Clinical trials internet resource
November 2004
Ethical considerations
The ethical implications of conducting clinical trials are wide-ranging and much debate has been generated on best practice. Useful bioethics resources on the
internet include the
Wellcome Trust - go the website here,
The Centre of Medical Law and Ethics at King's College London - go to the website here,
and the
Institute of Medicine, Law and Bioethics - go to the website here.
Below is a brief outline of some of the main ethical considerations of conducting clinical trials.
Randomised controlled trials
The unique feature of RCTs is the randomisation of participants into different treatment arms. This is only acceptable if the health professional and patient are uncertain about which among two or more alternatives is preferable. At any stage, however, patients must have the choice to withdraw and should be supported if that is their decision. In addition, it is the duty of doctors to obtain informed consent from all participants.
Risk
Research brings the risk of causing harm, in the practical sense of possibly damaging or disadvantaging a patient, and of doing wrong in the moral sense of ignoring the autonomy of that individual. People are wronged if they are deprived of choice or if their values are transgressed on the assumption that the best clinical outcome is necessarily what is best for them. The possibility of harm cannot be entirely eliminated from research or treatment. However, by insisting that patients have adequate information and choice about participation, doctors can minimise this possibility. In any situation, the more risky or invasive the procedure, the greater attention must be paid to the patient’s understanding of and consent to it. It is the responsibility of the researchers and the research ethics committees to ensure that any foreseeable risks are minimised.
When considering the risks of participation in clinical trials, it may be helpful to note that there is an apparent contradiction between treatment within trials and treatment outside of trials. Within a trial, a doctor must give full information on the new treatment and possible alternatives to the patient. However, outside of a trial the information a patient receives is not regulated, particularly about alternatives, and some evidence suggests that non-trial treatment is therefore more risky (Parmar, 2002, personal communication) [Go to note 35].
Fraud in medical research
It is the responsibility of local research ethics committees to ensure that patient research is free from commercial bias. However, recently there has been concern that both research and the publication of research papers has increasingly come under the control of the sponsors of the study. The International Committee of Medical Journal Editors, in an effort to contribute to maintaining and improving the integrity of the scientific record, now requires contributors to disclose details of their own and their funders’ roles in the studies. They ask contributors to sign a statement that confirms they accept full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish [Go to note 36]. In addition, authors are encouraged to declare potential conflicts of interest at the end of papers submitted for publication.
The BMA emphasises that fraud is totally unacceptable, and the Association of the British Pharmaceutical Company fully supports the principle that investigators conducting clinical trials are entitled to scientific independence [Go to note 37]. Any investigator found to have submitted fraudulent data may be referred to the General Medical Council or prosecuted for the criminal offence of fraud. Guidelines have been produced by the GMC - go to the website here, the MRC - go to the website here and Committee on Publication Ethics - go to the website here.
The Department of Health has published a Research Governance Framework - read more here. [Go to note 38] that defines the broad principles of good research governance and is key to ensuring that health and social care research in the NHS is conducted to high scientific and ethical standards. It also sets out the responsibilities of research sponsors and requires that organisations willing to take on these duties will need to be included on a "List of Recognised Sponsors". Industry funded research must follow the International Conference on Harmonisation’s Good Clinical Practice Guidelines - download as a PDF here. [Go to note 39].
Health professionals who want to withdraw from a trial
Ethically no one involved in a clinical trial, either a health professional or a volunteer, should be forced to continue against their wishes. A doctor must consider their duty of care towards the patients involved if considering leaving the trial. They should only agree to participate when all their questions have been answered by the principal investigator, and should state all reservations prior to joining the trial. The GMC (2002) guides [Go to note 34] that doctors working in research must complete research projects involving patients or volunteers, or do their best to ensure that they are completed by others, except where results indicate a risk that participants may be harmed or no benefit can be expected.