In pharmacoepidemiology studies, exposure data originate mainly from four sources: data on prescribing (e.g. CPRD primary care data), data on dispensing (e.g. PHARMO outpatient pharmacy database), data on payment for medication (namely claims data, e.g. IMS LifeLink PharMetrics Plus) or from data collected from surveys. The population included in these data sources follows a process of attrition: drugs that are prescribed are not necessarily dispensed, and drugs that are dispensed are not necessarily ingested. In Primary non-adherence in general practice: a Danish register study (Eur J Clin Pharmacol 2014;70(6):757–63), 9.3% of all prescriptions for new therapies were never redeemed at the pharmacy, although with some differences between therapeutic and patient groups. The attrition from dispensing to ingestion is even more difficult to measure, as it involves uncertainties about what dispensed drugs are actually taken by the patients and about the patients’ ability to account accurately for their intake. In particular, paediatric adherence is additionally dependent on parents.
Exposure definitions can include simple dichotomous variables (e.g. ever exposed vs. never exposed) or they can be more detailed, including estimates of exposure windows (e.g. current vs. past exposure) or levels of exposure (e.g. current dosage, cumulative dosage over time). Consideration should be given to the level of detail available from the data sources on the timing of exposure, including the quantity prescribed, dispensed or ingested and the capture of dosage instructions when evaluating the feasibility of constructing such variables. This will vary across data sources and exposures (e.g. estimating contraceptive pill ingestion is typically easier than estimating rescue medication for asthma attacks). Discussions with clinicians regarding sensible assumptions will inform variable definition.
The Methodology chapter of the book Drug Utilization Research. Methods and Applications (M. Elseviers, B. Wettermark, A.B. Almarsdottir et al. Ed. Wiley Blackwell, 2016) discusses different methods for data collection on drug utilisation.
|10. Specific topics|
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|