Once the approvals required for your study have been obtained, the practical work can start. Study participants are recruited and the data collection starts.
The implementation of a clinical study shall follow the documentation approved by the ethical review board and, for studies involving medicines and medical devices, also the documentation approved by the Medical Products Agency.
If you make any significant change to an application that has been approved by an ethical review board, you must apply for a modification. An application for a modification shall be made in writing to the ethical review board. You must describe the changes you want to make, and attach the relevant appendices. If the change is significant, for example a change to the study design, the study hypothesis or the group of study participants used, an entirely new application for ethical review is required. What constitutes a significant change must be determined from case to case. More information can be found in the ethical review board’s Guidance on application for an ethical review (pdf, 174 kB).
If you carry out a clinical study involving medicines and have received authorisation from the Medical Products Agency, you must apply to the Medical Products Agency if you want to make any significant change. Minor changes shall be notified to the Medical Products Agency via EudraCT, the European database for clinical medicine studies. Information on what constitutes a significant change and what an application for change shall include is available on the Medical Products Agency’s website.
For clinical studies using medical devices registered with the Medical Products Agency, a notice of modification of the study plan and/or clinical investigator shall be made via the e-service notification of clinical trial on the Medical Products Agency’s website.
A clinical study may only be conducted if the study participants have consented to participate, and the consent is only valid if the study participants have received information in advance on the research to be carried out. The consent shall be voluntary, expressed and defined. The study participants shall consent to the research to be conducted, the personal data handling that participation in the study entails, and as applicable the saving of samples in a biobank. The consent shall be documented.
Special rules apply for study participants who are younger than 18 years. Study participants who have turned 15 years but not 18 years and who understand what the research entails for him or her shall be informed about and themselves consent to the research. In other cases when the research subject has not turned 18 years, the guardians shall be informed of and consent to the research. However, the study participant shall as far as possible be informed himself or herself, and the research may not be carried out out, despite the guardians’ approval if a study participant who is younger than 15 years understands what participation in the study means to him or her, and objects to it being conducted.
Information on obtaining consent (pdf, 93 kB) is available on the website of the ethical review boards, and you can also find guidance in the brochure Personal data in research – what rules apply? (pdf, 252 kB, in Swedish). The brochure is produced by the Swedish Data Protection Authority in collaboration with the Central Ethical Review Board, Statistics Sweden and the National Board of Health and Welfare.
In order to conduct a clinical study, you often need to compare data collected in the study with data from the participants’ medical records. Data in medical records is covered by professional confidentiality. When a patient wishes to take part in a clinical study, he or she may waive the confidentiality that covers his or her medical records with a care provider. Such a waiver makes it possible for the care provider to issue data to those who need to partake of data from the patient’s medical records within the framework for the study. A waiver of confidentiality is usually given in conjunction with the patient consenting to take part in a study.
A template for confidentialty undertaking has been produced by the Swedish Academy of Pharmaceutical Sciences’ clinical trials section together with LIF and the Medical Products Agency.
Data, that is to say information from the study, shall be collected in a format that can later be analysed, reported and published in a secure way. The study participant’s consent before any therapy, the effect of a therapy, observations and any side effects shall be documented.
Collection and handling of data shall be done using processes that make them easy to verify and trace back to the source, for example during an audit by an auditing public agency or, for medicine studies, by the sponsor. All study data and their sources must also be stored in a secure way in order to function as a reliable reference for future use. In the event of any randomising, the randomising process shall be documented.
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). 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.
The same requirement for documentation in TMF applies for medical devices.
Monitoring is a requirement for clinical studies of medicines and medical devices to be CE-marked. 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 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).
The clinical investigator in a clinical study of a medicine or a medical device 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.
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.
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 board.
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), 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.
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).
For clinical trials with medical devices, a report shall be drawn up and the Medical Products Agency shall be given access to the report on request.
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