Composition of the coordinating centre and trial steering committee {5d}
ICH
ADVERSE EVENTS, EVENT, RECRUITMENT
The trial involves screening, seeking consent, giving the trial treatment, and collecting baseline and outcome data (mostly from the hospital notes). A Trial Management Group (TMG) will oversee the trial progress, while the LSHTM CTU Global Health Trials Group will coordinate day-to-day trial management. The TMG will consist of the Protocol Committee members and the data manager. The TMG and trial manager will act on behalf of the sponsor and ensure that the sponsor’s responsibilities are carried out. These responsibilities include (but are not limited to) the following: report to the TSC, maintain the Trial Master File, identify sites, assess site suitability, confirm all approvals are in place before enrolment of participants and release of the trial treatment, provide training, provide study materials, data management, 24-h unblinding service, monitoring, ensure data security and quality and observe data protection laws, safety reporting, ensure trial is conducted in accordance with the ICH GCP, progress updates, respond to questions about the trial, statistical analysis, and publication of trial results.The Protocol Committee will be responsible for developing the protocol. Subsequent changes to the final protocol will require the agreement of the TSC. Members will be included as authors on the final published protocol.The TSC will include (but is not limited to) an independent chair, experienced obstetrician, clinical trialist, clinical representative from a low- and middle-income country (LMIC), a statistician, lay representative, and some members of the TMG (see Additional file We will identify a National Coordinating Investigator for each participating country, who will be responsible for ensuring that all national approvals including those from regulatory agencies, ethics committees and relevant import licences are in place before the trial starts in their country. Additionally, they will support the LSHTM CTU Global Health Trials Group by ensuring recruitment is on target, safety reporting to all relevant agencies, and site training and monitoring as required.A site principal investigator will coordinate the trial at each participating hospital. Site-specific responsibilities detailed in an agreement in advance of starting the trial will include the following:Supervise the study at their site, comply with the final trial protocol and amendments, obtain all appropriate approvals, and account for trial treatmentsEnsure the trial is conducted in line with ICH GCP and fulfils all national and local regulatory requirementsKeep the trial staff aware of the current state of knowledge, the trial, and its procedures (there are training materials to assist with this)Delegate trial responsibilities to suitably trained, qualified personnel and document delegationEnsure that all potentially eligible women are considered promptly for the trial and consent is obtained in line with local approved proceduresEnsure that the data are collected, completed, and sent to the CTU Global Health Trials Group in a timely manner, including adverse events reportingEnsure the Investigator Study File is up-to-date and completeAllow access to source data, including participants’ medical records, for monitoring, audit, and inspectionBe responsible for archiving all original trial documents including medical records, Investigator Study File, consent forms, and data forms for at least 10 years after the end of the trialThe trial will be conducted in accordance with the current approved protocol, GCP, relevant regulations guidance provided in the ISF, and the trial’s standard operating procedures. A detailed monitoring plan will be developed. In summary, the LSHTM CTU Global Health Trials Group will closely monitor the trial to ensure the rights, safety, and well-being of the trial participants and the accuracy of the data. All coordinating centres and site teams will be trained in the trial procedures and provided with extensive guidance. We will use central monitoring methods. A sample of consent forms from all sites will be monitored to check they are properly completed. Data management and statistical checks (central statistical monitoring) will ensure the inclusion criteria are met and the trial treatment is administered in line with the protocol. Outcome event rates will be monitored. Quantitative variables will be monitored to check data validity using statistical methods such as the coefficient of variation and runs test. Sites with unusual event rates or low variability or randomness in the data will be selected for further monitoring.Sites flagged as high risk by central monitoring procedures may require onsite monitoring with source data verification. Site self-monitoring will also be carried out where needed. The site PI/delegate will monitor themselves against a standardised checklist. Site investigators and their institutions will provide access to source data and all trial-related documents for monitoring, audits, ethics committee review, and regulatory inspection. All trial-related and source documents including medical records, original consent forms, and original CRFs must be kept safely. Investigators must plan in advance of the trial start where the trial-related documents will be stored and how they will be accessed. All documents must be made available for up for 10 years after the end of the overall trial.Deviations from clinical trial protocols and GCP occur commonly in clinical trials. A protocol deviation is a departure from the approved protocol’s procedures made with or without prior approval. Such departures may be major or minor/administrative. Most deviations do not result in harm to trial subjects or affect the scientific value of the trial. All deviations must be reported to the LSHTM CTU Global Health Trials Group within 24 h of it becoming known to the trial team.A serious breach is defined as ‘a breach of GCP or the trial protocol which is likely to affect to a significant degree (a) the safety or physical or mental integrity of the subjects of the trial or (b) the scientific value of the trial’. If suspected, the site should inform the LSHTM CTU Global Health Trials Group within 24 h. The LSHTM CTU Global Health Trials Group will report all serious breaches to the relevant regulatory authorities and REC within the timeline required by each participating country.