Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators

Todd C Skaar; Rachel A Myers; Roger B Fillingim; John T Callaghan; Emily Cicali; Michael T Eadon; Erica N Elwood; Geoffrey S Ginsburg; Sheryl Lynch; Khoa A Nguyen; Aniwaa Owusu Obeng; Haesuk Park; Victoria M Pratt; Marc Rosenman; Azita Sadeghpour; Saskia Shuman; Rajbir Singh; Emma M Tillman; Simona Volpi; Kristin Wiisanen; Almut G Winterstein; Carol R Horowitz; Deepak Voora; Lori Orlando; Hrishikesh Chakraborty; Sara Van Driest; Josh F Peterson; Larisa A Cavallari; Julie A Johnson; Paul R Dexter; IGNITE Pragmatic Trials Network

doi:10.1111/cts.70005

Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators

Clin Transl Sci. 2024 Aug;17(8):e70005. doi: 10.1111/cts.70005.

Authors

Todd C Skaar¹, Rachel A Myers², Roger B Fillingim³, John T Callaghan¹, Emily Cicali⁴, Michael T Eadon^{1

5}, Erica N Elwood⁴, Geoffrey S Ginsburg⁶, Sheryl Lynch¹, Khoa A Nguyen⁴, Aniwaa Owusu Obeng^{7

8

9}, Haesuk Park^{10

11}, Victoria M Pratt¹², Marc Rosenman^{13

14}, Azita Sadeghpour¹⁵, Saskia Shuman¹⁶, Rajbir Singh¹⁷, Emma M Tillman¹, Simona Volpi¹⁸, Kristin Wiisanen⁴, Almut G Winterstein^{10

11}, Carol R Horowitz¹⁹, Deepak Voora¹⁵, Lori Orlando¹⁵, Hrishikesh Chakraborty²⁰, Sara Van Driest²¹, Josh F Peterson²², Larisa A Cavallari⁴, Julie A Johnson⁴, Paul R Dexter^{23

24}; IGNITE Pragmatic Trials Network

Affiliations

¹ Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Medicine, Clinical Research Unit, Duke University School of Medicine, Duke University, Durham, North Carolina, USA.
³ Department of Community Dentistry and Behavioral Science, University of Florida College of Dentistry, Gainesville, Florida, USA.
⁴ Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
⁵ Division of Nephrology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁶ All of Us Research Program, National Institutes of Health, Bethesda, Maryland, USA.
⁷ Pharmacy Department, Mount Sinai Health System, New York, New York, USA.
⁸ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁹ Department of Medicine, Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁰ Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
¹¹ Center for Drug Evaluation and Safety, University of Florida, Gainesville, Florida, USA.
¹² Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹³ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁴ Ann & Robert H. Lurie Children's Hospital of Chicago and Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
¹⁵ Duke Precision Medicine Program, Department of Medicine, Duke University, Durham, North Carolina, USA.
¹⁶ The Institute for Family Health, New York, New York, USA.
¹⁷ Department of Medicine, Meharry Medical College, Nashville, Tennessee, USA.
¹⁸ Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland, USA.
¹⁹ Institute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
²⁰ Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA.
²¹ Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²² Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²³ Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²⁴ Regenstrief Institute, Inc., Indianapolis, Indiana, USA.

Abstract

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.

Publication types

Multicenter Study
Pragmatic Clinical Trial

MeSH terms

Adult
Analgesics, Opioid* / adverse effects
Analgesics, Opioid* / therapeutic use
Chronic Pain* / drug therapy
Cytochrome P-450 CYP2D6* / genetics
Cytochrome P-450 CYP2D6* / metabolism
Female
Humans
Male
Middle Aged
Pain Management / methods
Pain Measurement
Pharmacogenomic Testing
Precision Medicine / methods

Substances

Analgesics, Opioid
Cytochrome P-450 CYP2D6