WP07 – Trial Organization and Governance

Objectives

  • To develop effective management structures to ensure all centres operate to the same high standard
  • Finalize Trial protocol
  • To establish Trial Coordinating Centre (TCC)
  • To develop study informed consent procedures, manual of operations and SOPs to ensure the uniform, high quality conduct of the trial and reliable capture of study data.
  • Finalize terms of reference and protocol for blinded Potential Endpoints Adjudication (PEPA) committee.

Workpackage Description

Task 1: Effective management structures.

Develop effective management structures to ensure that all centres operate to the same high standard with regard to trial protocol, SOPs, training, safety standards, ethical guidelines and resource allocation.

Task 2: Finalize Trial Protocol.

The Steering Committee will approve the finalized version of the trial protocol which will be forwarded to the Trial Coordinating Center (TCC) to be operationalized.

Task 3: Establish Trial Coordination Centre.

The TCC will be responsible for coordinating the day-to-day running of the clinical trial, facilitating the interaction between sites and the development of all study documentation, Case Report Forms, SOPs and the manual of operations. It will be chaired by the Project Coordinator, Dr. Denis O’Mahony, who will serve as the Trial PI. It will be staffed by a clinical trial coordinator, data manager, data technician, trial monitor and study biostatistician, administrative assistant and endpoint liaison officer. All approved critical study documents will be maintained in the clinical trial masterfile at the TCC. The TCC will be responsible for generating all approved revisions of study documentations and for version control. The electronic Case Report form (eCRF) will be translated into the appropriate national languages by ClinInfo. It will host a conference call every month initially by phone/video conference to address study progress, with additional meetings or subgroup meetings as needed.

Task 4: Develop and Finalize Study Monitoring plan.

The Study monitoring plan and associated elements of site initiation plan will be developed by the TCC and approved by the Ethics and Safety Review Group (ESRG). The Study monitor will complete site initiation visits prior to study commencement. The Study monitor will review study progress using central data monitoring as per the study database (WP10). The monitor will visit each site at approximately 1 month after both the initiation of the control and intervention phases of the trial and at least once per 6 months thereafter. The monitor will ensure compliance with informed consent procedures and the overall appropriate ethical and high quality conduct of the study, and will further ensure the uniform application of the manual of operations, all SOPs and especially with the Trial endpoint ascertainment policy across different study sites. The monitor will report back in parallel to both the TCC and the SSC. A summary of the routine monitoring reports will be forwarded by the SSC to the SAB and independent Ethics and Safety Review Group (see WP09 also) every 6 months. Urgent actionable items will be forwarded directly to the SAB/ESRG from the study monitor at request of the study monitor, the study PI or a majority vote of the SSC.

Task 5: Informed Consent Process.

The TCC will develop the patient and the Phase I and Phase II participating physician informed consent forms, SOP and supporting documentation for both physicians and clinical staff. The TCC will ensure that the study protocol complies with ICH GCP requirements and European laws regulating the conduct of clinical trials, particularly with regard to vulnerable subjects such as older cognitively impaired patients. The proposed forms will be reviewed by the independent Ethics and Safety Review Group (ESRG, WP09). The consent form will be submitted to the Cork Teaching Hospitals Research Ethics Committee. Once approved, the patient informed consent form and information brochure will be translated by ClinInfo and will be individualized to the local site along with local investigator names and contact information, and thereafter submitted for approval to the various local ethics committees.

Task 6: Finalize composition, protocol and SOPs for the Potential End Point Adjudication (PEPA) Committee.

The Blinded trial endpoints committee will consist of project PI, the 12 site Principle and co-Investigators, at least 3 appropriate physicians, approved by the Scientific Advisory Board. The review will be facilitated by an Endpoint Liaison Officer, based at the Clinical Research Facility at UCC, who will ensure uniform application of committee protocols over time.

Task 7: Study close out.

Following completion of follow-up for last patient the TCC will oversee the close out of the study and will submit necessary regulatory document for study completion.

WP Leader

Prof. Dr. Joseph Eustace (UCC)

Participating Partners

University College Cork (UCC)
Ghent University Hospital (UGENT)
Servicio Madrileño de Salud (SERMAS)
Instituto Nazionale di Riposo e Cura per Anziani, Ancona (INRCA)
University of East Anglia (UEA)
Landspitali University Hospital Reykjavik (LUH)
University of Iceland (UoI)
ClinInfo S.A. (CLIN)
Grampian Health Board (NHSG)