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N-of-1 Trials in the Medical Literature: A Systematic Review

Gabler, Nicole B. PhD, MHA*; Duan, Naihua PhD†,‡; Vohra, Sunita MD, FRCPC, MSc§; Kravitz, Richard L. MD, MSPH

doi: 10.1097/MLR.0b013e318215d90d
Original Articles
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Background N-of-1 trials (multiple crossover studies conducted in single individuals) may be ideal for determining individual treatment effects and as a tool to estimate heterogeneity of treatment effects (HTE) in a population. However, comprehensive data on n-of-1 trial methodology and analysis is lacking. We performed this study to describe n-of-1 trial characteristics, examine treatment changes resulting from n-of-1 trial participation, and to determine if trial reporting is adequate for estimating HTE.

Methods We undertook a systematic review of n-of-1 trials published between 1985 and December 2010. Included trials were those having individual treatment episodes as the unit of randomization and reporting individual-specific treatment effects. We abstracted trial characteristics, treatment change information, and analytic methods.

Results We included 108 trials reporting on 2154 participants. Approximately half (49%) of the trials used a statistical cutoff to determine a superior treatment, whereas the remainder used a graphical comparison (25%) or a clinical significance cutoff (20%). Sixty-seven trials, reporting on 488 people, provided treatment change information: 54% of participants had subsequent treatment decisions consistent with the results of the trial, 8% had decisions inconsistent with trial results, and 38% had ambiguous results. Less than half of the trials (45%) reported adequate information to facilitate the calculation of HTE.

Conclusion N-of-1 trials are a useful tool for enhancing therapeutic precision in a range of conditions and should be conducted more often. To facilitate future meta-analysis, and the estimation of HTE, researchers reporting n-of-1 trial results should clearly describe individual data.

*Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA

New York State Psychiatric Institute

Departments of Psychiatry and Biostatistics, Columbia University, New York, NY

§CARE Program, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

Department of Internal Medicine and Center for Healthcare Policy and Research, University of California, Davis, CA

This project was funded by Pfizer, Inc. Dr Vohra receives salary support from Alberta Innovates–Health Solutions.

Reprints: Nicole B. Gabler, PhD, MHA, University of Pennsylvania School of Medicine, 110 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021. Email: gabler@upenn.edu.

© 2011 Lippincott Williams & Wilkins, Inc.