英寸、厘米和码：被忽视的定义选择会阻碍吗啡等效性的解释。

Inches, Centimeters, and Yards: Overlooked Definition Choices Inhibit Interpretation of Morphine Equivalence.

机构信息

Injury Prevention Research Center.

Department of Health Outcomes & Biomedical Informatics, University of Florida College of Medicine, Gainesville, FL.

出版信息

Clin J Pain. 2021 Aug 1;37(8):565-574. doi: 10.1097/AJP.0000000000000948.

DOI:10.1097/AJP.0000000000000948

PMID:34116543

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8270512/

Abstract

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.

摘要

目的

在临床实践和研究中，使用吗啡标准化剂量来解释分子效力。在指南、法律和支付方中，每天 90 毫克吗啡当量（MME）被认为是“高剂量”风险阈值。尽管被广泛引用，但“CDC 定义”的每日 MME 缺乏明确界定的分母。我们的目标是评估在不同竞争定义中，分母对“高剂量”分类的依赖性。

方法

为了确定定义变体，我们回顾了文献和电子处方工具，得出了 4 个独特的定义。我们利用加利福尼亚州（CA）和佛罗里达州（FL）的处方药物监测计划数据（2018 年 7 月至 9 月），对 3916461 名接受门诊阿片类镇痛药治疗的患者进行了一项基于人群的队列研究。主要结局是比较 4 种定义时，患者是否被认为是“高剂量”（>90MME/d）。我们计算了由于定义引起的异质性的 I2。

结果

在 9436640 个处方中，有 42%存在重叠，这导致分母定义影响每日 MME 值。在不同的定义中，平均每日 MME 值相差 3 倍（范围：CA 为 17 至 52，FL 为 23 至 65mg）。在不同的定义中，“高剂量”人群的比例范围为 5.9%至 14.2%（FL）和 3.5%至 10.3%（CA）。仅定义上的差异就会影响一项试图确定佛罗里达州比加利福尼亚州“高剂量”处方增加多少的假设监测研究：从增加 39%到增加 84%。荟萃分析显示存在很强的异质性（I2 范围：86%至 99%）。在敏感性分析中，包括单位区间 90.0 至 90.9，将“高剂量”人群比例增加了 15%。