Substantial modifications to an approved clinical trial must be approved by the ethics committee before being implemented. Exempt from this requirement are measures which have to be taken immediately in order to protect the participants.
The investigator shall submit to the ethics committee any application documents specified in Annex 3 which are affected by the modification. At the same time, the investigator shall provide information on the reasons for the modification.
The following are considered to be substantial modifications:
modifications affecting the participants’ safety and health, or their rights and obligations;
modifications to the protocol, and in particular modifications based on new scientific knowledge which concern the trial design, the method of investigation, the endpoints or the form of statistical analysis;
a change of trial site, or conducting the clinical trial at an additional site;
a change of sponsor, coordinating investigator or investigator responsible at a trial site; or
the extension of a deadline in accordance with Articles 23, 23a and 50; in the application to the ethics committee, the investigator shall indicate whether the application documents are still up-to-date, particularly with regard to the scientific relevance of the question; if this is not the case, the investigator shall submit updated application documents.
The ethics committee shall reach a decision on substantial modifications within 30 days. Article 26 applies mutatis mutandis.
If a site at which a clinical trial is to be additionally conducted does not lie within the responsibility of the ethics committee which granted approval, the procedure is governed by Article 27mutatis mutandis.
Other modifications must be notified to the ethics committee in the annual safety report specified in Article 43.