Research responsible institution

The institution where the project manager is employed is the responsible coordinating research institution for the study. This institution is also the data controller according to General Data Protection Regulation (GDPR), either alone or as a joint controller together with the cooperating institutions.

Project manager

The project manager (in person) is responsible for the day-to-day conduct of the research project, and should have the necessary research qualifications and experience to be able to fulfil the obligations.

In multicentre studies there will be one project manager for all Norwegian cooperating institutions. However, each institution will be research responsible for the research conducted in its own institution.

Project team members in cooperating institutions

Cooperating institutions should enter into a written agreement describing each partner’s responsibilities and tasks.

There should be a dedicated project team member (Researcher/Investigator) responsible for the conduct of the study in each institution. This person acts on behalf of the project manager, as delegated (defined in the written agreement). 

Roles and Responsibility overview

Tasks can be delegated. Delegation should be in writing. (See Delegation Log - Appendix 2).

The project manager has the overarching responsibility to ensure that the team members have sufficient competence to conduct the delegated tasks. Only tasks can be delegated, not the responsibility.

Developing research protocol

A detailed Research Protocol must be developed. It has to be version controlled and it should be signed by a representative for the research responsible institution and by the project manager. The Protocol - Template from the Transcelerate website is recommended to use.

Examples of Research Protocols are available at NorCRINs website.

If the institution has a department for research support this department could possibly be available for advice when it comes to writing protocols. A statistician should be consulted for study design and calculating number of participants (power analysis) if this is not within the project manager’s expertise.

For studies where participants are randomized to intervention or studies where treatment is blinded for the subjects/researcher, see Randomisation, Blinding and Unblinding - SOP 1.2.b.

Patient Reported Outcome (PRO)

Many research protocols contain patient questionnaires and other data reported directly from the study participants. In enclosure 9.1 the use of PROs is further expanded.

Subject information sheet and consent form

Before consenting to a study all study subjects must be informed both verbally and in writing and must be given ample time before deciding. Written consent must be obtained before any study specific procedures are performed. A study specific procedure may be e.g. asking the subject to be fasting at the first visit, if this is not standard procedure in usual patient care. It is possible to apply to REK for exemption.

The subject information sheet and consent form should be created based on REK’s templates and must receive REK’s approval before it is used. The content should be easily understood by the study subjects and as a general rule the participants should sign and date the consent form themselves. REK also has templates for situations where the next of kin will have to consent on behalf of the subject. In veileder til medisinsk og helsefaglig forskning  more information regarding different consent scenarios can be found.

If new information becomes available that may alter the subject’s opinion about participating in the study, a new consent for continuing in the study must be obtained, either by signing an updated patient information sheet/consent form or as an amendment to the originally signed document. The amended documents must have approval by the REK before they are used. In case of emergency, i.e. new safety information, subjects should be informed verbally before the written documents are available. All consents (written or verbal) should be documented in the patient’s medical records.

Approvals prior to study start

Internal approval of the study

Most institutions have a process of obtaining internal approval from the institution, both from department or clinic leader and from the information security officer (this role may be held by the data protection officer in some institutions).

Regional Committee for Medical and Health Research Ethics  (REK)

All studies under the health research act need to be approved by the Regional Ethics Committee before starting. This implies that documents like Research Protocol and patient information sheet/patient consent form must be part of the application to the REK. All written information to be provided to the study participants have to be approved by the REK, e.g. questionnaires and adverts/recruitment material.

Changes to the research protocol after approval

If changes to the Research Protocol are required after approval, an updated version (with version number) and amendment form, must be sent to REK for approval before the changes can be implemented. This is described in the Health Research Act § 11 and on the REK’s homepage.

Changes that are required to ensure the participants safety should be implemented immediately. It is recommended to inform the REK by telephone in these cases and to follow up with the written amendment form as soon as possible.

Please Note! If the project is delayed and cannot be completed before the study end date approved by REK, an amendment form must be sent to REK in due time to get an extension. Data cannot be collected, analysed or otherwise processed after the approved study end date. 

Register the study at ClinicalTrials.gov  and helsenorge.no

All clinical studies testing or comparing different treatments should be registered at clinicaltrials.gov before starting, including observational studies. Such registration may be a prerequisite for publication of the study results later. This process may take weeks to complete, ensure complete before recruitment starts. Please follow your institution’s procedures for registering a study at clinicaltrials.gov.

Ministry of Health and Care Services has requested all clinical studies to be registered at the web site kliniskestudier.helsenorge.no. The clinical studies are first registered at the hospital web-site and transferred from there to the helsenorge platform. Contact local research support at your institution, or search for procedure in the institution’s quality system, for instructions.

Study start

After all approvals are obtained and agreements signed (cooperating units/institutions), the study start can be planned. The project manager must ensure that the study staff is trained in all applicable study procedures. This could be done in a study start/kick-off meeting at each site or at a joint meeting for all study sites. Documentation of the training (agenda, minutes, participant lists, agreed delegation lists) should be archived in the study files (TMF and ISF).  

Accountability

Depending on the nature of the study, accountability of the intervention in the study or other equipment may be useful. Accountability of Intervention - Appendix 3 can be adjusted as needed for this use. 

Monitoring

Monitoring is an independent quality control performed to ensure that the study complies with the protocol and regulations. The monitor pays special attention to the participant’s rights and safety, and the quality of the data. There is no requirement for monitoring of studies covered by this guideline. However, independent risk-based monitoring of any study may increase its quality. The extent of monitoring in a study with a risk based monitoring approach would depend on several factors, e.g. complexity of the study, patient numbers involved, staff experience etc. Specific monitoring report templates are developed to accommodate interventional studies, Initiation Report CIO - Appendix 11; Monitoring Report CIO - Appendix 12; Close-Out Report CIO - Appendix 13.

Handling, storage and transmission of research data and samples

The project manager is responsible for adequate statistical competence, systems and equipment for recording data, data handling and storage of data and samples.

The institution will have routines for storage of research data. The main rule is that all study data must be captured without direct recognisable personal information. All subjects screened for study participation and who have signed a consent form should be registered and pseudonymised in a Screening Log - Appendix 4. All subjects included in the study will have a study number that will follow the data (consent form, questionnaires, CRF etc.). A code list connecting the subject number to the subject must be kept with limited access (Subject ID-Log - Appendix 5).

Study data for each subject are recorded in a study specific «Case Report Form» (CRF) that reflects the Research Protocol. Data that are not described in the Research Protocol (and hence not approved by REK) cannot be collected. The CRF may be electronic (e.g. web based) or on paper. Participating institutions must follow internal procedures for obtaining any applicable approvals for safe transfer of data from local institution to external database.

Developing and completing CRF are further described in Case Report Form and Patient Reported Outcome - SOP 1.12.a.

Data handling should either be described in the Research Protocol or in separate “Data Management Plan” The database must be ”locked” prior to analysing the data, to ensure that data are not changed after the analysis has started. NorCRIN LM SOP for Data Management describes this in detail. 

Data handling is further described in Data Management - SOP 1.12.b.

Source documents

As a ground rule any data collected in the study should origin from a source document. The source document is the first entry point of data. This could be e.g. the subjects medical records, a laboratory report, a subject questionnaire. Some data may be recorded on work sheets before entered into the eCRF, in these cases the work sheets are source data.  In this way the data can be reconstructed if needed and is especially important for the main study endpoints.

Reporting

The project manager and responsible project team member in multicentre studies must follow internal reporting routines as applicable. In addition, project manager must submit anend of study notification to REK. Additional or extraordinary reports will only be required in cases where REK deems this necessary.

In trials involving radiation therapy, accidents and abnormal events related to the radiation treatment are to be reported immediately to the Norwegian Radiation Protection Authority (Statens Strålevern). If there are no acute danger for life, health or environment it can be reported within normal working hours. This can be reported verbally, followed by written report within 3 days.

Storage of documentation and archiving

The project manager is responsible for developing a study specific plan for safe keeping and archiving of project documentation. Throughout the study life cycle it is recommended to keep documentation and correspondence on both centre level (Investigator Site File) and study level (Trial Master File). For Table of Content for the study files, see Table of Content ISF - Appendix 8;Table of Content TMF - Multicentre Study - Appendix 9; Table of Content ISF/TMF - Single Centre Study Clinical Intervention and Obsevational Studies - Appendix 10 . The study files are to be archived according to the routines in each institution. Patient data (including de-identified data) cannot be stored or archived for a longer period than stated in the REK approval and must be destroyed or anonymized (destroying subject ID log) at this date. Ensure that also other documents that have direct person identifying data and subject number (e.g. consent forms) are destroyed.

Study reports and publications

The CONSORT-group has developed a minimum set of recommendations for reporting randomized trials that may be very useful for writing publications for studies comparing two groups. For other study designs, useful information is found here.

Deviations to the routines at each institution should be followed. NorCRIN Protocol Deviation Handling - SOP 1.10.b can be used for studies under this guideline, adjust as applicable.

• Delegation Log - Appendix 2
• Accountability of Intervention - Appendix 3
• Screening Log - Appendix 4
• Subject ID-Log - Appendix 5
• Table of Content ISF - Appendix 8
• Table of Content TMF - Multicentre Study - Appendix 9
• Table of Content ISF/TMF - Single Centre Study Clinical Intervention and Obsevational Studies - Appendix 10
• Initiation Report CIO - Appendix 11
• Monitoring Report CIO - Appendix 12
• Close-Out Report CIO - Appendix 13