TY - JOUR
T1 - A Useful and Sustainable Role for N-of-1 Trials in the Healthcare Ecosystem
AU - Selker, Harry P.
AU - Cohen, Theodora
AU - D’Agostino, Ralph B.
AU - Dere, Willard H.
AU - Ghaemi, S. Nassir
AU - Honig, Peter K.
AU - Kaitin, Kenneth I.
AU - Kaplan, Heather C.
AU - Kravitz, Richard L.
AU - Larholt, Kay
AU - McElwee, Newell E.
AU - Oye, Kenneth A.
AU - Palm, Marisha E.
AU - Perfetto, Eleanor
AU - Ramanathan, Chandra
AU - Schmid, Christopher H.
AU - Seyfert-Margolis, Vicki
AU - Trusheim, Mark
AU - Eichler, Hans Georg
N1 - Funding Information:
This work was supported by the National Institutes of Health Center for Advancing Translational Science (NIH/NCATS) Grant Number UL1TR002544 in support of the Tufts Clinical and Translational Science Institute and by NIH/NCATS Grant Number U24TR001609 in support of the Johns Hopkins‐Tufts Trial Innovation Center.
Publisher Copyright:
© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics
PY - 2021
Y1 - 2021
N2 - Clinicians and patients often try a treatment for an initial period to inform longer-term therapeutic decisions. A more rigorous approach involves N-of-1 trials. In these single-patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double-blinded, random sequence of alternating periods to determine the most effective treatment for that patient. However, to date, these trials are rarely done outside of research settings and have not been integrated into general care where they could offer substantial benefit. Designating this classical, N-of-1 trial design as type 1, there also are new and evolving uses of N-of-1 trials that we designate as type 2. In these, rather than focusing on optimizing treatment for chronic diseases when multiple approved choices are available, as is typical of type 1, a type 2 N-of-1 trial tests treatments designed specifically for a patient with a rare disease, to facilitate personalized medicine. While the aims differ, both types face the challenge of collecting individual-patient evidence using standard, trusted, widely accepted methods. To fulfill their potential for producing both clinical and research benefits, and to be available for wide use, N-of-1 trials will have to fit into the current healthcare ecosystem. This will require generalizable and accepted processes, platforms, methods, and standards. This also will require sustainable value-based arrangements among key stakeholders. In this article, we review opportunities, stakeholders, issues, and possible approaches that could support general use of N-of-1 trials and deliver benefit to patients and the healthcare enterprise. To assess and expand the benefits of N-of-1 trials, we propose multistakeholder meetings, workshops, and the generation of methods, standards, and platforms that would support wider availability and the value of N-of-1 trials.
AB - Clinicians and patients often try a treatment for an initial period to inform longer-term therapeutic decisions. A more rigorous approach involves N-of-1 trials. In these single-patient crossover trials, typically conducted in patients with chronic conditions, individual patients are given candidate treatments in a double-blinded, random sequence of alternating periods to determine the most effective treatment for that patient. However, to date, these trials are rarely done outside of research settings and have not been integrated into general care where they could offer substantial benefit. Designating this classical, N-of-1 trial design as type 1, there also are new and evolving uses of N-of-1 trials that we designate as type 2. In these, rather than focusing on optimizing treatment for chronic diseases when multiple approved choices are available, as is typical of type 1, a type 2 N-of-1 trial tests treatments designed specifically for a patient with a rare disease, to facilitate personalized medicine. While the aims differ, both types face the challenge of collecting individual-patient evidence using standard, trusted, widely accepted methods. To fulfill their potential for producing both clinical and research benefits, and to be available for wide use, N-of-1 trials will have to fit into the current healthcare ecosystem. This will require generalizable and accepted processes, platforms, methods, and standards. This also will require sustainable value-based arrangements among key stakeholders. In this article, we review opportunities, stakeholders, issues, and possible approaches that could support general use of N-of-1 trials and deliver benefit to patients and the healthcare enterprise. To assess and expand the benefits of N-of-1 trials, we propose multistakeholder meetings, workshops, and the generation of methods, standards, and platforms that would support wider availability and the value of N-of-1 trials.
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U2 - 10.1002/cpt.2425
DO - 10.1002/cpt.2425
M3 - Review article
C2 - 34551122
AN - SCOPUS:85117408270
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
ER -