Transparency requirements for publication of clinical data
In the times of changing legislation, the requirements for the provision of clinical data to Regulatory Authorities and their subsequent publication can be confusing. Ongoing trials may have been submitted under the Clinical Trial Directive 2001/20/EC (CTD) or the Clinical Trial Regulation (EU) No 536/2014 (CTR), which have differing authority submission obligations and differing requirements for providing public access to clinical data. This short article explains the requirements for regulatory submission of clinical documentation for trials submitted under the CTD and the CTR, as well as the requirements according to EMA Policy 70 that apply to products assessed under the EMA’s centralised procedure.
Clinical Trial Directive
For clinical trials that were submitted and approved under the EU CTD, certain Member States require the final clinical study report (CSR) to be submitted to the national competent authorities where the trial was undertaken at end of study. Generally, the submission must be made within 12 months of the end of a clinical trial, with the exception of paediatric trials which have a shortened timeframe. This is specified in the “CT-1” guideline ‘Communication from the Commission; Detailed guidance on the request to the competent authorities for authorisation of a clinical trial on a medicinal product for human use, the notification of substantial amendments and the declaration of the end of the trial’ available at this link.
The CSR submitted to any national competent authority is not publicly disclosed, however, the relevant results must be posted in EudraCT (following the same timelines) which will ultimately be disclosed to the public. The exception to this is Phase 1 adult trials that are not part of an agreed Paediatric Investigation Plan, where the results will never be publicly disclosed.
Clinical Trial Regulation
The CTR allows for transparency of clinical data from clinical trials conducted in the EU, whether the trials are associated with a Marketing Authorisation or not. A previous article has been published on the S-cubed website describing the revised transparency rules that are due to be introduced 2nd quarter of 2024 when the new Clinical Trials Information System (CTIS) public website is available (link). The article introduced CTIS, the EU wide submission portal and database, which acts as both a single entry-point for the submission of clinical trial data and as a clinical trial database providing the public access to the relevant data. For category 2 and 3 trials (integrated Phase 1 and 2, Phase 2 and 3) undertaken in the EU, the following documents will be published after first Member State approval of the clinical trial submitted within CTIS:
- Protocol, synopsis and patient facing documents
- SmPC, if available
- Subject information and informed consent form
- Recruitment arrangements
For category 1 trials (solely Phase 1) undertaken in the EU, the protocol, synopsis and patient facing documents are published 30 months after the end of adult trials in the EU/EEA or upon results submission for paediatric trials. The SmPC (if applicable), subject information, informed consent form and recruitment arrangements are never published for any category 1 trial.
Within one year from the end of a clinical trial in all EU Member States, the final summary of results and the lay person summary of results must be uploaded into CTIS for all EU trials. Within 30 days of Marketing Authorisation approval, or upon withdrawal of the Marketing Authorisation Application, the clinical study report must be uploaded into CTIS for all EU trials. These documents will be made publicly available as soon as submitted within CTIS, apart from the final and lay summary of results for adult category 1 trials where publication will be delayed until 30 months after the end of trial in the EU/EEA.
There is, therefore, a provision within the CTR for the submission and publication of the clinical study report and summary of results within CTIS (link) and applies to all investigational medicinal products regardless of whether they have a Marketing Authorisation.
EMA Policy 70
In addition to the transparency requirements associated with the CTD/CTR, the EMA have a policy for the publication of any clinical data generated from trials conducted worldwide and submitted to the EMA in support of a Marketing Authorisation Application, known as Policy 70. An article introducing the EMA Policy 70 has also been published on the S-cubed website (link), which describes the EMA policy to increase transparency through the publication of clinical data submitted under the centralised Marketing Authorisation procedure, whether positive, negative or withdrawn. The EMA will work with sponsors to obtain an appropriately redacted clinical data package, comprising the clinical study report with certain appendices, the clinical overview and the clinical summaries. The EMA will publish the clinical data package 60 days after the European Commission decision on a successful Marketing Authorisation or within 150 days after receipt of a withdrawal letter. The publication is made within the EMA clinical data website.
There is, therefore, a provision within EMA Policy 70 for the clinical study report, clinical overview and clinical summary to be published within the EMA clinical data publication portal (link) from worldwide trials that have been submitted as part of the centrally authorised procedure.
Summary
A helpful table comparing the EMA Policy 70 on the publication of clinical data with the CTR, in terms of their scope and information published, is provided with the EMA clinical data publication webpage (link). The requirements for protection of personal data and company confidential information (CCI) is common for both Policy 70 and the CTR and should be appropriately redacted within all clinical documentation that may be disclosed to the public.
Any questions?
If you have any questions about the on this topic or want to reach out regarding your own clinical programme, please don’t hesitate to get in touch. You can contact us via email (info@s-cubed.co.uk), or by telephone (S-cubed Ltd: +44 1235 772260).