Skip to main content
SpringerLink
Log in

Randomized Controlled Trials 1: Design

  • Protocol
  • First Online:
Clinical Epidemiology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1281))

Abstract

Today’s clinical practice relies on the application of well-designed clinical research, the gold standard test of an intervention being the randomized controlled trial. Principles of the randomized control trial include emphasis on the principal research question, randomization, blinding; definitions of outcome measures, of inclusion and exclusion criteria, and of comorbid and confounding factors; enrolling an adequate sample size; planning data management and analysis; preventing challenges to trial integrity such as drop-out, drop-in, and bias. The application of pretrial planning is stressed to ensure the proper application of epidemiological principles resulting in clinical studies that are feasible and generalizable. In addition, funding strategies and trial team composition 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
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
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

  1. Umscheid CA, Margolis DJ, Grossman CE (2011) Key concepts of clinical trials: a narrative review. Postgrad Med 123:194–204

    Article  PubMed Central  PubMed  Google Scholar 

  2. Fuchs FD, Klag MJ, Whelton PK (2000) The classics: a tribute to the fiftieth anniversary of the randomized clinical trial. J Clin Epidemiol 53:335–342

    Article  CAS  PubMed  Google Scholar 

  3. Gross CP, Krumholz HM, Van Wye G, Emanuel EJ, Wendler D (2006) Does random treatment assignment cause harm to research participants? PLoS Med 3:e188

    Article  PubMed Central  PubMed  Google Scholar 

  4. Robinson EJ, Kerr C, Stevens A, Lilford R, Braunholtz D, Edwards S (2004) Lay conceptions of the ethical and scientific justifications for random allocation in clinical trials. Soc Sci Med 58:811–824

    Article  PubMed  Google Scholar 

  5. Kerr C, Robinson E, Stevens A, Braunholtz D, Edwards S, Lilford R (2004) Randomisation in trials: do potential trial participants understand it and find it acceptable? J Med Ethics 30:80–84

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Whelton PK (1994) Epidemiology of hypertension. Lancet 344:101–106

    Article  CAS  PubMed  Google Scholar 

  7. Whelton PK, Gordis L (2000) Epidemiology of clinical medicine. Epidemiol Rev 22:140–144

    Article  CAS  PubMed  Google Scholar 

  8. Schulz KF, Grimes DA (2002) Allocation concealment in randomised trials: defending against deciphering. Lancet 359:614–618

    Article  PubMed  Google Scholar 

  9. Parker MJ, Manan A, Duffett M (2012) Rapid, easy, and cheap randomization: prospective evaluation in a study cohort. Trials 13:90

    Article  PubMed Central  PubMed  Google Scholar 

  10. Ivers NM, Halperin IJ, Barnsley J, Grimshaw JM, Shah BR, Tu K, Upshur R, Zwarenstein M (2012) Allocation techniques for balance at baseline in cluster randomized trials: a methodological review. Trials 13:120

    Article  PubMed Central  PubMed  Google Scholar 

  11. Weijer C, Grimshaw JM, Taljaard M, Binik A, Boruch R, Brehaut JC, Donner A, Eccles MP, Gallo A, McRae AD, Saginur R, Zwarenstein M (2011) Ethical issues posed by cluster randomized trials in health research. Trials 12:100

    Article  PubMed Central  PubMed  Google Scholar 

  12. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:145–153

    Article  CAS  PubMed  Google Scholar 

  13. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:154–160

    Article  CAS  PubMed  Google Scholar 

  14. Scott CT, Baker M (2007) Overhauling clinical trials. Nat Biotechnol 25:287–292

    Article  CAS  PubMed  Google Scholar 

  15. Hoare ZS, Whitaker CJ, Whitaker R (2013) Introduction to a generalized method for adaptive randomization in trials. Trials 14:19

    Article  PubMed Central  PubMed  Google Scholar 

  16. Brown CH, Ten Have TR, Jo B, Dagne G, Wyman PA, Muthen B, Gibbons RD (2009) Adaptive designs for randomized trials in public health. Annu Rev Public Health 30:1–25

    Article  PubMed Central  PubMed  Google Scholar 

  17. Mills EJ, Chan AW, Wu P, Vail A, Guyatt GH, Altman DG (2009) Design, analysis, and presentation of crossover trials. Trials 10:27

    Article  PubMed Central  PubMed  Google Scholar 

  18. Avins AL, Cherkin DC, Sherman KJ, Goldberg H, Pressman A (2012) Should we reconsider the routine use of placebo controls in clinical research? Trials 13:44

    Article  PubMed Central  PubMed  Google Scholar 

  19. D’Agostino RB Sr, Massaro JM, Sullivan LM (2003) Non-inferiority trials: design concepts and issues—the encounters of academic consultants in statistics. Stat Med 22:169–186

    Article  PubMed  Google Scholar 

  20. Snapinn SM (2000) Noninferiority trials. Curr Control Trials Cardiovasc Med 1:19–21

    Article  PubMed Central  PubMed  Google Scholar 

  21. Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hrobjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D (2013) SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ 346:e7586

    Article  PubMed Central  PubMed  Google Scholar 

  22. Bakris GL, Whelton P, Weir M, Mimran A, Keane W, Schiffrin E (2000) The future of clinical trials in chronic renal disease: outcome of an NIH/FDA/Physician Specialist Conference. Evaluation of Clinical Trial Endpoints in Chronic Renal Disease Study Group. J Clin Pharmacol 40:815–825

    Article  CAS  PubMed  Google Scholar 

  23. Ponticelli C, Zucchelli P, Passerini P, Cesana B, Locatelli F, Pasquali S, Sasdelli M, Redaelli B, Grassi C, Pozzi C, Bizzarri D, Banfi G (1995) A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int 48:1600–1604

    Article  CAS  PubMed  Google Scholar 

  24. Briel M, Lane M, Montori VM, Bassler D, Glasziou P, Malaga G, Akl EA, Ferreira-Gonzalez I, Alonso-Coello P, Urrutia G, Kunz R, Culebro CR, da Silva SA, Flynn DN, Elamin MB, Strahm B, Murad MH, Djulbegovic B, Adhikari NK, Mills EJ, Gwadry-Sridhar F, Kirpalani H, Soares HP, Abu Elnour NO, You JJ, Karanicolas PJ, Bucher HC, Lampropulos JF, Nordmann AJ, Burns KE, Mulla SM, Raatz H, Sood A, Kaur J, Bankhead CR, Mullan RJ, Nerenberg KA, Vandvik PO, Coto-Yglesias F, Schunemann H, Tuche F, Chrispim PP, Cook DJ, Lutz K, Ribic CM, Vale N, Erwin PJ, Perera R, Zhou Q, Heels-Ansdell D, Ramsay T, Walter SD, Guyatt GH (2009) Stopping randomized trials early for benefit: a protocol of the study of trial policy of interim truncation-2 (STOPIT-2). Trials 10:49

    Article  PubMed Central  PubMed  Google Scholar 

  25. Whitehead J (2004) Stopping rules for clinical trials. Control Clin Trials 25:69–70, author reply 71-2

    Article  PubMed  Google Scholar 

  26. Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA (1998) The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 339:584–590

    Article  CAS  PubMed  Google Scholar 

  27. Sweetman EA, Doig GS (2011) Failure to report protocol violations in clinical trials: a threat to internal validity? Trials 12:214

    Article  PubMed Central  PubMed  Google Scholar 

  28. Farrell B, Kenyon S, Shakur H (2010) Managing clinical trials. Trials 11:78

    Article  PubMed Central  PubMed  Google Scholar 

  29. Kasenda B, von Elm EB, You J, Blumle A, Tomonaga Y, Saccilotto R, Amstutz A, Bengough T, Meerpohl J, Stegert M, Tikkinen KA, Neumann I, Carrasco-Labra A, Faulhaber M, Mulla S, Mertz D, Akl EA, Bassler D, Busse JW, Ferreira-Gonzalez I, Lamontagne F, Nordmann A, Rosenthal R, Schandelmaier S, Sun X, Vandvik PO, Johnston BC, Walter MA, Burnand B, Schwenkglenks M, Bucher HC, Guyatt GH, Briel M (2012) Learning from failure–rationale and design for a study about discontinuation of randomized trials (DISCO study). BMC Med Res Methodol 12:131

    Article  PubMed Central  PubMed  Google Scholar 

  30. Sully BG, Julious SA, Nicholl J (2014) An investigation of the impact of futility analysis in publicly funded trials. Trials 15:61

    Article  PubMed Central  PubMed  Google Scholar 

  31. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869

    Article  CAS  PubMed  Google Scholar 

  32. Scherer RW, Langenberg P, von Elm E (2007) Full publication of results initially presented in abstracts. Cochrane Database Syst Rev MR000005

    Google Scholar 

  33. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 340:c869

    Article  PubMed Central  PubMed  Google Scholar 

  34. Plint AC, Moher D, Morrison A, Schulz K, Altman DG, Hill C, Gaboury I (2006) Does the CONSORT checklist improve the quality of reports of randomised controlled trials? A systematic review. Med J Aust 185:263–267

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medicine, Patient Research Centre, Health Science Centre, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John’s, NF, Canada, A1B 3V6

    Bryan M. Curtis

  2. Clinical Epidemiology Unit, Faculty of medicine, Memorial University of Newfoundland, St. John’s, NF, Canada, A1B 3V6

    Bryan M. Curtis, Brendan J. Barrett & Patrick S. Parfrey

Authors
  1. Bryan M. Curtis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brendan J. Barrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick S. Parfrey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bryan M. Curtis .

Editor information

Editors and Affiliations

  1. Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada

    Patrick S. Parfrey

  2. Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada

    Brendan J. Barrett

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Curtis, B.M., Barrett, B.J., Parfrey, P.S. (2015). Randomized Controlled Trials 1: Design. In: Parfrey, P., Barrett, B. (eds) Clinical Epidemiology. Methods in Molecular Biology, vol 1281. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2428-8_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2428-8_9

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2427-1

  • Online ISBN: 978-1-4939-2428-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation