Randomized Controlled Trials
This chapter covers the current gold standard for evaluating the effectiveness of therapeutic interventions, the randomized controlled trial (RCT). Key features of the RCT, regardless of sub-type, are randomization, allocation concealment, and blinding. These key features help reduce bias and the influence of confounding variables, making the randomized controlled trial eminently suitable to determine cause and effect relationships. Protocol design and registration prior to trial onset are important factors in determining the quality of the trial, and various trial design sub-types, including parallel, factorial, crossover, and cluster, are outlined and the strengths and weakness of each examined. Various checklists such as SPIRIT and CONSORT can be used to ensure proper reporting of both trial protocols and trial findings, to ensure clear, concise reporting. Finally, the shortcomings of RCTs and newer trial designs, such as comparative effectiveness research and pragmatic studies, designed to overcome some of these issues are examined, and ways to make clinical trial results more clinically applicable are discussed.
KeywordsRandomized controlled trials Blinding Factorial Pragmatic Factorial Cluster Crossover Pragmatic Comparative effectiveness
- Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K,... Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3): 200–7. https://doi.org/10.7326/0003-4819-158-3-201302050-00583.
- Community Intervention Trial for Smoking Cessation (COMMIT): I. cohort results from a four-year community intervention. Am J Public Health. 1995;85(2): 183–92.Google Scholar
- De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R,... International Committee of Medical Journal, E. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. N Engl J Med. 2004;351(12): 1250–1. https://doi.org/10.1056/NEJMe048225.
- Doll R. Controlled trials: the 1948 watershed. BMJ. 1998;317(7167): 1217–20.Google Scholar
- Feeley N, Cossette S, Cote J, Heon M, Stremler R, Martorella G, Purden M. The importance of piloting an RCT intervention. Can J Nurs Res. 2009;41(2):85–99.Google Scholar
- Gartlehner G, Hansen R, Nissman D, Lodhr K, Carey T. Criteria for distinguishing effectiveness from efficacy in systematic reviews. 2006. Retrieved from.Google Scholar
- Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD,... Sterne JA. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343: d5928. https://doi.org/10.1136/bmj.d5928.
- ICH. ICH harmonised tripartite guideline. Guideline for Good Clinical Practice E6(R1) 1996.Google Scholar
- Landorf KB. Clinical trials: the good, the bad and the ugly. In: Liamputtong P, editor. Research methods in health: foundations for evidence-based practice. 3rd ed. Melbourne: Oxford University Press; 2017. p. 275–90.Google Scholar
- Lesaffre E. Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis. 2008;66(2):150–4.Google Scholar
- Manchikanti L. Evidence-based medicine, systematic reviews, and guidelines in interventional pain management, part I: introduction and general considerations. Pain Physician. 2008;11(2):161–86.Google Scholar
- Mayer D. Essential evidence-based medicine. Cambridge: Cambridge University Press; 2004.Google Scholar
- Moher D, Hopewell S, Schulz K.F, Montori V, Gotzsche PC, Devereaux PJ,.... Consort. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg (Lond). 2012;10(1): 28–55.Google Scholar
- Scott A, Rucklidge JJ, Mulder RT. Is mandatory prospective trial registration working to prevent publication of unregistered trials and selective outcome reporting? An observational study of five psychiatry journals that mandate prospective clinical trial registration. PLoS One. 2015;10(8):e0133718. https://doi.org/10.1371/journal.pone.0133718.CrossRefGoogle Scholar
- The CONSORT Statement. The CONSORT statement. 2017. Retrieved from http://www.consort-statement.org/
- The James Lind Library. Avoiding biased comparisons. 2007a. Retrieved from http://www.jameslindlibrary.org/essays/bias/avoiding-biased-comparisons.html
- The James Lind Library. Differences in the way treatment outcomes are assessed. 2007b. Retrieved from www.jameslind.org
- The James Lind Library. Taking account of the play of chance. 2007c. 17 Dec 2009. Retrieved from www.jameslind.org
- Thorpe KE, Zwarenstein M, Oxman AD, Treweek S, Furberg CD, Altman DG,... Chalkidou K. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol. 2009;62(5): 464–75. https://doi.org/10.1016/j.jclinepi.2008.12.011.
- Witt CM, Aickin M, Baca T, Cherkin D, Haan MN, Hammerschlag R.,... Berman BM. Effectiveness Guidance Document (EGD) for acupuncture research – a consensus document for conducting trials. BMC Complement Altern Med. 2012;12:148. https://doi.org/10.1186/1472-6882-12-148.