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Inches, Centimeters, and Yards: Overlooked Definition Choices Inhibit Interpretation of Morphine Equivalence
Nabarun Dasgupta1, Yanning Wang2, Jungjun Bae3,4
1Injury Prevention Research Center.
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 I2 for 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 (I2 range: 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.
Insights
The 90 mg morphine equivalents (MME) per day threshold for high-dose opioid prescribing is inconsistently applied due to varying calculation methods. This definitional variation significantly impacts patient classification and comparisons across studies, limiting the threshold's clinical utility.
Area of Science:
- Pharmacology
- Public Health
- Health Services Research
Background:
- Morphine-standardized doses are used to standardize opioid potency in clinical practice and research.
- The 90 mg morphine equivalents (MME) per day threshold is a widely cited risk threshold for high-dose opioid prescribing.
- Current definitions of daily MME lack a clearly defined denominator, leading to potential inconsistencies.
Purpose of the Study:
- To assess the impact of different denominator definitions on the classification of patients receiving high-dose opioid therapy.
- To evaluate the variability in daily MME calculations across competing definitions.
Main Methods:
- A population-based cohort study was conducted using Prescription Drug Monitoring Programs data from California and Florida (July-September 2018).
- Four unique definitions of daily MME were identified and compared.
- The binary outcome was the classification of patients as receiving
- high dose
- (>90 MME/d) across the different definitions.
Main Results:
- Average daily MME varied up to 3-fold across definitions, with prevalence of high-dose patients ranging from 3.5% to 14.2%.
- Definitional variation alone could alter the estimated difference in high-dose prescribing between Florida and California by 39% to 84%.
- Meta-analyses showed strong heterogeneity (I2 range: 86%–99%) attributable to definitional differences.
Conclusions:
- The 90 MME threshold's utility is limited without harmonized calculation methods.
- Comparisons between studies using daily MME require explicit attention to definitional variations to ensure accurate interpretation and reduce heterogeneity.
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