Trial Recruitment Research Articles

Describing the content of trial recruitment interventions using the TIDieR reporting checklist: a systematic methodology review

BackgroundRecruiting participants to clinical trials is an ongoing challenge, and relatively little is known about what recruitment strategies lead to better recruitment. Recruitment interventions can be considered complex interventions, often involving multiple components, targeting a variety of groups, and tailoring to different groups. We used the Template for Intervention Description and Replication (TIDieR) reporting checklist (which comprises 12 items recommended for reporting complex interventions) to guide the assessment of how recruitment interventions are described. We aimed to (1) examine to what extent we could identify information about each TIDieR item within recruitment intervention studies, and (2) observe additional detail for each item to describe useful variation among these studies.MethodsWe identified randomized, nested recruitment intervention studies providing recruitment or willingness to participate rates from two sources: a Cochrane review of trials evaluating strategies to improve recruitment to randomized trials, and the Online Resource for Research in Clinical triAls database. First, we assessed to what extent authors reported information about each TIDieR item. Second, we developed descriptive categorical variables for 7 TIDieR items and extracting relevant quotes for the other 5 items.ResultsWe assessed 122 recruitment intervention studies. We were able to extract information relevant to most TIDieR items (e.g., brief rationale, materials, procedure) with the exception of a few items that were only rarely reported (e.g., tailoring, modifications, planned/actual fidelity). The descriptive variables provided a useful overview of study characteristics, with most studies using various forms of informational interventions (55%) delivered at a single time point (90%), often by a member of the research team (59%) in a clinical care setting (41%).ConclusionsOur TIDieR-based variables provide a useful description of the core elements of complex trial recruitment interventions. Recruitment intervention studies report core elements of complex interventions variably; some process elements (e.g., mode of delivery, location) are almost always described, while others (e.g., duration, fidelity) are reported infrequently, with little indication of a reason for their absence. Future research should explore whether these TIDieR-based variables can form the basis of an approach to better reporting of elements of successful recruitment interventions.

RecruIT: A cloud-native clinical trial recruitment support system based on Health Level 7 Fast Healthcare Interoperability Resources (HL7 FHIR) and the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM)

BackgroundClinical trials (CTs) are foundational to the advancement of evidence-based medicine and recruiting a sufficient number of participants is one of the crucial steps to their successful conduct. Yet, poor recruitment remains the most frequent reason for premature discontinuation or costly extension of clinical trials. MethodsWe designed and implemented a novel, open-source software system to support the recruitment process in clinical trials by generating automatic recruitment recommendations. The development is guided by modern, cloud-native design principles and based on Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) as an interoperability standard with the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) being used as a source of patient data. We evaluated the usability using the system usability scale (SUS) after deploying the application for use by study personnel. ResultsThe implementation is based on the OMOP CDM as a repository of patient data that is continuously queried for possible trial candidates based on given clinical trial eligibility criteria. A web-based screening list can be used to display the candidates and email notifications about possible new trial participants can be sent automatically. All interactions between services use HL7 FHIR as the communication standard. The system can be installed using standard container technology and supports more sophisticated deployments on Kubernetes clusters. End-users (n = 19) rated the system with a SUS score of 79.9/100. ConclusionWe contribute a novel, open-source implementation to support the patient recruitment process in clinical trials that can be deployed using state-of-the art technologies. According to the SUS score, the system provides good usability.

Effects of transcutaneous electrical nerve stimulation on pain, function, and descending inhibition in people with non-specific chronic low-back pain: a study protocol for a randomized crossover trial

BackgroundLow back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP.Methods/designThis study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2–125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05.DiscussionThis study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants.Trial registrationClinicalTrials.gov NCT05812885. Registered on 24th May 2023.

The overlap between randomised evaluations of recruitment and retention interventions: An updated review of recruitment (Online Resource for Recruitment in Clinical triAls) and retention (Online Resource for Retention in Clinical triAls) literature.

The Online Resource for Recruitment in Clinical triAls (ORRCA) and the Online Resource for Retention in Clinical triAls (ORRCA2) were established to organise and map the literature addressing participant recruitment and retention within clinical research. The two databases are updated on an ongoing basis using separate but parallel systematic reviews. However, recruitment and retention of research participants is widely acknowledged to be interconnected. While interventions aimed at addressing recruitment challenges can impact retention and vice versa, it is not clear how well they are simultaneously considered within methodological research. This study aims to report the recent update of ORRCA and ORRCA2 with a special emphasis on assessing crossover of the databases and how frequently randomised studies of methodological interventions measure the impact on both recruitment and retention outcomes. Two parallel systematic reviews were conducted in line with previously reported methods updating ORRCA (recruitment) and ORRCA2 (retention) with publications from 2018 and 2019. Articles were categorised according to their evidence type (randomised evaluation, non-randomised evaluation, application and observation) and against the recruitment and retention domain frameworks. Articles categorised as randomised evaluations were compared to identify studies appearing in both databases. For randomised studies that were only in one database, domain categories were used to assess whether the methodological intervention was likely to impact on the alternate construct. For example, whether a recruitment intervention might also impact retention. In total, 806 of 17,767 articles screened for the recruitment database and 175 of 18,656 articles screened for the retention database were added as result of the update. Of these, 89 articles were classified as 'randomised evaluation', of which 6 were systematic reviews and 83 were randomised evaluations of methodological interventions. Ten of the randomised studies assessed recruitment and retention and were included in both databases. Of the randomised studies only in the recruitment database, 48/55 (87%) assessed the content or format of participant information which could have an impact on retention. Of the randomised studies only in the retention database, 6/18 (33%) assessed monetary incentives, 4/18 (22%) assessed data collection location and methods and 3/18 (17%) assessed non-monetary incentives, all of which could have an impact on recruitment. Only a small proportion of randomised studies of methodological interventions assessed the impact on both recruitment and retention despite having a potential impact on both outcomes. Where possible, an integrated approach analysing both constructs should be the new standard for these types of evaluations to ensure that improvements to recruitment are not at the expense of retention and vice versa.

Willingness and motivation of Egyptian patients with diabetic retinopathy to participate in clinical trials

Purpose The aim of this study was to identify the motivational factors and the barriers of Egyptian diabetic retinopathy (DR) patients to recruitment in clinical trials. Patients and methods This is a cross-sectional study of the patients with diabetes mellitus attending the Outpatient Clinic of Zagazig University Hospital from September 2022 to December 2022. Patients with any degree of DR were included. A questionnaire was distributed to all participants. It included the sociodemographic and clinical characteristics and questions to identify the motivational factors or the barriers to participate in a clinical trial. The patients were categorized into two groups according to their tendency for recruitment: the first group that accepted participation, who were asked about the most motivational factors and the second group that refused participation, who were asked about their potential barriers. Results The study recruited 206 DR patients of whom 145 (70.4%) accepted to participate in clinical trials, while the remaining 61 (29.6%) patients refused to participate. Fear from blindness was the commonest motivational factor (93.1%) and the risk of side effects was the commonest barrier (100%). Acceptance to participate was higher among those with positive family history of diabetes mellitus (P=0.01). Refusal to participate was higher in mild nonproliferative DR patients (P&lt;0.001), while patients with proliferative DR and macular edema significantly accepted to participate (P&lt;0.001). High education was significantly associated with acceptance compared to those who refused to participate (81.1 vs. 18.9%, respectively, P=0.004). Ocular history of previous intervention was significantly associated with acceptance to participate (P=0.001). Conclusion Acceptance of DR Egyptian patients to participate in clinical trials was unpredictably high. The results of this questionnaire should encourage researchers to conduct more clinical trials.

The Phase III CONNEX programme assessing the efficacy and safety of iclepertin in patients with schizophrenia: Trial design and recruitment update

IntroductionIn a 12-week, Phase II (NCT02832037) trial, iclepertin (BI 425809), an inhibitor of glycine transporter-1, was generally well tolerated and significantly improved cognition in 509 patients with schizophrenia.ObjectivesThe Phase III CONNEX programme aims to confirm the efficacy, safety and tolerability of iclepertin in improving cognition and functioning across a larger cohort of patients with schizophrenia.MethodsThe CONNEX programme includes 3 randomised, double-blind, placebo-controlled parallel group trials in patients with schizophrenia (NCT04846868, NCT04846881, NCT04860830) receiving stable antipsychotic treatment. Each trial aims to recruit ˜586 patients, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 weeks on current drug and ≥35 days on current dose before treatment) who have functional impairment in day-to-day activities and interact ≥1 hour per week with a designated study partner. Patients with cognitive impairment due to developmental, neurological or other disorders, with a current DSM-5 diagnosis other than schizophrenia or receiving cognitive remediation therapy within 12 weeks prior to screening, will be excluded. Patients will be recruited from multiple centres across 41 countries in Asia, North and South America, Europe and the Asia-Pacific Region, and randomised 1:1 to receive either iclepertin 10 mg (oral administration; n=293), or placebo (n=293) once daily for 26 weeks. The primary endpoint is change from baseline in overall composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. The key secondary endpoints are change from baseline in total score on the Schizophrenia Cognition Rating Scale and change from baseline in the adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool.ResultsThe CONNEX programme is currently recruiting (Table); the first patients were enrolled in Aug–Sept 2021 and completion is expected in Q1 2025. The presentation will describe the current study status, information relating to screening failures, and the experience of collecting these data as part of a large multi-country, multicentre study.Table.The number of patients recruited by 31 August 2023CONNEX 1CONNEX 2CONNEX 3Screened565521493Randomised409360350Completed trial medication202184191ConclusionsIclepertin may represent the first efficacious medication for cognitive impairment associated with schizophrenia.FundingBoehringer IngelheimDisclosure of InterestC. Reuteman-Fowler Employee of: Boehringer Ingelheim, Z. Blahova Employee of: Boehringer Ingelheim, S. Ikezawa Consultant of: Boehringer Ingelheim Pharma GmbH, Lundbeck, Takeda Pharma, Sumitomo Dainippon Pharma, Employee of: International University of Health and Welfare, Mita Hospital, Tokyo, Japan, S. Marder Consultant of: Boehringer Ingelheim Pharma GmbH, Merck, Biogen and Sunovion, P. Falkai Consultant of: Boehringer Ingelheim Pharma GmbH, Boehringer Ingelheim Pharma Advisory Board, J. H. Krystal Shareolder of: Freedom Biosciences, Inc., Biohaven Pharmaceuticals, Sage Pharmaceuticals, Spring Care, Biohaven Pharmaceuticals Medical Sciences, EpiVario, RBNC Therapeutics, Terran Biosciences and Tempero Bio, Consultant of: Aptinyx, Atai Life Sciences, AstraZeneca Pharmaceuticals, Biogen, Biomedisyn Corporation, Bionomics, Boehringer Ingelheim International, Cadent Therapeutics, Clexio Bioscience, COMPASS Pathways, Concert Pharmaceuticals, Epiodyne, EpiVario, Greenwich Biosciences, Heptares Therapeutics, Janssen, Jazz Pharmaceuticals, Otsuka America Pharmaceutical, Perception Neuroscience Holdings, Spring Care, Sunovion Pharmaceuticals, Takeda Industries, Taisho Pharmaceutical Co.; Biohaven Pharmaceuticals, BioXcel Therapeutics, Cadent Therapeutics, Cerevel Therapeutics, Delix Therapeutics, EpiVario, Eisai, Jazz Pharmaceuticals, Novartis, PsychoGenics, RBNC Therapeutics, Tempero Bio and Terran Biosciences Advisory Boards

Brief Report on Global Clinician Practices in the First-Line Management of Metastatic Non-Small Cell Lung Cancer

IntroductionIn the dynamic landscape of metastatic NSCLC (mNSCLC) management, marked by several frontline options and the integration of next generation sequencing (NGS) for informed decision-making, barriers persist despite advancements. This includes challenges in clinical trial recruitment. To gain global insights into clinicians’ practices, we conducted a survey on their testing and management approaches for patients with mNSCLC. MethodsThe survey, conducted from July 12 to August 20, 2023, utilized multiple-choice questions and qualitative research questions, employing the Likert Scale for comprehensive insights. ResultsA total of 127 individuals responded, with 72% affiliated with academic health systems, and 55% practicing in the USA. Regarding testing practices, 93% consistently ordered NGS for non-squamous histology, while 54% did so for squamous cell histology. Concurrent tissue and liquid biopsies were routinely ordered by 28%, while 39% reported ordering both testing platforms concurrently for select cases only. Respondents cited logistical barriers, such as insufficient tissue and lack of infrastructure, as the most common hindrance to molecular testing (76%), followed by reimbursement challenges (56%) and concerns about delayed turnaround time (50%). While most respondents were confident in interpreting NGS results, 22% lacked confidence. Concerning treatment decisions, 72% preferred awaiting molecular testing results before initiating systemic therapy. Less than 50% routinely referred patients for clinical trials in the frontline setting for mNSCLC. For patients with disease expressing high PD-L1 levels, most oncologists preferred pembrolizumab monotherapy. For disease with low PD-L1 expression, a platinum doublet chemotherapy regimen combined with pembrolizumab was favored. In disease cases with negative PD-L1 expression, a platinum doublet chemotherapy regimen with pembrolizumab was preferred. Key factors influencing oncologists' preferred immune checkpoint inhibitor (ICI) included experience with one ICI over another, preferred status per national guidelines, availability of trial data with a significant follow-up period, and consideration of drug cost. ConclusionAlthough this study demonstrates an improved awareness and adoption of ordering NGS for the management of mNSCLC, it underscores the persistence of various barriers that must be addressed to improve upon the quality of care for patients diagnosed with mNSCLC.

A service-oriented approach to clinical trial recruitment for dementia and brain health: Methods and case examples of MyAlliance for Brain Health.

Recruitment of sufficient and diverse participants into clinical research for Alzheimer's disease and related dementias remains a formidable challenge. The primary goal of this manuscript is to provide an overview of an approach to diversifying research recruitment and to provide case examples of several methods for achieving greater diversity in clinical research enrollment. The University of Kansas Alzheimer's Disease Research Center (KU ADRC) developed MyAlliance for Brain Health (MyAlliance), a service-oriented recruitment model. MyAlliance comprises a Primary Care Provider Network, a Patient and Family Network, and a Community Organization Network, each delivering tailored value to relevant parties while facilitating research referrals. We review three methods for encouraging increased diversity in clinical research participation. Initial outcomes reveal an increase in underrepresented participants from 17% to 27% in a research registry. Enrollments into studies supported by the research registry experienced a 51% increase in proportion of participants from underrepresented communities. MyAlliance shifts power, resources, and knowledge to community advocates, promoting brain health awareness and research participation, and demands substantial financial investment and administrative commitment. MyAlliance offers valuable lessons for building sustainable, community-centered research recruitment infrastructure, emphasizing the importance of localized engagement and cultural understanding. MyAlliance led to a significant increase in the representation of underrepresented racial and ethnic groups and individuals from rural areas.The service-oriented approach facilitated long-term community engagement and trust-building, extending partnerships between an academic medical center and community organizations.While effective, MyAlliance required substantial financial investment, with costs including infrastructure development, staff support, partner organization compensation, and promotional activities, underscoring the resource-intensive nature of inclusive research recruitment efforts.

92 Honest Broker Tool to Automate Data Extraction from Clinical Research Data Warehouse

OBJECTIVES/GOALS: To describe an Honest Broker (HB) tool and workflow integrated with the Institutional Review Board (IRB) to automate requests, approvals and delivery of both de-identified and identified data extractions from a clinical research data warehouse (CRDW). METHODS/STUDY POPULATION: The HB tool has predefined domain tables and is closely integrated IRB for quick and easy review and approval. Investigators can access patient data using query tools, barcodes from biospecimens or build a query in TriNetX and provide the patient list as an input for the HB tool. For de-identified data extraction, the required data domain tables and date ranges can be selected and submitted in the HB tool. For identified data extractions, investigators with an approved IRB protocol can enter the protocol number and the approved date range in the HB tool. This request is automatically forwarded to the IRB for review. RESULTS/ANTICIPATED RESULTS: For de-identified data extraction, an email alert is automatically sent to the investigator once the data extract is completed. For identified data extraction, if IRB approves the request, an HB is immediately notified to release the data. Data release triggers two emails to the investigator: (1) a link to an encrypted zipped file with the requested data, and (2) a password to unlock the encrypted file. If the request is denied, the IRB sends an email to the investigator with the reason for denial and options for remediation. The entire HB workflow is accomplished in a secure environment with an audit trail from the initial data request to data download by the investigator. Since the launch of the HB tool, the time from data request to delivery is approximately an hour for deidentified data and 24 hrs for identified data. DISCUSSION/SIGNIFICANCE: The HB tool has increased successful data delivery in support of publications, grant submissions, and clinical trial recruitment. Optimization of data extraction from the CRDW through automation and integration with the IRB can minimize interaction with data analysts and IRB staff, thus accelerating the conduct of clinical research.

Recruitment and retention of clinical trial participants: understanding motivations of patients with chronic pain and other populations.

This paper aims to present and discuss the issues, challenges, and strategies related to recruitment and retention in clinical trials involving participants with chronic pain. The randomized controlled clinical trial (RCT) is widely regarded as the gold standard for evaluating clinical interventions. However, it is crucial to acknowledge and address the challenges associated with recruiting and retaining participants. To prioritize the experience of the study population, targeted outreach strategies and a patient-centric approach are necessary. Researchers should consider incorporating recruitment and retention strategies during the study design phase. Implementing multi-pronged recruitment methods, leveraging relationships with community providers, and involving representatives of the patient population are helpful approaches. Effective communication and maintaining a professional environment are vital for optimizing engagement and supporting the successful execution of clinical trials involving participants with chronic pain.

Using X, Facebook QR codes to optimise recruitment to a feasibility trial Enhancing Men’s Awareness of Testicular Diseases (E-MAT) in a cluster randomised Study Within A Trial (SWAT): Lessons learned.

Background Eight out of ten adults use social media, yet its efficacy in recruitment in clinical trials remains under-explored. The purpose of this SWAT was to determine which recruitment method, X, Facebook or QR code via posters, was more efficient and cost effective for recruiting participants to the host trial. Methods A cluster randomised cross-over design evaluated three recruitment strategies, X, Facebook and QR code. Seven Gaelic Athletic Association (GAA) clubs were randomised to receive either X, Facebook, or QR code. The seven clubs were re-randomised twice more, two weeks apart. There were two primary outcomes: 1. proportion of participants who consent to participate, relative to the number of players contacted; and 2. proportion of participants who consent to participate, relative to the number of players who clicked the link to register their interest. Results Fifty participants were randomised to three recruitment methods, and 47 were retained in the host trial. Participants mainly heard about the study through friends, with some engagement via social media platforms Facebook and X, and little to no engagement with the QR code. Primary outcomes were hindered by the inability to disaggregate data by GAA club. Economic outcomes revealed QR code as the costliest strategy, and while X was cheaper than Facebook in terms of the number of clicks, Facebook demonstrated better recruitment and retention and thus reduced the costs per participant. Conclusions While the inability to disaggregate data by club was a limitation, the study revealed that Facebook outperformed X and QR codes in terms of recruitment and participant retention and was thus considered to be more cost effective. The findings emphasise the importance of considering engagement patterns and cost-effectiveness in designing recruitment strategies for clinical trials, especially within the dynamic landscape of social media use.

Abstract 6374: Socio-demographic predictors of recruitment in neuroblastoma therapeutic clinical trials

Abstract The generalizability of clinical trial outcomes hinges upon the equitable access and enrollment of diverse patient populations. Yet, disparities persist that may influence enrollment patterns. In neuroblastoma, the impact of ethnicity, socioeconomic status (SES), distance to care, and age at diagnosis on enrollment in therapeutic trials remains underexplored. We aimed to investigate these factors in neuroblastoma patients to identify potential disparities in clinical trial participation. We utilized the Childhood Cancer Research Network data, selecting neuroblastoma cases from 2008-2015, excluding those &amp;gt;21 years old or with incomplete data. We focused on factors influencing enrollment in therapeutic trials (ANBL0032, ANBL0421, ANBL0531, ANBL0532, ANBL0621, ANBL0931, ANBL1021, ANBL1221, ANBL1232). Key predictors examined were ethnicity, age at diagnosis, SES (via Yost Index), and distance to care from home to treatment hospital. We employed Poisson regression to calculate adjusted risk ratios (aRR) and 95% confidence intervals for trial participation. Analyzing 3,148 neuroblastoma cases from the CCRN registry, the ethnic composition was as follows: 68% were non-Hispanic White, 14% Hispanic, and 10% NH Black and SES distribution was even across quintiles. Age at diagnosis was a significant factor in trial enrollment: children &amp;gt;2 years were 94% more likely to enroll than those under 2 years (p &amp;lt; 0.001). Race, ethnicity, SES, and distance to care showed no significant effect on enrollment, all with non-significant p-values. In CCRN, neuroblastoma patient's age at diagnosis was a determinant in therapeutic trial enrollment, providing insight into design strategies to encourage trial participation. While common barriers like race, ethnicity, SES, and distance to care did not impact enrollment in our cohort, the significant role of age highlights an area where focused efforts can ensure that all age groups have equitable access to the potential benefits of therapeutic trials. Category N aRR (95% CI) p-value Race and Ethnicity Non-Hispanic (NH) White 2139 ref Hispanic (All races) 436 0.93 (0.81, 1.08) 0.36 NH Black 320 1.07 (0.93, 1.23) 0.33 NH Asian/Pacific Islander 98 1.14 (0.89, 1.47) 0.30 NH American Indian/Alaska Native 17 0.95 (0.48, 1.88) 0.89 Other 138 0.94 (0.75, 1.17) 0.55 SES (Yost Index) Quintile 1 493 0.88 (0.75, 1.02) 0.09 Quintile 2 524 0.95 (0.83, 1.10) 0.53 Quintile 3 606 0.98 (0.86, 1.11) 0.71 Quintile 4 554 0.92 (0.80, 1.06) 0.24 Quintile 5 563 ref Age at Diagnosis &amp;lt;2 year 1790 ref &amp;gt;2 years 1354 1.94 (1.76, 2.12) &amp;lt;0.001 Distance to Care 0-25 miles 1520 ref &amp;gt;25-50 miles 535 1.05 (0.93, 1.18) 0.36 &amp;gt;50-100 miles 412 0.97 (0.85, 1.11) 0.91 &amp;gt;100-250 miles 239 0.99 (0.87, 1.13) 0.60 &amp;gt;250 miles 82 0.99 (0.77, 1.28) 0.97 Citation Format: DeVon Hunter-Schlichting, Jeannette Sample, Kate Knowles, David Van Riper, Logan Spector, Erin Marcotte. Socio-demographic predictors of recruitment in neuroblastoma therapeutic clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6374.

Abstract 1311: Planning for health equity in oncology trials: Expectations and feasibility

Abstract Achieving diverse representation in oncology studies is an ongoing challenge., Responding to calls to advance health equity in clinical trials, Congress amended the Food Drug and Cosmetic Act to require trial sponsors to submit a “diversity action plan” to the FDA with a study’s protocol. This requirement to plan for diverse trial recruitment drives a need to innovate approaches for site selection and trial recruitment that go beyond mirroring race-ethnicity distributions from the US Census or disease prevalence. We present a novel framework that nests clinical trials in a longitudinal patient registry to achieve diverse representation across multiple domains, evaluate site-selection and recruitment strategies, and examine health equity across the cancer patient journey. Implementing a registry to support longitudinal data collection (i.e., a cohort study), we establish a continuous view of participant characteristics including demographic and social determinants of health, treatment received, and relevant outcomes. Nesting clinical trials within the structure of the cohort, we can select sites and recruit for diverse representation to achieve equity goals. This framework involves a multi-layer analysis of external population statistics and internal reference registry to gauge the pool of eligible participants and calibrate the sampling strategy and recruitment expectations to the realities of clinical representation. Moreover, where clinical representation differs from population statistics, the registry offers an opportunity to report benchmarks for diversity and compare to site-level and study-level realized enrollment and feasibility. In conclusion, the path to health equity in oncology trials depends on a capacity to ask and answer the right questions in planning. What specific aspects of diversity are we aiming to capture? How do these aspects impact outcomes? We advocate for a dynamic planning process that continuously reevaluates goals and strategies in the face of enrollment data and evolving population demographics. By utilizing a registry with longitudinal follow-up, we can set forth clear expectations, transparently report on the progress of inclusion efforts, and candidly address feasibility challenges. We present a structured framework for trial sponsors to not only comply with the forthcoming requirement for diversity action plans, but ultimately to advance the goal of equitable cancer care through research that truly reflects the complex intersectional diversity of those impacted by the disease. Citation Format: Halcyon G. Skinner, Caroline Marra, April I. Alexandrow, Hamsa L. Subramaniam, Nathan C. Nussbaum, Joseph B. Franklin, Edgar P. Simard, Amy P. Abernethy. Planning for health equity in oncology trials: Expectations and feasibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1311.

The Frailty Reduction via Implementation of Exercise, Nutrition, and Deprescribing (FRIEND) Trial: Study Protocol and Recruitment Results.

Virtually all adults in aged care facilities are frail, a condition which contributes to falls, cognitive decline, hospitalisation, and mortality. Polypharmacy, malnutrition, sedentariness, and sarcopenia are risk factors amenable to intervention. The Asia-Pacific Frailty Management Guidelines recommend anabolic exercise and the optimisation of medications and nutrition. However, no study has evaluated this best practice intervention triad in aged care. The Frailty Reduction via the Implementation of Exercise, Nutrition, and Deprescribing (FRIEND) Trial (ANZCTR No.ACTRN12622000926730p) is a staged 6-month translational trial evaluating resident outcomes, staff/caregiver knowledge, and institutional implementation in a Townsville aged care facility. Residents received high-intensity resistance exercise and balance training and medication and nutrition optimisation co-implemented by investigators (exercise physiologist, geriatrician, pharmacist, and nutritionist) and facility staff. Staff and caregivers completed comprehensive education modules and training. We report the trial protocol and recruitment results. 29 residents (21 female, age: 88.6 ± 6.3 years) were recruited. At baseline, the residents were frail (frailty scale nursing home (FRAIL-NH); 6.3 ± 2.4/14), cognitively impaired (Montreal Cognitive Assessment; 13.8 ± 6.8/30), functionally impaired (Short Physical Performance Battery; 4.9 ± 3.1/12, 6 min walk distance; 222.2 ± 104.4 m), and were prescribed numerous medications (15.5 ± 5.9). Two residents died and one withdrew before the intervention's commencement. Thirty family members and 19 staff (carers, allied health assistants, nurse managers, registered nurses, lifestyle-leisure officers, kitchen/hospitality staff, and senior leadership) were recruited to receive frailty education modules. The FRIEND trial is currently being implemented with results expected in mid-2024. This is the first trial to evaluate the implementation of the best practice frailty guidelines including anabolic exercise and medication/nutritional optimisation in residential aged care.

A Web-Based Physical Activity Promotion Intervention for Inactive Parent-Child Dyads: Protocol for a Randomized Controlled Trial.

Low levels of physical activity are associated with numerous adverse health outcomes, yet sedentary lifestyles are common among both children and adults. Physical activity levels tend to decline steeply among children aged between 8 and 12 years, even though children's behavioral patterns are largely governed by familial structures. Similarly, parents' activity levels have been generally reported as lower than those of nonparents of comparable age. For this reason, family-based physical activity promotion interventions are a potentially valuable and relatively underresearched method for mitigating physical activity declines as children develop into adolescents and for increasing physical activity in parents. This study aims to assess the efficacy, feasibility, and acceptability of a novel theory-based web-based physical activity promotion intervention among parent-child dyads in Finland who do not meet physical activity recommendations at baseline. Participants (target N=254) will be recruited from the general population using a panel company and advertisements on social media and randomly assigned to either an immediate intervention group or a waitlist control group. The intervention consists of 4 web-based group workshops over the course of 10 weeks, web-based tasks and resources, and a social support chat group. Data on physical activity behavior and constructs from the integrated behavior change model will be collected through self-report surveys assessing physical activity, autonomy support, autonomous motivation, attitude, subjective norm, perceived behavioral control, intention, self-monitoring, habit, and accelerometer measurements at baseline, post intervention, and 3 months post intervention. Exit interviews with participants will assess the feasibility and acceptability of the intervention procedures. This study will reveal whether the intervention changes leisure-time physical activity among intervention participants relative to the control group and will examine the intervention's effects on important theoretical predictors of physical activity. It will also yield data that can be used to refine intervention materials and inform further implementation. Trial recruitment commenced in September 2023, and data collection should be completed by December 2024. The planned intervention has potential implications for both theory and practice. Practically, the use of an entirely web-based intervention may have scalable future uses for improving physical activity in 2 key populations, while also potentially informing on the value of dyadic, family-based strategies for encouraging an active lifestyle as an alternative to strategies that target either parents or children independently. Further, by assessing change in psychological constructs alongside potential change in behavior, the intervention also allows for important tests of theory regarding which constructs are most linked to favorable behavior change outcomes. ClinicalTrials.gov NCT06070038; https://clinicaltrials.gov/study/NCT06070038. DERR1-10.2196/55960.

A Social Media-Delivered Melanoma Prevention Program for Young Women Engaged in Frequent UV Tanning: Protocol for a Randomized Controlled Trial.

Rates of melanoma have increased dramatically in the United States over the past 25 years, and it has become among the most prevalent cancers for young adult women. Intentional skin tanning leads to a pattern of intense and intermittent UV radiation exposure that is associated with increased risk of melanoma. Frequent tanning is most common among young women and is linked to a variety of sociocultural pressures that negatively impact body image and drive appearance control behaviors. Unfortunately, there are no established interventions designed for frequent tanners. This intervention addresses this gap with unique content informed by body image and acceptance-based interventions. The intervention is delivered using Facebook secret groups, an approach designed to support behavior change and ensure scalability. This study aims to describe the rationale and methodology of a randomized controlled trial of a melanoma prevention program targeting young women engaged in frequent indoor or outdoor UV tanning. Participants are women aged 18-25 years who report high-risk tanning (ie, at least 10 indoor tanning sessions in the past 12 months or 10 outdoor sessions in the previous summer). After recruitment and screening, participants completed a baseline survey and were randomly assigned to receive the intervention or an attention-matched control condition. Both conditions were 8-week-long Facebook groups (approximately 25 members each) with daily posting of content. Follow-up surveys are administered at 3, 8, and 18 months after baseline. The primary trial outcome is the combined number of indoor and outdoor tanning sessions reported at the 8-month follow-up. Hypothesized intervention mediators are assessed at the 3-month follow-up. This project was funded by a National Cancer Institute award (R01 CA218068), and the trial procedures were approved by the University of Kentucky Institutional Review Board in February 2020. Trial recruitment and enrollment occurred in 6 waves of data collection, which started in February 2022 and closed in May 2023. The study is closed to enrollment but remains open for follow-ups, and this protocol report was prepared before data analyses. As of February 2024, all participants have completed the 8-month follow-up assessment, and data collection is scheduled to close by the end of 2024 after the collection of the 18-month follow-up. This trial will contribute unique knowledge to the field of skin cancer prevention, as no fully powered trials have examined the efficacy of an intervention designed for frequent indoor or outdoor tanning. The trial may also contribute evidence of the value in translating principles of body image and acceptance-based interventions into the field of skin cancer prevention and beyond. If successful, the use of the Facebook platform is intended to aid in dissemination as it provides a way to embed the intervention into individuals' everyday routines. ClinicalTrials.gov NCT03441321; https://clinicaltrials.gov/study/NCT03441321. DERR1-10.2196/56562.

Abstract P122: A Semi-Automated Tool Can Increase Stroke Clinical Trial Recruitment

Introduction: Stroke is a major public health problem, and stroke-related research is crucial. However, enrollment in randomized controlled stroke trials of acute therapies is challenging, leading to missed patients during the screening phase. The current screening process is person-dependent and can be highly variable across stroke team members, time of the day, and hospitals. High-volume stroke centers participate in more than 15 simultaneous NIH and industry-sponsored stroke trials. We hypothesize that a HIPAA-compliant screening tool can optimize screening and increase trial enrollment. Methods: This tool is a HIPAA-compliant application, developed by the Power Team at the University of Pittsburgh Medical Center, using Microsoft Power Apps. It has three purposes: screening, maintaining the database, and reporting. The screening process begins with patient demographics, and basic stroke-related data, followed by acute ischemic, subacute ischemic, and hemorrhagic stroke trial groups. Users can select their preferred subgroup of studies and continue filling in the rest of the form by answering pertinent questions. Upon form submission, the tool calculates the patient’s eligibility status for each trial in that group. The database is immediately available on the opening page or on the cloud. After submission, this can be edited, e.g., refusal for enrollment, or change in the patient’s condition. Reporting can be automated by using Power tools or it can be done manually. For manual reporting, the database gives filtering options based on time frames, patients, trials, and more. Results: The tool is in the testing phase, and we expect to have enrollment data by the time of the meeting. Conclusions: This tool has several advantages over manual screening. First, it reduces the orientation time for new research team members. Second, it mitigates the risk of overlooking potentially eligible patients in time-sensitive scenarios. Third, it is highly customizable by editing the codebook and can be adjusted per research site. This can be particularly helpful for smaller hospitals surrounded by underserved areas and can decrease health disparities by extending the chance of clinical trial participation. Fourth, it automatically maintains an up-to-date data log, which can be extracted at various intervals, such as monthly or per study. This not only streamlines the data recording but also simplifies reporting to study sponsors. Lastly, it expedites trial completion by accelerating the enrollment process. In conclusion, this tool can have significant benefits for research teams and for the broader public.

Observational Study for Clinical Trials Participation in Malaysia

Introduction: This observational study was conducted to assess the knowledge, attitudes, and perceptions (KAP) of Malaysians toward participating in clinical trials. It also aimed to look for factors that will influence people’s willingness to participate in trials. We planned and developed future outreach, education tools, and recruitment strategies to increase clinical trial enrolment. Methods: A cross-sectional study was carried out on a randomly selected sample of 398 Malaysian literate adults. An online questionnaire was created and distributed to the respondents. Descriptive statistics were presented in the form of frequency and percentages. The chi-square test was employed to find the association between independent variables. Results: The majority had good knowledge (61.3%) and high awareness (88.7%) of clinical trials. However, most of them were not willing to take part in a clinical trial if they were assigned to a group of unlicensed drugs (90.2%) or randomly assigned (66.1%). The main reasons for participating in trials were recommendations from doctors (46.5%) and the potential for their own benefit (45.7%). Younger age was positively associated with the necessity and confidentiality of clinical trials. Most respondents indicated negative perceptions towards the safety of clinical trials regardless of demographic variables. Conclusion: We gained a better understanding of Malaysian people who are potential participants in a future clinical trial. These findings could help clinical researchers improve their understanding of the participants and develop effective outreach strategies for clinical trial recruitment and retention.

Reducing Sample Size While Improving Equity in Vaccine Clinical Trials: A Machine Learning-Based Recruitment Methodology with Application to Improving Trials of Hepatitis C Virus Vaccines in People Who Inject Drugs.

Despite the availability of direct-acting antivirals that cure individuals infected with the hepatitis C virus (HCV), developing a vaccine is critically needed in achieving HCV elimination. HCV vaccine trials have been performed in populations with high incidence of new HCV infection such as people who inject drugs (PWID). Developing strategies of optimal recruitment of PWID for HCV vaccine trials could reduce sample size, follow-up costs and disparities in enrollment. We investigate trial recruitment informed by machine learning and evaluate a strategy for HCV vaccine trials termed PREDICTEE-Predictive Recruitment and Enrichment method balancing Demographics and Incidence for Clinical Trial Equity and Efficiency. PREDICTEE utilizes a survival analysis model applied to trial candidates, considering their demographic and injection characteristics to predict the candidate's probability of HCV infection during the trial. The decision to recruit considers both the candidate's predicted incidence and demographic characteristics such as age, sex, and race. We evaluated PREDICTEE using in silico methods, in which we first generated a synthetic candidate pool and their respective HCV infection events using HepCEP, a validated agent-based simulation model of HCV transmission among PWID in metropolitan Chicago. We then compared PREDICTEE to conventional recruitment of high-risk PWID who share drugs or injection equipment in terms of sample size and recruitment equity, with the latter measured by participation-to-prevalence ratio (PPR) across age, sex, and race. Comparing conventional recruitment to PREDICTEE found a reduction in sample size from 802 (95%: 642-1010) to 278 (95%: 264-294) with PREDICTEE, while also reducing screening requirements by 30%. Simultaneously, PPR increased from 0.475 (95%: 0.356-0.568) to 0.754 (95%: 0.685-0.834). Even when targeting a dissimilar maximally balanced population in which achieving recruitment equity would be more difficult, PREDICTEE is able to reduce sample size from 802 (95%: 642-1010) to 304 (95%: 288-322) while improving PPR to 0.807 (95%: 0.792-0.821). PREDICTEE presents a promising strategy for HCV clinical trial recruitment, achieving sample size reduction while improving recruitment equity.

Optimizing Patient Recruitment in Global Clinical Trials using Nature-Inspired Metaheuristics

A common problem seen in the ineffective execution of global multicenter trials is the frequent inability to recruit a sufficient number of patients. A myriad of barriers to recruiting enough patients timely exist and may include practical limits on the number of recruiting sites imposed by the various countries, as well as administrative, cost and unanticipated issues. The Poisson-gamma recruitment model is a widely accepted statistical tool used to predict and track recruitment at different levels of a trial and make inference. An optimal recruitment plan can be designed using mathematical optimization, however, the search is complicated with multiple nonlinear objectives and constraints that arise from regulatory and budgetary considerations. We review nature-inspired metaheuristic algorithms which are powerful, flexible, general purpose optimization tools and demonstrate their capability and utility in optimizing complex recruitment designs for global clinical trials using the Poisson-gamma model as an exemplary model. This research opens up new avenues for improving the efficiency and effectiveness of patient recruitment in clinical trials, thereby potentially accelerating the development of new medical treatments.