TY - JOUR
T1 - Evaluating the stability of opioid efficacy over 12 months in patients with chronic noncancer pain who initially demonstrate benefit from extended release oxycodone or hydrocodone
T2 - Harmonization of Food and Drug Administration patient-level drug safety study data
AU - Farrar, John T.
AU - Bilker, Warren B.
AU - Cochetti, Philip T.
AU - Argoff, Charles E.
AU - Haythornthwaite, Jennifer
AU - Katz, Nathaniel P.
AU - Gilron, Ian
N1 - Funding Information:
J.T. Farrar received research grants and contracts from the US Food and Drug Administration and National Institutes of Health as well as consulting fees from Analgesic Solutions, Aptinyx, Biogen, Opioid Postmarketing Consortium, Daiichi Sankyo, DepoMed, Evadera, Jansen, Lilly, Novartis, Vertex, and Pfizer; DSMB services from NIH-NIA; and Cara Therapeutics. W.B. Bilker served as a member of a DSMB for Genentech. C.E Argoff served as a consultant for Collegium Pharmaceuticals, Teva Pharmaceuticals, Pfizer, Kaleo, Daiichi Sankyo, and Astra Zeneca. J. Haythornthwaite serves as the Treasurer of the United States Association for the Study of Pain. N.P. Katz is an employee of WCG Analgesic Solutions, a clinical research services company with many clients in the pharmaceutical and medical device industry. I. Gilron received industry research support from Biogen, Eupraxia, Novaremed, and Teva. The remaining authors have no conflicts of interest to declare.
Funding Information:
This work was funded by FDA-BAA-17-00123 HHSF223201710131C. The article was written solely by the authors but was reviewed by the Office of Neuroscience-Division of Anesthesiology, Addiction Medicine, and Pain Medicine (DAAP) at the Food and Drug Administration for confidentiality issues and to provide feedback on the clarity of manuscript. J.T. Farrar was the principal author. W.B. Bilker was the principal statistician, and P.T. Cochetti was the data analyst. All three had direct access to the FDA DAARTS and all available data. Drs. Charles E Argoff, Ian Gilron, Jennifer Haythornthwaite, and Nathaniel P. Katz served as primary consultants on the analysis from the outset of the project with input at multiple time points, and each thoroughly reviewed and commented on the article. The study results have been presented to the FDA had been submitted for presentation at the International Association for the Study of Pain in 2020 in Amsterdam which was cancelled.
Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and either physical function or pain interference in patients treated for 12 months with abuse deterrent formulations of oxycodone and hydrocodone. All available studies in the Food and Drug Administration Document Archiving, Reporting, and Regulatory Tracking System were included. Patient-level demographics, baseline data, exposure, and outcomes were harmonized. Individual patient slopes were calculated from a linear model of pain, physical function, and pain interference to determine response over time. Opioid dose was summarized by change between baseline and the final month of observation. Patients with stable or less pain, stable or lower opioid dose, and stable or better physical function (where available) met our prespecified criteria for maintaining long-term benefit from chronic opioids. Of the complete data set of 3192 patients, 1422 (44.5%) maintained their pain level and opioid dose. In a secondary analysis of 985 patients with a measured physical function, 338 (34.3%) maintained their physical function in addition to pain and opioid dose. Of 2040 patients with pain interference measured, 788 (38.6%) met criteria in addition. In a carefully controlled environment, about one-third of patients successfully titrated on opioids to treat chronic noncancer pain demonstrated continued benefit for up to 12 months.
AB - Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and either physical function or pain interference in patients treated for 12 months with abuse deterrent formulations of oxycodone and hydrocodone. All available studies in the Food and Drug Administration Document Archiving, Reporting, and Regulatory Tracking System were included. Patient-level demographics, baseline data, exposure, and outcomes were harmonized. Individual patient slopes were calculated from a linear model of pain, physical function, and pain interference to determine response over time. Opioid dose was summarized by change between baseline and the final month of observation. Patients with stable or less pain, stable or lower opioid dose, and stable or better physical function (where available) met our prespecified criteria for maintaining long-term benefit from chronic opioids. Of the complete data set of 3192 patients, 1422 (44.5%) maintained their pain level and opioid dose. In a secondary analysis of 985 patients with a measured physical function, 338 (34.3%) maintained their physical function in addition to pain and opioid dose. Of 2040 patients with pain interference measured, 788 (38.6%) met criteria in addition. In a carefully controlled environment, about one-third of patients successfully titrated on opioids to treat chronic noncancer pain demonstrated continued benefit for up to 12 months.
KW - 12-month studies
KW - Back pain
KW - Chronic noncancer pain
KW - FDA
KW - Individual patient data
KW - Meta-analysis
KW - Opioid
KW - Osteoarthritis
KW - Treatment
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UR - http://www.scopus.com/inward/citedby.url?scp=85122305159&partnerID=8YFLogxK
U2 - 10.1097/j.pain.0000000000002331
DO - 10.1097/j.pain.0000000000002331
M3 - Article
C2 - 34261978
AN - SCOPUS:85122305159
SN - 0304-3959
VL - 163
SP - 47
EP - 57
JO - Pain
JF - Pain
IS - 1
ER -