Objective: Morphine-standardized doses are used in clinical practice and research to account for molecular potency. Ninety milligrams of morphine equivalents (MME) per day are considered a "high dose" risk threshold in guidelines, laws, and by payers. Although ubiquitously cited, the "CDC definition" of daily MME lacks a clearly defined denominator. Our objective was to assess denominator-dependency on "high dose" classification across competing definitions. Methods: To identify definitional variants, we reviewed literature and electronic prescribing tools, yielding 4 unique definitions. Using Prescription Drug Monitoring Programs data (July to September 2018), we conducted a population-based cohort study of 3,916,461 patients receiving outpatient opioid analgesics in California (CA) and Florida (FL). The binary outcome was whether patients were deemed "high dose" (>90 MME/d) compared across 4 definitions. We calculated I 2for heterogeneity attributable to the definition. Results: Among 9,436,640 prescriptions, 42% overlapped, which led denominator definitions to impact daily MME values. Across definitions, average daily MME varied 3-fold (range: 17 to 52 [CA] and 23 to 65 mg [FL]). Across definitions, prevalence of "high dose" individuals ranged 5.9% to 14.2% (FL) and 3.5% to 10.3% (CA). Definitional variation alone would impact a hypothetical surveillance study trying to establish how much more "high dose" prescribing was present in FL than CA: from 39% to 84% more. Meta-analyses revealed strong heterogeneity (I 2range: 86% to 99%). In sensitivity analysis, including unit interval 90.0 to 90.9 increased "high dose" population fraction by 15%. Discussion: While 90 MME may have cautionary mnemonic benefits, without harmonization of calculation, its utility is limited. Comparison between studies using daily MME requires explicit attention to definitional variation.
|Number of pages||10|
|Journal||Clinical Journal of Pain|
|State||Published - Aug 2021|
Bibliographical noteFunding Information:
Supported by FDA and BJA. US Food and Drug Administration, Silver Spring, MD (HHSF223201810183C) funded the efforts of N.D., B. A.C., and T.C. The US Department of Justice, Bureau of Justice Assistance, Washington, DC (2017-PM-BX-K038) funded the efforts of Y.W., J.B., and C.D. The BJA is a component of the Department of Justice’s Office of Justice Programs, which also includes the Bureau of Justice Statistics, the National Institute of Justice, the Office of Juvenile Justice and Delinquency Prevention, the Office for Victims of Crime, and the SMART Office. Funding agencies had no involve-ment in study design, analysis, interpretation, or decision to publish. N.D. is a part-time methods consultant to the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System of Denver Health and Hospitals Authority, a political subdivision of the State of Colorado. RADARS System had no knowledge of or involvement in this analysis. N.D. has no relationship with any pharmaceutical manufacturer or distributor. The remaining authors declare no conflict of interest.
© 2021 Lippincott Williams and Wilkins. All rights reserved.
- Prescription Drug Monitoring Programs (PDMP)
- milligrams of morphine equivalents (MME)
ASJC Scopus subject areas
- Clinical Neurology
- Anesthesiology and Pain Medicine