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N-of-1 trials are a tapestry of heterogeneity

  • Salima Punja
    Affiliations
    Department of Pediatrics, University of Alberta, 1702 College Plaza, 8215—112 Street NW, Edmonton, Alberta T6G 2C8, Canada
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  • Cecilia Bukutu
    Affiliations
    Department of Pediatrics, University of Alberta, 1702 College Plaza, 8215—112 Street NW, Edmonton, Alberta T6G 2C8, Canada

    Knowledge Utilization Studies Program, Faculty of Nursing, University of Alberta, 3rd Floor Edmonton Clinic Health Academy, Edmonton, Alberta T6G 1C9, Canada
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  • Larissa Shamseer
    Affiliations
    Clinical Epidemiology Program, Ottawa Hospital Research Institute, Center for Practice Changing Research Building, 501 Smyth Road, PO Box 201B, Ottawa, Ontario K1H 8L6, Canada
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  • Margaret Sampson
    Affiliations
    Department of Library Services, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada
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  • Lisa Hartling
    Affiliations
    Alberta Research Centre for Health Evidence, Department of Pediatrics, University of Alberta, 4-472 Edmonton Clinic Health Academy, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada
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  • Liana Urichuk
    Affiliations
    Information & Evaluation Services for Addiction & Mental Health, Addiction and Mental Health, Alberta Health Services-Edmonton Zone, 9942 108 Street, Edmonton, Alberta T5K 2J5, Canada
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  • Sunita Vohra
    Correspondence
    Corresponding author. 1702 College Plaza, 8215—112 Street NW, Edmonton, Alberta T6G 2C8, Canada. Tel.: 780-492-6445; fax: 780-492-5883.
    Affiliations
    Complementary and Alternative Research and Education Program (CARE), Department of Pediatrics, University of Alberta
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      Abstract

      Objectives

      To summarize the methods of design, analysis, and meta-analysis used in N-of-1 trials.

      Study Design and Setting

      Electronic search for English language articles published from 1950 to 2013. N-of-1 trials were selected if they followed an ABAB design and if they assessed a health intervention for a medical condition. Elements of design, analysis, and meta-analysis were extracted.

      Results

      We included 100 reports representing 1,995 participants. N-of-1 trials have been conducted in over 50 health conditions. Most reports incorporated the use of elements that maintain methodological rigor, including randomization, blinding, and formal outcome assessment; however, many failed to address trial registration, funding source, and adverse events. Most reports statistically analyzed individual N-of-1 trials; however, only a small proportion of included series meta-analyzed their results.

      Conclusions

      N-of-1 trials have the ability to assess treatment response in individual participants and can be used for a variety of health interventions for a wide range of medical conditions in both clinical and research settings. Considerable heterogeneity exists in the methods used in N-of-1 trials.

      Keywords

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      References

        • Guyatt G.
        • Keller J.
        • Jaeschke R.
        • Rosenbloom D.
        • Adachi J.D.
        • Newhouse M.T.
        The N-of-1 randomized controlled trial: clinical usefulness. Our three-year experience.
        Ann Intern Med. 1990; 112: 293-299
        • Kazdin A.E.
        Single-case research designs: methods for clinical and applied settings.
        Oxford University Press, New York1982
        • Guyatt G.
        • Sackett D.
        • Adachi J.
        • Roberts R.
        • Chong J.
        • Rosenbloom D.
        • et al.
        A clinician’s guide for conducting randomized trials in individual patients.
        Can Med Assoc J. 1988; 139: 497-503
      1. OCEBM Levels of Evidence Working Group, The Oxford levels of evidence 2, 2011, Oxford Centre for Evidence-Based Medicine. Available at www.cebm.net/index.aspx?o=5653. Accessed April 28, 2016.

        • Johannessen T.
        • Petersen H.
        • Kristensen P.
        • Fosstvedt D.
        The controlled single subject trial.
        Scand J Prim Health Care. 1991; 9: 17-21
        • Senn S.
        Suspended judgment: N-of-1 trials.
        Controlled Clin Trials. 1993; 14: 1-5
        • Vohra S.
        • Shamseer L.
        • Sampson M.
        • Bukutu C.
        • Schmid S.H.
        • Tate R.
        • et al.
        CONSORT extension for reporting N-of-1 trials (CENT) 2015 statement.
        J Clin Epidemiol. 2016; 76: 9-17
        • Tate R.L.
        • Perdices M.
        • Rosenkoetter U.
        • Wakim D.
        • Godbee K.
        • Togher L.
        • et al.
        Revision of a method quality rating scale for single-case experimental designs and n-of-1 trials: the 15-item Risk of Bias in N-of-1 Trials (RoBiNT) Scale.
        Neuropsychol Rehabil. 2013; 23: 619-638
        • Zarin D.A.
        • Young J.L.
        • West J.C.
        Challenges to evidence-based medicine.
        Soc Psychiatry Psychiatr Epidemiol. 2005; 40: 27-35
        • Zucker D.R.
        • Ruthazer R.
        • Schmid C.H.
        Individual (N-of-1) trials can be combined to give population comparative treatment effect estimates: methodologic considerations.
        J Clin Epidemiol. 2010; 63: 1312-1323
        • Punja S.
        • Eslick I.
        • Duan N.
        • Vohra S.
        • the DEcIDE Methods Center N-of-1 Guidance Panel (Gabler N, Kaplan H, Kravitz R, Larson E, Pace W, Schmid C, Sim I)
        Design and implementation of N-of-1 trials: a user’s guide. An ethical framework for N-of-1-Trials: clinical care, quality improvement, or human subject research? (Chapter 2).
        (AHRQ Publication No.13(14)-EHC122-EF) Agency for Healthcare Research and Quality, Rockville, MD2014
        • Schmid C.
        • Duan N.
        • the DEcIDE Methods Center N-of-1 Guidance Panel (Eslikc I, Gabler N, Kaplan H, Kravitz R, Larson E, Pace W, Schmid C, Sim I, Vohra S)
        Design and implementation of N-of-1 trials: a user’s guide. Statistical design and analytic considerations for N-of-1 trials (Chapter 4).
        (AHRQ Publication No.13(14)-EHC122-EF) Agency for Healthcare Research and Quality, Rockville, MD2014
        • Ross M.
        • Olson J.M.
        An expectancy-attribution model of the effects of placebos.
        Psychol Rev. 1981; 88: 408-437
        • Rutherford B.R.
        • Marcus S.M.
        • Wang P.
        • Sneed J.R.
        • Pelton G.
        • Devanand D.
        • et al.
        A randomized, prospective pilot study of patient expectancy and antidepressant outcome.
        Psychol Med. 2013; 43: 975-982
        • Paterson C.
        Seeking the patient’s perspective: a qualitative assessment of EuroQol, COOP-WONCA Charts and MYMOP2.
        Qual Life Res. 2004; 13: 871-881
        • Zucker D.R.
        • Schmid C.H.
        • McIntosh M.W.
        • D'Agostino R.B.
        • Selker H.P.
        • Lau J.
        Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment.
        J Clin Epidemiol. 1997; 50: 401-410
        • Schmid C.H.
        • Brown E.N.
        Bayesian hierarchical models.
        Methods Enzymol. 2000; 321: 305-330
      2. Sampson M, Shamseer L, Bukutu C, Barrowman N, Moher D, Vohra S. Systematic reviews of N-of-1 methods, analysis and meta-analysis. Cochrane Canada 8th Annual Symposium, Ottawa: 2010.

        • Gabler N.B.
        • Duan N.
        • Vohra S.
        • Kravitz R.L.
        N-of-1 trials in the medical literature: a systematic review.
        Med Care. 2011; 49: 761-768
        • Schulz K.F.
        • Altman D.G.
        • Moher D.
        • for the CONSORT Group
        CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials.
        BMJ. 2010; 340: c332
        • Plint A.C.
        • Moher D.
        • Morrison A.
        • Schulz K.
        • Altman D.G.
        • Hill C.
        • et al.
        Does the CONSORT checklist improve the quality of reports of randomized controlled trials? A systematic review.
        Med J Aust. 2006; 185: 263-267