Toward a global harmonization of service infrastructure in academic clinical trial units: an international survey.

Background: Clinicians around the world perform clinical research in addition to their high workload. To meet the demands of high quality Investigator Initiated Trials (IITs), Clinical Trial Units (CTUs) (as part of Academic Research Institutions) are implemented worldwide. CTUs increasingly hold a key position in facilitating the international mutual acceptance of clinical research data by promoting clinical research practices and infrastructure according to international standards. Aim: In this project, we aimed to identify services that established and internationally operating CTUs - members of the International Clinical Trial Center Network (ICN) - consider most important to ensure the smooth processing of a clinical trial while meeting international standards. We thereby aim to drive international harmonization by providing emerging and growing CTUs with a resource for informed service range set-up. Methods: Following the AMEE Guide, we developed a questionnaire, addressing the perceived importance of different CTU services. Survey participants were senior representatives of CTUs and part of the ICN with long-term experience in their field and institution. Results: Services concerning quality and coordination of a research project were considered to be most essential, i.e., Quality management, Monitoring and Project management, followed by Regulatory & Legal affairs, Education & Training, and Data management. Operative services for conducting a research project, i.e., Study Nurse with patient contact and Study Nurse without patient contact, were considered to be least important. Conclusion: To balance the range of services offered while meeting high international standards of clinical research, emerging CTUs should focus on offering (quality) management services and expertise in regulatory and legal affairs. Additionally, education and training services are required to ensure clinicians are well trained on GCP and legislation. CTUs should evaluate whether the expertise and resources are available to offer operative services.

The carbon footprint of clinical trials: a global survey on the status quo and current regulatory guidance.

INTRODUCTION: All economic sectors including the service sector, along with healthcare, education and research, need to reduce their greenhouse gas emissions to limit global temperature increases. In this study, we aim to globally assess the awareness and current actions taken by Academic Research Institutions (ARIs) or governments regarding the reduction of carbon dioxide equivalent (CO2e) emissions for clinical research. METHODS: We designed a cross-sectional survey-based study, which was distributed within the International Clinical Trials Center Network (ICN). The survey population comprised representatives of the ICN who had extensive experience in academic clinical research and profound knowledge and understanding of the local context. RESULTS: The response rate was 80%. Responding ARIs were from 15 different countries and 4 continents. Around half of the ARIs reported that almost none of their research projects considered reducing their carbon footprint. The other half of the ARIs were not familiar with this subject at all. According to 60% of the respondents, greenhouse gas emissions are not assessed by Institutional Review Boards (IRBs)/Ethics Committees (ECs) or competent authorities, while 40% did not know. Neither IRBs/ECs nor competent authorities currently advise sponsors and investigators on reducing the carbon footprint of their clinical research projects. As for reducing greenhouse gas emissions in clinical research, virtual conferences and meetings were the most commonly implemented measures by ARIs across all regions. Finally, we have put together an action plan/checklist advising researchers on carbon footprint reduction for clinical trials. CONCLUSION: Currently, greenhouse gas emissions are neglected during the planning phase of a research project, and they are not yet addressed or assessed by default during the approval procedures by IRBs/ECs or competent authorities. Thus, all involved stakeholders within clinical research need to be made aware of it through advice from ARIs and IRBs/ECs, among others.

Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.

INTRODUCTION AND HYPOTHESIS: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.

How COVID-19 changed clinical research strategies: a global survey.

OBJECTIVE: Clinical research has faced new challenges during the COVID-19 pandemic, leading to excessive operational demands affecting all stakeholders. We evaluated the impact of COVID-19 on clinical research strategies and compared different adaptations by regulatory bodies and academic research institutions in a global context, exploring what can be learned for possible future pandemics. METHODS: We conducted a cross-sectional online survey and identified and assessed different COVID-19-specific adaptation strategies used by academic research institutions and regulatory bodies. RESULTS: All 19 participating academic research institutions developed and followed similar strategies, including preventive measures, manpower recruitment, and prioritisation of COVID-19 projects. In contrast, measures for centralised management or coordination of COVID-19 projects, project preselection, and funding were handled differently amongst institutions. Regulatory bodies responded similarly to the pandemic by implementing fast-track authorisation procedures for COVID-19 projects and developing guidance documents. Quality and consistency of the information and advice provided was rated differently amongst institutions. CONCLUSION: Both academic research institutions and regulatory bodies worldwide were able to cope with challenges during the COVID-19 pandemic by developing similar strategies. We identified some unique approaches to ensure fast and efficient responses to a pandemic. Ethical concerns should be addressed in any new decision-making process.

The concept of General Consent in Switzerland and the implementation at the University Hospital Zurich, a cross-sectional study.

BACKGROUND: General Consent (GC) allows the further use of health-related data/samples for multiple, unspecified research projects and/or for the collection in databases and biobanks in Switzerland. The application of General Consent in the context of human research is regulated within the scope of the Human Research Act. At the University Hospital Zurich patients are informed about General Consent to which they can agree (GC = yes) or disagree (GC = no) to the use of their routinely collected data/samples in research. In this paper, we investigated the association of demographic and medical factors on a patient's General Consent choice. METHODS: In this cross-sectional study, we investigated the association of age, gender, number of visits and number of diagnoses on General Consent choice. The study population was stratified by General Consent status group (GC choice: Yes, No, Not issued) and examined by means of descriptive statistics, comparative statistics and a multinomial and logistic regression model. A p-value of 0.001 was determined as significant. RESULTS: The female gender was found to associate with decreased odds in positive General Consent choice (<0.001) whereas age (<0.001) and number of diagnoses (<0.001) were associated with increased odds in positive General Consent choice (reference "GC = no" group). The number of visits (<0.001) as well as the number of diagnoses associated (<0.001) with increased General Consent collection (increase in positive as well as negative General Consent status). CONCLUSION: General Consent is an innovative concept that simultaneously informs patients about human research in accordance with Swiss regulations and promotes research with routinely collected data and biological samples in an era with large information repositories. Our results show that medical and demographic factors may influence a patient's choice. Therefore, approaching these populations and taking additional care to adequately inform and ensure ethical conformity and behaviour is essential. Flexible communication channels may help us reach this goal.

A FHIR-Based eConsent App for the Digital Hospital.

Research projects with humans is a highly regulated field that is currently undergoing rapid changes due to developments in eHealth and mHealth. While a patients data and samples must be thoroughly protected, they are also an invaluable source for fundamental and cutting edge research. There are processes in place to obtain a patient's consent for the use of their data and samples for research. These approaches could be more flexible, user-friendly and modernised. There is a high demand among all parties for a unified, yet differentiated, dynamic and personalised eConsent. An Android app has been developed that brings any existing consent form to mobile devices, including the integration of the process into existing hospital IT using established data standards, such as FHIR and the ResearchStack open source framework.The app is user-tested and shown to work in a hospital setting. Lack of eIdentification and legal drawbacks were determined as the main obstacles for immediate implementation.

The N-terminal region of acyl-CoA synthetase 3 is essential for both the localization on lipid droplets and the function in fatty acid uptake.

Cytosolic lipid droplets (LDs) are storage organelles for neutral lipids derived from endogenous metabolism. Acyl-CoA synthetase family proteins are essential enzymes in this biosynthetic pathway, contributing activated fatty acids. Fluorescence microscopy showed that ACSL3 is localized to the endoplasmic reticulum (ER) and LDs, with the distribution dependent on the cell type and the supply of fatty acids. The N-terminus of ACSL3 was necessary and sufficient for targeting reporter proteins correctly, as demonstrated by subcellular fractionation and confocal microscopy. The N-terminal region of ACSL3 was also found to be functionally required for the enzyme activity. Selective permeabilization and in silico analysis suggest that ACSL3 assumes a hairpin membrane topology, with the N-terminal hydrophobic amino acids forming an amphipathic helix restricted to the cytosolic leaflet of the ER membrane. ACSL3 was effectively translocated from the ER to nascent LDs when neutral lipid synthesis was stimulated by the external addition of fatty acids. Cellular fatty acid uptake was increased by overexpression and reduced by RNA interference of ACSL3. In conclusion, the structural organization of ACSL3 allows the fast and efficient movement from the ER to emerging LDs. ACSL3 not only esterifies fatty acids with CoA but is also involved in the cellular uptake of fatty acids, presumably indirectly by metabolic trapping. The unique localization of the acyl-CoA synthetase ACSL3 on LDs suggests a function in the local synthesis of lipids.