A randomized controlled trial is a type of study design that has been called the “gold standard” for evaluating a treatment or therapy.
In this type of trial, the study participants are divided into randomly assigned groups. In the simplest form, this is two groups or ‘arms’, where one (treatment) group is assigned to the therapy being tested and one (control) group is assigned to placebo or the ‘standard of care’ (aka, the current best treatment).
For example, if you have developed Drug X for treating metastatic lung cancer, the trial would compare Drug X versus standard chemotherapy, not placebo. This is because 1. it would be unethical to deprive study participants of any therapy and 2. the study should compare the new drug to what we already do, not to doing nothing.
In a double-blinded randomized controlled trial, both the researchers and the study participants do not know what group any given patient is in. This helps reduce bias, a type of error in which the way the trial is performed falsely favors or disfavors one outcome over the other. Sometimes it is not possible or impractical to blind a research trial, however. For instance, if the new drug is an infusion by vein and the standard of care is a pill, it would be dangerous to give people infusions by vein for no reason, so this type of trial is generally done without double-blinding.
A randomized controlled trial helps reduce bias. In research, the term “bias” means there are flaws in the study design or data collection. Without randomization, when doctors assign patients to a particular treatment, they may inadvertently introduce bias into the study. For example, doctors might favor a particular treatment in a sicker patient, which would make the treatment group sicker on average. Then, any measured effect might be because the patients were sicker rather than because the drug made them sicker. Randomization assigns groups randomly, which ideally makes the treatment group and the control group more similar. This helps eliminate other factors which are not the treatment which might cause a difference between the groups.
A disadvantage of a randomized controlled trial is that they are generally more expensive and more slow than other types of clinical trial, because they require picking a population in advance, assigning groups, blinding, and measuring the outcome. Another disadvantage is that they can be less applicable to the general population because they might study a smaller group of people who might not resemble the total population. For example, Caucasians are overrepresented in randomized controlled trials in the US relative to other groups, so the findings from these trials might or might not apply to people of other ethnicities.1-5 Some efforts have been made to address this issue in the US, including the National Institutes of Health (NIH) Revitalization Act of 1993, the FDA Safety and Innovation Act of 2012, and the creation of annual “FDA Drug Trial Snapshots” describing trial demographics beginning in 2015.
- Chen, M.S., Jr, Lara, P.N., Dang, J.H.T., Paterniti, D.A. and Kelly, K. (2014), Twenty years post‐NIH Revitalization Act: Enhancing minority participation in clinical trials (EMPaCT): Laying the groundwork for improving minority clinical trial accrual. Cancer, 120: 1091-1096. doi:10.1002/cncr.28575
- Eshera, Noha BSc1; Itana, Hawi BSc1; Zhang, Lei PhD2; Soon, Greg PhD3; Fadiran, Emmanuel O. PhD1,* Demographics of Clinical Trials Participants in Pivotal Clinical Trials for New Molecular Entity Drugs and Biologics Approved by FDA From 2010 to 2012, American Journal of Therapeutics: November/December 2015 - Volume 22 - Issue 6 - p 435-455 doi: 10.1097/MJT.0000000000000177
- Downing NS, Shah ND, Neiman JH, Aminawung JA, Krumholz HM, Ross JS. Participation of the elderly, women, and minorities in pivotal trials supporting 2011-2013 U.S. Food and Drug Administration approvals. Trials. 2016;17:199. Published 2016 Apr 14. doi:10.1186/s13063-016-1322-4
- Geller SE, Koch AR, Roesch P, Filut A, Hallgren E, Carnes M. The More Things Change, the More They Stay the Same: A Study to Evaluate Compliance With Inclusion and Assessment of Women and Minorities in Randomized Controlled Trials. Acad Med. 2018;93(4):630-635. doi:10.1097/ACM.0000000000002027
- U.S. Food and Drug Administration. 2018 Drug Trials Snapshots Summary Report. Accessed June 18, 2020. Google Scholar