Substantial modifications to the trial protocol must be reported to an ethical committee in the form of a supplementary protocol. Changes can only be implemented once the ethical committee has approved the supplementary protocol. The sponsor or the trial responsible must take necessary safety measures to protect the trial subjects.
What are Significant Protocol Modifications?
Substantial modifications include those that may affect the safety of trial subjects, interpretation of the scientific documentation the project is based on, execution, or management of the project.
For example, modifications may pertain to:
- Inclusion and exclusion criteria
- Trial design
- Number of trial subjects
- Trial procedures
- Trial medications
- Dosage changes
- Duration of treatment
- Efficacy parameters
- Modifications regarding the trial responsible or trial sites
- Content modificantions in the written information material for trial subjects, e.g., regarding side effects and risks
- Modifications in sponsor contracts (regarding finance, data access, or publication).
The committee system has compiled a list of the most common modifications in a research project and which changes are considered substantial and thus reportable. The list is not exhaustive, and the trial responsible always has the responsibility to report substantial modifications to the committee system. Read here. (link to form – list of changes in approved projects).
If new information emerges during the trial about effectiveness, risks, side effects, complications, or disadvantages of the trial, or if the trial's design is significantly modified, the trial subject must be informed about it, and renewed consent must be obtained (§ 16 in the regulation on information and consent, etc.).
Identity
A supplementary protocol must be consistent with the main protocol. If the modifications go beyond the substantial modifications that can be approved in an existing project according to the committee law, it is considered a new research project that must be reported independently. For example, if the purpose of the project is modified or there is a more extensive change in the trial's design.
Note on the difference between the main protocol and supplement (PDF)
If you are unsure whether the modification can be considered a supplementary protocol, you should contact the committee that approved the original protocol.
How Do You Report Protocol Modifications?
The reporting of substantial modifications must be made to the committee that approved the original research project (committee law § 27, paragraph 2).
The trial responsible and sponsor must jointly report the modifications electronically using a digital signature.
You apply electronically by filling out a reporting form at the following link: http://www.drvk.dk/anmeldelse.
In addition, you must submit the following material in separate PDF versions to the competent ethical committee:
- A filled-out and signed modification notification form
- The revised trial protocol with clearly marked changes/omissions to be approved (track changes), dated, and with version number (if many and substantial changes necessitate a new version of the protocol)
- Any new material developed in connection with the current modification
- Where modifications necessitate this, submit revised:
- Written participant information/s
- Procedure for providing oral participant information
- Consent declaration/s. If there is a need to obtain new consent from the trial subjects, this should be described
- Recruitment material
- Any questionnaires.
- New/revised documents should be dated and given version numbers, so they can be distinguished from previously approved versions.
The above should be sent to the competent ethical committee's email address, using a digital signature:
Find contact information for the regional ethical committees
Contact information for the national committee
Reporting a supplementary protocol/amendment for a medicinal trial can be done via the joint reporting portal DKMAnet (only for known users of DKMAnet). Further guidance on this can be found on The Danish Medicines Agency's website..
Case Handling of Supplementary Protocols
Supplementary reports are usually processed continuously in the committee system, so there are no deadlines for reporting supplementary protocols.