November 2025
Disclosure Roundup

The MHRA has clarified that Route B substantial modifications receive automatic approval only from the licensing authority within 14 calendar days of validation. The ethics committee does not provide automatic approval for Route B substantial modifications and follows the same review process as Route A substantial modifications, issuing a combined decision within 35 calendar days. These amendments come into force April 28, 2026.

The CTIS structured data form has been updated to expand editability for non-substantial modifications (non-SM). Previously non-editable fields can now be edited, with restrictions such as “addition/removal not allowed” or “existing sites only edited/deleted.” Updates affect Part I (Trial Details, Sponsor, Products) and Part II (Country Specific Details), with no changes to field content, structure, or requirements. Editable (AMSC) renamed Editable (AM).

The EMA published version 6.1 of the CTIS Sponsor Handbook with administrative clarifications. Section 1.2 updates the OMS organization registration process; change requests are now submitted via EMA Service Desk rather than directly through the OMS portal. Sections 4.3.1 and 4.8 provide expanded examples of substantial and non-substantial modifications, clarifying which protocol and dossier changes fall under each pathway.

The European Medicines Agency published updated CTIS transparency guidance (v2.1), Annex I, and quick guide (v1.9), clarifying publication requirements for historical trials. Non-Substantial Modifications (NSM) Part I submitted after Nov. 6, 2025 trigger publication of Part I documents (protocol, synopsis), requiring sponsors to ensure proper redaction. Substantial Modification Part I for a change of sponsor may require a prior NSM Part I submission if documents contain confidential information.

The ISRCTN has refreshed its website with enhancements to both the application form and the update your record form. Changes include structured primary outcome fields, mandatory data-sharing plans, and streamlined study date terminology. These updates make the registration process quicker and easier. Existing applications can be completed as usual. Sample form available at isrctn.com.

The Federal Institute for Drugs and Medical Devices (BfArM) has published operational guidance on common validation considerations for clinical trial applications and substantial modifications under EU Regulation 536/2014. The guidance covers frequent technical issues, including cover letter requirements, CTIS data entry protocols, document naming conventions per CTCG standards, ASMF procedures, and Investigator's Brochure currency requirements.

ClinicalTrials.gov has introduced XML file upload capability for the Protocol Section through a new "Upload Protocol Record (XML) (Modernized)" link in the Records menu, offering an alternative to manual data entry. The update also includes refined field-level validations for Baseline Characteristics, Outcome Measures, and Adverse Events in the Results Section to enhance data quality.

National Competent Authorities (NCAs) and Ethics Committees have announced a coordinated fast-track approach for evaluating multinational clinical trials in the EU/EEA. The new approach, known as FAST-EU (Facilitating and Accelerating Strategic Trials), introduces clear timelines and structured coordination to improve predictability in trial evaluations. The initiative is expected to start in January 2026.