Specific rules for medical devices

Please note that as from 26 May 2021, new rules for clinical studies involving medical devicesexternal link will apply.

The clinical study must not start until it has been approved by the approval bodies in question. During implementation of the study, the clinical investigation plan (CIP) approved by the authorities must be followed.

The Medical Products Agency recommends that all studies of medical devices that require a permit are conducted according to ISO 14155 Clinical investigation of medical devices for human subjects – Good clinical practice. ISO 14155 includes guidance on role allocation and responsibilities in a clinical study, and you can read more on this in the Planning section. This standard is available free of chargeexternal link, opens in new window to employees of the Swedish Association of Local Authorities and Regions (SALAR), including Swedish healthcare personnel, via an agreement between SIS and SALAR. 

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 (in Swedish)external link, opens in new window. When it comes to clinical studies involving medical devices that require a permit, there are further requirements for the patient information and consent procedure; these are specified in ISO 14155 Chapter 4.7 Informed consent.

Summarise documentation in study folders

ISO 14155 contains information on the study documentation that needs to be drawn up for clinical studies involving medical devices that require a permit. 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.

Guidance to the content of the site and sponsor files is available in ISO 14155 Annex E.

Initiation visit

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. Guidance is available in ISO 14155 Chapter 6.2 Investigation site initiation. The monitor shall write a report of the meeting.

Handling of medical devices in clinical studies

It shall be possible to track medical devices and any comparison devices in a clinical study requiring a permit from their dispatch to the trial site until they are returned or destroyed when the study ends.

There are specific requirements for what is to be documented, such as the unique identification of each product, expiry date, date the investigator received the product and date of return. ISO 14155 Chapter 6.8 Investigational device accountability has further information.

Medical devices in a clinical study shall be marked according to national legislation. This is described in the Medical Product Agency’s regulations on medical devices (LVFS 2003:11, in Swedish)external link, opens in new window, Appendix 1, Item 13.3 Information from the manufacturer.

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

Adverse events and device deficiencies shall be report during the course of any study requiring a permit, and also be summarised in a final report. The reporting of adverse events and device deficiencies is important, both for the persons taking part in the study and for future patients. Processes for reporting must be in place before the study starts.

The sponsor has overall responsibility for classifying all adverse events and device deficiencies and for the safety reporting for the clinical study. 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.

All serious adverse events, and device deficiencies that could have led to serious adverse events shall be reported to the Medical Products Agency according to the timeframes described in the clinical investigation plan. Please note that serious adverse events shall be reported, irrespective of whether the sponsor and investigator consider that there is a link between the device and/or the procedure, or not. The EU Commission’s guidelineexternal link, opens in new window MEDDEV 2.7/3 revision 3 contains guidance on registration and reporting of adverse events and device deficiencies, including timeframes for reporting.

Further information on general requirements for handling and reporting of adverse events and device deficiencies in clinical studies involving medical devices that require a permit is available in ISO 14155 Chapter 6.4, 8.2.5 and 9.8.

For studies that do not require a permit from the Medical Products Agency, other rules apply for reporting negative events and incidents. Read more on the page about medical devices.

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 Planning section. 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 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 Chapter 6.8 Documents and data control.

Implementing monitoring

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).

Monitoring is a requirement for medical device studies requiring a permit, and shall 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 design and complexity.

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, but must have scientific and clinical prior knowledge about:

  • the purpose and use of the product being tested
  • the clinical investigation plan
  • the process for handling the trial participants’ data and consent
  • the sponsor’s quality systems and procedures
  • ISO 14155
  • regulatory requirements

All monitoring activities shall be documented in a written report to the sponsor.

More detailed information about monitoring of clinical studies involving medical devices is available in ISO 14155 Chapter 8.2.4 Monitoring, and Chapter 7.2 Routine close-out.

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 study 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 Agencyexternal link, opens in new window 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 Medical Products Agency and the ethical review board. 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. ISO 14155 Chapter 7 Suspension, termination and close-out of the clinical investigation has guidelines for the activities to 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 Chapter 7.2 Routine close-out.