Skip to main content
SpringerLink
Log in

Randomized Controlled Trials

  • Reference work entry
  • First Online:
Handbook of Research Methods in Health Social Sciences

  • 900 Accesses

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 649.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 849.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Altman DG, Bland JM. How to randomise. BMJ. 1999a;319(7211):703–4.

    Article  Google Scholar 

  • Altman DG, Bland JM. Statistics notes. Treatment allocation in controlled trials: why randomise? BMJ. 1999b;318(7192):1209.

    Article  Google Scholar 

  • Arnold DM, Burns KEA, Adhikari NKJ, Kho ME, Meade MO, Cook DJ. The design and interpretation of pilot trials in clinical research in critical care. Crit Care Med. 2009;37(1 Suppl):S69–74.

    Article  Google Scholar 

  • Barr K, Smith CA, de Lacey SL. Participation in a randomised controlled trial of acupuncture as an adjunct to in vitro fertilisation: the views of study patients and acupuncturists. Eur J Integr Med. 2016;8(1):48–54. https://doi.org/10.1016/j.eujim.2015.10.006.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Committee for Proprietary Medicinal Products. Points to consider on switching between superiority and non-inferiority. Br J Clin Pharmacol. 2001;52(3):223–8.

    Article  Google Scholar 

  • 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 

  • Cornfield J. Randomization by group: a formal analysis. Am J Epidemiol. 1978;108(2):100–2.

    Article  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.

    Article  Google Scholar 

  • Doherty S. History of evidence-based medicine. Oranges, chloride of lime and leeches: barriers to teaching old dogs new tricks. Emerg Med Australas. 2005;17(4):314–21.

    Google Scholar 

  • Doig GS, Simpson F. Randomization and allocation concealment: a practical guide for researchers. J Crit Care. 2005;20(2):187–91.; discussion 191–83. https://doi.org/10.1016/j.jcrc.2005.04.005.

    Article  Google Scholar 

  • Doll R. Controlled trials: the 1948 watershed. BMJ. 1998;317(7167): 1217–20.

    Article  Google Scholar 

  • Donner A, Klar N. Pitfalls of and controversies in cluster randomization trials. Am J Public Health. 2004;94(3):416–22.

    Article  Google Scholar 

  • Fanelli D. Do pressures to publish increase scientists’ bias? An empirical support from US states data. PLoS One. 2010;5(4):e10271. https://doi.org/10.1371/journal.pone.0010271.

    Article  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 

  • Ganju J, Rom D. Non-inferiority versus superiority drug claims: the (not so) subtle distinction. Trials. 2017;18(1):278. https://doi.org/10.1186/s13063-017-2024-2.

    Article  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 

  • Gluud LL. Bias in clinical intervention research. Am J Epidemiol. 2006;163(6):493–501. https://doi.org/10.1093/aje/kwj069.

    Article  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.

    Article  Google Scholar 

  • Hill AB. The clinical trial. N Engl J Med. 1952;247(4):113–9. https://doi.org/10.1056/nejm195207242470401.

    Article  Google Scholar 

  • Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ. 1999;319(7211):670–4.

    Article  Google Scholar 

  • ICH. ICH harmonised tripartite guideline. Guideline for Good Clinical Practice E6(R1) 1996.

    Google Scholar 

  • Jairath N, Hogerney M, Parsons C. The role of the pilot study: a case illustration from cardiac nursing research. Appl Nurs Res. 2000;13(2):92–6.

    Article  Google Scholar 

  • Juni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ. 2001;323(7303):42–6.

    Article  Google Scholar 

  • Kalish LA, Begg CB. Treatment allocation methods in clinical trials: a review. Stat Med. 1985;4(2):129–44.

    Article  Google Scholar 

  • Katz MH. Study design and statistical analysis: a practical guide for clinicians. Cambridge: Cambridge University Press; 2006.

    Book  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, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. Ann Intern Med. 2001;134(8):657–62.

    Article  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.

    Article  Google Scholar 

  • Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ, Group C. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA. 2006;295(10):1152–60. https://doi.org/10.1001/jama.295.10.1152.

    Article  Google Scholar 

  • Sackett DL. Bias in analytic research. J Chronic Dis. 1979;32(1–2):51–63.

    Article  Google Scholar 

  • Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995;273(5):408–12.

    Article  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.

    Article  Google Scholar 

  • Suresh KP. An overview of randomization techniques: an unbiased assessment of outcome in clinical research. J Hum Reprod Sci. 2011;4(1):8–11. https://doi.org/10.4103/0974-1208.82352.

    Article  Google 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.

    Article  Google Scholar 

  • Viboud C, Boelle PY, Kelly J, Auquier A, Schlingmann J, Roujeau JC, Flahault A. Comparison of the statistical efficiency of case-crossover and case-control designs: application to severe cutaneous adverse reactions. J Clin Epidemiol. 2001;54(12):1218–27.

    Article  Google Scholar 

  • 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.

Download references

Author information

Authors and Affiliations

  1. NICM, Western Sydney University (Campbelltown Campus), Penrith, NSW, Australia

    Mike Armour & Carolyn Ee

  2. NICM and Translational Health Research Institute (THRI), Western Sydney University, Penrith, NSW, Australia

    Genevieve Z. Steiner

Authors
  1. Mike Armour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carolyn Ee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Genevieve Z. Steiner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mike Armour .

Editor information

Editors and Affiliations

  1. School of Science and Health, Western Sydney University, Penrith, NSW, Australia

    Pranee Liamputtong

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Armour, M., Ee, C., Steiner, G.Z. (2019). Randomized Controlled Trials. In: Liamputtong, P. (eds) Handbook of Research Methods in Health Social Sciences. Springer, Singapore. https://doi.org/10.1007/978-981-10-5251-4_94

Download citation

Publish with us

Policies and ethics

Search

Navigation