Randomized controlled trials - a matter of design

Abstract

Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

Keywords: CONSORT; RCT; randomized clinical trials; study design; validity.

Figure 1

Flow diagram for parallel randomized trials comparing two groups. Notes: According to the CONSORT statement, the different phases of a randomized controlled trial can be separated into enrollment, allocation, follow-up, and data analysis. These phases should be described exactly with the respective number of patients to provide a quick and simple overview of the study process. Reproduced from Schulz KF, Altman DG, Moher D, et al. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials. 2010;11:32, with permission of BioMed Central. Abbreviation: CONSORT, Consolidated Standards of Reporting Trials.