Work package 4: Clinical Trial Management, Pharmacovigilance and Safety
Description of the work package
This work package is led by Dr Ingrid Klingmann of Pharmaplex bvba, a Belgium based small to medium enterprise (SME) with extensive expertise as a pharmaceutical development, clinical trial management and site support organisation working with study-specific networks of project managers, monitors and other allied functional teams required for successful completion of clinical trials. Dr. Klingmann has wide-ranging experience in implementation of clinical development programmes all over Europe.
The tasks included our work package are described below:
- Clinical Trial Management: This work package provides a Clinical Trial Management Plan and ensure the legally required GCP-infrastructure and expertise to the Sponsor of the four clinical trials that are part of the LENA project. This includes compilation and submission of the required documentation (including protocol und Investigational Medicinal Product Dossier) to enable Clinical Trial Authorisation by the respective national competent authorities and favourable opinions from the responsible ethics committees in all involved countries (including import license for study medication to be shipped into our project partner in non-EU country Serbia). The network of clinical trial sites has been established on the basis of thorough feasibility information generated before submission of the Full Project Proposal. Contractual arrangements with investigators and their hospitals will be in place to clearly define roles and responsibilities in the respective trials. The sites will then be assisted with regard to familiarisation with the studies, resource identification, documentation (Investigator Site Files and Trial Master File) and study medication management (including interaction with the hospital pharmacies as far as required). The timelines for all study activities are being defined in detail, agreed upon with all sites, and proactively managed by the clinical trial project manager. Resources for project management and supervision are being defined, identified in the respective countries, trained and supervised by the Lead Clinical Project Manager, Dr. Klingmann. Efficient communication and close collaboration within the study teams and with the LENA Project Management and Scientific Management Team will be established. Risks to the timely preparation and conduct of the trials will be identified upfront and proactive risk mitigation strategies will be defined and agreed with the Project Leader, the Sponsor, and the Work Package Leaders.
- Quality Management: We will ensure that the clinical trials in the vulnerable populations to be investigated in the LENA project are performed according to the highest ethical and GCP standards. To allow the different LENA partners to work according to their usual procedures as far as they are defined and fulfill the LENA quality expectations, the project-specific quality infrastructure will integrate the respective SOPs and Work Instructions. In a Quality Manual the overall quality infrastructure will be compiled including, e.g., the description of the applicable external standards, roles, responsibilities and authorities of the team members, document control, and SOP system with Work Instructions, Forms and Guidelines as well as the LENA approach to training of study teams, to change management, to prevention and detection of misconduct and fraud as well as to the preparation for audits and inspections. A risk-adapted approach to monitoring, based on close collaboration with our Data Management Unit, will be described.
- Pharmacovigilance: While the Phase I study will be performed in healthy male and female adult subjects, the patient populations to be investigated in the three patient studies are severely sick children with a high mortality risk. Frequent hospitalisation and other serious adverse events are highly likely. Close follow-up of the safety information and a robust decision-making infrastructure are needed throughout the clinical trial duration to be able to proactively identify safety problems and to address them promptly and appropriately. This requires very intense and reliable safety data collection and monitoring which will be ensured through comprehensive training of the investigators and site staff of the clinical trial sites in adverse event collection, assessment and reporting. They will be assisted by well-trained and readily available monitors, an experienced Medical Monitor (Dr. Klingmann), and a professional pharmacovigilance organisation for Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting and Development Safety Update Report (DSUR) preparation at the Erasmus MC-Sophia Children Hospital in Rotterdam. An independent Data and Safety Monitoring Board (DSMB) oversees all activities from a compliance perspective.