National regulatory authorities can provide medication safety warnings on drug use. This project is looking into the influence of safety advisories relating to heart arrhythmias on drug utilization in 4 countries, including the United Kingdom and has two distinct parts. In part I a descriptive study is performed to describe time-trends in the use of 24 different drugs with a safety warnings issued and analyse differences before and after the date this warning was issued. In part II, we will assess whether issuing a warning for cardiac rhythm for 3 different drugs (citalopram, escitlopram, hydroxazine) has resulted in changing of prescribing these drugs to patients before and after the warning, looking at starting and stopping these drugs. Sertraline will be used a control drug. We will assess start/stopping of such drugs before and after the date of the warning and assess whether certain predictors such as cardiovascular disease, modify the way prescibers treat patients with these drugs.
This CPRD study is part of a multi-country study aiming to improve the understanding of the effects of national regulatory medication safety warnings on healthcare delivery and patient safety using data from the UK, Canada, Australia and Denmark. Quantitative analyses for this project include (I) an interrupted time series study to assess the association of drug safety advisories for 24 different drugs in the period 2009-2015 with changes in drug utilization before and after , and (II) a cohort study evaluating the impact of drug safety advisories relating to cardiac arrhythmias for citalopram/escitalopram and hydroxyzine.
We will identify all prescriptions for all relevant study drugs during the study period, 2 years before and 2 years after the advisory. In part I, the number of users each month is counted with the number of patients having at least one day of person-time in a month being the denominator. In part II, a cohort study will be conducted to determine whether patient risk factors, including underlying heart conditions, concomitant medication use, age, and gender, modifify the effect of cardiac arrhythmia advisories on citalopram/escitalopram/hydrozazine initiation and stopping. For each patient having a Read code for an indication for the use of these drugs, starts are defined as having a prescription of a study drug within 7 days of a visit. Stopping will be defined as not having a new prescription issued within 90 days of the end of a prior prescription.Otherwise the patient is classified as a continuer. The end of a prior prescription will be defined as the date of the prior prescription + days’ supply. Interrupted time series analysis (for I) and generalized linear models to estimate whether patient risk factors modifiy the effect of cardiac arrhythmia advisories on monthly initiation and stopping will be used (for II).
Part I: prevalence of drug use
Part II: Initiation; stopping of citalopram/escitalopram/sertraline/hydroxyzine
Patrick Souverein - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Aukje Mantel-Teeuwisse - Collaborator - Utrecht Institute for Pharmaceutical Sciences
Marie L De Bruin - Collaborator - Utrecht University