This chapter suggests that rigorous ethical review by RECs is a powerful preventative measure in tackling research misconduct. Researchers conducting any research in the NHS are required to submit their proposals to a REC for ethical approval before starting their project. A REC is in a unique position, being the most independent body regulating the ethical conduct of clinical research.30
to ensure that only reliable investigators are recruited. Companies should reject any potential investigator about whom there are doubts arising from past involvement in a research project.
LRECs should know of an investigator's involvement in concurrent trials.31 It has been suggested that local investigators could be registered as suitable after an initial screening test; thereafter suitability could be a matter of an administrative checklist. This, however, may not be the most appropriate way to deal with the moral aspects of suitability.
• The suitability of the site could be judged by a site visit to determine whether the facilities contain the necessary equipment and experienced support staff to conduct the research. Excellent "hotel" facilities, however, do not necessarily guarantee good research.
• The suitability of the project for local participants could be judged by consideration of the current disease patterns, particular social and cultural needs of the local population, and the need to protect patients with rare or "fashionable" conditions from unwarranted scientific curiosity.
Process of ethical review
RECs are required to review research projects for their ethical acceptability. In this process, members should be mindful that:
• they must protect patients and the public against harm from research and against useless studies, which are unethical;32
• they should encourage research that will in the long run improve health care and health32 and facilitate ethically acceptable attempts to identify new and better treatments from which all may potentially benefit.
The fundamental principles of ethics committee review are the same, whether the research in question is a large multicentre study or a smaller scale local investigation, the review should be effective and the process should be efficient. The Briefing Pack for Research Ethics Committee Members33 sets out structured approach to ethical analysis (Table 13.1).
Table 13.1 Assessment template.
What a research ethics committee looks for
Validity of the research
• How important is the research question?
• Can the research answer the question being asked?
Welfare of the research subject
• What will participating in the research involve?
• Are any risks necessary and acceptable?
Dignity of the research subject
• Will consent be sought?
• Will confidentiality be respected?
Box 13.1 Application form: details to be provided by the researcher
• Details of applicant
• Details of project
• Recruitment of subjects
• Details of interventions
• Risks and ethical problems
• Compensation and confidentiality
These principles are translated into practice in the standard application form, model patient information sheet, and consent form used by most research ethics committees (Box 13.1).
From the application form members will then be able to form a view on the points to consider as laid out in HSG(91)5.
Consideration of the protocol
A curriculum vitae is required from the principal applicant. Basic scientists are required to hold honorary NHS contracts in order to have access to patients or their data. Do the skills of the investigator match the subject of the study? Where supervision is appropriate, is it adequate? A figurehead expert could be too busy to provide personal supervision.
Supervision becomes particularly important where students, at whatever level, are carrying out research on NHS patients or their records. Excuses like, "It is only a little blood" or "Only a few questions" or "A quick look at notes", may disguise the fact that patients could simply be the means to serve the ends of the student. Much research undertaken by students on human participants ignores compliance with established conventions, such as the Declaration of Helsinki6 and other guidelines that are designed to protect those taking part in biomedical research.
Researchers should set out their method clearly in this section. Members will consider the importance of the research question, whether the study design can answer the question being asked, and whether the research is necessary. Research that duplicates other work unnecessarily or that is not of sufficient quality to contribute something useful to existing knowledge is in itself unethical.
RECs require scrupulous observance of scientific standards including, where appropriate, the use of sound, accepted statistical techniques to produce reliable and valid data. In a randomised controlled trial, does equipoise exist? Will comparisons be made against comparators and not placebo, as in line with the fifth version of the Declaration of Helsinki?6 In qualitative research will appropriate, validated tools be used?
Researchers must show that the selection of participants is fair and appropriate. Sometimes groups are excluded unfairly. Should women of child-bearing potential be involved? Should there be an upper age limit? Must many people with learning disabilities be excluded because of impaired ability to consent? What about the selection of children? About 40% of drugs used to treat children are not licensed for that purpose, because few drug companies are willing to undertake such trials. All sections of the community should be able to benefit from the results of research.
Participants should be recruited through a known intermediary. Direct approaches from a researcher would be a breach of confidentiality. Methods of direct recruitment are currently under scrutiny by RECs.
Will written consent be sought? Will consent be given freely? Will participants be offered the ability to take part or to refuse/withdraw? There are particular requirements when consent is being sought for the use of tissue or blood in genetic studies, where samples may be stored for a future, unspecified, research purpose. Guidelines from the MRC and Royal College of Pathologists are of relevance.34-38
As part of the consent process, would-be participants need full information, clearly expressed and without details that could mislead. Model patient information sheets are now available. Those for genetic studies must acknowledge the participant's right to know or their right not to know. There must be protection of patient data in line with the Data Protection Act 1998, with particular attention to systems for ensuring confidentiality of personal information and the security of these systems.39 Members will need to know that researchers understand the levels of security between coded and anonymised samples.
Genetic information has great potential in drug development. It is very important in research that involves genetic testing that participants understand the significance of the information generated, its power, predictiveness, and implications for the welfare of other family members. Members will want to know that consent is truly informed, and that issues about storage, confidentiality, privacy, and feedback of information to trial participants have been dealt with adequately.
Researchers must make clear the risk of possible side effects, whether they are known or unknown. Drug interactions and exclusion criteria have to be considered; a warning about the simultaneous taking of over-the-counter remedies may need to be given. Will there be physical discomfort from invasive techniques, such as repeated venepunctures or endoscopies? Could there be psychological distress from intrusive questionnaires? Will extra visits or travelling be acceptable?
Researchers need to show that they understand the ethical problems. Answers here will reveal how the health and welfare of those who take part will be affected, including their rights, safety and well-being. Are there any risks to taking part and, if so, are they necessary and/or acceptable? Might the use of databases for recruitment lead to the overresearching of a core group of patients with specific diseases? Participants should be told what alternatives exist and what will happen at the end of the trial, and whether trial medication or trial therapy will continue to be available.
The indemnity for the study must be appropriate, and evidence must be furnished. This should be in keeping with the Association of British Pharmaceutical Industry guidelines on no-fault compensation, NHS indemnity or university insurance cover for ethically approved studies. Participants who are NHS patients may receive reimbursement of expenses but not for taking part in studies. Any form of inducement is unacceptable.
Will confidentiality be respected? Most information about people drawn from interviews, medical records, scientific tests, and surveys is confidential. Members will want to know how researchers will collect, store, and process confidential information in line with recent guidelines.39 They need to know that researchers have ensured that their work is consistent with the law and that participants have agreed at the outset what information about them will be used.
The process of ethical review when there is no local researcher
This applies particularly to epidemiological and health services research. In November 2000, an operational modification of the MREC system was introduced to cover the situation where there is no need for a local researcher and hence no need for local scrutiny by an LREC.40 It will use the technical cooperation of the patient's local clinician without designating the clinician as a local researcher.
Hence researchers need to undergo close scrutiny in the process of ethical review.
Post-approval duties of RECs are limited to requiring the submission of an annual progress report, amendments, and reports of adverse events.11 Despite calls6'10 for RECs to follow up the studies that they approve, RECs in the UK do not have a role in monitoring studies as they proceed. The principal investigator, the research sponsor, and the care organisation, and not the research ethics committee, are responsible for ensuring that a study follows the agreed protocol and for monitoring its progress.3 Arrangements exist in Canada and Italy for such monitoring.
RECs in the UK are advisory bodies. They must maintain independence when formulating their advice on the ethics of the proposed research in order that their advice is seen to be impartial. They are managerially independent of NHS Trust R&D structures.3 They are not legal entities in themselves, are not financed to take on monitoring duties, and have no executive function.
Commercially sponsored studies are closely monitored by project managers and clinical research associates working to well-defined standard operating procedures. The MRC have set up trial steering committees to oversee the scientific acceptability and the overall conduct of their trials with an independent data monitoring and ethics committee to analyse the data.35 Other funding organisations are following the same model with a trial committee to monitor the trial progress and implement any recommendations made by the independent data monitoring committee. Such committees regularly review the unblinded data and primary outcome measures and can recommend the early termination of studies, if necessary.
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