This page contains information for those involved in the submission of applications for Clinical Trials of Investigational Medicinal Products (CTIMPs).
The combined review service, formerly called Combined Ways of Working (CWoW), provides CTIMP applicants and sponsors with a single application route and co-ordinated review leading to a single UK decision.
As of 1 January 2022, combined review is the way all new CTIMP applications must be made. If you are a first-time user, please contact us at firstname.lastname@example.org for help to get started.
For all CTIMP applicants and sponsors, there are important differences in the service to understand and actions you can take to prepare for the changes. These are explained below, along with specific information for combined review applications involving ionising radiation and/or a medical device. Please explore our contents section and find out more.
Please note: CTIMP applications via combined review must be submitted using a new part of the Integrated Research Application System (IRAS).
The benefits of using combined review
Combined review offers a single application submission and co-ordinated review leading to a single UK decision for Clinical Trials of Investigational Medicinal Products (CTIMPs). It was developed by the HRA and the Medicines and Healthcare products Regulatory Agency (MHRA), working closely with the National Institute for Health Research (NIHR), Clinical Research Networks and the devolved administrations.
Benefits for CTIMP sponsors, Contract Research Organisations (CROs) and investigators include:
- a single application for Clinical Trial Authorisation and Research Ethics Committee (REC) opinion
- a co-ordinated review process that ensures REC and MHRA outcomes are consistent and aligned
- a streamlined and efficient application process – a single submission; a co-ordinated review; combined communications to request further information; and a single communication to confirm the final decision - some users report a 30 per cent improvement in overall trial set up times
- a single unified request for changes or clarifications from the MHRA and the REC
- REC opinion and MHRA authorisation delivered together
- the same streamlined application and review process for subsequent substantial amendments to the trial authorisation
- improved access to the NIHR Clinical Research Network (CRN)’s Study Support Service for researchers, with the opportunity to apply for support earlier and receive an eligibility decision sooner through the CRN’s new Non-commercial Portfolio Application service
What should sponsors and CROs be doing to prepare?
Combined review must now be used for all new CTIMP and combined IMP/device trials. Sponsors and investigators are advised to familiarise themselves with the process. As applications are completed and submitted in a new part of IRAS, the following preparations are needed:
- register for an account in the new part of IRAS
- sponsor organisations are selected from existing options in IRAS. If your organisation does not appear on the list, send the full name of the organisation and the sponsor contact e-mail address to email@example.com so the details can be added to the system
- ensure you are aware of the key guidance documents - links below
- contact us for support with your first combined review application at firstname.lastname@example.org
We recommend you complete the first three steps now. This will help avoid any delays and ensure you are ready to begin an application. You should also consider any impacts on your internal processes and procedures.
What’s different about the new system?
Submissions via combined review have some key differences. They are:
- You must submit to the REC and the MHRA together; there is no provision to make separate submissions via this process. This may require organisations to work differently.
- Individuals can view and revise the application information in the system instead of generating a PDF of an in-progress application. You may need to think about how things like QC processes can be undertaken within the system instead of generating a PDF. You can give collaborators view-only or read-write access to the system for this.
- Messages from the system, for example Requests for Further Information (RFIs) or a final outcome issued, only go to a specific set of contacts. Therefore if organisations have different teams working on different parts of the application, you must have effective internal communication mechanisms in place.
- You will receive a consolidated initial outcome. If there is anything that needs to be addressed for the trial to be approved, you should respond within 14 days. If you need more time to respond to an RFI, you can formally request an extension. Email email@example.com and let us know how much time beyond the usual 14 days is needed. Applicants receive a final decision on their application within 10 days of receipt of a response to an RFI.
CTIMP studies involving ionising radiation
We are currently developing a new module that will support combined review applicants whose research involves ionising radiation, so in future these studies can be managed end to end in the new system.
For now, if your trial proposes ionising radiation exposures you should continue to use standard IRAS to complete the following elements of your application:
- Medical Physics Expert (MPE) and Clinical Radiation Expert (CRE) review – Part B section 3 in the IRAS form, for all studies involving exposure to ionising radiation
- ARSAC Preliminary Research Assessment (PRA) form, for studies involving exposure to radioactive materials.
The IRAS Form should then be uploaded as a PDF supporting document in new IRAS.
For full instructions on how to make your submission, please see our IRAS Help. We also have a dedicated webinar for CTIMPs that involve radiation. You can access this via the link in our Webinars section below.
There is no change in the process to submit an application to ARSAC.
Combined trials of an investigational medicinal product and an investigational medical device (IMP/Device trials)
On 1 January 2022, combined review also became the way all new combined IMP/Device trial applications are made. If you are planning a new IMP/Device application, visit our IRAS Help for instructions on how to make your submission.
Key guidance and documents
To get started, please read the guidance below. If you have any questions, please contact us at firstname.lastname@example.org
Webinars for CTIMP applicants, sponsors and NHS/HSC organisations
To help you with the transition to combined review, we are running more of our free, live webinars during January. They are designed for different user groups involved in CTIMPs and provide an overview of the changes and how they may impact you, depending on your role.
You can reserve your place using our online booking system. This is where you will also find our combined review webinar recordings. You will need to register for an account on the Learning Management System.