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Review by a local medical research ethics committee of the conduct of approved research projects, by examination of patients' case notes, consent forms, and research records and by interview

BMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7094.1588 (Published 31 May 1997) Cite this as: BMJ 1997;314:1588
  1. Trevor Smith, scientific advisera,
  2. Edward J H Moore, medical advisera,
  3. Hugh Tunstall-Pedoe, committee memberb
  1. a Tayside Committee on Medical Research Ethics, East Day Home, King's Cross Hospital, Dundee DD3 8EA
  2. b Cardiovascular Epidemiology Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY
  1. Correspondence to: Dr Smith
  • Accepted 14 March 1997

Abstract

Objective: To monitor the conduct of medical research projects that have already been approved by the local medical research ethics committee.

Design: Follow up study of ethically approved studies (randomly selected from all the studies approved in the previous year) by examination of patients' case notes, consent forms, and research records and by interview of the researchers at their workplace.

Setting: Tayside, Scotland (mixed rural and urban population).

Subjects: 30 research projects approved by Tayside local medical research ethics committee.

Main outcome measures: Adherence to the agreed protocol, particularly for recruitment (obtaining and recording informed consent) and for specific requirements of the ethics committee, including notification of changes to the protocol and of adverse events.

Results: In one project only oral consent had been obtained, and in a quarter of the studies one or more consent forms were incorrectly completed. Inadequate filing of case notes in five studies and of consent forms in six made them unavailable for scrutiny. Adverse events were reported, but there was a general failure to report the abandoning or non-starting of projects; in two studies the investigators failed to notify a change in the responsible researcher.

Conclusions: Monitoring of medical research by local medical research ethics committees promotes and preserves ethical standards, protects subjects and researchers, discourages fraud, and has the support of investigators. We recommend that 10% of projects should undergo on-site review, with all others monitored by questionnaire. This would require about six person hours of time and a salary bill of c £120 per study monitored.

Key messages

  • Positive monitoring or audit of research projects by local medical research ethics committees is supported by medical researchers

  • Ten per cent of projects should undergo on-site review

  • All other projects should be monitored by questionnaire

  • Patients should also complete a questionnaire

Introduction

Medical research on patients or healthy volunteers in Britain is subject to appraisal by local medical research ethics committees, which may impose conditions on or changes to the proposed protocols. Follow up is not routine, so we do not know whether an approved protocol is the protocol that is subsequently used. We therefore conducted an on-site audit of how a random sample of approved research projects had been or were being conducted.

Subjects and methods

The Tayside local medical research ethics committee was formed in 1990 as a joint committee of the Tayside Health Board and the University of Dundee and consists of 12 members–six medically qualified members, a nurse, a lay chairman, and four lay members– supported by a secretariat. The committee meets monthly to discuss all submissions for Tayside–some 310 a year. The submissions are on detailed standard proposal forms, which contain guidance to researchers on the committee's requirements, including the need, after approval, to notify subsequent protocol amendments and adverse events.

We selected at random a stratified sample of 39 of the 311 projects approved one year previously, and in each case we asked the investigators for a review meeting at their workplace and to complete a questionnaire. At the meeting the assessors–one lay member and one medically qualified member–(a) discussed responses to the questionnaire; (b) completed a reviewers' questionnaire for recording further details of the visit; (c) inspected consent forms; and (d) inspected case records.

The assessors recorded details in a standard format, from which data were subsequently entered into the committee's database (Microsoft Access) to facilitate analysis of the results. They also wrote to the researchers summarising the main points raised at the meeting and advising them of any changes in procedures needed to meet the committee's requirements. Substantial problems or issues of interest were reported at the next committee meeting.

Results

Had the study begun?

Of the 39 studies initially selected for review, nine had not begun because they had not been funded; eight of these had been abandoned without the committee being notified. Of the 30 projects that had begun, 20 were independent projects initiated from universities, the government, or the NHS; eight were hospital based (five) or general practice based (three) studies sponsored by pharmaceutical companies; and two were from a contract research drug development unit.

Non-recruitment, refusal, and withdrawal

A common reason given for difficulties in recruitment was that doctors did not wish to recruit patients who were stabilised on current treatment, with the result that potential patient numbers were restricted. In six studies some recruited patients had withdrawn, either unilaterally or in discussion with the researcher. These were isolated events, affecting only 1% of recruited patients, and they did not seem to raise ethical concerns. In addition, doctors terminated other patients' participation through failure of symptoms to improve, excess pain from the underlying condition, and symptoms of Alzheimer's disease.

Complying with protocol

One department failed to inform the committee of a change in principal researcher and another that a group of patients had been placed in the care of a previously unidentified researcher. In three studies important protocol amendments had been made without being reported to the committee; two studies had been terminated prematurely without notification, one because of poor recruitment. In five other studies minor protocol amendments, not directly affecting patients, had not been notified.

Adverse events

Patients had experienced adverse events in nine studies. Although unpleasant, most of these events were not serious. Serious adverse events had been notified to the committee.

Availability of a study report

Researchers in the 20 independent projects were committed to publish, with three full papers and two abstracts published in professional journals, two local reports, and four papers in preparation.

Informed consent

In 29 studies patients gave informed consent. In the remaining study, which involved patients with Alzheimer's disease, consent was obtained from relatives. In one, non-invasive study, the researcher approached patients for oral consent while they were in labour.

Availability and completeness of consent forms and case records

Figure 1) shows the availability and completeness of consent forms and case records. In six studies consent forms, although completed, were not available for scrutiny when needed. In 13 other studies one or more consent forms were initially missing. In one study doctors had thought that consent was not necessary for non-invasive research, in another a collaborating researcher thought that oral consent was enough, and in a third the researcher's supervisor had been a healthy volunteer without following the recruitment requirements.

Fig 1
Fig 1

Availability and accuracy of completion of consent forms and case records (values are numbers of studies)

In one third of studies one or more consent forms had been completed incorrectly. Although patients had signed all of the forms, they had either not answered individual questions or had ticked a box indicating that they had not received enough information, not had an opportunity to ask questions, etc. In five studies the doctor had not countersigned all of the forms.

In nearly half of the studies a proportion of research case records were not available for inspection because they were filed with the patient's hospital case notes in use elsewhere (fig 1). Some hospital case notes were bulky, and researchers and reviewers had considerable difficulty in finding relevant consent forms and records. On an additional five occasions no case records were available. In two studies sponsored by drug companies the legibility of copies of records retained by the researcher was poor. The errors in completion detected in several studies were all minor and did not affect their validity.

Discussion

Concern for research subjects

We were reassured that, in recruiting participants, investigators were placing the interests of patients before those of their projects and were willing to withdraw patients from studies when it was against their interests to continue. Most projects attracted sufficient participants and yielded potentially valuable information. Investigators were strongly committed to publishing their results.

Notifying changes and adverse events

Investigators did not sufficiently recognise the need for protocol amendments to be approved either by the full local medical research ethics committee meeting if important or by the chairman's action if minor. (Investigators have approval to implement only what a local medical research ethics committee originally endorses.) There was no evidence of failure to report serious adverse events: in such cases investigators and sponsors are anxious to share responsibility for allowing the study to continue.

Availability of case records and valid consent forms

Examination of case records provides a means of assessing the thoroughness with which data relevant to the scientific validity of the study and the patients' welfare are being recorded. There was a clear need for improving access to research case records.

Care needs to be given to the timing of the consent process. Researchers and coworkers must always obtain informed consent from patients, even in non-invasive studies and even when the subject is a research collaborator, such as a supervisor. Researchers must scrutinise consent forms to ensure that participants have completed them correctly and are satisfied with the information provided before they countersign them and start the study. We found no instances of researchers failing to obtain written consent from patients in studies involving identifiable risk or discomfort.

Educational value of ethical review

Researchers have recently strongly criticised local medical research ethics committees on various grounds,1 2 3 4 summarised in a recent editorial5 to which one of us replied with points in their favour.6 Uncertainty has been expressed by the professional bodies about the need for review after ethical approval has been given.7 8 9 The 30 principal researchers whom we approached were, however, supportive of the work of the committee and of the need for such review.

Constructive feedback to the specific researchers was an essential part of the exercise. The discussions were of educational value through the reviewers to the committee, contributing then to advice given to researchers with the proposal forms and in the annual reports. Awareness of the possibility of review after ethical approval provides an added incentive not to cut corners and to maintain standards, thereby helping to protect research participants from potential harm and investigators from criticism, as well as providing a disincentive to potential fraud.

The Tayside local medical research ethics committee intends to seek the views of patients and healthy volunteers on their experiences during and after participation in research projects. Several researchers expressed the need for this.

Cost of ethical review

A review visit involves about six person hours of work for the assessors and was estimated as costing some £120, based on the time of a medical consultant and a lay scientific adviser. In addition, an hour or more of the researcher's time for the visit and preparation time must be taken into account.

Conclusion

Public confidence in medical research and the willingness to cooperate will continue only if the research is seen to be conducted to the highest ethical standards. The existence of an effective system for the ethical review of research shows that efforts are being made to maintain these high standards. That there is room for improvement in Tayside, which has high standards of patient care and staff training, leads us to recommend that all local medical research ethics committees should randomly select a minimum of 10% of approved projects for subsequent on-site review by members of the committee; that all remaining projects should be reviewed by questionnaire; and that patients should also be asked to complete a questionnaire.

Acknowledgments

We gratefully acknowledge the willing help given by the researchers who participated in this study. We also thank Mr H D Sheldon (chairman), Mr M Finlayson (secretary), and other members of the Tayside committee on medical research ethics for their support and encouragement; and Tayside Health Board, the University of Dundee, and Dundee Teaching Hospitals NHS Trust for providing the facilities that made the study possible.

Funding: None.

Conflict of interest: None.

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