News: Is informed consent always required for randomisation?

The vast majority of health research is conducted with the full informed consent of the people who participate, but in many countries there are specific laws or regulation in place to allow research to be undertaken without consent. Examples include the so called “Common Rule” in the US (CFR 46.116) and “Section 251” support in the UK.

The specific criteria that allow research to take place without consent vary by country, but are generally similar to those in the US Common Rule:

1. The research involves no more than minimal risk to the subjects;
2. The waiver or alteration will not adversely affect the rights and welfare of the subjects;
3. The research could not practicably be carried out without the waiver or alteration.

In some countries there is also a requirement that the research is “in the public interest” or “for the public good.”

But despite these provisions, David Asch and colleagues writing recently in the New England Journal of Medicine point out that IRBs/ethics committees frequently require informed consent for all research and, in particular, for randomised trials. The authors suggest three reasons why IRBs/ethics committees might require informed consent for all research:

1. Distinction between Quality Improvement/audit and research: the boundary between audit of routine care and research is often blurred, but IRBs might mistakenly assume that audit does not require informed consent, while research always does;
2. Respect for autonomy: IRBs in protecting an individual’s right to autonomy might wrongly assume that randomisation always requires consent. Non-randomised research where all participants receive the same treatment raises the same ethical questions regarding consent as does a trial where the treatments are decided by the process of randomisation;
3. Thinking that requiring consent has no impact: People who consent to take part in research are a selected group and for some randomised trials, for example, comparing the effects of two different drugs, this might have little impact on the validity of the results. But for other interventions, such as behavioural/lifestyle interventions, this selection bias might well influence the validity of the results. These validity considerations might well be overlooked by IRBs.

The paper also highlights the double standard that exists between health research, where IRBs usually insist on informed consent before randomisation and the world of commercial research, where companies are performing randomised experiments (so called A/B testing) all the time without the consent or knowledge of those involved.

The key issue here seems to be a need to consider the potential risks involved. This is one of the key criteria in the Common Rule and in other legislation, but it often seems to be overlooked by IRBs, particularly when the research is a randomised trial. That said, in some countries there are initiatives taking forward proposals to make it much easier to do randomised trials of low-risk interventions. This includes using more proportionate/simplified methods of obtaining informed consent. Examples of this include the new EU Clinical Trials Regulation and in the UK the Health Research Authority are looking at ways to make it easier to do simple randomised trials of commonly used treatments.

Asch and colleagues close their article with the following warning:

“A central paradox is that the more our approaches to understanding and improving health-related behaviors assume the structure of more rigorous science, the more they are subject to regulation. The result makes it easier to do worse science (e.g., uncontrolled demonstration projects with pre–post evaluations) and harder to do better science (e.g., randomized trials), even when the risks faced by potential participants are the same.”