@article{5a63fd7a3d61433d8cba0f1d23ce88b9,
title = "Demonstrating Heterogeneity of Treatment Effects Among Patients: An Overlooked but Important Step Toward Precision Medicine",
abstract = "Although heterogeneity in the observed outcomes in clinical trials is often assumed to reflect a true heterogeneous response, it could actually be due to random variability. This retrospective analysis of four randomized, double-blind, placebo-controlled multiperiod (i.e., episode) crossover trials of fentanyl for breakthrough cancer pain illustrates the use of multiperiod crossover trials to examine heterogeneity of treatment response. A mixed-effects model, including fixed effects for treatment and episode and random effects for patient and treatment-by-patient interaction, was used to assess the heterogeneity in patients{\textquoteright} responses to treatment during each episode. A significant treatment-by-patient interaction was found for three of four trials (P < 0.05), suggesting heterogeneity of the effect of fentanyl among different patients in each trial. Similar analyses in other therapeutic areas could identify conditions and therapies that should be investigated further for predictors of treatment response in efforts to maximize the efficiency of developing precision medicine strategies.",
author = "Gewandter, {Jennifer S.} and McDermott, {Michael P.} and Hua He and Shan Gao and Xueya Cai and Farrar, {John T.} and Katz, {Nathaniel P.} and Markman, {John D.} and Stephen Senn and Turk, {Dennis C.} and Dworkin, {Robert H.}",
note = "Funding Information: Financial support for this project was provided by the ACTTION public-private partnership, which has received unrestricted research contracts, grants, or other revenue from the FDA, multiple pharmaceutical and device companies, philanthropy, and other sources. Funding Information: Financial support for this project was provided by the ACTTION public-private partnership, which has received unrestricted research contracts, grants, or other revenue from the FDA, multiple pharmaceutical and device companies, philanthropy, and other sources. This article was reviewed and approved by the Executive Committee of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public?private partnership with the US Food and Drug Administration (FDA). Publisher Copyright: {\textcopyright} 2019 The Authors Clinical Pharmacology & Therapeutics {\textcopyright} 2019 American Society for Clinical Pharmacology and Therapeutics",
year = "2019",
month = jul,
doi = "10.1002/cpt.1372",
language = "English",
volume = "106",
pages = "204--210",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Wiley-Blackwell",
number = "1",
}