Clinical Research Associates Research Articles

Efficiency of eSource Direct Data Capture in Investigator-Initiated Clinical Trials in Oncology

BackgroundClinical trials have become larger and more complex. Thus, eSource should be used to enhance efficiency. This study aimed to evaluate the impact of the multisite implementation of eSource direct data capture (DDC), which we define as eCRFs for direct data entry in this study, on efficiency by analyzing data from a single investigator-initiated clinical trial in oncology.MethodsOperational data associated with the targeted study conducted in Japan was used to analyze time from data occurrence to data entry and data finalization, and number of visits to the site and time spent at the site by clinical research associates (CRAs). Additionally, simulations were performed on the change in hours at the clinical sites during the implementation of eSource DDC.ResultsNo difference in time from data occurrence to data entry was observed between the DDC and the transcribed data fields. However, the DDC fields could be finalized 4 days earlier than the non-DDC fields. Additionally, although no difference was observed in the number of visits for source data verification (SDV) by CRAs, a comparison among sites that introduced eSource DDC and those that did not showed that the time spent at the site for SDV was reduced. Furthermore, the simulation results indicated that even a small amount of data to be collected or a small percentage of DDC-capable items may lead to greater efficiency when the number of subjects per site is significant.ConclusionsThe implementation of eSource DDC may enhance efficiency depending on the study framework and type and number of items to be collected.

Site research infrastructure and institutional performance: A report from the Voting Body of the Children’s Oncology Group (COG).

e23113 Background: National Cancer Institute (NCI) sponsored cooperative group clinical research has led to significant improvements in outcomes for childhood cancer in the United States. COG is the world’s largest cooperative group, comprised of 218 institutions in good standing. There are no benchmark data of the necessary research infrastructure for successful participation in COG research. Objectives: 1) To ascertain the research personnel (RP) devoted to COG research at each member institution. 2) To compare available resources with institutional performance. Design. Methods: A REDCap® survey was designed and sent to all 218 COG institutional principal investigators (PI) with a 4-week window to complete the survey with scheduled reminders. Questions included number of and types of RP [clinical research associates (CRA), nurses, and regulatory]. To measure performance, we used the 2022 Institutional Report Card from COG that reports open trials and enrollments at each site. Sites were categorized into 4 groups based on self-reported new oncology patients diagnosed per year. We compared the number of RP to the a) number of studies open, b) enrollment on therapeutic and non-therapeutic studies. We ranked performance into quartiles by institution size. Results: 134 PIs (61%) answered some or all questions on the survey. All institutional sizes were well-represented. Total number of RP varied dramatically, even among institutions of similar size, with median number 3 RP, range 0.9-28.5. Comparing the number of open studies to regulatory personnel at site, those institutions in the top quartile for each group (except very smallest) had a minimum of 91 studies open and had at least 1 FTE for regulatory, while those in the lowest quartiles (10-67 studies open) had < 1 FTE. Total number of RP were similarly correlated with the number of enrollments, with mean of 12.5 and median 15 enrollments for each RP. Conclusions: Sites successful at opening COG studies and enrolling patients had more research personnel. We show to perform in the top quartiles, there should be at least 1 FTE dedicated to regulatory issues and another 1 FTE for every 12-15 enrolled subjects. [Table: see text]

120 Impact of Undergraduate Clinical Research Experience: Highlighting the UCLA Clinical and Translational Science Institute Research Associates Program (CTSI-RAP)

OBJECTIVES/GOALS: CTSI-RAP is a professional development program that provides undergraduate students with clinical research exposure and training. Students support UCLA research faculty by assisting with all aspects of the research process, including recruiting participants, data management, and presentations. METHODS/STUDY POPULATION: CTSI-RAP onboards a 15-20 volunteer student cohort annually in a competitive application and interview process with less than a 10% acceptance rate. Since the inaugural cohort in 2013, over 160 students have participated. The program engages hundreds of students each year through the recruitment process, campus clinical research events, and student-led conference opportunities. Evaluation surveys developed through REDCap in 2022 sought to assess the program’s impact on undergraduate experiences, professional development, and post-graduate careers. Surveys distributed to investigators and their study teams evaluated the student’s clinical research knowledge and engaged student involvement. RESULTS/ANTICIPATED RESULTS: Based on evaluation surveys, the CTSI-RAP program received excellent reviews from both students and their assigned study teams. 100% of students and faculty would recommend the program to a friend or colleague. 30% of students present or publish annually, indicating a wealth of meaningful contributions made by students. 90% of students go on to attend medical school, health-related graduate school, or other health-related employment. Several students continue working in clinical research through gap-year employment. As demonstrated by the high caliber of student and faculty experiences, CTSI-RAP has created an esteemed and valued symbiotic infrastructure to support clinical research endeavors at UCLA. DISCUSSION/SIGNIFICANCE: Through clinical research career exploration and professional skill-building in undergraduate careers, the CTSI-RAP program produces highly-trained future leaders in the field and benefits the capacity of UCLA research. CTSI-RAP provides a model for similar programs to be funded and implemented in other institutions.

125 Insights from a Process Improvement Co-op in the Development of an Informed Consent Professional Certificate (ICPC) Course

OBJECTIVES/GOALS: The objectives of the ICPC Course were 1) to define elements needed to 'build' a solid framework for the creation of an effective informed consent document; 2) to examine various regulatory references and their importance in the context of the informed consent process; and 3) to review helpful tips and best practices of the informed consent process. METHODS/STUDY POPULATION: This 7-week course was a multi-disciplinary effort by the Miami CTSI, the Regulatory and Monitoring Support Office and the Human Subjects Research Office (HSRO), as part of their co-op partnership. The CTSI’s Network of Clinical Research Professionals (NCRP) (over 1995 members and established to offer and enhance education, training, and overall career development and networking for the U’s diverse research workforce) served as the target audience. The lead HSRO official was the course content developer and served as instructor. The Director of the HSRO served as the certificate & program coordinator. Additionally, this course indirectly fulfilled part of the requirements of the Institution’s AAHRPP re-accreditation. RESULTS/ANTICIPATED RESULTS: 70 persons attended all sessions and received their certificate. A post-course survey was deployed (n=70). 69 respondents were extremely satisfied with course content; 67 were likely to recommend the course to a colleague. Feedback highlights include: appreciation for time taken to organize/offer the course; presenter knowledge and preparation; and that case studies/examples were up-to-date and applicable. As an added incentive to participate in the course, both the School of Nursing and the Medical School provided CEU credits and the Society of Clinical Research Associates (SOCRA) accepted documentation of candidate participation in continuing education programs for recertification. DISCUSSION/SIGNIFICANCE: Based on a need identified through a multi-disciplinary process, a successful Informed Consent Professional Certificate Course was created and implemented. Respondents indicate extremely high satisfaction with the course and felt it was very relevant and applicable to their practice.

Flexible approaches to eCOA administration in clinical trials: The site perspective

The Critical Path Institute convened the Support Flexible Approaches to PRO Data Collection project as part of the eCOA: Getting Better Together Initiative which was instigated to identify and address common challenges and drive positive change with eCOA implementation in clinical trials.The project aimed to identify clinical trial stakeholders’ concerns related to electronic PRO (ePRO) implementation and propose areas of improvement via simplification and flexibility. One workstream focused on patient-/site-centric approaches for simplification and surveyed representatives of clinical sites and site monitors for their perspectives. A semi-structured questionnaire was developed and distributed via snowball sampling to site professionals and clinical research associates (CRAs) that had ePRO experience who had been identified via representative groups or sponsor-led site networks. Responses were received from various site roles across a range of global regions; the largest contribution was from the United States. Topics raised included helpdesk capabilities, technical concerns, device types, and user interfaces among others and are discussed further in this paper. The feedback derived from the questionnaire provided the basis for concrete ideas that sponsors should consider incorporating into protocol design for participant visits, technology use, devices, and methods of back-up data collection.

Memantine for Pediatric Patients Receiving Cranial Irradiation: A Pilot Study

While memantine has become standard in certain adults receiving brain RT to decrease the cognitive impacts of RT, it is unknown whether pediatric patients can take and tolerate memantine or experience benefit. In this prospective single-arm feasibility study, we hypothesized pediatric patients receiving brain RT would tolerate memantine with good treatment adherence. Patients aged 4-18 years with a primary CNS malignancy (excluding WHO Grade IV astrocytoma and glioblastoma) receiving intracranial RT were eligible. A 6-month course of memantine was given during and after RT. Dosing began once daily at 5 mg with up-titration in 5 mg increments over 4 weeks to a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg BID. To reduce patient and clinical research associate (CRA) burden, medication adherence was tracked via the Medisafe Pill and Reminder application which study staff helped install on the patient or parent's smart phone. A paper pill diary was provided for those unable to use the app. The primary endpoint was to achieve 80% adherence rate to memantine in 80% of patients measured 1-month post-RT. Eighteen patients (14 male and 4 female, median age 11.5 years (range: 4-18)) were enrolled from 2020-2022. The study closed early after enrolling 18 of 20 planned patients to avoid competing with the phase III randomized Children's Oncology Group (COG) study AACL2031. One patient withdrew for cognition-altering substance-use, leaving 17 patients with data available for analysis. Histologies included germ cell tumor (n = 6), craniopharyngioma (n = 3), choroid plexus papilloma (n = 2), ependymoma (n = 2), glial/astrocytoma (n = 2), medulloblastoma (n = 1), and meningioma (n = 1). Thirteen had surgery, and 9 received chemotherapy. Eight received craniospinal irradiation (CSI). Median RT dose was 54 Gy (range 36-59.4) in 30 fractions (range: 20-33). At data freeze, all 17 had passed the 1-month post-RT time point. One patient discontinued memantine after a single dose due to nausea. Pill-reports were available for 14 of the remaining 16; two patients did not complete digital pill logs. For those with complete logs, all adherence rates were above 80%, with a median of 99.32% pill completion rate (range: 92.67-100). Seven (50%) took 100% of prescribed doses. Irrespective of adherence for the 2 unavailable for evaluation, the primary endpoint was still achieved. Grade 1 toxicities included headache (n = 6, 35%) and constipation (n = 1, 6%); there were no grade 2+ toxicities. At last follow-up, 15/16 have completed the full 6-month memantine course. Secondary endpoints including neurocognitive evaluations have not yet been met and will be the subject of future reports. Memantine is a feasible and well-tolerated addition to multi-modality treatment for pediatric brain tumors. Secondary endpoints of this study and results of the ongoing COG study are awaited to define the value of memantine in this population.

Impacts organisationnels et budgétaires de la mise en place des thérapies CAR-T cells au sein d’un centre hospitalier académique français

Belonging to the family of advanced therapy medicinal products, CAR-T cells have changed the management of hematological malignancies. These treatments are known to involve many actors in a complex process. The quotation of hospital stays associated with this therapeutic strategy is also unusual since there is currently no specific quotation. From November 2021 to May 2022, a study was conducted at the Nancy University Hospital to evaluate the organizational impact of CAR-T cell therapy on hospital actors and the budgetary impact of stays in care centers. Through this study, we have shown significant and variable organizational impacts: from 3.12% of an additional full-time equivalent for an administrative manager to 41.5% for a clinical research associate. These times, when compared to the hourly rates of the actors, generated high costs: 6582.81 € per patient, i.e. 15.60% of the total cost of hospitalization. Taking into account the current refund of hospital stays and the costs calculated above, the balance of an average hospital stay is a deficit of 674.10 € [±10,224.79] with a median of 1334.97 €. This study highlighted the workload generated by the management of these new therapies, as well as the fragile balance of financing hospital stays. To date, it seems necessary and even essential to adapt the quotations of the acts dedicated to CAR-T cells activity and to provide adequate funding through an adapted pricing system.

The future of clinical trials and drug development: 2050.

A workshop held at the 18th Annual Conference of the Pharmaceutical Contract Management Group in Krakow on 9 September 2022 asked over 200 delegates what the clinical trial landscape would look like in 2050. Issues considered included who will be running the pharmaceutical industry in 2050; how 'health chips', wearables and diagnostics will impact on finding the right patients to study; how will artificial intelligence be designing and controlling clinical trials; and what will the role of the Clinical Research Associate, the critical observer, documenter and conductor of a clinical trial need to look like by 2050. The consensus was that, by 2050, if you are working in clinical trials, you will be a data scientist. We can expect to see an increasing role of new technologies and a new three-phase registration model for novel therapies. The first phase will involve an aspect of quality evaluation and biological proof-of-concept probably involving more preclinical modelling and engineered human cell lines and fewer animal studies than currently used. Once registered, new products will enter a period of adaptive clinical development (delivered as a single study) intended to establish safety. This phase will most likely take around 1-2 years and explore tailored options for administration. Investigations will most likely be conducted in patients, possibly in a 'patient-in-a-box' setting (hospital or healthcare centre, virtual or microsite). On completion of safety licencing, drugs will begin an assessment of efficacy in partnership with those responsible for reimbursement - testing will be performed in patients, possibly where individual patient involvement in safety testing will offer some reimbursement deal for future treatment. Change is coming, though its precise form will likely depend on the creativity and vision of sponsors, regulators and payers.

Expanding access to treatment for stimulant use disorder in a frontier state: A qualitative study of contingency management and TRUST program implementation in Montana

BackgroundThe client population eligible for treatment services supported by State Opioid Response (SOR) grant funding, administered by the Substance Abuse and Mental Health Services Administration (SAMHSA), was expanded to include individuals with a stimulant use disorder (stimUD) in 2020. Due to a significant need to improve services for individuals with stimUD in Montana, the Behavioral Health and Developmental Disabilities Division (BHDD) of the Montana Department of Public Health and Human Services used the grant opportunity to work with experts in the field of stimUD to pilot contingency management (CM) and the Treatment for Individuals who Use Stimulants (TRUST) treatment model. The CM protocol included twice weekly visits for twelve weeks, using an escalating schedule of gift card incentives contingent upon stimulant-negative urine samples. TRUST is a multi-component treatment program, incorporating exercise, group therapy, and individual therapy with content guided by cognitive behavioral therapy (CBT) and clinical research associate (CRA) materials. In addition to SOR dollars, BHDD used additional funding for CM reinforcers provided by state tax dollars to meet research-supported target incentive totals. MethodsIn this pilot project, TRUST/CM was implemented by four state-approved treatment providers and three Federally Qualified Health Centers (FQHCs), all of which had little prior experience with CM as a component of their treatment programs for stimUD. This article examines the processes of training staff, the experiences among staff with initial implementation of the treatment model, and the client characteristics of initial pilot treatment cohorts. Data for this study include primary qualitative data collected from providers, as well as client characteristics collected on the SAMHSA Government Performance and Results Act (GPRA) data collection form. ResultsSeven sites were trained in TRUST/CM, and these sites enrolled a total of 70 patients in the program. Qualitative data collected through interviews with site staff revealed the following themes: the value of intensive technical assistance being integrated in the program, concerns about staff retention and loss of expertise, adjustments of target client populations, and the importance of creative strategies for the provision of evidence-informed incentive totals. ConclusionsTRUST/CM was implemented throughout Montana, including rural and urban communities. Qualitative and quantitative data support that providers viewed the CM component as beneficial for treatment retention and improved outcomes for people with stimUD. These implementation study results provide insight into challenges and solutions for providers who are considering the implementation of CM within either a state-approved substance use treatment clinic or FQHC.

Clinical Source Data Production and Quality Control in Real-world Studies: Proposal for Development of the eSource Record System.

An eSource generally includes the direct capture, collection, and storage of electronic data to simplify clinical research. It can improve data quality and patient safety and reduce clinical trial costs. There has been some eSource-related research progress in relatively large projects. However, most of these studies focused on technical explorations to improve interoperability among systems to reuse retrospective data for research. Few studies have explored source data collection and quality control during prospective data collection from a methodological perspective. This study aimed to design a clinical source data collection method that is suitable for real-world studies and meets the data quality standards for clinical research and to improve efficiency when writing electronic medical records (EMRs). On the basis of our group's previous research experience, TransCelerate BioPharm Inc eSource logical architecture, and relevant regulations and guidelines, we designed a source data collection method and invited relevant stakeholders to optimize it. On the basis of this method, we proposed the eSource record (ESR) system as a solution and invited experts with different roles in the contract research organization company to discuss and design a flowchart for data connection between the ESR and electronic data capture (EDC). The ESR method included 5 steps: research project preparation, initial survey collection, in-hospital medical record writing, out-of-hospital follow-up, and electronic case report form (eCRF) traceability. The data connection between the ESR and EDC covered the clinical research process from creating the eCRF to collecting data for the analysis. The intelligent data acquisition function of the ESR will automatically complete the empty eCRF to create an eCRF with values. When the clinical research associate and data manager conduct data verification, they can query the certified copy database through interface traceability and send data queries. The data queries are transmitted to the ESR through the EDC interface. The EDC and EMR systems interoperate through the ESR. The EMR and EDC systems transmit data to the ESR system through the data standards of the Health Level Seven Clinical Document Architecture and the Clinical Data Interchange Standards Consortium operational data model, respectively. When the implemented data standards for a given system are not consistent, the ESR will approach the problem by first automating mappings between standards and then handling extensions or corrections to a given data format through human evaluation. The source data collection method proposed in this study will help to realize eSource's new strategy. The ESR solution is standardized and sustainable. It aims to ensure that research data meet the attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, and available standards for clinical research data quality and to provide a new model for prospective data collection in real-world studies.

Trouble for trials - The worrying state of the research nurse workforce

Clinical research nurses (CRNs) are a specialty of Registered Nurses that are highly trained to support the breadth of clinical trial operations and manage participant care in community settings new to research. CRNs are uniquely equipped with a scope of practice that permits product administration, participant assessments, and data management. As clinical trials and their management expand beyond traditional, site-based operations models to decentralized or remote models, the need becomes great to ensure adequate staffing of experienced research professionals, such as CRNs. However, the 2020 National Nursing Workforce Survey reported consecutive contractions in the number of CRNs practicing in the U.S in both 2017 and 2020 surveys when compared to previous reports in 2013 and 2015. The Society of Clinical Research Associates 2020 Salary Survey further described much of the current CRN workforce as nearing or at retirement age, raising concern for additional reductions. This workforce contraction tangents one of the highest volumes of clinical trial starts in modern history, prompting concern for adequate staffing of CRNs to facilitate continued examination of novel therapies and devices. Complex investigative products and evolving safety profiles coupled with an increased focus on community participant enrollment requires CRN involvement in heightened safety monitoring and interdisciplinary communication among clinical providers and research collaborators. This paper examines the contributory factors of the CRN workforce contraction and response efforts at professional and organizational system levels.

Salivary Dysfunctions and Consequences After Radioiodine Treatment for Thyroid Cancer: Protocol for a Self-Controlled Study (START Study).

BackgroundFollowing radioiodine (131I) therapy of differentiated thyroid cancer, the salivary glands may become inflamed, leading to dysfunctions and decreases in patients’ nutritional status and quality of life. The incidence of these dysfunctions after 131I-therapy is poorly known, and no clinical or genetic factors have been identified to date to define at-risk patients, which would allow the delivered activity to be adapted to the expected risk of salivary dysfunctions.ObjectiveThe aims of this study are to estimate the incidence of salivary dysfunctions, and consequences on the quality of life and nutritional status for patients after 131I-therapy; to characterize at-risk patients of developing posttreatment dysfunctions using clinical, biomolecular, and biochemical factors; and to validate a dosimetric method to calculate the dose received at the salivary gland level for analyzing the dose-response relationship between absorbed doses to salivary glands and salivary dysfunctions.MethodsThis prospective study aims to include patients for whom 131I-therapy is indicated as part of the treatment for differentiated thyroid cancer in a Paris hospital (40 and 80 patients in the 1.1 GBq and 3.7 GBq groups, respectively). The follow-up is based on three scheduled visits: at inclusion (T0, immediately before 131I-therapy), and at 6 months (T6) and 18 months (T18) posttreatment. For each visit, questionnaires on salivary dysfunctions (validated French tool), quality of life (Hospital Anxiety and Depression scale, Medical Outcomes Study 36-Item Short Form Survey), and nutritional status (visual analog scale) are administered by a trained clinical research associate. At T0 and T6, saliva samples and individual measurements of the salivary flow, without and with salivary glands stimulation, are performed. External thermoluminescent dosimeters are positioned on the skin opposite the salivary glands and at the sternal fork immediately before 131I administration and removed after 5 days. From the doses recorded by the dosimeters, an estimation of the dose received at the salivary glands will be carried out using physical and computational phantoms. Genetic and epigenetic analyses will be performed to search for potential biomarkers of the predisposition to develop salivary dysfunctions after 131I-therapy.ResultsA total of 139 patients (99 women, 71.2%; mean age 47.4, SD 14.3 years) were enrolled in the study between September 2020 and April 2021 (45 and 94 patients in the 1.1 GBq and 3.7G Bq groups, respectively). T6 follow-up is complete and T18 follow-up is currently underway. Statistical analyses will assess the links between salivary dysfunctions and absorbed doses to the salivary glands, accounting for associated factors. Moreover, impacts on the patients’ quality of life will be analyzed.ConclusionsTo our knowledge, this study is the first to investigate the risk of salivary dysfunctions (using both objective and subjective indicators) in relation to organ (salivary glands) doses, based on individual dosimeter records and dose reconstructions. The results will allow the identification of patients at risk of salivary dysfunctions and will permit clinicians to propose a more adapted follow-up and/or countermeasures to adverse effects.Trial RegistrationClinicalTrials.gov NCT04876287; https://clinicaltrials.gov/ct2/show/NCT04876287International Registered Report Identifier (IRRID)DERR1-10.2196/35565

A multilevel intervention increased accrual of Native Hawaiians and other Pacific Islanders to a national breast cancer screening trial.

6547 Background: The University of Hawaii Cancer Center (UHCC) Minority/Underserved NCI Community Oncology Research Program (Hawaii MU NCORP) provides access to NCI-sponsored clinical trials in Hawaii. The Hawaii MU NCORP is dedicated to increasing minority and underserved accruals to clinical trials. Native Hawaiian women have the highest breast cancer incidence and mortality; only 26% of Micronesian women in Hawaii over the age of 40 have ever had a mammogram. In 2018, the Hawaii MU NCORP became a recruitment site for the ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST). A pilot study was launched in 2019, to support our NCORP recruitment of underrepresented Native Hawaiian and other Pacific Islander (NHPI) women to the TMIST study. Subsequently, specific funding was provided by the NCI’s Center to Reduce Cancer Health Disparities that enabled the UHCC’s Office of Community Outreach and Engagement (COE) to develop an effective multilevel recruitment strategy together with the Hawaii MIU NCORP. Methods: To foster community awareness of the TMIST study among NHPI women, the UHCC COE hired a Community Health Educator (CHE). The CHE, a Pacific Islander woman, utilized small group educational sessions to provide culturally and linguistically appropriate cancer prevention information and promote the TMIST study to NHPI women in Hawaii. The CHE worked in partnership with Hawaii MU NCORP clinical research associates (CRAs) in these efforts. In 2020, statewide COVID-19 health and safety protocols were enacted, limiting public group interactions in Hawaii. Despite this challenge, the CHE successfully adapted the in-person educational sessions on clinical trials and TMIST to conduct sessions using Zoom and Facebook Messenger. Results: Before the hire of the CHE in 2019, only one Pacific Islander (Micronesian) woman was recruited to the TMIST in Hawaii. The CHE conducted 21 community health events with 426 attendees from 2019 to 2021. The Hawaii MU NCORP NHPI TMIST enrollment went from the 9.9% in 2018 to 2019, to 20.1% in 2019 to 2020 and to 33% in 2020 to 2021. To date, 18 Micronesian, 52 Native Hawaiian and 6 Other Pacific Islander women out of 353 participants ware enrolled. Conclusions: The multilevel intervention of our CHE, in collaboration with NCORP staff providing clinical trial awareness training and community outreach, resulted in increasing the enrollment of NHPI women to the TMIST Trial. CHE-led community health education sessions on cancer prevention can be delivered using emergent technologies and social media. The use of culturally and gender concordant CHEs working with CRAs have the potential to increase awareness and accruals to cancer clinical trials.

Impact of a personalised care plan for the elderly calling emergency medical services after a fall at home: The RISING-DOM multi-centre randomised controlled trial protocol

BackgroundA growing number of emergency calls are made each year for elderly people who fall. Many of them are not taken to hospital or are rapidly discharged from the Emergency Department (ED). Evidence shows that, with no further support, this vulnerable population is particularly at risk of injuries, dependency and death. This study aims to determine the effectiveness of a comprehensive geriatric assessment and a tailored intervention in the elderly calling on an Emergency Medical Service (EMS) for a fall at home, but not conveyed to the ED or rapidly discharged from it (less than 24 h from hospitalisation), to the time to institutionalisation or death.MethodsRising-Dom is a two-arm randomised (ratio 1:1), interventional, multi-centre and open study. Community-dwelling elderly people (≥ 70 years) who call an EMS for a fall at home are recruited. The intervention group receives home visits by a nurse with a comprehensive fall risk assessment and a personalised intervention care plan with a planned follow-up (six nurse home visits and five nurse phone calls). Subjects enrolled in the usual care-control group continue to receive their routine care for the prevention or treatment of diseases. Primary (time to institutionalisation or death) and secondary (unscheduled hospitalisations, additional EMS calls relating to falls, functional decline and quality of life) outcome data will be collected for both groups through five phone calls made by Clinical Research Associates (CRA) blind to the participants’ group during the follow-up period (24-months). Twelve hospital centres in the South-West of France are participating in the study as study sites. The inclusion period started in October 2019 and will end in March 2022. By the end of this period, 1,190 subjects are expected to be enrolled.DiscussionStudies on elderly home falls have rarely concerned people who were not taken to hospital. The Rising-Dom intervention scheme should enhance understanding of features related to this vulnerable population and investigate the impact of a nurse care at home on delaying death and institutionalisation.Trial registrationClinicaltrials.gov identifier: NCT04132544. Registration date: 18/10/2019. Sponsor: University Hospital, Toulouse. https://www.clinicaltrials.gov/ct2/show/NCT04132544?term=rising-dom&draw=2&rank=1

Challenges and Barriers to Adverse Event Reporting in Clinical Trials: A Children's Oncology Group Report.

Adverse event (AE) reporting is crucial for determining safety of trials. Adverse events are captured manually by clinical research associates (CRAs) and research nurses (RNs), and prior studies show underreporting. It is necessary to understand AE reporting training, processes, and institution-level differences to improve AE capture. A 26-item questionnaire regarding AE reporting training, identification, tracking, and challenges was distributed to all Children's Oncology Group (COG) CRAs and RNs from February 15 to March 11, 2019, regardless of if they report AEs based on limitations of COG rosters. Results were tabulated. Institutions were grouped by self-reported full-time equivalents and compared using χ2 tests. Of 1315 CRAs and 2703 RNs surveyed, 509 (12.7%) responded. Of those, 369 (64.9%) representing 71.8% of COG institutions report AEs. Only data from respondents who report AEs were collected and analyzed. There was a range in AE training; COG training modules were most common (79.7%). There was wide variability in AE ascertainment; only 51.2% use standardized approaches at their site. There was no standard AE tracking method; larger sites more commonly use spreadsheets (P = 0.002) and smaller sites more commonly use paper (P = 0.028). The greatest AE reporting challenges were differences between protocols (70%) and between AE definitions and documentation (53%). Half of the respondents endorsed 6 of 13 proposed tools for improving reporting including online AE reporting modules (75.3%), tip sheets for interpreting Common Terminology Criteria for Adverse Events definitions (67.5%), and standardized AE tracking forms (66.9%). Only half of the respondents reported that all colleagues at their site followed the same AE reporting practices, and there was no dominant AE tracking approach across the respondents. There is wide variability in AE reporting training and practices. Numerous challenges exist, including differences between trials, challenges in interpreting AE definitions, and engaging clinicians. Respondents are eager for additional central resources. These results provide a roadmap for areas of potential improvement.

Patients’ perceptions of care coordination among NCORP therapeutic clinical trial participants: A matched case-control study.

e13504 Background: Effective coordination of care (CC) is a critical component of high-quality cancer care; however, many patients with cancer continue to receive poorly coordinated care. CC experiences among therapeutic clinical trial (CT) participants are relatively unknown. We examined cancer patients’ perceptions of CC among CT participants using a validated Care Coordination Instrument (CCI). Methods: The study sample (N = 90) consisted of 45 CT participants and 45 matched non-participants from archival data from our prior CC studies. 171 patients who participated in therapeutic cancer clinical trials through the Hawaii Minority/Underserved NCI Community Oncology Research Program (NCORP) between 2015 and 2020 were contacted for study participation, and 26% completed the CCI. The CCI measures overall perceptions of CC and across 3 domains (Communication, Navigation, Operational). Paired t-tests were used to compare overall and domain scores between CT participants and non-participants. The two groups were matched by age, gender, cancer type (breast, GI, other), and clinical stage. Results: Among CT participants, the mean age was 61.7 ( SD = 9.4), and the majority were female (67%) and Asian (56%). The most common cancer types were breast (27%) and GI (16%), with 24% with stage III disease. CT participants reported significantly higher total CC scores than non-participants (62.5 vs. 55.8; p = .0008). Similar trends were found for Navigation ( p = .007) and Operational ( p = .001) domain scores. 29% of CT participants reported receiving high-intensity CC assistance from their clinical research associates (CRAs), and 27% indicated receiving moderate-level CC assistance. Responses to open-ended questions regarding CC revealed that CT participants received assistance with a variety of CC activities from their CRAs, including scheduling appointments and explaining test results and procedures. Conclusions: Patients who participate in therapeutic cancer clinical trials report more positive perceptions of CC compared to non-participants. Qualitative data suggest that significant care coordination support is provided by the clinical research associate. The results underscore the importance of CC support provided by CRAs who may be an unrecognized component of the healthcare delivery team. CC provided by CRAs may contribute to improved quality and value of cancer care for patients enrolled on therapeutic clinical trials.

Evaluation of Data Errors and Monitoring Activities in a Trial in Japan Using a Risk-Based Approach Including Central Monitoring and Site Risk Assessment

BackgroundRisk-based monitoring (RBM) is a slow uptake in some trial sponsors. There are three main reasons for this. First, there is the fear of making large investments into advanced RBM technology solutions. Second, it is considered that RBM is most suitable for large, complex trials. Third, there is the fear of errors in both critical and non-critical data, appearing as reduced on-site monitoring is being conducted.MethodsOur RBM team identified, evaluated, and mitigated trial risks, as well as devised a monitoring strategy. The clinical research associate (CRA) assessed the site risks, and the RBM team conducted central monitoring. We compared all data errors and on-site monitoring time between the partial switching sites [sites that had switched to partial source data verification (SDV) and source data review (SDR)] and the 100% SDV and SDR sites (sites that had implemented 100% SDV and SDR).ResultsPartial switching sites did not require any critical data correction and had a smaller number of data corrections through on-site monitoring than the 100% SDV and SDR sites. The RBM strategy reduced the on-site monitoring time by 30%.ConclusionsThe results suggest that RBM can be successfully implemented through the use of site risk assessment and central monitoring with practically no additional investment in technology and still produced similar results in terms of subject safety and data quality, as well as the cost savings that have been reported in global complex studies.

Understanding the Barriers to Pediatric Oncologist Engagement and Accrual to Clinical Trials in National Cancer Institute-Designated Community Oncology Research Programs.

PURPOSE:Clinical trial participation leads to progress in cancer care. Principal investigators (PIs) and clinical research associates (CRAs) play key roles in the provision and maintenance of clinical trial portfolios at their sites. Previous studies have evaluated the educational and resource needs of adult oncology providers, but nothing to date has focused on providers of pediatric oncology care. We aimed to identify the educational needs and clinical trial participation barriers at National Cancer Institute Community Oncology Research Program (NCORP) Children’s Oncology Group (COG) sites to improve the quality of site investigator engagement.METHODS:Quality improvement surveys of pediatric clinical research staff at NCORP sites were performed. The first was a web-based inquiry of NCORP COG PIs and lead CRAs to assess their general understanding of NCORP organizational structure and needs. The second survey of COG PIs was conducted by one-on-one telephone interviews aimed at identifying specific barriers to physician engagement and patient enrollment in clinical trial research.RESULTS:The majority of NCORP COG PIs and CRAs (63%) reported an incomplete understanding of NCORP structure, with approximately half expressing interest in developing stronger collaborations and engagement. Most NCORP COG PIs reported at least one shared barrier to clinical trial enrollment (78%), with inadequate protected time and research support (39% each) being the most frequently cited barriers.CONCLUSIONS:Contributions to pediatric cancer clinical research at COG NCORP sites could be enhanced through improved education, resources, and time allocation.

The use of cannabis and perceptions of its effect on fertility among infertility patients.

STUDY QUESTIONWhat is the prevalence of cannabis use and the perceptions of its impact on fertility among infertility patients?SUMMARY ANSWERA total of 13% of infertility patients used cannabis within the last year, and current usage is associated with patient perceptions of negative effects of cannabis on fertility and pregnancy.WHAT IS KNOWN ALREADYCannabis use is increasing among the general population and pregnant women, particularly in places where cannabis use is legal despite having known and potential negative effects on fertility and pregnancy.STUDY DESIGN, SIZE, DURATIONA cross-sectional patient survey study was performed between July 2017 and September 2017. Patients attending a university-affiliated hospital-based fertility clinic (n = 290) were invited to complete a written survey. Inclusion criteria were limited to the ability to read English. There were no exclusion criteria.PARTICIPANTS/MATERIALS, SETTING, METHODSOf the 290 patients approached, 270 (93%) agreed to participate. The questions covered demographics, cannabis usage, perceptions of the effect of cannabis on fertility and pregnancy, cessation of use due to infertility and personal history of disclosing cannabis use to healthcare providers (HCP).MAIN RESULTS AND THE ROLE OF CHANCEThe results showed that 13% of respondents disclosed use of cannabis in the past year (past year users) and 38% had not used cannabis in the past year but had previously used cannabis (>1 year users) while 49% had never used cannabis (never users). Baseline demographics were similar for the three groups, but across four measures of fertility and pregnancy health, past-year users perceived less of a negative effect compared to >1 year users, and never users (P values of 0.02, 0.03, 0.01, <0.001 for questions on pregnancy, offspring health, male fertility and female fertility, respectively). Of past year users, 72% said they had or would disclose use to their HCP, but only 9.4% reported that their HCP had actually instructed them to discontinue use.LIMITATIONS, REASONS FOR CAUTIONSelf-reported patient surveys are subject to reporting bias and may not reflect actual use and perceptions.WIDER IMPLICATIONS OF THE FINDINGSThis study suggests that cannabis use is common among infertility patients. Given the known negative impacts of cannabis on pregnancy, the authors would have expected informed infertility patients to cease cannabis use as part of their efforts to conceive. As the prevalence of cannabis use in the last year among infertility patients is similar to that in the general Canadian population, it is unclear whether the prevalence of cannabis use in the sample population merely reflects the average usage in society or, after taking into account those who reduced their usage to improve their fertility, is a factor contributing to infertility and thus prompting fertility referral. Given concern about the potential negative impact of cannabis use on fertility, and that only 9% of past year users had been instructed by an HCP to cease cannabis use, HCPs should consider the benefits of counselling about cannabis cessation for patients who are attempting to conceive. Future research should focus on analysing the effects of cannabis use on female fertility and determining whether a reduction in use among patients with infertility can improve conception rates.STUDY FUNDING/COMPETING INTEREST(S)Michelle Shin, Clinical Research Associate, is supported by the University of Toronto GREI Fellowship Fund, which is sponsored by unrestricted research grants from EMD Serono, Merck Canada and Ferring Pharmaceuticals. The authors have no potential conflicts of interest to disclose.

The TOSCA Registry for Tuberous Sclerosis-Lessons Learnt for Future Registry Development in Rare and Complex Diseases.

Introduction: The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to provide insights into the clinical characteristics of patients with Tuberous Sclerosis Complex (TSC). The aims of this study were to identify issues that arose during the design, execution, and publication phases of TOSCA, and to reflect on lessons learnt that may guide future registries in rare and complex diseases.Methods: A questionnaire was designed to identify the strengths, weaknesses, and issues that arose at any stage of development and implementation of the TOSCA registry. The questionnaire contained 225 questions distributed in 7 sections (identification of issues during registry planning, during the operation of the registry, during data analysis, during the publication of the results, other issues, assessment of lessons learnt, and additional comments), and was sent by e-mail to 511 people involved in the registry, including 28 members of the Scientific Advisory Board (SAB), 162 principal investigators (PIs), and 321 employees of the sponsor belonging to the medical department or that were clinical research associate (CRA). Questionnaires received within the 2 months from the initial mailing were included in the analysis.Results: A total of 53 (10.4%) questionnaires were received (64.3% for SAB members, 12.3% for PIs and 4.7% for employees of the sponsor), and the overall completeness rate for closed questions was 87.6%. The most common issues identified were the limited duration of the registry (38%) and issues related to handling of missing data (32%). In addition, 25% of the respondents commented that biases might have compromised the validity of the results. More than 80% of the respondents reported that the registry improved the knowledge on the natural history and manifestations of TSC, increased disease awareness and helped to identify relevant information for clinical research in TSC.Conclusions: This analysis shows the importance of registries as a powerful tool to increase disease awareness, to produce real-world evidence, and to generate questions for future research. However, there is a need to implement strategies to ensure patient retention and long-term sustainability of patient registries, to improve data quality, and to reduce biases.