On August 31, 2021, MHRA launched new systems functionality to support the combined review of Clinical Trials of Investigational Medicinal Products (CTIMPs). The combined review service (previously known as ‘combined ways of working’) offers a single application submission route and a coordinated review for CTIMPs, resulting in a combined regulatory and ethics decision on a clinical trial.
The trial sponsors can now manage their complete trial lifecycle via combined review using the Integrated Research Application System (IRAS) – from initial application through to amendments, safety reporting, end of trial notification and submission of summary results. From January 01, 2022, the combined review will become the only way to apply for CTIMP approvals.
Formerly known as the Combined Ways of Working (CWoW), the new Combined Review Service, will be utilised to submit new Clinical Trials of Investigational Medicinal Products (CTIMPs) applications from January 01, 2022. It encompasses a “single submission, a coordinated review, and combined communications” process to facilitate all communications between the authority and all the CTIMP sponsors and applicants.
The system will allow the sponsor or applicant to submit a single application to both the MHRA and Research Ethics Committee (REC). The consequent MHRA authorization and REC opinion would thereby be delivered together in one step. This streamlined process will also apply to further requests sponsors or applicants make for any substantial amendments to the trial authorisation. The system will also allow viewing and revision of the application information directly in the system.
The facilitate the transition, NHS has released a step by step guide to using IRAS for combined review – Health Research Authority (hra.nhs.uk).
The Business Plan 2021/2022 released by the UK HRA focuses on 3 main objectives: High-quality research integrating the interests of participants, public involvement, and iterating the importance of transparency standards. Making services user-friendly and efficient to improvise research environments and lastly to strengthen the organization in terms of integrity and values.
The plan specifies the delivery of the next phase of the Make It Public transparency strategy in the form of definitive timelines. Provisions to facilitate registration of all clinical trials of medicinal products prospectively, and releasing a tool that would allow the public to see all approved research studies and their findings.
European Medicines Agency published a few documents related to the Clinical Trial Information System, on July 29, 2021.
The Clinical Trial Information System (CTIS) – Sponsor Handbook provides detailed information regarding the use of the new system including user management, documents submissions throughout the life-cycle of a clinical trial and directions for users during the 3-year transition period. Section 9 explains data transparency. The data and documents submitted to the CTIS for the trial will be made available to the public. Personal and commercial confidential information are exempted from publication. Thus, the system will accommodate for two versions of the trial documents, one ”for publication” (redacted) and one ”not for publication” (not redacted). Provisions for deferrals will be applicable for redacted documents.
Additionally, the below templates were also made available on the same day. All these templates provide an overview of the system covering screenshots of the different sections associated with each type of application:
CTIS Structured data form Instructions – initial application, additional MSC, substantial and non-substantial modifications: Provides guidance on the data fields sponsors will fill in CTIS when creating an initial application (IN), an additional member state concerned application (AMSC), a substantial modification (SM) and a non-substantial modification (non-SM). It also covers the document types involved in each form and the availability of publication and deferrals for these.
CTIS Structured data form Instructions – multi-trial substantial modification: Provides guidance on the data fields sponsors will fill in CTIS when creating a multi-trial substantial modification. This application differs from the above-mentioned ones in the way that i) it has all fields that are editable in the Form section ii) there is no MSCs section and iii) Part I and II are not editable; are pre-populated. It also covers document type, publication and deferral related details.
CTIS Structured data form – Notifications: Provides guidance on the data fields sponsors will fill in the ‘Notifications’ sections in CTIS. The different notifications include start, end and restart of both trial and recruitment, temporary halt, global end of trial, unexpected event, serious breach, urgent safety measure, inspection and updating results date.
The new Danish Act on research ethics treatment of clinical trials of medical devices, etc., introduces changes in the rules governing the marketing of medical devices in Denmark. The amendment will adapt to Danish legislation under Regulation 2017/745 on medical devices (MDR) and Regulation 2017/746 on medical devices for in vitro diagnostics (IVDR).
The manufacturers’ duty to report to the Danish Medicines Agency may apply for six months after the EU Commission has announced that the joint European database for medical devices (EUDAMED) is operational. Then the rules of the regulation on manufacturers’ duty to report incidents, reports on results of investigations of incidents and safety-related corrective measures will apply directly, so that manufacturers must report through EUDAMED to the competent authorities.