What is an N-of-1 trial? What is involved? Can I set up one with my treating physician? We are very honored to have Chad Ruoff, MD, a distinguished member of our Medical Advisory Board and an Adjunct Clinical Assistant Professor at the Stanford Center for Sleep Sciences and Medicine, answer these questions.
I just learned what an N-of-1 trial is. How do I set one up?
An N-of-1 trial is an experimental clinical study design used to study various treatment(s) in one patient. An N-of-1 trial allows the patient to try both active treatment(s) and placebo. This contrasts with more traditional research studies in which the patient is randomized to either placebo or an active treatment.
For example, in a N-of-1 trial, a patient could take medication “A” for a period of two weeks, then change to a placebo for a period of two weeks, then change to medication “B” for a period of two weeks, then back to placebo and repeat this sequence again. Sometimes there is a ‘washout period’, during which no drug is administered to a patient, to allow a return to his/her baseline. Ideally, the patient should be blinded from knowing whether he /she is taking medication “A”, “B”, or placebo. Further, it is even better if both the patient and physician/investigator are blinded from knowing whether the patient is taking medication “A”, “B”, or placebo.
The next step is to determine what test(s) will be used to evaluate the effectiveness of the medications/treatments. A simple way to evaluate a treatment response is to have the patient complete a survey or questionnaire (e.g., Epworth Sleepiness Scale) at the beginning and end of each period (i.e., subjective assessment). Another option, although much more expensive and labor intensive, would be to have the patient complete an objective test (e.g., nighttime sleep study or daytime sleep study) at the beginning and end of each period (i.e., objective assessment).
Although the idea of an N-of-1 trial seems very straightforward since it only requires one patient, there are many challenges and risks in developing and carrying out any research protocol. Given the complexity of creating and carrying out an N-of-1 trial, it is imperative to discuss any attempt to conduct research with your treating physician(s). If an N-of-1 trial isn’t feasible for some reason (e.g., the treating physician(s) might not have expertise in creating an N-of-1 trial), clinical care itself often starts out with one medication to treat a condition. If the patient does not respond to the first medication, then the treating physician will change to a different medication and so on. Therefore, clinical medicine in some ways resembles the design of an N-of-1 trial, except that in clinical medicine a patient should always understand what s/he is taking (i.e., not be blinded to the treatment) and rarely, if ever, is a placebo given.
Reference: 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: pp. 9-17
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Disclaimer for Ask The Doctor: The medical information provided is meant for educational purposes only and is not a substitute for professional medical care and advice. Each person is different, and questions about a personal health condition should be discussed with your own healthcare professional.