Comparison of dispensed medications and forensic-toxicological findings to assess pharmacotherapy in the Swedish population 2006 to 2013

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: cardiovascular agents; drug utilization; forensic toxicology; pharmacoepidemiology; prescription registry; psychotropic drugs; validation.