INTRODUCTION
Following inspection by the Medicines and Healthcare products Regulatory Agency (MHRA) in August 2011, it was identified that the Standard Operating Procedures (SOPs) employed by the R&D Department for the governance of research across the Gloucestershire Consortium were no longer fit for purpose.
It was proposed that a more comprehensive system of SOPs was required to ensure that robust systems were in place to manage both the set-up and approval of research projects as well as their post approval management and monitoring. This was particularly important if the Consortium Trusts wished to continue sponsoring Clinical Trials of Investigational Medicinal Products (CTIMPs).
Since the Inspection Report, a series of draft SOPs have been produced and this paper summarised the main purpose of each SOP, as well as highlighting where further SOPs will be required.
All SOPs are currently in a draft form, pending agreement through the Consortium. Because of this, some of the SOPs have gaps, where references to other number SOPs are yet to be finalised. It is, however, hoped that the main body of the SOPs are clear and otherwise accurate in relation to the procedures and processes they describe.
Information about the Standard Operating Procedures
1. R&DSOP01 – Preparation, Review and Approval of Standard Operating Procedures for Research
Relatively self-explanatory, this SOP outlines the procedure for developing, maintaining and updating R&D SOPs. While anyone can suggest an SOP for development or updating, the responsibility for managing SOPs lies within the R&D Office to promote consistency. A template SOP is provided and the SOP includes a flow-chart of the development process.
County-wide SOPs will be signed-off at the R&D Consortium while the SOP provides guidance on the sign-off of Trust Specific SOPs if required.
2. R&DSOP02 – Research Related Adverse Event Reporting
This SOP sets out definitions of the various Adverse Events (AEs) and the procedures for reporting them. It includes information on defining Seriousness and Causality as well as identifying when AEs should be reporting to the Sponsor, Ethics and MHRA, depending on the type of AE. It also sets out the timeframes within which reporting should take place.
The SOP is based on guidance provided by the MHRA, included in the Medicines for Human Use (Clinical Trials) Regulations 2004 and in the EU Legislation, Eudralex, Volume 10. As such, it is part of UK law and cannot be changed.
See link to a process flow-chart
3. R&DSOP03- Delegation of Sponsor and Investigator Responsibilities in CTIMPs
This SOP sets out generic responsibilities for the relevant stakeholders on CTIMPs. It is based on the responsibilities set-out in the appendices of the NIHR Standard Clinical Trial Agreement templates. It can be adjusted to suit each trial. Although specifically set-up for CTIMPs it can also be adapted for non-CTIMPs as required.
4. R&DSOP04 – Setting up and running a CTIMP
This SOP provides an overview of the stages required to set-up and run a CTIMP. It can also be used for reference in non-CTIMPs as required or appropriate. As an overview, it refers to other SOPs that describe particular processes, such as Scientific Review, in more detail.
This SOP will require some further review to ensure that references and links to other relevant SOPs are accurate and up to date.
5. R&DSOP05 – Monitoring Research Studies
Outlines the monitoring process for all studies, largely mirroring the processes already in place but which were not written down.
6. R&DSOP06 – Hosting CTIMPs and Other Clinical Studies
This SOP should be read in conjunction with others, including SOP04 and provides guidance for what is required when one of the local trusts is acting as Host for an externally sponsored study. Requirements around ethical approval, MHRA, monitoring and recruitment are provided, with references to other SOPs as appropriate.
7. R&DSOP07 – Training
Sets out the requirements for training and where necessary training courses can be accessed. The main focus relates to the trust requirements around Good Clinical Practice training.
8. R&DSOP08 – Risk Assessment of Studies
SOP08 sets out guidance related to performing risk assessments of studies, whether locally developed and sponsored or externally sponsored. It utilises a combination of common sense and formal risk assessment tools provided by the NIHR to categorise every study as LOW, MEDIUM or HIGH Risk. This will inform the overall level and rigour of governance approach and approval required. It is expected to be read alongside R&DSOPs 11 and 13.
9. R&DSOP09 – Setting up an R&D Study File and Electronic Record
This is likely only to be relevant to the R&D team as it standardises the approach to setting up study files for governance review ensuring consistency. This will enable easier location of information for all members of the R&D team. There is also guidance on setting up electronic records on the R&D Shared Drive as the start of a move towards reducing the amount of paper printed for each study, recognising that a lot of the paperwork is rarely looked at beyond the initial review. There is also a move towards online storage of study documents via software such as CSP (Coordinated System for gaining NHS Permissions) which is used nationally for all NIHR Portfolio study approvals. The “paperless office” will be an ongoing project and this SOP is apt to change depending on how this works in practice.
10. R&DSOP10 – Scientific Review
The R&D Office already provides a Scientific Review (previously known as Peer Review) service for all locally sponsored studies and this process is formalised in the SOP. The Review is largely carried out via the R&D Office staff but, where there is variation by trust, this is identified in the SOP.
11. R&DSOP11 – Governance Approval Process
This SOP provides an overview of the whole governance process from conception of an idea, through Scientific Review and Ethics, to Trust Approval. The overview is provided in relation to a number of different study types to highlight differences in process between them, such as the differences between processing student projects and CTIMPs. It also provides guidance on the variation within these processes for specific trusts where appropriate. For example, slight differences will apply to 2gether studies that are taking place with Hereford.
The overall process is complex and depends on a large number of variables, so a catch-all process is impossible to identify. It is hoped that this overview provides enough guidance to point researchers in the right direction if they have questions about the process.
Flow-charts are also provided and it should be read in conjunction with SOPs 08 and 11 as well as other as relevant.
12. R&DSOP12 – Adding Studies to ReDA
This SOP provides guidance on the minimum dataset required for adding studies to the R&D Research Database (ReDA – Research Database Application). As such it will only be of relevance to R&D Administration Staff, but will hopefully ensure records are consistent and accurate.
13. R&DSOP13 – R&D Approval Review and Completing the Governance Checklist
The R&D review is part of the overall governance process outlined in R&DSOP11 and this SOP provides more information about how that is undertaken in relation to the Governance Checklist used with all studies.
14. R&DSOP14 – Governance Breaches
This outlines the process for identifying, recording and investigating governance breaches that may occur in relation to research. This is separate to Adverse Event reporting and could relate to incidents such as studies going ahead without approval, or activity going ahead above standard practice and which is not in the approved protocol.
15. R&DSOP15 – Processing Studies through NIHR CSP
This is another SOP that will be mostly relevant to the R&D Managers and relates to the governance checks that are undertaken during the Trust Approval review. It outlines the activity that needs to take place and imposes time frames on that activity to ensure approvals meet targets for approval set by the NIHR.
Other SOPs
There will be further SOPs coming shortly, these could include, but are not limited to:
- Issuing Trust Approval Letters
potentially introducing a “provisional” opinion for LOW Risk studies where some minor information is awaited by the R&D Manager.
To define who is able to sign what, in relation to trust approval letters, contracts, confidentiality agreements and ethics application, dependent on the Risk Classification of the study in question.
Procedures for archiving R&D Files for closed studies, as well as site files and CRFS for closed studies.
- Trial Management File set-up
To provide standardised guidance on the set-up of Trial Management Files where they are not provided by the study sponsor.
Guidance for local researchers when designing documents for own account/student research. This is may be more appropriate as a guide on the R&D Intranet site with hints and tips about the things to look out for, with links to the National Research Ethics Survey website which has more detailed guidance on Information Sheets and Consent Forms.
To provide guidance on what needs to be done locally before initiating a study. This is often organised by the study sponsor, so this SOP may be unnecessary.
- Contract Development and Negotiation
To ensure consistency of approach when contracts are required.
REVIEW
We would appreciate any comments you may have on these to enable a period of “consultation in use” where they can be refined and finalised to ensure they are fit for purpose.
Any further suggestions of SOPs that are required would also be welcomed.