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What Ever Happened to N-of-1 Trials? Insiders' Perspectives and a Look to the Future

Authors

  • RICHARD L. KRAVITZ,

    1. University of California, Davis; Columbia University; New York State Psychiatric Institute; Miami University; University of California, Los Angeles
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  • NAIHUA DUAN,

    1. University of California, Davis; Columbia University; New York State Psychiatric Institute; Miami University; University of California, Los Angeles
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  • EDMUND J. NIEDZINSKI,

    1. University of California, Davis; Columbia University; New York State Psychiatric Institute; Miami University; University of California, Los Angeles
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  • M. CAMERON HAY,

    1. University of California, Davis; Columbia University; New York State Psychiatric Institute; Miami University; University of California, Los Angeles
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  • SASKIA K. SUBRAMANIAN,

    1. University of California, Davis; Columbia University; New York State Psychiatric Institute; Miami University; University of California, Los Angeles
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  • THOMAS S. WEISNER

    1. University of California, Davis; Columbia University; New York State Psychiatric Institute; Miami University; University of California, Los Angeles
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Address correspondence to: Richard L. Kravitz, Division of General Medicine, UC Davis School of Medicine, 4150 V. Street, Suite 2400 PSSB, Sacramento, CA 95817 (email: rlkravitz@ucdavis.edu).

Abstract

Context: When feasible, randomized, blinded single-patient (n-of-1) trials are uniquely capable of establishing the best treatment in an individual patient. Despite early enthusiasm, by the turn of the twenty-first century, few academic centers were conducting n-of-1 trials on a regular basis.

Methods: The authors reviewed the literature and conducted in-depth telephone interviews with leaders in the n-of-1 trial movement.

Findings: N-of-1 trials can improve care by increasing therapeutic precision. However, they have not been widely adopted, in part because physicians do not sufficiently value the reduction in uncertainty they yield weighed against the inconvenience they impose. Limited evidence suggests that patients may be receptive to n-of-1 trials once they understand the benefits.

Conclusions: N-of-1 trials offer a unique opportunity to individualize clinical care and enrich clinical research. While ongoing changes in drug discovery, manufacture, and marketing may ultimately spur pharmaceutical makers and health care payers to support n-of-1 trials, at present the most promising resuscitation strategy is stripping n-of-1 trials to their essentials and marketing them directly to patients. In order to optimize statistical inference from these trials, empirical Bayes methods can be used to combine individual patient data with aggregate data from comparable patients.

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