Clinical Research Assistants Research Articles

Reimagining the joint task force core competency framework for rural and frontier clinical research professionals conducting hybrid and decentralized trials.

Introduction: Clinical research professionals (i.e., clinical research assistants, clinical research nurses, clinical research coordinators, etc.), as outlined by the Joint Task Force (JTF) Core Competency Framework, are highly trained to support the breadth of clinical trial operations and manage participant care. Clinical research professionals are uniquely equipped with a scope of practice that permits product administration, participant assessments, and data management. As clinical trials grow in complexity and their management expands beyond traditional, site-based operations models to decentralized and/or hybrid models, the need becomes great to ensure adequate staffing. However, rural hospitals frequently lack the research staff or patient recruiters that would allow them to support decentralized clinical trials across a sizeable rural geographic demographic. Methods: This paper examines the contributory factors of the clinical research professional workforce contraction and response efforts at professional and organizational levels within a large, Magnet-designated healthcare system in the rural northwestern United States. Perspectives are shared on adapting the Core Competency Framework to reflect the unique strengths and opportunities towards decentralized trials in rural regions of the United States and areas of priority for workforce cultivation and retention. A descriptive survey was used to gather initial data identifying the current research perspectives of healthcare workers working across a rural community. Participants were asked to complete questions about the JTF Competency domains and behavior-based questions. Analysis: Both competency and behavior-based questions were asked and related to roles. These were then cross-referenced using a Rasmussen Ladder system. Descriptive statistics were conducted for sample characteristics, self-reported competency domain questions, and behavior questions. Results and discussion: Survey findings suggest that although healthcare workers and clinical research teams interact, they are unlikely to ask their patients to participate in research. Based on the limited response rate, results suggest that better education throughout the rural community could benefit from decentralized research efforts. Increased use of technology was also highlighted as an area of interest.

Development and psychometric evaluation of the Personality Disorder Severity ICD-11 (PDS-ICD-11) Clinician-Rating Form.

No clinician-rating tool has formally been developed to assess the ICD-11 model of personality disorder (PD) severity. We therefore developed and evaluated the 14-item personality disorder Severity ICD-11 (PDS-ICD-11) Clinician-Rating Form. A combined sample of 195 patients was rated by mental health professionals or clinical research assistants in New Zealand using the PDS-ICD-11 Clinician-Rating Form. Responses were subjected to item-response theory analysis and confirmatory factor analysis. In a subsample, we examined interrater reliability and convergence with self- and informant-reported measures of personality impairment, dysfunction in various psychopathology domains, and traditional PD symptoms. Item-response theory and confirmatory factor analyses supported the item functioning and unidimensionality, respectively, of the PDS-ICD-11 Clinician-Rating Form. The interrater reliability was very promising (intraclass correlation coefficient = 0.94, p < 0.001). PDS-ICD-11 Clinician-Rating Form scores were associated with established measures of personality dysfunction at large effect sizes. This initial development study suggests that the PDS-ICD-11 Clinician-Rating Form constitutes a psychometrically sound instrument that provides a clinically based impression of the severity of personality dysfunction according to the official ICD-11 description. More research is needed to corroborate its validity and utility, and a structured interview is warranted for diagnostic purposes. The final PDS-ICD-11 Clinician-Rating Form is included as online supporting information.

Ensuring quality control in a COVID-19 clinical trial during the pandemic: The experience of the Inserm C20–15 DisCoVeRy study

SettingHealth measures taken during the pandemic deeply modified the clinical research practices. At the same time, the demand for the results of the COVID-19 trials was urgent. Thus, the objective of this article is to share Inserm's experience in ensuring quality control in clinical trials in this challenging context. ObjectivesDisCoVeRy is a phase III randomized study that aimed at evaluating the safety and efficacy of 4 therapeutic strategies in hospitalized COVID-19 adult patients. Between March, 22nd 2020 and January, 20th 2021, 1309 patients were included. In order to guarantee the best quality of data, the Sponsor had to adapt to the current sanitary measures and to their impact on clinical research activity, notably by adapting Monitoring Plan objectives, involving the research departments of the participating hospitals and a network of clinical research assistants (CRAs). ResultsOverall, 97 CRAs were involved and performed 909 monitoring visits. The monitoring of 100% of critical data for all patients included in the analysis was achieved, and despite of the pandemic context, a conform consent was recovered for more than 99% of patients. Results of the study were published in May and September 2021. Discussion/conclusionThe main monitoring objective was met thanks to the mobilization of considerable personnel resources, within a very tight time frame and external hurdles. There is a need for further reflection to adapt the lessons learned from this experience to the context of routine practice and to improve the response of French academic research during a future epidemic.

What does a department need to get involved in clinical trials?

Clinical trials are conducted to evaluate the usefulness of a drug, medical treatment, surgical intervention, radiological procedure, behavioral intervention, or preventive health care strategy. Clinical trials are challenging, time-consuming, and need careful planning and execution. There are certain requirements for an academic unit to be ready for conducting quality research, especially clinical trials. These include logistical concerns, infrastructure, appropriately trained human resources, conformity with ethical compliances and regulatory compliances as per the laws governing the respective geographical regions.Infrastructure requirements include research division space, robust data archival system, archival of imaging data, laboratory services, information technology division and facilities for the appropriate consenting process. Human resources such as principal investigators, data managers, clinical research assistants and biostatisticians are needed to execute the clinical trial as per the study design. Adherence to ethical and regulatory standards; during the conduct of the clinical trial are imperative. Strict compliance with prevailing governing laws in the country is a prerequisite for a department to get involved in clinical trials. The department also needs to put in place an institutional ethics committee; the composition of which is often governed by regulatory laws. The ethical aspects of the trial undergo a formal scrutiny by an Institute ethics committee that ensures quality care to the patient, and safeguards the patient's rights and privileges.The academic unit of any department forms the core for possible research and pursuit of clinical trials. A department with rich clinical experience and expertise in the filed aids in the execution of quality research. The academic department must consider grant writing and multiple center collaborative research projects in due course of time to further enhance the quality of clinical trials and research output.

Abstract P051: The INSPIRE Study (Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation): scaling return of genomic results

Abstract Background: To enable genomic care for all City of Hope (COH) patients, we implemented an enterprise-wide Precision Medicine program including 7 of our clinical network sites. Consented patients with and without cancer are eligible to opt into germline testing (155 gene cancer predisposition panel and ACMG 59 Actionable Disorders panel) and paired tumor-normal whole exome/RNA transcriptome sequencing. All assays are CAP-CLIA approved. Results are added to the electronic medical record (EMR). We describe the process of implementation through return of results (RoR). Methods: Potentially eligible patients are identified by their provider or through the EMR. Clinical Research Assistants (n=8, main campus) and Advance Practice Providers (APPs) (n=14 Genetic Counselors or n=1 Genetics Nurse Practitioner) and Licensed Vocational Nurses (n=5, clinical network) consent patients in-person and remotely. Clinical Research Nurses (n=5) or APPs order testing through the EMR, with treating providers copied on somatic results and GCs copied on germline results. All results are systematically reviewed by GCs and/or the weekly COH Precision Oncology Tumor Board (POTB). Results: From July 9, 2020 through August 26, 2022 12,105 patients have been offered participation, with 10,376 (85.7%) enrolling (7,892 original consents/ 2,484 reconsents), 735 (6.1%) declining, 984 (8.1%) deferring, and 10 (.1% ) with other consent statuses. 98.9% (10,259/10,376) opted for cancer predisposition germline testing and 98.5% (10,225/10,376) opted for ACMG Actionable Disorders testing 91.5% (9,497/10,376) patients agreed to future contact about additional research studies. 6,512 somatic tests have been reviewed (representing 6,295 patients) and presented through POTB. Somatic genomic results are uploaded to the EMR via PDF and returned by the treating physician. Germline results are returned through the EPIC genomics module. To scale RoR, patients with negative results, variants of unknown significance, and carriers for recessive conditions are sent letters. Patients with a cancer predisposition P/LP variant are disclosed via phone by a GC and referred to COH Cancer Genomics for counseling whereas patients with P/LP non-cancer ACMG variants are referred for outside genetic counseling through the testing laboratory. To improve efficiency, we do not notify patients of non-actionable variant reclassifications. Conclusion: We outline a new care model for the delivery of germline and somatic genetic testing at scale. High consent and opt-in rates for germline testing demonstrate patient interest and feasibility. Future work is planned to assess the impact of testing on clinical care and outcomes. Citation Format: Ilana Solomon, Heather Hampel, Kevin McDonnell, Kathleen Blazer, Alex Capasso, Anuja Chitre, Sandra Dreike, Hunaydah Elfarawi, Lauren Gima, Christine Hong, Gregory Idos, Elisabeth King, Rachelle Manookian, Bita Nehoray, Wai Park, Michael Restrepo, Susan Shehayeb, Elise Sobotka, Duveen Sturgeon, Elyssa Zukin, Stacy W. Gray, Stephen B. Gruber. The INSPIRE Study (Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation): scaling return of genomic results. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P051.

Improving research personnel's hand hygiene adherence in the pediatric acute care setting during the COVID-19 pandemic: a quality improvement initiative.

Hand hygiene is critical in preventing the spread of healthcare-associated infections. Routine hand hygiene surveillance and education are common for clinical staff in pediatric acute care settings. However, nonclinical staff, including research personnel, are often excluded from these programs and therefore represent a gap in ongoing infection control efforts. This project aimed to evaluate the impact of evidence-based interventions on improving hand hygiene adherence among research personnel in the pediatric emergency department to meet provincial targets set for clinical staff. We used a Plan-Do-Study-Act approach to carry out a peer-driven, multimodal hand hygiene improvement strategy involving education, surveillance, and feedback targeted to research assistants working in a pediatric emergency department. Two anonymous peer evaluators observed hand hygiene practices in several specific instances (eg, before/after patient interactions) and determined adherence a priori. In an open sample of clinical research assistants (Ntotal = 22), hand hygiene adherence increased from 12.5% to 89.1% over 11 months. Increases in adherence were particularly notable before entering the patient environment compared to exiting. Hand hygiene interventions targeting research personnel show potential success in acute care. Further quality improvement initiatives in larger research personnel samples must robustly evaluate the framework's effectiveness.

Acute fungicide self-poisoning - a prospective case series

Background Pesticide self-poisoning is a global clinical and public health problem. While self-poisoning with insecticides and herbicides has been extensively studied, there is minimal literature on acute fungicide self-poisoning. We aimed to study the clinical course and outcome of fungicide self-poisoned patients recruited to a prospective cohort in Sri Lanka. Methods We conducted a prospective study of patients presenting with fungicide self-poisoning to nine hospitals in Sri Lanka between 2002 and 2020. Patients were enrolled by clinical research assistants, with clinical outcomes being recorded at regular review for each patient. Results We identified 337 cases of self-poisoning with fungicides (alcohol as only co-ingestant), including 28 different fungicides across 5 different fungicide classes. Median time from ingestion to examination was 3.1 (1.8–5.7) h. Nearly all presented to hospital fully conscious (GCS 15, 15–15)— only 27 patients (8.0%) presented with reduced GCS (<15) and only 2 (0.6%) had GCS 3/15. Most patients (333/337, 98.8%) made a full recovery, of whom only eight (2.37%) required intubation and ventilation. Four patients died (case fatality rate: 1.2%; 95% CI 0.0–23.4) after ingestion of edifenphos (n = 2), propamocarb and pyraclostrobin. Conclusion Fungicide self-poisoning appears to be less hazardous than insecticide or herbicide self-poisoning, with a substantially lower case fatality in the same cohort. Edifenphos is an exception to this ‘less toxic’ rule; as a WHO Class Ib highly hazardous pesticide, we recommend its withdrawal from, and replacement in, global agricultural practice. Propamocarb should be listed in the WHO hazard classification as propamocarb hydrochloride to reflect the higher toxicity of the common agricultural formulation. Pyraclostrobin currently has no WHO classification; one is urgently required now that its ingestion has now been linked the death of a patient. Additional prospective clinical data on fungicide self-poisoning is required to expand knowledge on the effects of these diverse compounds.

The Incident Feedback Committee (IFC): A Useful Tool to Investigate Errors in Clinical Research.

In clinical practice, an objective of safety management is to identify preventable causes of adverse events to avoid the incidents from recurring. Likewise, in the field of clinical research adequate methods to investigate incidents that impair the quality of a clinical trial are needed. Understanding the causes of errors and undesirable incidents can help guarantee participant safety, improve the practices of research coordinators, investigators, and clinical research assistants and help to minimize research costs. Here, we present the main features of our Incident Feedback Committees (IFC) in clinical research, with outcomes over 5 years. Methods: The IFC has adapted the ALARM and ORION post-event methods with investigations focused on ‘the incidents’ occurring during research studies. It sought the root causes contributing to these incidents and proposed corrective actions. Results: Since our IFC was set up in 2015 it has examined 52 incidents from nine studies. The most frequent causes mainly concerned the working environment (54%). Most incidents had two or more causes. Some corrective actions were planned for ongoing or future studies. Conclusion: IFCs provide a useful and much-appreciated method of analysing incidents in the performance of clinical research. A multicentre study is needed to evaluate the effect of IFCs on the quality of an establishment’s clinical research, at the individual level (patient safety) and also at the system level (changes in the organization of tasks).

Efficacy and safety of high-dose esomeprazole-amoxicillin dual therapy for Helicobacter pylori rescue treatment: a multicenter, prospective, randomized, controlled trial.

Background:High-dose dual therapy (HDDT) with proton pump inhibitors (PPIs) and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of high-dose PPI–amoxicillin dual therapy and bismuth-containing quadruple therapy for H. pylori rescue treatment.Methods:This was a prospective, randomized, multicenter, non-inferiority trial. Patients recruited from eight centers who had failed previous treatment were randomly (1:1) allocated to two eradication groups: HDDT (esomeprazole 40 mg and amoxicillin 1000 mg three times daily; the HDDT group) and bismuth-containing quadruple therapy (esomeprazole 40 mg, bismuth potassium citrate 220 mg, and furazolidone 100 mg twice daily, combined with tetracycline 500 mg three times daily; the tetracycline, furazolidone, esomeprazole, and bismuth [TFEB] group) for 14 days. The primary endpoint was the H. pylori eradication rate. The secondary endpoints were adverse effects, symptom improvement rates, and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study. The HDDT group achieved eradication rates of 75.4% (248/329), 81.0% (248/306), and 81.3% (248/305) asdetermined by the intention-to-treat (ITT), modified intention-to-treat (MITT), and per-protocol (PP) analyses, respectively. The eradication rates were similar to those in the TFEB group: 78.1% (257/329), 84.2% (257/305), and 85.1% (257/302). The lower 95% confidence interval boundary (−9.19% in the ITT analysis, − 9.21% in the MITT analysis, and −9.73% in the PP analysis) was greater than the predefined non-inferiority margin of −10%, establishing a non-inferiority of the HDDT group vs. the TFEB group. The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group (11.1% vs. 26.8%, P < 0.001). Symptom improvement rates and patients’ compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy, with fewer adverse effects and good treatment compliance, suggesting HDDT as an alternative for H. pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov, NCT04678492.

Impact of COVID-19 disease on clinical research in pediatric and congenital cardiology

BackgroundCOVID-19 triggered an unprecedented crisis affecting society at every level. Research in pediatric and congenital cardiology is currently in full development and may have been disrupted. The aim of the study was to determine the impact of COVID-19 on pediatric and congenital cardiology clinical research and to analyze decision-making and adaptation processes, from a panel of ongoing academic and industry-sponsored research at the time of the pandemic. MethodsThis observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care pediatric and congenital cardiology centers. Investigators and clinical research assistants from each participating research center completed an online survey questionnaire, and each principal investigator underwent a 1-h web-based videoconference interview. ResultsA total of 34 study questionnaires were collected, reporting that 18 studies were totally suspended. Upon the investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to that in non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study. ConclusionThe impact of the COVID-19 pandemic on clinical research in pediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies.

Fostering diversity and a culture of inclusion in clinical research by training and hiring community members as clinical research assistants.

The University of Pittsburgh (Pitt) Clinical and Translational Science Institute (CTSI) and the nonprofit Bidwell Training Center co-developed a new program for translational workforce diversification and development to foster diversity and inclusion in clinical research. The STricklAnd Research Training (START) program provides students in the Medical Assistant program at Bidwell a career path in clinical research. We created a 12-hour didactic package that covers responsible conduct of human subjects research and good clinical practice as an add-on to existing vocational curriculums. Students have the option of completing a clinical research-related externship at Pitt, which includes mentoring, shadowing, and protocol-specific training on a study team whose intention is to hire them as a clinical research assistant. Those who accept a position at Pitt receive continued mentorship, education, and professional development through Pitt CTSI. In the first three cohorts, two of which had access to research externships at Pitt, 92% of students successfully completed the instruction in clinical research. We plan to expand START to new venues to train and hire local community members from diverse backgrounds who can bring their lived experience to research programs.

Protocol for a multicenter, randomised controlled trial of surgeon-directed home therapy vs. outpatient rehabilitation by physical therapists for reverse total shoulder arthroplasty: the SHORT trial

BackgroundReverse total shoulder arthroplasty (RTSA) has emerged as a successful surgery with expanding indications. Outcomes may be influenced by post-operative rehabilitation; however, there is a dearth of research regarding optimal rehabilitation strategy following RTSA. The primary purpose of this study is to compare patient reported and clinical outcomes after RTSA in two groups: in one group rehabilitation is directed by formal, outpatient clinic-based physical therapists (PT group) as compared to a home therapy group, in which patients are instructed in their rehabilitative exercises by surgeons at post-operative appointments (HT group). Secondary aims include comparisons of complications, cost of care and quality of life between the two groups.MethodsThis randomised controlled trial has commenced at seven sites across the United States. Data is being collected on 200 subjects by clinical research assistants pre-operatively and post-operatively at 2, 6, and 12 weeks, 6 months, 1 and 2 year visits. The following variables are being assessed: American Shoulder and Elbow Surgeons (ASES), pain level using the numeric pain scale, the Single Assessment Numeric Evaluation (SANE) score, and shoulder active and passive range of motion for analysis of the primary aim. Chi square and t-tests will be used to measure differences in baseline characteristics of both groups. Repeated measures linear mixed effects modeling for measurement of differences will be used for outcomes associated with ASES and SANE and scores, and range of motion measures. Secondary aims will be analyzed for comparison of complications, cost, and quality of life assessment scores using data obtained from the PROMIS 29 v. 2, questionnaires administered at standard of care post-operative visits, and the electronic health record. Subjects will be allowed to crossover between the PT and HT groups, and analysis will include both intention-to-treat including patients who crossed over, and a second with cross-over patients removed, truncated to the time they crossed over.DiscussionRTSA is being performed with increasing frequency, and the optimal rehabilitation strategy is unclear. This study will help clarify the role of formal physical therapy with particular consideration to outcomes, cost, and complications. In addition, this study will evaluate a proposed rehabilitation strategy.Trial registrationThis study is registered as NCT03719859 at ClincialTrials.gov.

Impact of COVID-19 disease on clinical research in paediatric and congenital cardiology

BackgroundCOVID-19 triggered an unprecedented crisis affecting our society at every level. Clinical research in paediatric and congenital cardiology is currently in full development and may have been disrupted.AimsTo determine the impact of COVID-19 in paediatric and congenital cardiology clinical research and to analyse decision-making and adaptation processes, from a panel of on-going academic and industry-sponsored research at the time of the pandemic.MethodsThis observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care paediatric and congenital cardiology centres. Investigators and clinical research assistants from each participating research centre filled in an online survey questionnaire, and each principal investigator underwent a one-hour web-based videoconference interview.ResultsFrom a total of 34 study questionnaires and 288 enrolled patients at the time of the pandemic, 18 studies were declared as totally suspended. Upon investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study.ConclusionsThe impact of the COVID-19 pandemic on clinical research in paediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies.

Abstract 51: Breast Biopsy Report Abstraction Process From A Community And Hospital Based Screening And Treatment Programme In A Lmic (Kenya) Between January 2017 – December 2019

Abstract Purpose: There is no standardized way of reporting the pathological lab results therefore there is inadequate reporting in Low- and Middle-Income Countries like Kenya. Proper documentation of the lab results is key in providing appropriate care to breast cancer patients, policymaking, designing, implementing, and evaluating cancer control activities. There is need to standardize reporting of the pathological breast cancer lab results. Methods: The biopsy results for all the Africa Breast and Cervical Cancer Program (ABCCP) in Kenya patients seen between the year 2017 to 2019 were received, photocopied, and filed in box files. Biopsy reporting was done by various pathologists within the country. To standardize the reporting, a data abstraction questionnaire was developed from Protocol for the Examination of Resection Specimens From Patients With Invasive Carcinoma of the Breast (7th Edition, 2012) adapted from the American College of Pathologists programmed into an Open Data Kit. Raw abstracted data was verified against corresponding images to identify misclassifications by the consultant. Sensitivity and specificity for correct classification by the clinical and non-clinical research assistants was calculated and evaluated. Results: A total of 1490 records were abstracted in 3 weeks, out of which 529 records were breast biopsy results. On average, the research assistants abstracted 83 (42 - 195) records. The research assistants were able to correctly classify 284 cases as malignant and 202 cases as benign with a Sensitivity of 92% and Specificity of 92%. Upon review of the data by the consultant, the total misclassified records were 18 benign classified as malignant and 25 malignant cases classified as benign. There was no statistically significant difference (p = 0.1125) in the classifications between the clinical and non-clinical abstraction staff. Conclusion: There was high sensitivity and specificity on correctly classifying the biopsy results for both well trained clinical and non-clinical staff. Citation Format: Stephen Karuru Maina, Emmah Achieng, Hussein Elias, Kibet Kibor, Chite Asirwa. Breast Biopsy Report Abstraction Process From A Community And Hospital Based Screening And Treatment Programme In A Lmic (Kenya) Between January 2017 – December 2019 [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 51.

Case fatality of agricultural pesticides after self-poisoning in Sri Lanka: a prospective cohort study

SummaryBackgroundPesticide poisoning is among the most common means of suicide globally, but can be prevented with regulation of the most hazardous agents. We aimed to compare the lethality of pesticides ingested by our cohort, seek evidence on variation between human and regulatory animal toxicity, and establish change over time in the case fatality of individual pesticides in Sri Lanka.MethodsWe examined the case fatality of agricultural pesticides in a prospective cohort in nine hospitals serving rural populations in Sri Lanka. We included all patients (>11 years) who had presented to a South Asian Clinical Toxicology Research Collaboration study hospital during the study period. Patients were enrolled by clinical research assistants and were regularly reviewed. Identification of the ingested pesticide was generally on the basis of history or positive identification of the container, supported by nested blood analysis.FindingsFrom March 31, 2002, to Dec 31, 2019, 34 902 patients (median age 29 years [IQR 21–40]; 23 060 [66·1%] male) presented with a possible or known pesticide self-poisoning. We identified 23 139 specific pesticides that were ingested. Poisoning was fatal in 2299 (6·6%) patients. Case fatality varied greatly from 0·0% (several substances) to 41·8% (paraquat). The three most toxic agents (ie, paraquat, dimethoate, and fenthion) were banned between 2008 and 2011. Since 2013, the five agents causing the most deaths (ie, profenofos, propanil, fenobucarb, carbosulfan, and quinalphos) had a case fatality of 7·2–8·6%. A steady decline was seen in overall case fatality of pesticide poisoning (10·5% for 2002–06 to 3·7% for 2013–19), largely attributable to pesticide bans. A modest fall in case fatality for non-banned pesticides was also seen.InterpretationDeclines seen in case fatalities of poisonings with non-banned pesticides suggest that medical management improved over time. The human data for acute toxicity of pesticides should drive hazard classifications and regulation. We believe that a global benchmark for registration of pesticides should include a less than 5% case fatality after self-poisoning, which could prevent many deaths and have a substantial effect on global suicide rates.FundingThe Wellcome Trust and the National Health and Medical Research Council of Australia.TranslationsFor the Sinhala and Tamil translations of the abstract see Supplementary Materials section.

Regulatory, scientific, and ethical issues arising from institutional activity in one of the 90 Italian Research Ethics Committees

BackgroundThis paper highlights the issues that one of the 90 Italian Research Ethics Committees (RECs) might encounter during the approval phase of a clinical trial to identify corrective and preventive actions for promoting a more efficient review process and ensuring review quality. Publications on the subject from Italy and the rest of Europe are limited; encouraging constructive debate can improve RECs’ service to the subject of the clinical trial.MethodsWe retrospectively reviewed a cohort of 822 clinical trial protocols, initially reviewed by REC, from June 2014 to December 2018. Data collected for each protocol were type of trial, sample size, use of placebo, number and kind of revisions requested by the REC before approval, and time taken for approval. Data for each protocol were collected by a trained clinical research assistant using the REC’s files and electronic archives.ResultsAlmost 45% of the reviewed studies (374/822) required clarifications, significant changes to the documentation, or minor changes before final approval.ConclusionsPreventive measures are needed to reduce the number of requested corrections and thus also the time required for approval, while maintaining review quality. All critical points and proposals presented in this paper require harmonization through updates to European regulations, as regulatory harmonization produces better compliance with rules and reduces the number of changes required before the trials’ final approval. Such updates include the development of standardized formats for informed consent, the verification of any evidence in favor of using off-label treatments over placebo as comparators, using multidisciplinary staff in clinical trials with children and adolescents, improving the legal definition of RECs to assign responsibilities and ensure independence, and providing guidance for RECs to engage clinical research assistants in internal audits.

Un exemple de réorganisation dans le fonctionnement d’un Centre d’investigations cliniques en période de confinement national suite à la pandémie COVID-19

ContexteLe Centre d’investigations cliniques de l’Hôpital Saint-Louis (CIC-1427) est une structure dédiée qui accueille des patients inclus dans des essais cliniques essentiellement de phases précoces (première administration chez l’homme, phases I et II). Ces patients sont accueillis dans des locaux autorisés et validés par l’Agence régionale de santé (ARS). En mars 2020, face à la pandémie de la COVID-19 et aux mesures de confinement national de la population décidées, par le gouvernement français, le CIC-1427 a dû adapter rapidement ses procédures de fonctionnement pour assurer la sécurité des patients et de son personnel.ObjectifAssurer une prise en charge optimale des patients inclus dans les essais cliniques de phases précoces, tout en respectant les bonnes pratiques cliniques (BPC) et les bonnes pratiques professionnelles des CIC (BPP des CIC), les exigences des promoteurs de chaque protocole, la sécurité des patients et du personnel multidisciplinaire (infirmiers, aide-soignants [AS], assistants de recherche clinique [ARC], coordonnateur d’études cliniques [CEC]), chefs de projets, cadre de santé et médecins investigateurs), dans le contexte de la crise sanitaire liée à la COVID-19.Méthodes et résultatsDe par son activité, nécessitant des tâches en présentiel, chaque personnel de l’équipe spécialisée en recherche clinique du CIC-1427 a dû adapter son activité quotidienne aux contraintes de la crise sanitaire. De nouvelles procédures spécifiques ont été rapidement élaborées, pour faire face à la pandémie. La plupart des visites médicales sur site ont été remplacées par des téléconsultations avec bilans biologiques dans les laboratoires de proximité, les « remote monitoring » ont remplacé les visites de monitoring sur site, les traitements ont été envoyés au domicile de chaque patient via des coursiers après accord des CPP (Comité de protection des personnes) de chaque protocole. Les visites indispensables ont pu être maintenues sur site grâce à l’implication sans faille de notre équipe soignante et sous condition de mise en place d’un protocole sanitaire adapté.ConclusionGrâce à l’implication de l’ensemble de notre équipe de recherche multidisciplinaire, et malgré les difficultés rencontrées, chaque patient a pu bénéficier d’un suivi personnalisé et poursuivre son traitement protocolaire. Les procédures mises en place ont également permis la collecte d’un maximum de données de sécurité et d’efficacité pour les promoteurs des essais cliniques et le respect des bonnes pratiques réglementaires. L’ensemble de ces mesures prises dans le contexte de l’urgence sanitaire, lors de la première vague épidémique, ont permis d’aborder plus sereinement la suite de l’épidémie.

We'll Deal With That Later.

We'll Deal With That Later Lauren T. Southerland, Jennifer A. Frey, and Russell Williams The office was empty and all the plants were dead. And while it is not atypical to find plants struggling for life in my personal office, it is not normal to find them in everyone's offices. It was mid-April and we had been in quarantine for COVID-19 and working from home for over a month. Initially, I had been better about nipping into my office to get supplies and things I needed, but once I had permission to take my work desktop home, my bedroom became my primary research space. I hadn't realized until I walked back in that day in April that four weeks had passed of doing all our work from home and no one had been in to water the plants. Even the cactus was drooping and brown. My research team and I had been working on starting up an interventional study to try to reduce COVID-19 infections in healthcare workers, and we were meeting in person to put the final pieces in place. My research manager Jennifer Frey and I needed to process map every element of the study, from where we would meet with potential participants to where we would draw samples and swab nasal passages. Hopefully clinical research would be easier to resurrect than the wilted cacti and dried-up spider plants. On a whim I decided to take every plant I could find home with me to see what could be saved. For everyone in the world the pandemic has been difficult. For an emergency medicine physician who also does clinical research and just took on the leadership role of Director of Clinical Research for the Department, it was very difficult. Add in navigating remote schooling for 4 kids, including a 3 year old boy who is part-tornado, and work challenges were now work-life tournaments with both sides competing ferociously over every minute of time I had. The kids quickly adapted and developed shrewd attack plans: sneaking into the bedroom office to try to make crazy faces during work Zoom calls or nabbing my cell phone so I couldn't double-secure login to hospital websites. Even with my amazing husband at home full time, trying to sort through the 7 websites, (which means 21 different logins between the 3 school age kids) and figuring out how to upload things like "paragraph fluency readings" and kindergarten art projects, it was hard. I can't imagine how unmanageable it was for single parents. Who knows if they were learning anything. We'll worry about the gap in their education later. . . . When COVID hit, we had a team of paid undergrad students, clinical research assistants, research coordinators, and managers recruiting and running 11 different studies in the Emergency Department. In late March, all non-critical research was halted and employees were sent to work from home. We scrambled to find encrypted, HIPAA compliant laptops for everyone. We had several studies that required follow up phone calls to participants. The team figured out how to use the hospital operator service to mirror calls so patient participants only saw the hospital number and not their personal cell phones when they called from home. Jen ordered headsets for the team off Amazon. We'll figure out reimbursement later . . . Our studies ranged from the management of septic shock to identifying delirium in older patients to urine microbiomes. All those were halted as being non-critical and we quickly pivoted to starting up several COVID trials. We'll worry about the consequences to our other studies later . . . This was my first interventional drug trial. An interventional drug trial typically takes 12–18 months of work to ensure that all the appropriate regulations, permissions, and operating procedures are in place. We had to condense that down to 4–6 weeks. You could almost hear the echoing screech as the entire research mechanism at this large academic hospital switched gears to the all-COVID setting. The number of committee decisions, permissions, and signed contracts was amazing. It was lots of late nights, early mornings, and learning on the fly. The...

Development of a multi-component intervention to promote participation of Black and Latinx individuals in biomedical research.

Barriers to research participation by racial and ethnic minority group members are multi-factorial, stem from historical social injustices and occur at participant, research team, and research process levels. The informed consent procedure is a key component of the research process and represents an opportunity to address these barriers. This manuscript describes the development of the Strengthening Translational Research in Diverse Enrollment (STRIDE) intervention, which aims to improve research participation by individuals from underrepresented groups. We used a community-engaged approach to develop an integrated, culturally, and literacy-sensitive, multi-component intervention that addresses barriers to research participation during the informed consent process. This approach involved having Community Investigators participate in intervention development activities and using community engagement studios and other methods to get feedback from community members on intervention components. The STRIDE intervention has three components: a simulation-based training program directed toward clinical study research assistants that emphasizes cultural competency and communication skills for assisting in the informed consent process, an electronic consent (eConsent) framework designed to improve health-related research material comprehension and relevance, and a "storytelling" intervention in which prior research participants from diverse backgrounds share their experiences delivered via video vignettes during the consent process. The community engaged development approach resulted in a multi-component intervention that addresses known barriers to research participation and can be integrated into the consent process of research studies. Results of an ongoing study will determine its effectiveness at increasing diversity among research participants.

Abstract A083: Diversifying breast cancer clinical trial accrual: An approach to recruitment at a Comprehensive Cancer Center

Abstract Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress of preventative measures and treatments for all races and ethnicities. However, Northern European whites (NE/W) continue to be disproportionally enrolled (e.g., 93.5% were non-Hispanic white in the STAR trial), while minorities such as Asians, blacks, Latinas, and Native Americans (NA) lag in participation. Current studies suggest that minorities are not approached as frequently as NE/W; however, they are just as willing to participate. Here we present a successful recruitment strategy to improving minority accrual in CTs at a Comprehensive Cancer Center located in Duarte, CA. Method: Results from community focus groups suggested the need to mentor local youth who strive to pursue a career in the medical field. Consequently, from February 2016 to July 2018, four bilingual, bicultural clinical research assistants (CRAs) were recruited from the catchment area of City of Hope (CoH). The CRAs, in collaboration with seven surgeons, two radiologists, and one medical oncologist, led the recruitment for three nontherapeutic BC prevention CTs at CoH. Results: All four CRAs were 1) first-generation American, 2) fluent in Spanish or Vietnamese, 3) born and raised in Southern California, and 4) pre-health. Of the 3,148 patients who were screened, 398 were eligible for enrollment, 369 consented, and 58 declined. Primary languages and races/ethnicities of those who declined include the following: 7% Armenian, 9% Chinese, 78% English, 2% Thai, and 5% Spanish; 28% Asian, 3% black, 28% Latina, 2% NA, and 67% white (22% NE, 17% Middle Eastern/North African). Demographics of the consenting population include the following: primary language - &amp;gt;1% Armenian, 4% Chinese, 89% English, &amp;gt;1% Korean, and 7% Spanish; race/ethnicity - 14% Asian, 6% black, 30% Latina, 5% NA, and 75% white (40% NE). Of the white population (n = 277), 11% were Middle Eastern/North African, 53% NE, and 36% Latina. Accrual surpassed both the CoH catchment area (11.3% Asian, 8% black, 24% Hispanic, 1% NA, and 32% NE/W) and the CoH interventional/nontherapeutic CT population (10% Asian/Pacific Islander, 4% black, 21% Hispanic, &amp;gt;1% NA, and 55% NE/W). Conclusion: Contrary to current accrual of CTs, here we show that minorities can have a large representation in CT accrual, as long as they are provided the opportunity. Accrual of Asians, Latinas, and NAs exceeded the catchment area and accrual of other CoH CTs. Interestingly, Chinese-speaking women comprised the highest declination group of the non-English speakers, and Asians and Latinas declined the most outside of non-whites. Cultural competency and bilingualism appear to be characteristics of a CRA that may help in accruing minority women into CTs. Our findings suggest that they are just as willing to participate, and the first step is to simply ask. Citation Format: Tanya A. Chavez, Christine Thai, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney A. Vito, Noé R. Chávez, Alan Nuñez, Ellen J. Rippberger, Angela K. Wong, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni Idassi, Kendall J. Kennedy, Terry Hyslop, Carola M. Zalles, Christopher Sistrunk, Victoria L. Seewaldt. Diversifying breast cancer clinical trial accrual: An approach to recruitment at a Comprehensive Cancer Center [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A083.