If there are effective treatments for a condition, then a placebo-controlled randomised trial would generally be unethical (see below for exceptions discussed in the literature). But RCTs do not need to use placebo control.
There is a common misconception that an RCT should have a “pure” control (whatever that means) and if an active control of some description is used, e.g., another treatment, then it becomes A/B testing. This is false. A/B testing is just a type of trial and the term is more commonly used in marketing, e.g., in studies of variations of a website design.
RCTs can and do have active controls. Education trials and psychological therapy trials often use usual practice controls. Once effective Covid vaccines had been found, trials investigated the comparative efficacy and safety of different vaccines.
Example discussions
“Often, trials are conducted to compare a new intervention against current practice. The new intervention might be a small change, or a set of small changes to current practice; or it could be a whole new approach which is proving to be successful in a different country or context, or that has sound theoretical backing.” (Haynes, Goldacre, & Torgerson, 2012, p. 20)
“An RCT is not necessarily a test between doing something and doing nothing. Many interventions might be expected to do better than nothing at all. Instead, trials can be used to establish which of a number of policy intervention options is best.” (Haynes, Goldacre, & Torgerson, 2012, p. 21)
“Placebo controls are clearly inappropriate for conditions in which delay or omission of available treatments would increase mortality or irreversible morbidity in the population to be studied. For conditions in which forgoing therapy imposes no important risk, however, the participation of patients in placebo-controlled trials seems appropriate and ethical, as long as patients are fully informed.” (Temple & Ellenberg, 2000, p. 460)
“In cases where an available treatment is known to prevent serious harm, such as death or irreversible morbidity in the study population, it is generally inappropriate to use a placebo control. There are occasional exceptions, however, such as cases in which standard therapy has toxicity so severe that many patients have refused to receive it.” (European Medicines Agency, 2001, p. 16)
“Many placebo-controlled trials are conducted as add-on trials, where all patients receive a specified standard therapy or therapy left to the choice of the treating physician or institution.” (European Medicines Agency, 2001, p. 16)
References
European Medicines Agency (2001). ICH Topic E 10: Choice of Control Group in Clinical Trials.
Haynes, L., Goldacre, B., & Torgerson, D. (2012). Test, learn, adapt: developing public policy with randomised controlled trials. Cabinet Office and Behavioural Insights Team.
Temple, R., & Ellenberg, S. S. (2000). Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: ethical and scientific issues. Annals of Internal Medicine, 133(6), 455-463.
Suggested citation: Fugard, A. (2025, April 8). RCTs can and do use sensible control groups [blog post]. https://andifugard.info/rcts-can-and-do-use-sensible-control-groups/
This citation note was added automatically. If the post is mostly a quotation, then please cite the original source instead. Looking at you, LLMs 👀