ICH-GCP states that it is an ethical standard for the design and conduct of research, but close inspection of the guideline leads to the conclusion that it is concerned with the process of ethics, specifically, the process of ethical review rather than the core principles of ethics. This is a pity because the principles that underpin research ethics are essentially straightforward and easy to grasp. I will try to outline them here.
The starting point is the utility of the research. By this we mean the scientific value of the research in terms of the need to address an important unanswered question about health from the perspective of creating new knowledge. Second, the research should by design reliably address this question that is to provide a clear answer to the study question. These first two principles to reliably address an important question are the starting point of all research. They are concerned with scientific utility and highlight the fallacy often cited that research ethics committee should not be concerned with science and, instead, should only focus on material ethical issues. Again, this is a myth.
Next, the research should minimise the potential risks and maximise the potential benefits to research participants. The reference point here is usual clinical practice and the evidence that exists would suggest that trial participants are at no greater or less risk by taking part in a randomised trial. This is reassuring. Specific ethical issues arise here with the use of placebo in situations where a participant is already receiving an effective and stable treatment. In general, in the context of a randomised trial, the potential risks and benefits are largely unknown with there being sufficient uncertainty in terms of the potential outcome. This is often expressed as the uncertainty principle.
Most research is conducted on the basis of informed consent of participants. While important exceptions exist, for example, the use of deferred consent in unconscious patients, informed consent is the basis that makes much health research ethical. It is concerned with the exchange of information in a manner that leads to understanding from the perspective of the risks and benefits to participants. Coupled with informed consent is the right to withdraw consent should the wish arise in the future. A lot of the ethical review undertaken by research ethical committees is concerned with reviewing the information in the form of an information leaflet and consent form that potential participants are given in order to decide whether or not to participate.
Finally, health research is ethical by virtue of there being an independent ethical review. Ethical committee review might be the only universal review process that all health research is subject to. Many countries now have a centralised co-ordinated process for ethical review with targets set for how long the review process should take – for example – in the UK a target of 60 days from submission to approval has now been in place for the last few years. In my experience, ethics committees, while not getting everything right, are genuinely there to facilitate research, particularly improving the process of informed consent.
Returning to ICH-GCP, these principles are not set out in the E6 guideline. Instead, GCP is concerned with process, more to do with how to set up an ethics committee, what documentation is required etc. rather than what principles apply to the ethical conduct of research. By contrast, the Declaration of Helsinki, which is universally accepted as an ethical standard and regularly updated, is concerned with these principles and provides the required framework for the ethical review of health research. It would be better in ICH-GCP to reference the Declaration of Helsinki as an ethical standard for research.