SUPPLEMENTARY OPERATIONAL GUIDELINES FOR NHS RESEARCH ETHICS COMMITTEES - November 2000

1. Introduction

1. Many research projects undertaken in the NHS take place across numerous sites, sometimes clustered together, but often spread widely throughout the country. It is a requirement that all such multi-centre research has a named "principal investigator", who has the prime ethical responsibility for the project and its implementation throughout the UK. This is the individual who applies to a Research Ethics Committee (REC) for ethical approval of the protocol, which includes the patient information sheet and the proposed arrangements for taking consent.
2. 2. For much multi-centre research, especially where a modification of the standard patient treatment is involved (e.g.therapeutic research, clinical trials), there is a clear role for a "local researcher" at each research site. This person takes local responsibility for the research project, and there is thus a need for local scrutiny of the suitability of this individual and the local research facilities..
3. 3. This is in direct contrast to some types of non-therapeutic research, where there is no need for a local individual to be formally part of the research team. In some of these cases there is no need for any direct contact with the patient or research subject. In others, further patient contact needs to be made only by the principal investigator or members of the specialist research team, once patient consent is obtained. This is particularly, but not exclusively, the case for much epidemiological and health services research. [Conversely some projects in these disciplines still retain a distinct need for a named local researcher, just as in the case of therapeutic research, and therefore each project needs to be considered individually].
4. 4. In many instances, although there is a need for further patient contact, this can be carried out very efficiently and safely, and much more conveniently for the patient, simply by using the technical co-operation of the patient's local clinician(s) without designating them as "local researchers".

2. Background

1. Experience by local and multi-centre research ethics committees (LRECs and MRECs) in reviewing research proposals has exposed the need for a more efficient way of undertaking the ethical review of projects where there is no need for someone to be designated as a local researcher. Many LRECs themselves have questioned the need for a local REC opinion in these cases, as long as sufficient safeguards are confirmed to be in place during the ethical review of the protocol by another REC in the NHS.
2. 2. A working party was established to look at the complex issues and possible solutions. It was chaired by Dr Hugh Davies, Chairman of London MREC. The membership is shown in Annex A. A report from the Davies group was circulated to all LRECs and MRECs in the UK. From the report and the many helpful comments received, an operating system for ethical review of multi-centre research where there is no local researcher has now been formulated.
3. 3. It is an operational modification to the existing system of ethical review described in HSG(91)5 for England and 1992(GEN)3 for Scotland, which established Local Research Ethics Committees throughout the NHS, and in HSG(97)23 in England and MEL(1997)8 for Scotland, by which the MREC system was established.

3. Categories of research where there is no local researcher

These are considered under 5 headings

• Data the use of which use does not require ethical review by RECs
• Use of data regarded as being in the public domain
• Establishment of a new disease or patient database for research purposes, and the use of such a database with no patient contact
• The use of such a database, with subsequent patient contact
• The use of an existing database, collected for previous research or other purposes.

1. It is currently well accepted that collection and analysis of some data does not require review by a NHS Research Ethics Committee. Examples would be the Adverse Drug Reaction reporting Scheme of the Committee on Safety of Medicines, Prescription Event Monitoring, National Morbidity Surveys and Post Market Surveillance of new medications.

B. Use of data regarded as being in the public domain

1. Principle 7 of the Council for International Organisation of Medical Sciences (part of WHO) states that "investigators do not need to obtain informed consent to use publicly available information for epidemiological studies".
2. Use of many databases in the public domain (eg death certificates, ONS data) will usually fall outside the remit of MRECs/LRECs. Nevertheless, potential researchers should contact the guardians of any such databases to find out if ethical review is required, and if so whether an internal ethics committee is available. If not, an MREC will offer an ethical opinion on request.

C. Establishment of a new Disease or Patient Database for Research Purposes, and the use of such a database with no patient contact

1. An example would be the attempt to ascertain the prevalence of a rare disease or medical complication. In order to collect the information, the principal investigator might wish to contact local NHS health care professionals through the appropriate professional networks.

2.The principal investigator should apply to the appropriate MREC for ethical approval. The MREC will consider, among other things

• whether consent is required
• the method used for collecting the information
• the nature of the information
• how it is to be stored
• its intended use
• who will have access to it
  

3. Ethical approval by an MREC will cover the entire UK and there is no requirement subsequently to apply to LRECs.

4. It remains the responsibility of the principal investigator to ensure that in undertaking the collection, storage or use of the data, he is not contravening the legal or regulatory requirements of any part of the UK in which the data is collected, stored or used.

D. The use of such a database, but with subsequent patient contact.

1. An example might be a request to collect further data, or a sample of blood to be analysed at the principal investigator's laboratory for research purposes. The principal investigator should apply to the same MREC that approved the establishment of the database.

2. The MREC will review the ethical aspects of the research proposal, which include among other things

• issues relating to the establishment of the existing database · the scientific quality and relevance of the proposal
• the reasons for, and nature of, the patient contact
• the methods of seeking and of obtaining consent
• the information to be made available to the research subject
• the nature of any procedures to be undertaken
• scrutiny of those who will undertake local tasks (the principal researcher and his team, and the type and grade of local clinician)
• issues concerning indemnity

1. The local clinician will provide the samples/data to the researchers but will play no other part in the research.

2. This limited technical involvement of the local clinician does not now require the opinion of the LREC. The LREC should be informed of the project, and the name and contact details of the local clinician involved. If (unusually) the LREC has any reason to doubt that the local clinician is competent to carry out the tasks required, it should inform both the clinician and the MREC that gave ethical approval.

3. The local clinician must inform his NHS organisation of his co-operation in the research project and the nature of his involvement, just as he would if he were a local researcher. He should ensure with the NHS organisation that local indemnity arrangements are adequate.

4. It remains the responsibility of the principal investigator to ensure that in subsequently undertaking the collection, storage or use of the data or research sample, he is not contravening the legal or regulatory requirements of any part of the UK in which the research material is collected, stored or used. v. If the research requires a change in therapy, more substantial data collection or monitoring, or the need for the local clinician to perform tasks possibly outside his routine competence, then he should be regarded as a "local researcher" and not a "technical co-operator". The reviewing MREC will regard the research as being outside this revised system of review, and the local researcher would require appropriate scrutiny - currently by the LREC - as in the current standard system for ethical review of multi-centre research.

E. The use of an existing database, collected for previous research or other purposes.

1. The researcher should apply to an MREC. Where the database was established for research purposes, application should be made to the MREC that previously approved its establishment.

2. The MREC will wish to review the ethical issues of researcher access to the existing database for new purposes.

3. It remains the responsibility of the principal investigator to ensure that in gaining access to or subsequently using the data, he is not contravening the legal or regulatory requirements of any part of the UK in which the data is collected, stored or used. He should do this in full and active collaboration with the guardian of the database.

4. Subsequent use of the database is governed by the same principles laid out above in Section D.

4. Communications

1. Standard forms of communication must continue to be used, with correct version numbers and dates.

2. Standard format letters will be available for principal researchers and local clinicians to inform the necessary branches of the NHS (LRECs and NHS management). The MREC administrator will provide these.

5. Guidance notes for researchers.

1. A researcher who thinks that his research proposal falls into any of the categories that now allow exemption from application to an LREC after MREC approval should state this in the covering letter that accompanies his application to the MREC.

2. The MREC administrator and Chairman, or the staff of the Central Office for Research Ethics Committees (COREC), may be able to advise potential applicants in advance whether or not this is likely to be the case, but the final decision rests with the MREC.

3. The application to the MREC should be on the standard MREC form. Occasionally the MREC may require supplementary information prior to its consideration of your application.

4. Having studied your application, the MREC will make the decision about the need for subsequent scrutiny by LRECs. The MREC administrator will then provide you with the necessary standard paperwork, and further guidance about what to do next.

5. Researchers should consult and be guided by the MRC Guidelines on Personal Information in Medical Research, which can be found on the MRC web-site: http://www.mrc.ac.uk

Annex A Membership of the Working Group