Research in an intercultural context: mediator-investigators of epidemiological health studies, bridges between two worlds.

Context: French Guiana is a French overseas department where very different linguistic, cultural and societal populations live together in a small area. Health issues and their specific epidemiological profiles call for research projects crossing several cultures. In this context, health mediators have a role to play in research. The aim of this study was to describe the perceptions, attitudes and opinions on research of mediators and researchers collaborating on research projects, and to describe the strengths and difficulties encountered during this cooperation. Methods: The Inter-med project was conducted in French Guiana between February 2022 and April 2023 on the base of semi-directive interviews with mediators, or researchers, all working in health research in the intercultural context of French Guiana. The socio-demographic characteristics of the participants were described. An inductive thematic analysis was carried out on all the interviews, and word occurrence analysis on certain themes. The information was triangulated with field coordination notebooks from two epidemiological surveys conducted in French Guiana between 2021 and 2022. Results: A total of 26 semi-structured interviews were conducted and 1,328 notebook pages analyzed. Mediation was described as an indispensable interface between the world of research and that of the population targeted by a survey. Mediators have a role to play at different stages of projects, in respect of good clinical practice, ethics and legislation. They act as interfaces between languages, concepts and representations. Their profession remains under-defined and under-dimensioned. The jobs offered are often precarious. Mediation work is emotionally costly, calls on soft skills and requires a combination of rigor and flexibility. All these aspects are implemented in the specific world of research, where there are common concepts and divergent perceptions. Researchers and mediators converge on a common goal: improving health. Conclusion: This study covers several aspects of the development and implementation of research projects. Respect for good clinical practice and people, transparency and data quality are redundant concerns, and this study touches on ethnocentrism, stigmatization and cultural representations. This study points out that the integration and recognition of mediators could be beneficial in research conducted in a cross-cultural context.

Patient Advocates for Clinical Research (PACER): A Step Toward Ethical, Relevant, and Truly Participatory Clinical Research in India.

Background Clinical research presents a promising path for improving healthcare in contemporary India. Yet, researchers identify gaps in trust, awareness, as well as misconceptions about being a '"guinea pig." We proposed building the capacity of training patient advocacy groups (PAGs) in patient-centered clinical research and through them creating aware patients as research partners. Methodology Patient Advocates for Clinical Research (PACER) is a tiered program to share information and education about clinical research with PAGs. Tier one is a self-paced online learning course, followed by workshops on clinical research, Good Clinical Practice, research consent, case studies, and group discussions. Results A total of 20 PAGs represented by 48 participants, active in areas of pediatric cancer, breast cancer, multiple myeloma, type I diabetes, spinal muscular atrophy, sickle cell disease, and inflammatory bowel diseases, participated. Among 48 participants 30 successfully completed the online course (multiple-choice question evaluation score cut-off >70%), attaining an average score of 23.9 ± 2.1 out of 30. Overall, 48 participants attended workshop 1 and 45 workshop 2, with 140 participants joining the focus group discussion (FGD). An overall improvement of 9.4% (𝜒2 = 46.173; p < 0.001) for workshop 1 and 8.2% (𝜒2 = 25.412; p < 0.001) for workshop 2 was seen in knowledge gain about clinical research. The FGD raised issues such as misleading information from research teams, unethical recruitment, incomprehensible information sheets, and limited trial-related knowledge fostering fear of participation in clinical research. Conclusions Multimodal and tiered learning of clinical research such as that used by PACER has a good participatory and learning response from PAGs and may be further explored.

Education pathways and key tasks for research nurses in Europe, results from a VACCELERATE online survey.

AIM: This article aims to provide a comprehensive overview of the educational pathways and responsibilities of research nurses in Europe, particularly focusing on their essential role in conducting research in clinical settings, including clinical trials, while adhering to ethical and regulatory standards. BACKGROUND: Research nurses play a crucial role in clinical research settings, especially in clinical trials, ensuring adherence to ethical and regulatory standards. Understanding their educational pathways and responsibilities is essential for promoting consistency and quality in research practices across Europe. DESIGN: Between October and November 2022, relevant European nursing education authorities, including those focused on research nursing, were contacted to participate in an online cross-sectional survey. The survey aimed to gather information about research nurse education and training in their respective countries. METHODS: The study followed a cross-sectional design. Contacts were made with European nursing education authorities based on recommendations from the VACCELERATE National Coordinators and the VACCELERATE Site Network. Participating organizations were invited to complete an online survey regarding research nurse education in their countries. RESULTS: Responses were obtained from 37 European countries, a response rate of 74%. The most common terms used to refer to nurses involved in clinical trials and epidemiological studies were "study nurse" (62%) and "clinical research nurse" and "research nurse" (43% each). The requirements to become a research nurse varied across countries, with a nursing degree necessary in 87% of countries and Good Clinical Practice (GCP) courses mandatory in 81%. Local providers of research nurse courses existed in 84% of countries, coordinated by online organisations (51%) or universities/hospitals (46%). The most common tasks assigned to research nurses were the administration of investigational medicinal products (from 78% in observational studies to 89% in phase IV trials) and blood sample processing (84% in phase II and IV trials). CONCLUSIONS: This study provides valuable insights into research nurse education and tasks in European countries. It highlights the need for standardisation to enhance consistency and quality of training across Europe.

Transitional dynamics in oncology clinical trials: evaluating the impact of Clinical Trials Act on cooperative groups.

OBJECTIVE: large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown. METHODS: a survey was conducted across the nine major cooperative groups that constitute the Japan Cancer Trials Network to assess the impact of Clinical Trials Act on the number of newly initiated trials from fiscal year (from 1 April to 31 March) 2017 to 2022 and that of ongoing trials on 1 April in each year from 2018 to 2023. RESULTS: the number of newly initiated trials dropped from 38 trials in fiscal year 2017 to 26 trials in fiscal year 2018, surged to 50 trials in fiscal year 2019, but then gradually decreased to 25 trials by fiscal year 2022. Specified clinical trials decreased from 32 trials in fiscal year 2019 to 12 trials in fiscal year 2022. The number of ongoing trials was 220 trials in 2018, peaked at 245 trials in 2020, but then gradually decreased to 219 trials by 2023. The number of specified clinical trials has been in consistent decline. By April 2023, of the 20 ongoing non-specified clinical trials, nine adhered to Clinical Trials Act and 11 followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects. CONCLUSION: the number of multicentre clinical trials in oncology gradually decreased after the Clinical Trials Act's enforcement, which underscores the need for comprehensive amendment of the Clinical Trials Act to streamline the operational process.

Good Statistical Practice-development of tailored Good Clinical Practice training for statisticians.

BACKGROUND: Statisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the UK NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA). METHODS: The Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU) Statisticians Operational Group and funded by the National Institute for Health and Care Research (NIHR), to develop materials to enable role-specific GCP training tailored to statisticians. Review of current GCP training was undertaken by survey. Development of training materials were based on MHRA GCP. Critical review and piloting was conducted with UKCRC CTU and NIHR researchers with comment from MHRA. Final review was conducted through the UKCRC CTU Statistics group. RESULTS: The survey confirmed the need and desire for the development of dedicated GCP training for statisticians. An accessible, comprehensive, piloted training package was developed tailored to statisticians working in clinical research, particularly the clinical trials arena. The training materials cover legislation and guidance for best practice across all clinical trial processes with statistical involvement, including exercises and real-life scenarios to bridge the gap between theory and practice. Comprehensive feedback was incorporated. The training materials are freely available for national and international adoption. CONCLUSION: All research staff should have training in GCP yet the training undertaken by most academic statisticians does not cover activities related to their role. The Good Statistical Practice (GCP for Statisticians) project has developed and extensively piloted new, role-specific, comprehensive, accessible GCP training tailored to statisticians working in clinical research, particularly the clinical trials arena. This role-specific training will encourage best practice, leading to transparent and reproducible statistical activity, as required by regulatory authorities and funders.

Impact of coronavirus disease 2019 pandemic on good clinical practice trials in oncology.

Aim: Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population, so many recommendations have been approved to ensure optimal management. Clinical research was notably impacted by COVID too. This review aims to analyze the challenges occurred during a pandemic for the management of enrolled patients (enrollment, use of telemedicine visits, study procedures) and for the clinical trials system (from feasibility to selection visit, site initiation visit, monitorings, use of e-signature, deviations and discontinuations). Methods: The studies included in the present review were selected from PubMed/Google Scholar/ScienceDirect databases. Results: During the first phase of pandemic many clinical trials were suspended in accrual and, as the pandemic progressed, recommendations were established to guarantee the safety and the continuity of care of enrolled patients. In addition, lot of new strategies was found during the pandemic to reduce the negative consequences on clinical trial performance and to guarantee new opportunities of care in the respect of good clinical practice (GCP) in a bad scenario. Conclusions: Among all modifiers, investigators would prefer to maintain the positive ones such as pragmatic and simplified trial designs and protocols, reducing in-person visits when not necessary and to minimizing sponsor and contract research organizations (CROs) visits.

The revamped Good Clinical Practice E6(R3) guideline: Profound changes in principles and practice!

The International Council for Harmonisation has released a draft version E6(R3) of the Good Clinical Practice Guideline for public consultation. The objective of the revamped guideline is to make the new provisions applicable across diverse clinical trial types and settings and to remain relevant as technological and methodological advances occur. E6(R3) includes profound changes in the structure and content of E6(R2) version, which will impact all the trial conduct processes from planning to reporting. This guideline's focus on principles, digital technology, ethics, and quality will increase the responsibilities of the ethics committees, the investigator, and the sponsor. This brief review discusses the impact of the guideline on trial conduct and the challenges of implementation in India.

ISO 9001:2015 standard implementation in clinical trial centers: An exploratory analysis of benefits and barriers in Italy.

Background: In the last decade many clinical research centers in Italy have increasingly implemented and improved their quality standards and effectiveness of processes through the adoption of a quality management system also according to the certification ISO 9001:2015. Objective: The aim of this project is to evaluate expected benefits and barriers of ISO 9001 certification for a Clinical Trial Center. Material and methods: On April 2021, the Italian Group of Data Manager and Clinical Research Coordinator spread an anonymous online survey to healthcare professionals operating in clinical research and quality management systems at research sites. Results: Reported benefits of ISO oriented Quality Management System adoption include continual improvement and better-quality processes (73.3%), assuring corrective actions (63.6%), planning internal audits (60.2%) and risk management approach (60.7%). The most important barriers to QMS implementation are increased logistical and/or organizational activities (40.9%) and insufficient training on quality programs (29.5%). Conclusions: Implementing a quality management system represents a challenge for the Clinical Trial Center and helps to improve quality standards and risk management approach. The use of electronic tools is poor and could be increased in the future. Lastly, improvement of continuous QMS trainings should be necessary for updating professionals and optimizing activities within the Clinical Trial Center.

"How do I keep this live in my mind?" Allied Health Professionals' perspectives of barriers and enablers to implementing good clinical practice principles in research: a qualitative exploration.

BACKGROUND: Allied health professionals (AHPs) engaged in research are expected to comply with Good Clinical Practice (GCP) principles to protect participant safety and wellbeing and enhance data integrity. Currently, few studies have explored health professionals' perceptions of implementing and adhering to GCP principles in research with none of these including AHPs. Such knowledge is vital to guide future interventions to increase adherence to GCP principles. This study aimed to identify the barriers and enablers AHPs experience when applying GCP principles to research conduct in a public hospital and health service, as well as their perceived support needs. METHODS: The study used a qualitative descriptive study approach guided by behaviour change theory. AHPs currently undertaking ethically approved research within a public health service in Queensland, Australia were interviewed to explore barriers and enablers to adherence to GCP principles and support needs, with interview questions guided by the Theoretical Domains Framework (TDF). The TDF was chosen as it allows for a systematic understanding of factors influencing implementation of a specific behaviour (i.e., GCP implementation) and can be used to inform tailored interventions. RESULTS: Ten AHPs across six professions were interviewed. Participants identified both enablers and barriers to implementing GCP across nine domains of the TDF and enablers across three additional domains. Examples of enablers included strong beliefs about the importance of GCP in increasing research rigour and participant safety (i.e. from TDF - beliefs about consequences); applying clinical skills and personal attributes when implementing GCP (i.e., skills), available training and support (i.e., environmental context and resources); and alignment with their moral sense to 'do the right thing' (i.e., professional identity). Barriers to GCP implementation were generally less commonly reported but included reduced time to implement GCP and a sense of 'red tape' (i.e., environmental context and resources), a lack of knowledge of GCP principles (i.e., knowledge) and a fear of making mistakes (i.e., emotions), and varying relevance to individual projects (i.e., knowledge). Suggestions for support were identified beyond training, such as physical resources (e.g., prescriptive checklists, templates and scripts), additional time, and regular one-on-one mentoring support. CONCLUSION: Findings suggest that while clinicians recognise the importance of GCP and want to implement it, they report barriers to its practical implementation. GCP training alone is unlikely to address these barriers to implementing GCP in daily practice. Findings suggest that GCP training may be more useful to AHPs when it is tailored to the allied heath context and supplemented with additional supports including check-ups from experienced researchers and access to prescriptive resources. Future research however is needed to investigate the effectiveness of such strategies.

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.

Streamlining clinical research: an ESMO awareness call to improve sponsoring and monitoring of clinical trials.

BACKGROUND: During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research. METHODS: A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care. RESULTS: The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP. CONCLUSIONS: This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients.

Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis.

Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or false. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings. As evidence synthesis authors of the Cochrane COVID-19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a research integrity assessment (RIA) tool for randomized controlled trials for the update of this Cochrane review. In this paper, we explain the rationale and application of the RIA tool in this case study. RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, author group, plausibility of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40% of studies in the first update of the review. RIA is a complementary tool prior to assessing "Risk of Bias" aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.

SNMMI Clinical Trial Network Research Series for Technologists: Application of Good Clinical Practice to Clinical Research in Medical Imaging.

This article is part of a series developed by the Clinical Trials Network of the Society of Nuclear Medicine and Molecular Imaging to offer training and information for molecular imaging technologists and researchers about various aspects of clinical research. This article covers the topic of good clinical practice and how that relates to those portions of the Code of Federal Regulations that govern clinical research in the United States, such as title 21, part 312, and the Common Rule. The purpose of this article is to inform technologists and researchers about standard roles, documents, guidance, and processes that are elemental to the conduct of clinical trials and to offer additional resources for learning about these processes.

Comparison of Good Clinical Practice Inspection Processes for Marketing Applications Between the United States Food and Drug Administration and the European Medicines Agency.

BACKGROUND: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) began collaboration on Good Clinical Practice (GCP) inspections for marketing applications since 2009. The main characteristics of the GCP inspection processes between FDA and EMA were never evaluated. This is the first analysis comparing the GCP inspection processes between the two agencies. METHODS: We examined and analyzed the key characteristics of the GCP inspection processes, including the geographical distribution, inspection types and timelines from application submission to final inspection reporting for marketing applications from September 2009 through December 2015. RESULTS: Fifty-five shared applications were included for analysis. For these applications, a total of 433 GCP inspections were conducted in 47 countries. Most clinical investigator (CI) inspections were conducted in regions outside of each agency's own regulatory jurisdiction, while most sponsor/contract research organization (CRO) inspections were conducted in the U.S. by both agencies. Twenty-eight shared applications included common sites inspected by both agencies. There were 15 joint inspections conducted for seven of these applications and the remaining applications had common sites inspected by both agencies at separate times. Of the joint inspections, 73% were conducted in the U.S and 20% in the E.U. The median time from submission of an application to generation of final inspection reports was 232 days for FDA and 204 days for EMA, with no significant differences noted among applications with and without common sites. CONCLUSION: The inspection processes and timelines between the two agencies were similar, providing support for continued FDA-EMA GCP collaboration.

Analysis of ethical review issues of informed consent form for clinical trials of registered anti-tumor drugs in our hospital / 中国药房

OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.

Study on good clinical practices among researchers in a tertiary healthcare institute in India.

BACKGROUND: Good clinical practice (GCP) is put in place to protect human participants in clinical trials as well as to ensure the quality of research. Non-adherence to these guidelines can produce research that may not meet the standards set by the scientific community. Therefore, it must be ensured that researchers are well-versed in the GCP. But not much is known about the knowledge and practices of the GCP in the medical colleges of North India. AIM: To assess the knowledge and practices of researchers about GCP and analyze these with respect to the demographics of participants. METHODS: This is a cross-sectional study. A self-structured questionnaire about GCP, after expert validations, was circulated among researchers, at a tertiary healthcare institute, All India Institute of Medical Sciences (AIIMS), Rishikesh. A total of 59 individuals, who were selected by universal sampling, participated in the study. All healthcare workers who have been investigators of Institutional Ethics Committee-approved research projects, except residents and faculty, and are still a part of the institute have been included in the study. The study was approved by the Institutional Ethics Committee of AIIMS, Rishikesh. We used descriptive analysis and the Chi-squared test to analyze data. P value < 0.05 was considered significant. RESULTS: Out of 59 participants, only 11 (18.6%) were certified for GCP. Most of the participants (64.4%) had "Average" knowledge, 33.9% had "Good" knowledge and 1.7% had "Poor" knowledge. Only 49% of participants had satisfactory practices related to GCP. There was a significant difference in the knowledge based on the current academic position for the items assessing knowledge of institutional review board (P = 0.010), confidentiality & privacy (P = 0.011), and participant safety & adverse events (P < 0.001). There was also a significant difference in knowledge of research misconduct (P = 0.024) and participant safety & adverse events (P = 0.011) based on certification of GCP. There was a notable difference in the practices related to recruitment & retention on the basis of current academic position (P < 0.001) and certification of GCP (P = 0.023). We also observed a considerable difference between the knowledge and practices of GCP among the participants (P = 0.013). CONCLUSION: Participants have basic knowledge of GCP but show a lack thereof in certain domains of GCP. This can be addressed by holding training sessions focusing on these particular domains.

Protocol for a cluster randomised controlled feasibility study of Prehospital Optimal Shock Energy for Defibrillation (POSED).

Aims: The Prehospital Optimal Shock Energy for Defibrillation (POSED) study will assess the feasibility of conducting a cluster randomised controlled study of clinical effectiveness in UK ambulance services to identify the optimal shock energy for defibrillation. Methods: POSED is a pragmatic, allocation concealed, open label, cluster randomised, controlled feasibility study. Defibrillators within a single UK ambulance service will be randomised in an equal ratio to deliver one of three shock strategies 120-150-200 J, 150-200-200 J, 200-200-200 J. Consecutive adults (≥18 years) presenting with out of hospital cardiac arrest requiring defibrillation will be eligible. The study plans to enrol 90 patients (30 in each group). Patients (or their relatives for non-survivors) will be informed about trial participation after the initial emergency has resolved. Survivors will be invited to consent to participate in follow-up (i.e., at 30 days or discharge).The primary feasibility outcome is the proportion of eligible patients who receive the randomised study intervention. Secondary feasibility outcomes will include recruitment rate, adherence to allocated treatment and data completeness. Clinical outcomes will include Return of an Organised Rhythm (ROOR) at 2 minutes post-shock, refibrillation rate, Return of Spontaneous Circulation (ROSC) at hospital handover, survival and neurological outcome at 30 days. Conclusion: The POSED study will assess the feasibility of a large-scale trial and explore opportunities to optimise the trial protocol.Trial registration: ISRCTN16327029.

ESHRE certification of ART centres for good laboratory and clinical practice.

STUDY QUESTION: Three years after the start of the ESHRE ART Centre Certification (ARTCC) programme, what is the current state of the system, in terms of the interest expressed in it and experiences during the assessment of ART services? SUMMARY ANSWER: As of 1 December 2021, 25 European ART centres have been involved in the various stages of certification and the most common recommendations from inspectors were the need for documented training, verification of competencies for all staff members, verification of laboratory and clinical performance indicators, implementation of a quality management system and avoidance of overusing ICSI and add-ons. WHAT IS KNOWN ALREADY: European Union (EU) legislation has included ART activities in the EU Tissue and Cells Directives (EUTCDs). Following inspections by national EUTCD authorities, many details regarding documentation, laboratory environment, handling of reproductive cells and tissues, traceability, coding and patient testing have become standardized. However, the EUTCDs do not cover all ART-specific aspects. For this reason, the ARTCC was established to focus on peculiar areas, including relevant staff qualifications, training, continuing professional development, workload, equipment suitability, (non)-evidence-based laboratory and clinical methods used, treatment approaches according to ESHRE guidelines, recommendations and laboratory and clinical key performance indicators. STUDY DESIGN SIZE DURATION: The article reviews the state-of-the-art of the ESHRE certification of ART centres for good clinical and laboratory practice over an initial 3-year period of operation, including the number of ART centres involved in the different stages of certification and the most common recommendations by inspectors. PARTICIPANTS/MATERIALS SETTING METHODS: In 2016, the ARTCC working group began to establish a new ESHRE ARTCC programme. Since then, the working group has organized 4 preparatory courses and appointed 37 inspectors (19 clinicians, 17 embryologists and one paramedical). A tool to verify compliance with ESHRE recommendations for good laboratory and clinical practice was developed. The ARTCC has been open for applications since September 2018. In Step 1, the applicant enters basic information about the ART centre, staff and ART activities into the application platform. After review and approval, the applicant is given the opportunity to enter Step 2 and provide detailed online checklists on general, laboratory, clinical services and clinical outcomes. Two inspectors (one clinician and one embryologist) independently evaluate the submitted checklists. The condition to proceed to evaluation is a positive mean score (at least 66%) from each of the four checklists. In Step 3, a live site visit (or virtual owing to the coronavirus disease 2019 (COVID-19) pandemic) is organized and the inspectors prepare a final report with appropriate recommendations. The application may be rejected at any time if the criteria required to advance to the next stage are not met. The ARTCC programme is currently available for European countries listed in ESHRE internal rules, available on the ESHRE website. The certificate is valid for 3 years, after which an application for renewal can be submitted. MAIN RESULTS AND THE ROLE OF CHANCE: Over a 3-year period (until 1 December 2021), 63 ART centres from 25 countries started applying through an online platform. So far, 38 applications did not progress owing to lack of completion of the initial application within a 1-year period or because applications came from non-European countries. Of the remaining 25 applications, 8 centres have been inspected and 7 centres have been certified. The most common recommendations given by inspectors to assessed centres were the need for documented training, verification of competencies, skills and continuing professional development for all staff members, verification of laboratory and clinical performance indicators and implementation of a quality management system. The inspectors identified some recurring areas of medically assisted reproduction that deviate from good practice: the overuse of ICSI, preimplantation genetic testing for aneuploidies, freeze-all and other add-ons. They often reported that the clinical outcomes could not be objectively assessed because of non-inclusion of the started cycles or the frequent use of freeze-all cycles. LIMITATIONS REASONS FOR CAUTION: No major modifications have been made to the application platform and checklists since the early stages of the certification programme. However, in this short time, quite a few changes in clinical practice have occurred, especially concerning the more frequent use of the 'freeze-all' strategy. As a result, problems arose in the evaluation of clinical outcomes. In addition, because of the COVID-19 pandemic, site visits were substituted by the implementation of virtual visits. While this enabled the certification programme to continue, it is possible that certain critical details that would have been noticed during a traditional site visit may have been overlooked. WIDER IMPLICATIONS OF THE FINDINGS: Regular monitoring of the observations of ARTCC inspectors and analysis of their reports is certainly useful to harmonize inspectors' criteria in the assessment process and to identify chronic deficiencies in clinical and laboratory practice. Non-conformities can be addressed by ESHRE through guidelines and recommendations, as well as through discussion with EU institutions and competent authorities. STUDY FUNDING/COMPETING INTERESTS: The ARTCC programme was developed and funded by ESHRE, covering expenses associated with the meetings. The Steering Committee members who are the authors of this article did not receive payments for the completion of this study. The inspectors were remunerated for their work with an honorarium. The authors have no conflicts of interest to declare.

Students' guide to documentation in clinical trials.

PURPOSE: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, support in clinical trials by students of human medicine and related disciplines has become of even greater importance than in pre-pandemic times. Documentation in clinical trials adheres to the principles of Good Clinical Practice (GCP), and healthcare professionals involved in the conduct of clinical trials-including students-are obliged to perform documentation in accordance with GCP principles. Unprecedented challenges have arisen with regard to the appropriate training of students as training courses in presence had largely to be suspended due to social-distancing regulations during the heyday of the COVID-19 pandemic. Therefore, novel training formats and self-study training materials for students working in clinical trials are urgently warranted. METHODS: To overcome this shortcoming and to define a common quality standard, an interdisciplinary, multiprofessional (physicians, study nurses, medical students), and binational (Germany, The Netherlands) expert panel convened and devised the Students' guide to documentation in clinical trials. RESULTS: Following a brief description of the different roles in clinical trials (e.g., sponsor, (principal) investigator, monitor) and an introduction into the principles of GCP, the documentation of adverse events, concomitant medication, medical history, and quality control are comprehensively discussed. The Guide concludes with a trilingual medical dictionary (English, German, Dutch) and with recommendations of pertinent literature for further reading. CONCLUSION: Serving both as textbook for self-training and as (quick-) reference work for the daily routine, the Guide has specifically been designed to complement, but not to replace practical training courses for students. While primarily addressed at students of human medicine and related disciplines, the Guide can also be of high relevance and utility to other healthcare professionals involved in the conduct of clinical trials.

Stakeholders' views on the most and least helpful aspects of the ICH E6 GCP guideline and their aspirations for the revision of ICH E6(R2).

Background: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has published the ICH E6(R2) Good Clinical Practice (GCP) guideline, which provides standards for the design, conduct, documentation, and reporting of clinical trials. Revision to E6(R2) is currently underway, aiming to adapt the guidance to the current regulatory environment. The Clinical Trials Transformation Initiative (CTTI) interviewed stakeholders, gathering their experiences implementing ICH E6 GCP and suggestions for revising the guidance. Methods: We conducted a qualitative descriptive study using in-depth interviews. Participants were purposefully selected to ensure diversity in geography, research role, and type of institution. Participants reflected on their aspirations for the ICH E6 GCP revision and described sections of the guidance that they found most and least helpful. Narratives were analyzed using applied thematic analysis. Results: Many participants found ICH E6 GCP generally clear and helpful. They appreciated that the guidance is globally accepted and serves as a common standard for research worldwide. Participants also noted opportunities for improvement, suggesting that the revised guidance should incorporate flexibility, simplify requirements, and accommodate advances in research conduct. They highlighted areas where language should be updated and concepts clarified and expressed a desire for transparency and inclusiveness in the revision process. Conclusion: Our findings show that many participants view the ICH E6(R2) guidance as helpful overall, although substantial room for improvement remains. We have provided the full report of these findings to ICH in hopes that it will be useful as the E6 GCP guideline is revised.