After the commencement of the clinical trial in Norway, the sponsor may make amendments to the protocol. If the amendments are considered substantial and are likely to have an impact on the safety of the trial subjects, change the interpretation of the scientific documents in support of the conduct of the trial or considered otherwise significant, the sponsor shall apply to Norwegian Medicines Agency (NoMA) for permission before the changes are implemented.
Non-substantial amendments on the other hand, do not require notification by the sponsor nor approval from NoMA. However, it is important to note that non-substantial amendments should be recorded and contained in the documentation when it is submitted, i.e. as part of a subsequent submission of a substantial amendment. NoMA accepts however, that from time to time there may be a need to inform us of certain changes that are non-substantial.
What is a Substantial Amendment?
It is the sponsor's responsibility to assess whether an amendment to a clinical trial is substantial. In order to provide some guidance in this matter, NoMA has compiled an overview of the various types of amendments that can be made to a clinical trial, and whether they can be viewed as substantial or non-substantial. Please see Overview of Amendments to a Clinical Trial.
What should be included in a substantial amendment application?
An application for a substantial amendment should contain:
- A cover letter (signed and dated), that includes the following information: EudraCT number, NoMA reference number, the study's Protocol code (version and date of last approved version), summary of changes, an overview/list of documents/files attached to the application, as well as any relevant information pertaining to the submission.
- A copy of the “Substantial Amendment Notification Form" (Annex II), signed and dated. You can find a copy of the Word template for this form on the European Commission's website EudraLex - Volume 10 - Clinical Trials Guidelines, Chapter 1. The form can be filled out in Word and will neeed to be converted to .pdf prior to submission.
- A copy of the revised document(s), including a description of changes:
- All changes in the revised document(s) must be clearly marked (e.g. with use of track changes/redline). A "clean" version of the revised document(s) must also be submitted.
- If the revised document(s) have many changes throughout the document, they should be summarised (old vs. new text) and explained. This summary can be included as a table or as free text under section F in the Substantial Amendment Notification Form, and/or a part of the introduction of the amended document, clearly titled «Summary of Changes».
- If the amendment entails changes to the originally submitted EudraCT application form, an updated EudraCT application form must be submitted, in both XML and PDF format.
- If applicable, supplementary information/documents can also be included in the submission (e.g. an updated risk/benefit assessment).
- If the substantial amendment is applicable to several clinical trials, the EudraCT numbers, NoMA reference numbers as well as the study titles and protocol codes (version and date of last approved version) must be included for all trials concerned, in both the cover letter and the application form. If the amendment entails changes to the originally submitted EudraCT application forms, updated forms must be submitted in both XML and PDF format for all clinical trials included in the submission.
Submission and Processing times
- An application for a substantial amendment to a clinical trial must be sent to firstname.lastname@example.org. Please ensure that the EudraCT number and NoMA reference number are clearly marked in the subject heading.
- The applicant will not receive confirmation of a valid application. However NoMA will notify the applicant if the application is not valid.
- Day 0 is the day after the substantial amendment has been submitted to the NoMA.
- Processing times for substantial amendment applications is 35 days. If the Regional Ethics Committee has approved the application, and the Norwegian Medicines Agency does not oppose the amendment within 35 days of receiving a valid application, the sponsor may implement the changes (according to the Norwegian Regulation for Clinical Trials of 30-10-2009, § 5-1). The substantial amendment is considered approved if the NoMA has not responded within 35 days. Please note that a confirmation of silent approval will not be sent to the applicant.
- Replies will be sent by e-mail to the email address given in the application form (Substantial Amendment Notification Form section D1). If the applicant would like contact person(s) other than those stated in the application form to receive a copy of the response, this must be clearly stated in the cover letter.
- Responses will be given in the same language (Norwegian or English) used in the submission cover letter.
- For substantial amendments that have received a positive opinion in VHP, the processing time for applications is 7 days. If the applicant has not received a reply after 7 days, the substantial amendment can be considered approved by the Norwegian Medicines Agency. Please note that a confirmation of silent approval will not be sent to the applicant.
The cost of an application for a substantial amendment is 5,160 NOK.
There are no fees for non-commercial clinical trials. Non-commercial clinical trials are defined as a trial conducted wholly or predominantly without influence from the pharmaceutical industry (on it design, start-up and implementation, as well as registration and publication of data).
An invoice will be sent to applicant once the application has been processed, and a written reply given. The invoice will include the EudraCT number as well as a NoMA reference number, and will be sent to the person/company specified in Section D1 of the Substantial Amendment Notification Form (unless stated otherwise in the cover letter).
Invoices will only be sent for substantial amendment applications where a written response was given.