Ethical issues and participant consent

This section contains the following:


The process of obtaining informed consent to take part in a trial including a choice not to take part requires steps to be taken to protect an individual’s right to make choices.  These steps include:

Researchers must also attend to the quality of a patient’s understanding as part of this process.  This includes an understanding of:

In obtaining informed consent, the investigator is required to comply with the applicable regulatory requirements, and should adhere to International Conference on Harmonization Guideline for Good Clinical Practice (ICH GCP - on the web) and the ethical principles that have their origin in the Declaration of Helsinki, and any local ethical guidelines.  

The process for obtaining informed consent usually involves providing information for participants.  Once a person has agreed to participate in a trial they are usually asked to sign a consent form.  Before the trial starts, the investigator should receive written approval of the consent form from an independent ethics committee.

Scenarios where special considerations apply:

Trials involving children

If the person eligible for the trial is under 16 years of age, approval of a parent or legal guardian is usually required.  People under 16 should also be asked to give consent where they are thought to have sufficient understanding and intelligence to make that decision; it does not depend upon a fixed age limit.

Trials with no consent

In emergency situations it is usually impossible to obtain informed consent (see Illustrated example - CRASH trial).  As research is necessary in these situations, recruitment without consent is provided for in the revised Declaration of Helsinki 1990 (Paragraph 1.13).

Cluster trials

Whilst ethical issues have been well elucidated in individual patient randomized trials of health care interventions, less attention has been paid to ethical issues arising in cluster randomized trials (Hutton 2002).  In our experience, it is helpful to distinguish between consent for trial participation (intervention allocation) and consent for data collection.  Edwards and colleagues (1999) distinguish between cluster – patient trials where the unit of allocation is the cluster but the level of intervention is the individual patient and cluster- cluster trials where the unit of allocation and intervention is the cluster.  Whilst individual patient consent for the intervention can be sought in cluster – patient trials, this is not the case for cluster-cluster trials.  In cluster - cluster trials, the health care organisation or professional acts as the ‘guardian’ for their patients choosing to participate in the trial if they think it is in the best interests of their patients.  This would raise concerns if the intervention promoted care that was not necessarily in the best interests of all patients (for example, failing to order a lumbar spine x-ray if a physician considered that a patient may have a malignancy but the patient did not fulfill the criteria suggested in the guidelines).  Under such circumstances professionals’ usual ethical responsibilities to do the best for their patients should over-ride the effects of any interventions promoting care that the professional may consider harmful for an individual patient.  It is important for researchers to make this explicit within the information sheet accompanying any trial (see Information for participants ).

Back to top

Things to consider when writing a protocol

Back to top

Illustrative example - WHO pre-eclampsia trial

The women will be recruited at antenatal clinics.  It will be emphasised that enrolment in the study is voluntary, that she can withdraw at any time from all or part of the study, and that any decision she takes in this respect will have no bearing on the medical care she and her family receive.  The study will be explained verbally, according to the information sheet and consent will be recorded with a signature or thumbprint.  Enrolment will be at the discretion of the staff responsible for each mother.  No treatment of any kind will be withheld from a mother because of her participation in the study and mothers who develop hypertension or pre-eclampsia will be given appropriate therapy.  (WHO Multicentre Randomized Trial of Calcium Supplementation for the Prevention of Pre-eclampsia - go to protocol)

Back to top

Illustrative example - Perinatal care trial

All control and intervention hospitals have to agree in advance to participate in the study.  Hospital responsible authority (director or equivalent) will provide written consent to participation before randomization.  Hospitals will be informed of the assignment to control or treatment group following randomization.  Individual health providers in the intervention hospitals will receive a fact sheet describing the objectives of the study, including the name and phone number of the country coordinator.  Birth attendants in the intervention hospitals will receive a fact sheet that provides them with information as to the format, length, and purpose of the training intervention; any benefits or risks they might incur as participants; their right to decline to participate without retribution; who to contact in case they have questions or concerns; and the fact that they will be informed of the results of the study.  Birth attendants selected as opinion leaders in the intervention hospitals will provide written consent to accept that role in the implementation of the intervention.  (CLAP Trial - go to protocol)

Back to top

Illustrative example - CRASH trial

Patients with head injury and impaired consciousness may be unable to give properly informed consent, and in this emergency situation it may not be medically appropriate to delay the start of treatment until proxy consent can be obtained.  Hence, the doctor in charge should take responsibility for entering such patients, just as they would take responsibility for choosing other treatments.  However, the requirements of the relevant ethics committee should be adhered to at all times.  An information leaflet on the study for patients and their friends and relatives will be available in all drug packs. (CRASH Trial - go to protocol)

Back to top

Additional resources

Trial Protocol Tool resource icon The Declaration of Helsinki

The general ethical requirements of clinical research worldwide are outlined in the Declaration of Helsinki issued by the World Medical Association in 1960 and revised in 1975.  This brief document has been accepted internationally as the basis for ethical research.

Back to top  

Web resource icon ICH guidelines for informed consent of trial subjects

These guidelines were developed for ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice

Back to top  

Trial Protocol Tool resource icon Consent Checklist

This checklist has been contributed by the Health Services Research Unit, University of Aberdeen.

Back to top  

Trial Protocol Tool resource icon Sample consent forms

These are a selection of consent forms that have been previously used to record informed consent.

Back to top

Trial Protocol Tool resource iconSpecial ethical issues in randomized trials text from 3rd edition of Clinical Epidemiology

This text has been contributed by Dave Sackett, who prepared it for the forthcoming 3rd edition of Clinical Epidemiology; A Basic Science for Answering Questions about Health Care, to be published by Lippincott, Williams & Wilkins in 2005.

Back to top

Trial Protocol Tool resource iconEthics in international health research

This article discusses the ethics of not using 'best treatment' in poorly resourced settings.

Back to top

Web resource icon Ethical Issues in Research Involving Human Participants (Need link)

This website contains 4650 citations relating to ethical issues in research involving human participants January 1989 - November 1998. This includes the following topics:

Back to top

Further reading

World Medical Association. Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA. 1997;277:925-6.

Alderson P. Consent to health treatment and research: differing perspectives. London: University of London, Institute of Education, Social Science Research Unit, 1992. 56 p.

Brazier M. Protecting the vulnerable: autonomy and consent in health care. New York: Routledge; 1991. 183 p. (Social ethics and policy series).

Buchanan AE, Brock DW. Deciding for others: the ethics of surrogate decision making. New York: Cambridge University Press; 1989. 422 p. (Studies in philosophy and health policy).

Faden RR, Beauchamp TL, King NMP. A history and theory of informed consent. New York: Oxford University Press; 1986. 392 p.

Hirsch SR, Harris J, editors. Consent and the incompetent patient: ethics, law, and medicine. Proceedings of a meeting held at the Royal Society of Medicine; 1986 Dec 9. London: Gaskell; 1988. 101 p. (Gaskell psychiatry series).

Palmer RN. Consent and confidentiality. London: Medical Protection Society; 1991. 26 p.

Tomes JP. Informed consent: a guide for the healthcare professional. Chicago: Probus Pub. Co.; c1993. 164 p.

Hutton JL. Are distinctive ethical principles required for cluster randomised controlled trials.  Statistics in Medicine 2001;20:473-88.

Edwards SJL, Lilford RJ, Braunholtz DA et al. Ethical issues in the design and conduct of cluster randomised controlled trials. BMJ 1999;318:1407-9.

Back to top

This page was last updated 21st September 2005.