Substantial modifications to a clinical investigation
Published:
Changes
The sponsor must notify of planned substantial modifications to clinical investigations. The Norwegian Medical Products Agency (NOMA) and the ethics committee (REK KULMU) must assess the notified changes before they can be implemented.
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What is a substantial modification?
A modification will be considered substantial if:
- The modification may have a substantial impact on the safety, health or rights of the subjects, or
- The modification may have substantial impact on the robustness or reliability of the clinical data generated by the investigation
Further guidance on what may be considered a substantial modification can be found in the EU Commission’s guidance document Q&A regarding clinical investigations (MDCG 2021-6) (pdf).
What documentation should be submitted?
Notification form
The form Clinical investigation – Substantial modification of clinical investigation under Medical Device Regulation must be filled out and signed.
Modified documents
The modified documents must be submitted in both a clean version and a track changes version.
Changes to investigator or investigational site
The sponsor must document that new investigators or new investigational sites are suitable to conduct the clinical investigation in accordance with the investigational plan (CIP).
- The competency of the investigator must be documented by his or her CV. This applies to the principal investigator at each site.
- The suitability of the investigational site must be documented by a statement from the person in charge of the investigational site.
How do I submit a notification of a substantial modification?
Until EUDAMED is available the notification must be submitted by email to kki@noma.no. The subject heading should include "Substantial modification of clinical investigation" and NOMAs case reference number. The email must include the CIV-ID and title of the investigation, and information on the sponsor and contact person.
On the same day an application must be submitted to the Norwegian Ethics Committees for Clinical Trials on Medicinal Products and Medical Devices (REK KULMU) using the REK portal. For more information, see REK KULMUs website.
When can the modification be implemented?
The sponsor may implement the notified modification no earlier than 38 days after the notification has been received by NOMA and REK KULMU, unless:
- NOMA has rejected the notification, or
- REK KULMU has issued a negative opinion
The processing time will be extended by an additional 7 days if there is a need to consult experts in the assessment of the notification. The sponsor will be notified if this is the case.