The n-of-1 trial: An opportunity for complementary and alternative medicine evaluation

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Jun 13 2006

This interesting article was brought to my attention by Dr. Tony Buffington at Ohio State. It is an extremely interesting rationale for the use of n-of-1 randomized trials, particularly for complementary and alternative medicine evaluation in the treatment of chronic, difficult to treat disorders. PBS/IC would seem to come under this rubric.

n-of 1 trials are single-patient randomized controlled trials (RCT) with multiple crossovers. They are applicable to chronic recurrent conditions that require long-term noncurative treatment. The study design is tailored to the individual condition being investigated. A rapid onset and offset of action of the intervention is advantageous. Shorter treatment periods allow for more periods of comparison and better odds of achieving statistical significance. A washout period may be necessary. Outcome measures can be negotiated between physician and investigator. The design uses a series of pairs of treatment periods. The patient receives active treatment during one period of each pair. In the other period the patients is given either an accepted standard treatment or placebo. Random allocation determines the order of the two treatment periods within each pair. Clinician and patient are blinded. Generally 3 pairs of treatment periods will suffice unless there is a dichotomous outcome which will require 5 paired periods to achieve statistical significance.

This article by Johnston and colleagues from the University of Alberta, Canada provides a compelling case for considering the use of n-of-1 trials in a syndrome like PBS/IC as a relatively inexpensive way to pick up signals that may warrant the time and expense and large numbers of patients required for a standard RCT. Perhaps this would be a better way to choose drugs to study than basing such decisions on larger, uncontrolled, anecdotal series.

By Philip M. Hanno, MD

Reference:

Journal of Alternative and Complementary Medicine, 10(6), 979-984, 2004.