Execution

Conducting a clinical trial of a medicinal product

Establish and maintain the trial master files

For a clinical trial of a medicinal product, trial master files must be established and maintained by both the sponsor and the investigator.

The files are established when the trial is initiated and must be updated continuously throughout the trial.

The trial master files contain:

• the documentation required before the trial can start
• documentation generated while the trial is being conducted
• documentation generated when the trial is completed

ICH-GCP provides detailed information about which documents must be held by the sponsor and the investigator before, during and after the trial. The European Medicines Agency also provides recommendations about the content of trial master files.

When the trial has been completed, the documentation must be sufficiently complete to allow the trial to be fully reconstructed.

The documentation is divided between:

• the investigator site file, which contains documentation relevant to the individual trial site
• the sponsor trial master file, which contains the overall documentation for the entire trial

Information that could identify trial subjects must not be included in the sponsor trial master file.

• Trial master file content under ICH-GCP E6, European Medicines Agency website External link.
• Recommendations for the content of trial master files, European Medicines Agency website External link.
• Templates for trial master files maintained by the investigator and sponsor. External link.
  

Monitor the trial

Monitoring is a quality-control measure and is required for clinical trials of medicinal products.

The monitor is appointed by the sponsor and conducts monitoring on the sponsor’s behalf. The monitor must be independent of the practical conduct of the clinical trial at the trial site.

The monitor needs scientific or clinical knowledge relevant to the trial and must be familiar with:

• applicable regulatory requirements
• ICH-GCP
• the trial protocol
• the investigational medicinal product
• the information provided to trial subjects
• the sponsor’s procedures

The monitor verifies that:

• the trial protocol is followed
• applicable laws and regulations are followed
• the collected data are complete and recorded correctly

Clinical Studies Sweden provides templates that can support the planning and conduct of monitoring, particularly when several monitors are working on the same trial.

Templates for planning and conducting monitoring External link.

Submit notifications through CTIS

For clinical trials conducted under Regulation (EU) No 536/2014, the sponsor must submit required notifications through the Clinical Trials Information System (CTIS).

The sponsor must notify relevant events, including:

• the start of the clinical trial
• the start of recruitment
• the first visit of the first trial subject
• the end of recruitment
• a temporary halt of the trial
• early termination of the trial

Notifications must be submitted within the applicable timeframe. For the events listed above, the timeframe is generally 15 days.

Notifications through CTIS under Regulation (EU) No 536/2014, EUR-Lex website External link.

Record and report adverse events

The investigator is responsible for continuously recording adverse events and abnormal laboratory results during the clinical trial. The investigator must report events to the sponsor in accordance with the procedures and timeframes specified in the trial protocol.

The sponsor is responsible for assessing the reported events and meeting the applicable regulatory reporting requirements.

Suspected unexpected serious adverse reactions (SUSARs) must be reported by the sponsor through the EudraVigilance database.

The trial protocol must clearly describe the procedures for safety reporting. These procedures must be in place before the clinical trial starts to protect study participants and future patients.

Safety reporting for clinical trials, European Medicines Agency website External link.

Submit an annual safety report

The sponsor must prepare an annual safety report for investigational medicinal products used in clinical trials.

The report should be prepared in accordance with the ICH guideline for the Development Safety Update Report (DSUR). It must include:

• a summary and assessment of relevant safety information
• an assessment of whether the benefit–risk balance has changed during the reporting period

The annual safety report is submitted through CTIS.

Annual safety reporting, Swedish Medical Products Agency website (in Swedish) External link.

Conducting a clinical investigation of a medical device

Clinical investigations of medical devices are governed by the EU Medical Devices Regulation (EU) 2017/745 (MDR), which came into effect on 26 May 2021.

Follow Good Clinical Practice

A clinical investigation must not start until the required approvals are in place. Information about applications and notifications is available in the Application chapter.

The investigation must be conducted in accordance with the Clinical Investigation Plan (CIP) approved by the authorities.

The Swedish Medical Products Agency recommends that clinical investigations of medical devices are conducted in accordance with ISO 14155:2026, Clinical investigation of medical devices for human subjects – Good Clinical Practice.

The standard includes guidance on the allocation of roles and responsibilities in a clinical investigation. More information about these roles is available in the Planning chapter.

Through an agreement between the Swedish Institute for Standards (SIS) and the Swedish Association of Local Authorities and Regions (SALAR), healthcare professionals in Sweden have free access to standards such as ISO 14155:2026 on the SIS website.

ISO 14155:2026, Swedish Institute for Standards' website External link.

Obtain informed consent

Before participating in a clinical investigation, subjects must provide informed consent unless an approved exception applies. Consent must be obtained in accordance with the Swedish Ethical Review Authority’s guidance on subject information and consent.

For clinical investigations of medical devices, the MDR and ISO 14155:2026 contain additional requirements for participant information and the consent process.

Template: Subject informaton, Clinical Studies Sweden (in Swedish) docx, 200 kB. (docx, 200 kB)

Supplementary Swedish legislation also applies to the consent process in clinical investigations involving minors and other people who do not have the capacity to provide consent.

For clinical investigations involving children:

• both guardians must provide informed consent on behalf of the child
• minors aged 15 or over who understand what participation involves must also provide informed consent

• Information for research participants, Swedish Ethical Review Authority website (in Swedish) External link.
• Medical Devices Regulation (EU) 2017/745 External link.
• Swedish legislation supplementing the EU regulations on medical devices, Swedish Parliament website (in Swedish) External link.

Maintain the investigation documentation

ISO 14155:2026 provides guidance on the documentation required for a clinical investigation of a medical device.

The documentation must be compiled and maintained in:

• an Investigation Site File at each investigational site
• a Sponsor File maintained by the sponsor

The files must contain the documents needed to assess how the investigation was conducted and its quality. When the investigation has been completed, the documentation must make it possible to reconstruct the investigation in full.

The Investigation Site File must contain the documents relevant to the individual investigational site. The Sponsor File must contain the overall documentation for all participating sites.

Information that could identify participants must not be included in the Sponsor File.

Conduct site initiation activities

Before the investigation starts, the sponsor or monitor should conduct a site initiation visit at each participating investigational site. Alternatively, a joint meeting may be held with the principal investigators and other study staff.

The purpose is to:

• review the Clinical Investigation Plan
• review the activities involved in the investigation
• ensure that each site has the necessary equipment and resources
• ensure that the required documentation and approvals are in place

The sponsor should document what was covered during the meeting and maintain a list of participants, including their names, initials, signatures and roles.

The monitor should prepare a formal report summarising the visit or meeting.

Manage and trace the medical devices

All medical devices used in the clinical investigation, including comparator devices, must be fully traceable from delivery to the investigational site until they are returned or appropriately disposed of.

The documentation must include:

• the device’s unique identifier
• its expiry date
• the date it was received by the investigator
• the date it was returned.

Devices evaluated in the clinical investigation must be clearly labelled: For clinical investigation use only.

The sponsor has overall responsibility for the medical devices. This includes:

• training staff in how to use the devices correctly
• ensuring that traceability documentation is maintained

The principal investigator is responsible for ensuring that the devices are used:

• only by authorised personnel
• in accordance with the Clinical Investigation Plan
• in accordance with other investigation-specific instructions

Report adverse events and device deficiencies

Specific safety-reporting requirements apply to clinical investigations involving:

• devices that are not CE marked
• devices used outside their intended purpose

The requirements also apply to serious adverse events related to investigation-specific procedures when a CE-marked device is studied within its intended purpose.

Reporting adverse events and device deficiencies is important for protecting subjects and future patients. Reporting procedures must be established before the investigation starts.

For investigations involving non-CE-marked devices or devices used outside their intended purpose, the sponsor must ensure that the following are reported immediately to the Swedish Medical Products Agency:

• serious adverse events related to the medical device, comparator device or investigation procedures
• device deficiencies that could have resulted in a serious adverse event if appropriate action had not been taken or if the circumstances had been less favourable.

Safety reporting, Swedish Medical Products Agency External link.

The sponsor has overall responsibility for safety reporting. The principal investigator is responsible for continuously recording and assessing adverse events and device deficiencies at the investigational site.

At the end of the clinical investigation, a summary of the safety reports and measures taken must be included in the clinical investigation report. More information is available in the Publication chapter.

Information about safety reporting and reporting timeframes is available in:

• the Medical Devices Regulation
• MDCG 2020-10/1
• ISO 14155:2026

MDCG-endorsed documents and other guidance, European Commission's website External link.

For investigations of CE-marked devices used within their intended purpose, the healthcare provider’s usual procedures for reporting adverse events and incidents apply.

Serious adverse events related to investigation-specific procedures must also be reported to the Swedish Medical Products Agency.

Reporting serious incidents, Swedish Medical Products Agency's website External link.

Collect and manage study data

A paper or electronic Case Report Form (CRF) must be prepared before the investigation starts. More information about CRFs and electronic systems is available in the Planning chapter.

Staff involved in data collection must be trained in:

• how to use the CRF correctly
• when data must be recorded

The principal investigator is responsible for confirming that the collected data are accurate, complete, legible and recorded within a reasonable timeframe.

Data generated during the investigation may be entered directly into the CRF. In these cases, the CRF contains the source data.

Source data may also come from documents such as:

• ECG printouts
• laboratory reports
• patient records
• worksheets

Data from these sources must be transferred consistently to the CRF.

The source data must be defined before the investigation starts. This supports consistent data management and ensures that the original records are preserved.

Verification of source data is an important part of the monitor’s quality review and may also be examined during a regulatory inspection.

All study data, including source data, must be stored securely and remain reliable for future reference.

Further guidance, including requirements for electronic CRFs, is available in ISO 14155:2026.

Monitor the investigation

Monitoring is a quality-control measure at participating investigational sites.

The monitor verifies that:

• the study staff have the required qualifications and conditions to conduct the investigation
• the Clinical Investigation Plan is followed
• applicable laws and regulations are followed
• data are recorded correctly in subjects’ Case Report Forms

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

Monitoring is mandatory for clinical investigations of medical devices and should be conducted before, during and after the investigation.

Before the investigation starts, the sponsor must prepare a monitoring plan. The scope and frequency of monitoring are determined by the investigation’s:

• risks
• design
• complexity.

The monitor is appointed by the sponsor and must be independent of the practical conduct of the investigation.

Further guidance is available in ISO 14155:2026. Information about the monitor’s qualifications is available in the Planning chapter.

Audit and inspection

An audit is conducted by the sponsor or by a third party appointed by the sponsor. It evaluates whether the investigation complies with:

• the Clinical Investigation Plan
• applicable laws and regulations
• requirements for conducting the investigation, managing data and reporting results

An audit may be conducted at any organisation or site involved in the clinical investigation and must be independent of monitoring.

An audit may be conducted to:

• verify compliance as part of the sponsor’s quality programme
• assess whether monitoring is effective
• investigate suspected misconduct
• prepare for a regulatory inspection

An inspection is a formal review conducted by the regulatory authority responsible for the clinical investigation. It may include an official examination of:

• investigation documentation
• equipment and resources
• data records
• quality-management measures

An inspection may take place at investigational sites or at other organisations involved in the investigation.

The principal investigator must make the investigation documentation available at the request of monitors, auditors or inspecting authorities.

Report substantial modifications

If a substantial modification is required during an ongoing clinical investigation, a notification of the modification must be submitted to the Swedish Medical Products Agency.

The Swedish Medical Products Agency coordinates the review with the Swedish Ethical Review Authority. No separate application for an amendment needs to be submitted to the Swedish Ethical Review Authority.

The notification must be submitted through the same electronic process used for the original application.

• Application for amendment, Swedish Medical Products Agency website External link.
• Special form for ethical review of amendment application, Ethical Review Authority website External link.
• Substantial modifications under the MDR, Swedish Medical Products Agency External link.
• Medical devices under the MDR, Swedish Ethical Review Authority website (in Swedish) External link.

Report a temporary halt or early termination

If the entire clinical investigation is temporarily halted or terminated early, this must be reported to the Swedish Medical Products Agency. The same applies if an individual investigational site is closed prematurely.

The reason must be documented. Reasons may include:

• a suspected unacceptable risk to subjects
• serious or repeated deviations from the investigation procedures at a site

If the investigation is temporarily halted or terminated early for safety reasons, the Swedish Medical Products Agency must be notified within 24 hours.

If the temporary halt or early termination occurs for another reason, the Agency must be notified within 15 days.

ISO 14155:2026 provides additional guidance on the procedures and activities required when an investigation is temporarily halted or terminated early.

Termination of the clinical investigation

When an investigational site has completed all final investigation activities and entered all data in the Case Report Forms, the monitor conducts a site close-out visit.

During the visit, the monitor verifies that:

• data reporting and documentation are accurate and complete
• outstanding queries have been resolved
• remaining materials and medical devices have been returned or appropriately destroyed

The sponsor is responsible for ensuring that all close-out activities are completed. The sponsor must also:

• verify that the data are complete and accurate
• conduct any final follow-up needed to resolve outstanding questions

Once these activities have been completed, the database can be considered final and complete. The database can then be locked and the statistical analysis can begin.

More information about statistical analysis is available in the Analysis chapter. Guidance on closing a clinical investigation is also available in ISO 14155:2026.

Conducting a performance study of an in vitro diagnostic medical device

Performance studies of in vitro diagnostic medical devices are governed by the EU In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR), which came into effect on 26 May 2022.

Follow Good Study Practice

A clinical performance study must not start until all required approvals from the relevant authorities have been obtained. Information about applications and notifications is available in the Application chapter.

The study must be conducted in accordance with the clinical performance study plan approved by the authorities.

The Swedish Medical Products Agency recommends that clinical performance studies of in vitro diagnostic medical devices are conducted in accordance with ISO 20916:2024, In vitro diagnostic medical devices – Clinical performance studies using specimens from human subjects – Good study practice.

The standard provides guidance on roles and responsibilities in a clinical performance study.

The main body of the standard and the annex on the handling of adverse events should be applied to all performance studies. Other annexes, including those addressing the clinical performance study plan, investigator’s brochure and recommended study documentation, are not mandatory for studies that only require notification rather than an application to the Swedish Medical Products Agency.

Through an agreement between the Swedish Institute for Standards (SIS) and the Swedish Association of Local Authorities and Regions (SALAR), healthcare professionals in Sweden have free access to many standards on the SIS website.

ISO 20916:2024, Swedish Institute for Standards' website External link.

Obtain informed consent

Before participating in a clinical performance study, subjects must provide informed consent unless an approved exception applies. Consent must be obtained in accordance with the Swedish Ethical Review Authority’s guidance on subject information and consent.

For clinical performance studies, the IVDR and ISO 20916:2024 contain additional requirements for subject information and the consent process.

Supplementary Swedish legislation also applies to the consent process in clinical performance studies involving minors and people who do not have the capacity to provide consent.

Information for study subjects, Swedish Ethical Review Authority website (in Swedish) External link.

Maintain the study documentation

ISO 20916:2024 provides guidance on the documentation required for a clinical performance study.

The documentation must be compiled and maintained:

• at each study site
• by the sponsor

The files must contain the documents needed to assess how the study was conducted and its quality. When the study has been completed, the documentation must make it possible to reconstruct the study in full.

The study site file must contain the documents relevant to the individual site. The sponsor file must contain the overall documentation for all participating sites.

Information that could identify subjects must not be included in the sponsor file.

Conduct site initiation activities

Before the study starts, the sponsor or monitor should conduct a site initiation visit at each participating study site. Alternatively, a joint meeting may be held with the principal investigators and other study staff.

The purpose is to:

• review the clinical performance study plan
• review the activities involved in the study
• ensure that each site has the necessary equipment and resources
• ensure that the required documentation and approvals are in place

The sponsor should document what was covered during the meeting and maintain a list of participants, including their names, initials, signatures and roles.

The monitor should prepare a formal report summarising the visit or meeting.

Manage and trace the IVD devices

All IVD devices used in the clinical performance study, including comparator devices, must be fully traceable from delivery to the study site until they are returned or appropriately disposed of.

The traceability documentation should include:

• the device’s unique identifier
• its expiry date
• the date it was received by the investigator
• the date it was returned

All IVD devices used in the study must be clearly labelled: For clinical performance study only.

The sponsor has overall responsibility for the devices. This includes:

• training staff in how to use the devices correctly
• ensuring that traceability documentation is maintained

The principal investigator is responsible for ensuring that the devices are used:

• only by authorised personnel
• in accordance with the clinical performance study plan
• in accordance with other study-specific instructions

Report adverse events and device deficiencies

Specific safety-reporting requirements apply to clinical performance studies under the IVDR.

The requirements also apply to studies of CE-marked devices used within their intended purpose when serious adverse events occur in connection with study-specific procedures.

Reporting adverse events and device deficiencies is important for protecting participants and future patients. Safety-reporting procedures must be established before the study starts.

During the study, the sponsor must ensure that the following are reported immediately to the Swedish Medical Products Agency:

• serious adverse events related to the IVD device, a comparator device or study procedures
• device deficiencies that could have resulted in a serious adverse event if appropriate action had not been taken or if the circumstances had been less favourable.

The sponsor has overall responsibility for safety reporting. The principal investigator is responsible for continuously recording and assessing adverse events and device deficiencies at the study site.

At the end of the study, a summary of the safety reports must be included in the final performance study report. More information about preparing the final report is available in the Publication chapter.

Safety reporting under the IVDR, Swedish Medical Products Agency External link.

Further information about safety reporting and reporting timeframes is available in the IVDR and ISO 20916:2024.

For studies of CE-marked devices used within their intended purpose, the healthcare provider’s usual procedures for reporting adverse events and incidents apply.

Serious adverse events related to study-specific procedures must also be reported to the Swedish Medical Products Agency.

Reporting serious incidents, Swedish Medical Products Agency External link.

Collect and manage study data

A paper or electronic Case Report Form (CRF) must be prepared before the study starts. More information about CRFs and electronic systems is available in the Planning chapter.

Staff involved in data collection must be trained in:

• how to use the CRF correctly
• when data must be recorded

The principal investigator is responsible for confirming that the collected data are accurate, complete, legible and recorded within a reasonable timeframe.

Data generated during the study may be entered directly into the CRF. In these cases, the CRF contains the source data.

Source data may also come from documents such as:

• ECG printouts
• laboratory reports
• patient records
• worksheets

Data from these sources must be transferred consistently to the CRF.

The source data must be defined before the study starts. This supports consistent data management and ensures that the original records are preserved.

Verification of source data is an important part of the monitor’s quality review and may also be examined during a regulatory inspection.

All study data, including source data, must be stored securely and remain reliable for future reference.

Further guidance, including requirements for electronic CRFs, is available in ISO 20916:2024.

Monitor the study

Monitoring is a quality-control measure at participating study sites.

The monitor verifies that:

• the study staff have the necessary qualifications and conditions to conduct the study
• the clinical performance study plan is followed
• applicable laws and regulations are followed
• data are recorded correctly in subjects’ Case Report Forms

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

Monitoring is mandatory for clinical performance studies and should be conducted before, during and after the study.

Before the study starts, the sponsor must prepare a monitoring plan. The scope and frequency of monitoring are determined by the study’s:

• risk assessment
• design
• complexity

The monitor is appointed by the sponsor and must be independent of the practical conduct of the study.

Further guidance is available in ISO 20916:2024. Information about the monitor’s qualifications is available in the Planning chapter.

Audit and inspection

An audit is conducted by the sponsor or by a third party appointed by the sponsor. It evaluates whether the study complies with:

• the clinical performance study plan
• applicable laws and regulations
• requirements for conducting the study, managing data and reporting results.

An audit may be conducted at any organisation or site involved in the study and must be independent of monitoring.

An audit may be conducted to:

• verify compliance as part of the sponsor’s quality programme
• assess whether monitoring is effective
• investigate suspected misconduct
• prepare for a regulatory inspection

An inspection is a formal review conducted by the relevant regulatory authority. It may include an official examination of:

• study documentation
• equipment and resources
• data records
• quality-management measures

An inspection may take place at study sites or at other organisations involved in the study.

The principal investigator must make the study documentation available at the request of monitors, auditors or inspecting authorities.

Report substantial modifications

If a substantial modification is required during an ongoing clinical performance study, a notification of the modification must be submitted to the Swedish Medical Products Agency.

The Swedish Medical Products Agency coordinates the review with the Swedish Ethical Review Authority. No separate application for an amendment needs to be submitted to the Swedish Ethical Review Authority.

The notification must be submitted through the same electronic process used for the original application.

• Substantial modifications under the IVDR, Swedish Medical Products Agency's website External link.
• In vitro diagnostic medical devices under the IVDR, Swedish Ethical Review Authority website (in Swedish) External link.

Report a temporary halt or early termination

If the entire clinical performance study is temporarily halted or terminated early, this must be reported to the Swedish Medical Products Agency. The same applies if an individual study site is closed prematurely.

The reason must be documented. Reasons may include:

• a suspected unacceptable risk to subjects
• serious or repeated deviations from study procedures at a site.

If the study is temporarily halted or terminated early for safety reasons, the Swedish Medical Products Agency must be notified within 24 hours.

If the temporary halt or early termination occurs for another reason, the Agency must be notified within 15 days.

ISO 20916:2024 provides additional guidance on the procedures and activities required when a study is temporarily halted or terminated early.

Close the clinical performance study

When a study site has completed all final study activities and entered all data in the Case Report Forms, the monitor conducts a site close-out visit.

During the visit, the monitor verifies that:

• data reporting and documentation are accurate and complete
• outstanding queries have been resolved
• remaining materials and IVD devices have been returned or appropriately destroyed

The sponsor is responsible for ensuring that all close-out activities are completed. The sponsor must also:

• verify that the data are complete and accurate
• conduct any final follow-up needed to resolve outstanding questions.

Once these activities have been completed, the database can be considered final and complete. The database can then be locked and the statistical analysis can begin.

More information about statistical analysis is available in the Analysis chapter. Guidance on closing a clinical performance study is also available in ISO 20916:2024.

Advanced therapy medicinal products (ATMPs)

Advanced therapy medicinal products (ATMPs) are biological medicinal products based on genes, cells or tissue engineering. ATMPs are regulated by common EU legislation supplemented by Swedish legislation.

The links below provide further information, regulatory guidance, templates and training.

• Advanced therapy medicinal products, Swedish Medical Products Agency website External link.
• Guides, templates and regulatory support, ATMP Sweden website External link.
• ATMP classification and regulatory information, European Medicines Agency website External link.
• Online course: Introduction to advanced therapies, Swedish Academy of Pharmaceutical Sciences website External link.

Research support for clinical trials involving advanced therapy medicinal products

Contact your regional node within Clinical Studies Sweden to find out what research support is available for your study.

Contact your regional node within Clinical Studies Sweden External link.