Supervisors info:
Ευάγγελος Τέρπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαρία Γαβριατοπούλου, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Φλώρα Ζαγουρή, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
The history of clinical research is riddled with numerous examples of exploitation, coercion, human life exposed to reckless danger and abuse of human rights due to lack of information, guidelines and legislative frameworks.
The establishment of rules, guidelines and legislative frameworks became a necessity since clinical trials is back bone of the evidence-based science that is required for developing and approving new/innovative investigational products and obtaining marketing authorization in the Western world. The rights, safety and well-being of the participants in clinical trials are now a priority and protected at all costs.
Greece follows the European Legislative Framework adapted to Greek reality with Ministerial Decisions as well as the 13 ICH GCP established Guidelines for all phases of clinical trials and in particular for interventional Phase III trials, which is the most predominant classification.
Within the Greek legislation, clear definitions and instructions have been established for all stakeholders involved in clinical trials, the most important being sponsor, clinical research organization and freelancers, investigator - institution and the competent approval authorities of the country.
Due to the majority of multinational and multicenter trials, the core documents included in clinical trials are based on the ICH GCP guidelines. The protocol, the informed consent form, the investigator brochure, and all other documents intended for the participants must be adapted to Greek reality in accordance with the directives that have been announced by the competent approval authorities (EOF/EED). Specific requirements have been established through ministerial decisions on the insurance policy as well as a standard template of the clinical trial financial agreement which is currently the national standard. Finally, the quality of life questionnaires used in each trial must also be adapted and validated in Greek reality by a specific process.
To initiate a clinical trial in Greece, a complete trial dossier needs to be submitted to all competent authorities. After the trial dossier is reviewed, the EOF needs to provide approval, the EED has to issue a positive opinion, as well as all four contractual parties are required to sign the clinical trial financial agreement.
Following approval, the preparation for research site activation begins. The investigator site files need to be sent to the research site, the principal investigator's team members must gain access to all electronic systems of the trial such as IVRS/IWRS, eCRF, the central platform for direct access to the test results of the participants as well as to quality of life platforms/questionnaires. For all the electronic systems in clinical trials, there are corresponding trainings that all members of the research team must attend and obtain the corresponding certificate.
Each member of the research team is given personal access, with unique codes that correspond to the tasks assigned to him by the principal investigator. These codes are personal, and it is the
Διπλωματική Εργασία _Χ . Ρόκκα. 9 |58 P a g e
responsibility of each member to preserve the confidentiality and must never share them with monitors, auditors or clinical trial inspectors even if requested.
The activation of the research center takes place after the onset of the site initiation visit. It is perhaps the most important and rigorous visit since all the organizational and technical details of the clinical trial and the research site are confirmed, ensured and documented. There is a full review of the protocol and inclusion/ exclusion criteria for the proper recruitment of participants as well as a detailed discussion on the informed consent process. Finally, the monitor trains the research site staff on investigational product receipt, storage, distribution, accountability and return/destruction.
The monitoring of a clinical trial lies with the sponsor who, through specific monitoring procedures and authorized with specific competence responsibilities (CRAs), ensures that the clinical trial is conducted, recorded and reported according to the protocol, standard operating procedures, good clinical practice and the applicable regulatory requirements.
During a clinical trial, all documents can be amended either by providing new information or by correcting any identified errors. All the amended documents must be submitted to the competent authorities and receive the corresponding approval/positive opinion for the continuation of the clinical trial.
All clinical trials subject to audits and inspections. Clinical trials can be audited either by the sponsor or by an external associate of the sponsor or even by the clinical research organization. Inspections can be carried out by all the regulatory authorities involved, at all stages of the clinical trial and are not limited to the Greek regulatory authority, the National Medicines Agency (EOF), but can also be from the European Medicines Agency (EMA) and the Food and Drug Administration of the United States (FDA) due to the multinational/multicenter nature of clinical trials and applications for marketing authorization of the investigational product.
The end of a clinical trial occurs when the Clinical Study Report is submitted, which must be clearly stated in the protocol including the report with the results of the clinical trial.
