Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Pharmacoepidemiol Drug Saf. 2018 Oct;27(10):1112-1122. doi: 10.1002/pds.4426. Epub 2018 Mar 23.
To investigate person-level agreement between medication exposure as predicted using the PRE2DUP (a prescription-based design to estimate continuous drug use) method and postmortem toxicological findings, in the Swedish population during the years 2006 to 2013.
Using the Swedish National Board of Forensic Medicine's toxicology database and the Swedish National Board of Health and Welfare's registries on causes of death, dispensed medications, and in-patient care, forensic-toxicological findings were compared with prescription-based estimates of drug use for 27 medications. We modeled expected drug-use periods with the PRE2DUP using an algorithm of demonstrated high validity that evaluates personal drug-purchasing patterns with consideration to possible stockpiling of drugs and package information. Excluding criteria included self-inflicted death and recent in-patient care.
In data from 18 627 performed autopsies, as well as 10 160 instances of dispensed drug use, the agreement between PRE2DUP drug-use periods and forensic toxicology was, overall, moderate (Cohen's kappa: 0.56 [95% confidence interval {CI}: 0.55-0.57]) with a positive predictive value, or predicted adherence rate, of 46.0%. The group-level predicted adherence and agreement were highest for antidepressants, at 71.0% (Cohen's kappa: 0.74 [CI: 0.73-0.76]), and lowest for cardiovascular drugs, at 21.5% (Cohen's kappa: 0.33 [CI: 0.31-0.36]). Predicted recreational use (negative predictive value) was low for all investigated drugs (0.0%-1.4%). The biological half-life explained 29% (P = 0.003) of the variability of the false-positive rate.
Measured agreement between PRE2DUP-based drug-use estimates and forensic-toxicological findings is dependent upon a number of factors, including true continuous drug use and postmortem detectability of the investigated drugs, as well as the occurrence of unconventional dosing and true non-adherence.
研究 2006 年至 2013 年期间，瑞典人群中基于处方的 PRE2DUP（一种估计连续药物使用的处方设计）方法预测的药物暴露与死后毒理学发现之间的个体水平一致性。
利用瑞典国家法医局毒理学数据库和瑞典国家卫生福利局死因登记处、处方药物和住院治疗登记处，将法医毒理学发现与 27 种药物的基于处方的药物使用估计进行比较。我们使用一种经过验证的高有效性算法，使用 PRE2DUP 模型来预测预期的药物使用期，该算法评估个人药物购买模式，同时考虑药物的可能囤积和包装信息。排除的标准包括自杀和最近的住院治疗。
在 18627 例进行的尸检以及 10160 例处方药物使用数据中，PRE2DUP 药物使用期与法医毒理学的总体一致性为中度（Cohen's kappa：0.56 [95%置信区间 {CI}：0.55-0.57]），阳性预测值或预测的依从率为 46.0%。组水平预测的依从率和一致性最高的是抗抑郁药，为 71.0%（Cohen's kappa：0.74 [CI：0.73-0.76]），最低的是心血管药物，为 21.5%（Cohen's kappa：0.33 [CI：0.31-0.36]）。所有研究药物的预测娱乐性使用（阴性预测值）均较低（0.0%-1.4%）。生物半衰期解释了假阳性率的 29%（P=0.003）的变异性。
基于 PRE2DUP 的药物使用估计值与法医毒理学发现之间的测量一致性取决于多个因素，包括真正的连续药物使用和所研究药物的死后可检测性，以及非常规剂量和真正不依从的发生。
