Specific rules for medical devices
New rules apply from 26 May 2021 - but some are delayed (preliminary) until 15 July 2021. Updates regarding the rules from 15 July will be published early autumn.
The clinical study must not start until it has been approved by the approval bodies in question. Read more about how to find out if your study requires application or registration to the Swedish Medical Products Agency on the page Planning on this website. During implementation of the study, the clinical investigation plan (CIP) approved by the authorities must be followed.
The Swedish Medical Products Agency recommends that clinical investigations of medical devices are conducted according to ISO 14155:2020 - Clinical investigation of medical devices for human subjects – Good clinical practice. The standard includes guidance on role allocation and responsibilities in a clinical investigation of medical devices, you can read more on this in the Planning section. This standard, among others, is available free of charge to employees of the Swedish Association of Local Authorities and Regions (SALAR), including Swedish healthcare personnel, via an agreement between Swedish Standards Institute (SIS) and SALAR and can be accessable through SIS website.
Medical device perspectives on consent from study participants
Ahead of all clinical studies and unless an exception has been approved, study participants shall provide informed consent according to the Ethical Review Authority’s guidance for study participant information and consent. When it comes to clinical investigatons of medical devices there are further requirements for the patient information and consent procedure; these are specified in the EU regulation on medical devices and ISO 14155:2020.
Summarise documentation in study folders
ISO 14155:2020 contains information on the study documentation that needs to be drawn up in aclinical investigation of medical devices involving medical devices. A summary of the documentation shall be held both by the investigator (site file) and by the sponsor (sponsor file). The summaries shall include all the documents required to make it possible to evaluate the implementation and quality of the study. After conclusion of the study, it shall be possible to reconstruct the study based on the documentation in the study files. The site 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. Information that can identify study participants must not be included in the sponsor file.
Ahead of the study start, the sponsor and/or monitor shall carry out an initiation visit to all participating clinics, or hold a joint meeting for all principal investigators and personnel. The purpose is to go through the study protocol and all study-related activities with the principal investigators and other personnel taking part in the work on the study, and to ensure the clinic has all the necessary equipment, resources and documentation, including approvals, to enable them to begin the study. The sponsor shall document a summary of the meeting content and a list of participants, with names, initials, signatures and functions. The monitor shall write a report of the meeting.
Handling of medical devices in clinical investigation
It shall be possible to track medical devices and any comparison devices in a clinical investigation of medical devices requiring a permit from their dispatch to the trial site until they are returned or destroyed when the study ends.
That means, for example, that such as the unique identification of each product, expiry date, date the investigator received the product and date of return shall be documented.
Medical devices that are evaluated in a clinical investigation shall be marked with the expression “for clinical investigation of medcial products only”.
The sponsor has overall responsibility for the medical device, and for educating clinic personnel in how to use the product and the documentation required for traceability. The principal investigator shall ensure that the medical device is only used by authorised users and in accordance with the clinical investigation plan (CIP) and other study instructions.
Safety reporting of device deficiencies and adverse events
In clinical investigations of medical devices with products that are not yet CE-marked or with products that are not used as intended, special safety reporting must be done during the course of the study. This also applies to tests on already CE-marked products that are used for the intended purpose if serious deviating events occur that are related to study-specific procedures.
The reporting of adverse events and product defects is important both for the people participating in the study and for future patients. Processes for reporting must be developed before the study starts.
The sponsor is responsible for ensuring that all serious adverse events that are related to the use of the medical device, a comparison product or the study procedure are reported to the Swedish Medical Products Agency during the course of the study. This also applies to product defects (device deficiency) which could have led to serious deviating events if appropriate measures had not been taken or if the conditions had been less favorable. The safety reporting is summarized at the end of the study and is included as part of the study's final report.
The sponsor has overall responsibility for safety reporting but the investigator is responsible for registering and assessing all adverse events and device deficiencies at the trial site on an ongoing basis. The investigator shall make an assessment of the degree of seriousness and links between the use of the medical device and the adverse event and reports this to the sponsor.
Further information onsafety reporting and and reporting of adverse events and device deficiencies is to be found in the EU regulation on medical devices, MDCG 2020-10/1 and in ISO 14155:2020.
For studies on CE-marked products used in the context of the intended purpose of the product, the regular routines of healthcare apply for reporting negative events and incidents. An exception applies, however, to serious deviating events that are related to study-specific procedures that must also be reported to the Swedish Medical Products Agency in these studies.
Medical device perspectives on data collection
The case report form (CRF) created in paper or electronic format during the planning of the study needs to be completed in good time before the study start, see also the page Planning on this website. The persons involved in data collection shall have been trained in how the case report form shall be used, and within what timeframes data must be registered. The principal investigator at a clinic shall confirm that the data collected are correct, complete, legible and registered within a reasonable time interval. The investigator shall also make data available to monitors, auditors and public authorities at inspections.
Data generated during the study can be registered direct in the case report form, and then constitutes source data. Source data can also be generated via, for example, ECG printouts or laboratory analysis reports, or be registered for the first time in patient notes or working papers, and then be transferred to the case report form. It is important to identify source data before the study start, to ensure data are handled uniformly, and that all original data are saved.
Checks of source data are an important part of the quality control carried out by the monitor during a study, and are also carried out at any inspection.
All study data including source data must also be stored in a secure way in order to function as a reliable reference for future use.
Information on the requirements for data collection in clinical studies involving medical devices, including specific requirements for electronic case report forms is available in ISO 14155:2020.
The monitoring is carried out as a quality control of participating trial sites. The monitor shall check that the personnel involved in the study have the correct qualifications and prerequisites, that the clinical investigation plan (CIP) and applicable laws and regulations are followed, that that data is correctly registered in the study participants’ case report forms (CRF). All monitoring activities shall be documented in a written report to the sponsor.
Monitoring is a requirement for clinical investigations of medical devices and should be carried out before, during and after the study. The sponsor shall draw up a monitoring plan for the study before it starts. The scope and frequency of the monitoring shall be based on an evaluation of the study’s risks, design and complexity and are described in the monitoring plan. More detailed information on monitoring can be found in ISO 14155: 2020.
The monitoring shall be carried out by a person, the monitor, who is independent of the investigator and appointed by the sponsor. A monitor may not be involved in the practical implementation of the study. Read more about the monitors qualifications on the page Planning on this website.
Audit and inspection
The audit involves the sponsor or a third party appointed by the sponsor conducting a scrutiny to evaluate compliance with the study protocol and applicable laws and regulations for study execution, data handling and reporting. An audit may be conducted at all parties involved in a study, and is independent and separate from the routine monitoring. The reasons why an audit is conducted vary, and may be part of the sponsor’s quality program, constitute a check of the effectiveness of the monitoring, be done in conjunction with a suspicion of misconduct, or as a preparation ahead of inspection.
An inspection is a scrutiny carried out by the supervisory authority for the clinical investigations of medical devices requiring a permit, and constitutes an official scrutiny and review of the study documentation, equipment, resources, registrations and quality measures at the clinics and other parties involved in the study.
The principal investigator is obliged to make study documentation available at the request of a monitor, auditor or inspection authority.
Change to an approved application, or interruption of an ongoing study
If you need to make a significant change to an application for a clinical study that has already been approved, then updated documentation and an application for a significant change shall be submitted to both the ethical review board and the Medical Products Agency, and to any other approval bodies involved. An application for a change to the ethical review board shall be made as per the earlier description, while an application of a significant change to the Medical Products Agency shall be made via the same electronic process used for the original application.
If, for any reason, the study needs to be interrupted, or an individual clinic closes down prematurely, this shall also be reported to the Swedish Medical Products Agency. The reason for the study interruption shall be documented, and may for example be a suspicion of an unacceptable risk for study participants, or a clinic that diverges seriously or repeatedly from the study processes. If the study is temporarily interrupted or terminated prematurely due to safety reasons, the Swedish Medical Products Agency must be notified within 24 hours. If the interruption / termination is made for other reasons, this must be reported within 15 days. ISO 14155:2020 has additional description ofthe activities that should be carried out in the event of an interruption or premature closure of a study.
Concluding a study and preparing for report writing
When a participating clinic has completed the final study activities, and registered and signed off all data in the case report form, the monitor shall carry out a closure visit. The monitor shall ensure that all data reporting and documentation are correct and complete, that all questions have been answered and that any remaining material is destroyed or returned.
The study sponsor is responsible for ensuring all closure activities have been completed, shall check that all study data are complete and correct, and carries out the final follow-up if there any uncertainties remain. Thereafter, the study database is considered final and complete, the database can be closed and the statistical analysis starts; see further information on the handling of data under the Analysis tab.
Guidance on closure activities for participating clinics is available in ISO 14155:2020.