6. Approvals for Clinical Research

The first step in the approvals process involves defining if your research question is research, or whether you will be conducting a service evaluation or audit. The HRA have a table and decision tool to help decide which category your project fits into and the rules/regulations for each vary on the type of project. As a broad outline, randomisation and generalisability of results are the defining parameters.

http://www.hra-decisiontools.org.uk/research.

The below table is useful to help decide which category your project fits into.

If the project is research, it will need approvals and the many pages of paperwork begins! This article will briefly outline what is needed and when greater advice should be sought from your trusts Research and Development/Innovation department on what is applicable to your project. We will not cover what is needed or how to obtain approvals for service evaluation or audits as these are trust specific.

Study Documents:

Firstly, engage with the research nursing or research delivery team in your trust. They will help to guide you through the approvals process and provide templates for study documents. Or find a doctor, nurse or physiotherapist from your department who has recently done a research project, as you may be able to use their forms. Study documents include- but are not limited to- the protocol, patient information sheet, consent form and case report form (results sheet). There are others, but your R&D team will confirm which ones you need depending on your study type.

Schedule of Events (SoECAT)

This is an excel sheet downloaded through IRAS (Integrated Research Application System). Ask for help from your trust R&D department help to fill this out. The form is concerned with attributing costs to your research, such as the time of the R&D staff, the room used, and the equipment. It is submitted to the clinical research network (CRN) where an AoRCD specialist will amend, sign off and approve it. Many grant funders also request this to assist in calculating costs/budgets. Approval comes in the form of an email with the then locked Excel sheet and the specialist approvers details.

Organisational Information Document

This details if the study is commercial or non-commercial and often includes the delegation log, which notes those insured to work on the research study. Check if the sponsor has their own delegation log format they prefer. The OID essentially acts as a contract between sponsor and investigation site and details what staff and equipment are needed. There are standard templates that are downloaded from IRAS. You just must amend them to suit the circumstances in which you will complete your project.

Intellectual Property

As a side note, it is useful to be aware of the different types of intellectual property concerning research. Background knowledge is knowledge that you already have. Foreground knowledge is knowledge that is produced during the project. Side-ground knowledge is produced outside the project during the project’s tenure. Post-ground knowledge is produced after the project’s tenure. Your trust with have an IP specialist who will help you define an IP strategy to protect the IP. Get them involved early as this may influence your dissemination plan which needs to be included in your protocol and IRAS forms.

University or NHS Sponsorship Approval

Every research study needs a sponsor. This could be your NHS trust, a university or even a commercial organisation. In essence the sponsor ensures the study protocol and gives the green light to start recruitment. They also approve all the study documents for submission to the Research Ethics Committee (REC) and HRA and/or MHRA.

You must:

• Submit all the study documents to the respective departments
• Seek approval from Sponsor, who provides the insurance and governance to conduct the research.
• Electronically submit sponsor details on IRAS.
• Send to IRAS for signature to the sponsor.
• Submit IRAS to M/HRA and phone HRA hotline to book in for REC.

REC and HRA approval forms

(Found on IRAS: https://www.myresearchproject.org.uk/)

To get REC and HRA approval you must complete a series of questions on IRAS about your study. This is reviewed by HRA for compliance with national policy and by REC for your projects ethical responsibility. Assessment by REC may be proportionate. A safe/low risk project may be assessed by a subcommittee, which is much faster, whereas a higher risk project needs a full committee review. Certain committees can approve radiation or studies involving prisoners. If you live in a devolved nation other than Wales, the process may be slightly different and your local R&D department will be able to advise you. HRA and REC approval comes in the form of letters, with approval that can be conditional or unconditional. The study documents may need amendments before unconditional approval is given. The approval must be stored in the site file.

MHRA Approval

If the study is carried out on a device or drug that does not have a CE mark or a UKCA mark it will be a clinical trial of an investigational medical product (CTIMP) [drugs and devices]. This is because the medication/device is being used out of its’ regulatory label. Applying for CTIMP approval is a long and expensive process with the MHRA, with changes usually needed to the documents. This should be planned into the time frame, as it usually takes 30-days for the MHRA to start processing the application but due to backlogs, this can be months. There is now a combined approvals process (HRA, REC and MHRA) for CTIMPS, as can be seen in the diagram.

Portfolio Adoption Form (no longer required in England)

This form is submitted using some of the IRAS questions to the Clinical Research Network (CRN) [note: the name is changing soon] automatically. The CRN is an NIHR (National Institute for Health and Care Research) organisation which supports research within NHS trusts and can provide research nurses to help. The CRN also employs the AoRCD specialists that help with the SoECAT mentioned above. A point of reference is the CRN will only support non-commercial research being carried out in England. For Scotland contact NHS Research Scotland (enquiries@nrs.org.uk), for Wales contact Health and Care Research Wales (portfolio@wales.nhs.uk) and for NI contact Northern Ireland Clinical Research Network (NICRN) (NICRNPortfolio@nicrn.hscni.net).

Additional forms:

Human Tissue Authority Approval

This is held by most organisations that carry out research using human tissue. There will be an approved person who is legally licensed.

Tissue Transfer Agreement

If you wish to transfer tissue between two different sites (such as a university and a hospital) you will need a Tissue Transfer Agreement. The agreement also outlines the terms and responsible persons for the storage of human tissue securely. Before disposing of tissue consider submitting it to a BIOBANK- destroying tissue is a waste if it can be used for future research!

NHS England and Improvement

Screening programmes such as the National AAA Screening Programme (NAAASP) are commissioned, governed, and regulated by NHSE&I. Each national screening programme has their own Research Advisory Committee. To recruit NAAASP patients, approval must be obtained from them.

What next:

Once you have HRA (and MHRA if applicable), REC and CRN approval, a copy must be saved in the site file.

You then need to ask your NHS trust for capacity and capability (C&C) approval, who check all approvals are in place. C&C approval usually comes in the form of an email. This should be saved in the site file and a copy sent to the Sponsor (if not the trust). In turn, the sponsor will issue a green light email for the study to begin. Again, these need saving to the site file. You can now start recruiting, and must submit annual updates to the Sponsor, REC and M/HRA. These and any amendments to the study must also be saved to the site file (i.e. changing patient cohort recruited).

Summary

Use the NHS, NIHR, M/HRA structure/websites and IRAS tools [the IRAS help feature is particularly useful]. Take advice from any experts you can find. For more complex studies, the approvals process can take over 6 months, so get it right first time! Please direct your questions to the SVT research committee at research@svt.org.uk But your R&D team are experts!

Written by: Siobhan Trochowski, Clinical Vascular Scientist Oxford University Hospitals NHS FT

Edited by: Dr Steven Rogers, Scientific Director, Manchester Academic Vascular Research & Innovation Centre (MAVRIC), Manchester University NHS FT and The University of Manchester. 24/10/2023