From prescription drug purchases to drug use periods – a second generation method (PRE2DUP)

Abstract

Background: Databases of prescription drug purchases are now widely used in pharmacoepidemiologic studies. Several methods have been used to generate drug use periods from drug purchases to investigate various aspects; e.g., to study associations between exposure and outcome. Typically, such methods have been fairly simplistic, with fixed assumptions of drug use pattern and or dose (for example, the assumed usage of 1 tablet per day). This paper describes a novel PRE2DUP method that constructs drug use periods from purchase histories, and verified by a validation based on an expert evaluation of the drug use periods generated by the method. Methods: The PRE2DUP method is a novel approach based on mathematical modelling of personal drug purchasing behaviors. The method uses a decision procedure that includes each person's purchase history for each ATC code, processed in a chronological order. The method constructs exposure time periods and estimates the dose used during the period by considering the purchased amount in Defined Daily Doses (DDDs), which is recorded in the prescription register database. This method takes account of stockpiling of drugs, personal purchasing pattern; i.e., regularity of the purchases, and periods of hospital or nursing home care where drug use is not recorded in the prescription register. The method can be applied to a variety of drug classes with different doses and use patterns by controlling restriction parameters for each ATC class, or even each drug package. In the presented example, the PRE2DUP method was applied to a register-based MEDALZ-2005 study cohort. All drug purchases (3,793,085) recorded in the Finnish prescription register between 2002 and 2009 for persons with Alzheimer's disease (28,093) were included. Results: Results of the expert-opinion based validation indicate that PRE2DUP method creates drug use periods with a relatively high correctness. Drugs with varying patterns of use and drugs used on a short-term basis only require more precise parameters. Conclusions: PRE2DUP method gives highly accurate drug use periods for most drug classes, especially those meant for long-term use.

Long-term use of benzodiazepines and related drugs among community-dwelling individuals with and without Alzheimer’s disease

“…The method also takes into account variations in purchase events. Purchases were linked to the same drug use period if the purchased amount of drug is enough to last to the next purchase with the calculated personal daily dose, allowing some stockpiling and taking into account the personal purchase regularity and possible hospitalizations (Tanskanen et al, 2015). Drugs during hospital stay are provided by the hospital and not recorded in the prescription register.…”

Antiepileptic Drug Use and the Risk of Stroke Among Community‐Dwelling People With Alzheimer Disease: A Matched Cohort Study

“…AED purchases were modeled to use periods for each person and for each Anatomical Therapeutic Chemical code during the follow‐up with a validated PRE2DUP (from prescription drug purchases to drug use periods) method18 In brief, based on each person's purchase history for each Anatomical Therapeutic Chemical code, this method constructs continuous drug use periods, calculates a sliding average of daily dose in defined daily doses, and combines purchases of the same drug by taking into account stockpiling, purchase regularity, dose changes, and periods of hospitalization/institutionalization18, 19 After modeling each drug substance, overlapping periods of AEDs were combined to retrieve time when any AED was used for use versus no‐use comparisons18 and similarly time on old versus new AED use.…”

Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease

“…We used a mathematical modelling method (PRE2DUP) to construct drug-use periods. 22 This allowed us to use time-dependent exposure in our analyses.…”

“…8,22 We based our model on sliding averages of daily dose, and we modelled each Anatomic Therapeutic Chemical classification system code separately for each participant according to purchase regularity, taking into account admissions to hospital, stockpiling of drugs and changing dose as described previously. 8,22 We defined use of benzodiazepines and Z-drugs by the following Anatomic Therapeutic Chemical classification system codes: N05BA and N05CD for benzodiazepines and N05CF for Z-drugs. Benzodiazepines prescribed in this study included diazepam, nitrazepam, chlordiazepoxide, clobazam, oxazepam, alprazolam, lorazepam and temazepam, whereas Z-drugs included zopiclone and zolpidem.…”