to clinical trials, even beyond the pandemic.

Effectiveness of sexual health influencers identified by an ensemble machine learning model in promoting secondary distribution of HIV self-testing among men who have sex with men in China: study protocol for a quasi-experimental trial

BackgroundHIV self-testing (HIVST), especially the secondary distribution of HIVST (SD-HIVST) initiated by sexual health influencers (SHIs), has been recognized as an effective strategy in promoting HIV testing, especially among men who have sex with men (MSM). This quasi-experimental study aimed to evaluate whether SHIs identified through the ensemble machine learning approach can distribute more HIVST than those who identified by the empiricalscale.MethodsWe will recruit eligible adults (≥18 years old) who were assigned male gender at birth, and willing to participate in potential SD-HIVST online. Participants will be assigned randomly to two groups (scale group or machine learning group), followed by a separate process of SHI identification based on the group assignment. After identification, all index participants (defined as identified SHIs who are verbally consented to participate in SD-HIVST or who directly order HIVST kits) will follow the same procedure for SD-HIVST acquisition and distribution. Index participants can order HIVST online and distribute them to members within their social networks (defined as alters) in-person or virtually through a personalized peer referral link. Once a unique alter uploads a photographed test result to the platform, both the alter and the corresponding index participant will receive a fixed incentive of 3 USD. The index MSM can order up to five HIVST in the first three months and ten HIVST in the following three months. Each index participant will need to complete a baseline survey at the first-time ordering and one to two follow-upbased on the times of ordering,, three months after ordering. This trial will be comparing 1) the mean number of alters motivated by each index participant in each group and 2) the mean number of newly-tested alters motivated by each index participant in each group.DiscussionIn promoting the efficacy of identifying SHIs for SD-HIVST, our study has the potential to enhance testing coverage, particularly among marginalized individuals and those who are reluctant to for HIV and other sexually transmitted infections.Trial registrationWe registered the study on the Chinese Clinical Trial Registry website on 4th November 2021, with registration number ChiCTR2000039632.

TH43. A NOVEL INTEGRATIVE OMICS APPROACH FOR POST-TRAUMATIC STRESS DISORDER

The clinical trials industry faces a number of challenges during the evolving coronavirus disease 2019 (COVID-19) pandemic, for example, site closures, mandatory self-isolation, travel restrictions, interruptions to delivery of investigational product, or staff or participants becoming infected with severe acute respiratory syndrome coronavirus 2. These challenges can pose difficulties in adhering to visit schedules, performing laboratory testing, conducting protocol-specified procedures, and administration of investigational product. As a result, clinical trial sites, contract research organizations, and sponsors have had to act swiftly to ensure that trial patients are safe and systems are in place for continuing trials. Protocols should also be amended to reflect changes and approved by an ethics board. The authors provide practical considerations and recommendations for dermatology clinical trial operations during the COVID-19 pandemic.

Another HIV vaccine fails, highlighting long-standing challenges in the field

HIV has bested another vaccine. After promising results in earlier rounds of testing, Johnson & Johnson’s experimental HIV vaccine failed in Phase 2 trials in women in Africa. The failure is the latest in the so-far fruitless effort to create a vaccine to prevent HIV infection, the world’s leading cause of infectious death. The results were particularly gutting, says April Randhawa, an infectious disease scientist with the HIV Vaccine Trials Network, because the J&J vaccine was the first one developed to encompass the broad variability of the virus rather than focus on one strain. “It’s devastating. We had a lot of high hopes for this vaccine,” Randhawa says. “For the clinical trial sites and study participants, I think it’s probably the hardest for them.” Developing a successful HIV vaccine will require overcoming technological and societal hurdles, Randhawa and other scientists say. Some vaccine candidates, like J&J’s, use a more traditional