Specific rules for medicines
Producing trial files
In clinical medicine studies, Trial Master Files (TMF), one for the clinical investigator and one for the sponsor, shall be produced at the start of the study and be updated continuously. The trial files shall include the necessary documents for initiating a study, and working documents generated during the process of the study. EMA has recommendations on what TMF should include (pdf, 279 kB) External link, opens in new window.. After conclusion of the study, it shall be possible to reconstruct the study based on the documentation in the TMF. The clinic file shall include all the documentation that is important for the own clinic, and the sponsor file shall include the overall documentation for all participating clinics. Please note that information that may identify patients must not be included in the sponsor file.
Monitoring is a requirement for clinical studies of medicines. The monitoring is carried out by a monitor who is employed by the sponsor or the clinical investigator. A monitor may not be involved in the practical implementation, but must have scientific and/or clinical prior knowledge about:
- the product being tested
- the protocol
- study participant information
- the sponsor’s procedures
- regulatory requirements
The monitoring is carried out as a quality control. The monitor shall ensure that the protocol is followed, that laws and regulations are complied with, and that data are correctly registered in the patient’s data collection form (CRF).
Reporting side effects
The clinical investigator in a clinical study of a medicine is responsible for registering and reporting any side effects continuously. The study protocol defines clearly how this is to be done. The definitions and the process differs between medicines and medical devices. As the side effect reporting is important both for the persons participating in the study and for future patients, procedures for side effect reporting must be in place before the study starts.
Ensuring that all data are complete and correct
Once the data collection in a clinical medicine study is completed, the sponsor responsible must go through and ensure that all data input into the database and the data collection forms (CRF) are complete and correct. This shall be documented with the clinical investigator’s signature on each form. In the event of any uncertainty, the clinical investigator should be questioned. The database is declared a “clean file”, once all the data have been checked, supplemented and corrected. After this, no changes can be made to data collected for the study in question, and statistical processing can start.
Summarising an annual safety report
A safety report including a summary of side effect reports (SAE) shall be produced annually for clinical studies of medicines (“Development Safety Update Report, DSUR). The report shall be sent to the Medical Products Agency and to the Ethical Review Authority.
ICH’s guidelines for Development Safety Update Report (pdf, 216 kB)
External link, opens in new window.Medical Product Agency's template for Development Safety Update Report (in Swedish) External link, opens in new window.
Reporting that the study is completed
No later than 90 days after a clinical medicine study has been completed (usually when the last patient has left the study), a common EU document (pdf, 26 kB) External link, opens in new window., End of Trial Notification, shall be sent to the Medical Products Agency, and the study shall be reported as concluded in the same database as the one it was registered in, EudraCT External link, opens in new window..
The study results shall be summarised in a report and be sent to the Medical Products Agency no later than 12 months after the conclusion of the medicine study. If children have taken part, the report must be sent within 6 months of the conclusion of the study. Guidelines are available on EMA’s website at “Structure and Content of Clinical Study Reports” (pdf, 370 kB) External link, opens in new window..