A randomized controlled trial (RCT) is used to test the efficacy and effectiveness of various interventions within an organized patient population, and is considered the “gold standard” for a clinical trial. An RCT uses a carefully planned experimental framework to compare an intervention with a control, investigating the effect of each treatment option on a defined outcome. After meeting strict qualifications in order to enroll in the clinical trial, each participant is randomly assigned to one of the treatment groups. Ideally, the study is "double-blinded," meaning that neither the participants nor the researchers know who is receiving the active intervention and who is receiving the control treatment.
Of all clinical research study designs, RCTs provide the strongest internal validity (i.e., this drug, taken at this dose, produces this outcome in this group of people). The randomization and blinding techniques imposed at the start of a study greatly reduce the likelihood that bias or confounding influences the results. Confounding occurs when external factors are more likely in one study group and have an independent impact on the measured outcomes (e.g., the intervention group has sicker patients than the control group).
RCTs have various potential limitations. First, the very characteristics that support an RCT’s strong internal validity can limit the study design’s external validity, or generalizability to the broader world of care beyond the study’s controlled environment. RCTs generally enroll a narrow set of patients without relevant comorbidities and rarely include children or the elderly in their study populations. Second, most RCTs are modest in size due to their expense and challenging logistics. This modest size limits RCTs’ ability to assess uncommon events. Third, many RCTs compare active treatments with placebo, rather than head-to-head with another active treatment, or choose to use comparators that may not be "right" or "best" for the analysis. Finally, the strict pre-set design of RCTs is occasionally abandoned by participants who may find themselves unhappy with their randomization or the constraints of the study; participants leaving a study (known as loss to follow-up) or requiring a treatment that might necessitate their transfer from the placebo to the intervention group may diminish the statistical power of the study.
The National Pharmaceutical Council has developed several resources to assist in understanding RCTs and other study designs. These include Making Informed Decisions: Assessing the Strengths and Weaknesses of Study Designs and Analytic Methods for Comparative Effectiveness Research, Demystifying CER: A Case Study Learning Guide, and videos.