title: 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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany; Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Saxony, Germany.
authors.forename: Peter Markus
authors.initials: PM
authors.lastname: Spieth
authors.affiliation: Pediatric Rheumatology and Immunology, Children's Hospital, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany.
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Kubasch
authors.affiliation: Institute of Clinical Pharmacology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Penzlin
authors.affiliation: Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Saxony, Germany; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Ben Min-Woo
authors.initials: BM
authors.lastname: Illigens
authors.affiliation: Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Barlinn
authors.affiliation: Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Saxony, Germany; Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, Oxfordshire, UK.
authors.forename: Timo
authors.initials: T
authors.lastname: Siepmann
keywords: CONSORT; RCT; randomized clinical trials; study design; validity