The trial protocol is the “manual” for a clinical trial and was developed by the coordinator in consultation with all recruiting centres. It documents the rationale and medical problem pursued by the trial, it's objectives, trial design, sample size calculation, inclusion and exclusion criteria, methods as well as statistical analyses. Accompanied by a risk analysis that will be, if necessary, updated during the trial, the protocol was designed to ensure that all parties involved in the clinical trial implement the trial consistently and systematically. Case report forms (CRFs) and working instructions (WIs) were developed in close cooperation with the coordinating investigator and relevant scientists from all partners involved. In addition, management activities focussed on obtaining all necessary approvals and patient insurance for all recruiting sites in different European countries. Legal activities included the development, negotiation and conclusion of various contracts between trial partners and the coordinator to allow for a better coordination of the trial.
Due to additional funding from the German Research Foundation (DFG), the trial grew from 300 to 500 patients, from 16 to 29 recruiting sites, and now includes Crawford type 1, 2 and 3 patients. Thus, the project underwent a major amendment in its early stage and changes were incorporated so as to benefit all aspects of the project. The first site was officially initiated in June, 2018 in Leipzig. Before recruitment can start, centres were provided with necessary forms, given access to the IT infrastructure set up by the co-ordinating investigator for the trial and enabled to use documentation tools smoothly.
Initial trial management covered the creation of a trial master file as well as a master copy for the investigation site files. A manual for on-site monitoring was prepared as part of the risk-based approach for quality management. Detailed groundwork was carried out for statistical monitoring.
To train staff members correspondingly, teaching material was conceptualised and developed. Upon request, practical sessions on the MIS²ACE procedure were discussed and training sessions have been organized. Trial management was also concerned with gathering feedback on trial implementation and progress from relevant consortium bodies such as the Trial Steering Committee (TSC) and the Expert Advisory Board (EAB). Their reviews were incorporated into the 1st trial protocol amendment. A similarly relevant and consultative role in the initial trial protocol development is played by the Data Safety and Monitoring Board (DSMB) which was set up under the coordination of the European Society of Cardiology (ESC).
In another strand of the project, work has started on health economics aspects as well as on aspects of patient involvement. A literature review was undertaken to select methods and develop an appropriate model structure for economic evaluation in aneurysm repair. It particularly served to determine the analytic scope and structure for cost-effectiveness comparisons of TEVAR and TAAA interventions. Apart from utilizing available trial data for this task, economic interpretations are supported by qualitative patient questionnaires. First drafts were made in close alignment with the development of the trial protocol. They were designed so as to obtain information around resource use and, under particular consideration of age and gender, reflect upon the impact of treatment on the quality of life in patients and their families.
