Documentation needed to review the CSR should be included in the CSR
appendices. It is not sufficient for such documents to be included only in
the TMF, which is not submitted in the marketing application.
Documents that provide critical information on a study, such as the
protocol (16.1.1), statistical methods (16.1.9), list of investigators and
study sites and sample case report forms, would always be needed by
reviewers assessing a study and should be included in the trial report
even if they are in a TMF. Certain documents may be required for the
CSR by individual countries or regions, in which case they should be
included. For example, according to ICH-GCP, an audit certificate
(16.1.8) should be provided when required by applicable law or
regulation. If there is any uncertainty about whether documents should
be included or not, the appropriate regulatory agency may be consulted.
Supportive documents, such as investigator CVs, ethics committee
approvals, informed consent forms, and batch numbers per subject are in
the TMF or clinical supply database and should generally not be included
in the CSR appendices.
Any documents not submitted and subsequently requested by the
regulatory authority would be expected to be provided promptly.