Database - Prescription Event Monitoring (D-PEM) study to identify, quantify and characterise identified adverse events associated with the use of a widely prescribed medication in primary care in the UK

Date of ISAC Approval: 
Lay Summary: 
Medication use is known to be associated with side effects also known as adverse events. These adverse events have been shown to occur at known frequencies in populations taking the medication and are listed on the summary of product characteristics (SmPC) and package leaflet (PL) documents associated with the medication. This study aims to investigate the usefulness of primary care electronic health records (EHR) databases in medication safety monitoring activities specifically related to the ability to detect and monitor adverse events. This study will assess whether specific adverse events known to be associated with the use of a widely prescribed medicinal product can be observed from patients medical records obtained from a primary care EHR database. Alendronic acid is widely prescribed in the treatment of osteoporosis (a bone-weakening disease) in post-menopausal women and has been selected as the study medication. This study will look at reasons for clinical consultations while patients are on the medication to identify and quantify known adverse events. It will also look at clinical consultations prior to starting the medication to describe these patients.
Technical Summary: 
This cohort study will assess whether specific identified safety risks associated with the use of a medication, widely prescribed in primary care, can be identified in a primary care EHR database. Patients will be identified from the CPRD GOLD database and the study conducted using the Database - Prescription Event Monitoring (D-PEM) methodology. The method of Prescription Event Monitoring (PEM) is well described and has been used for many years (1, 2). The PEM methodology in the UK was developed by the Drug Safety Research Unit and is a paper based method used to identify patients from prescriptions and detect safety signals from clinical event records. The purpose of this study is to examine whether using EHR database such as CPRD is feasible for conducting event monitoring and whether such use adds value to study methods in pharmacoepidemiology and pharmacovigilance and assess any problems or difficulties that may arise. Alendronic acid (once weekly 70mg dose) has been identified as the study drug. Patients will be identified who have been prescribed alendronic acid (between 2000 and 2003) and safety events on treatment identified within a 12 month observation period. Categorical data will be presented as tabulations; continuous data will be described using appropriate summary statistics. Reasons for consultations will be tabulated using grouping based on clinical code levels to allow for patterns to be identified and quantified as individual recording variation may preclude signal detection. Incidence risks and density calculations will be performed for safety events of interest. Incidence densities will be compared between time periods to allow for comparisons between: i) pre- and post-treatment exposure periods; ii) treatment exposure periods.
Health Outcomes to be Measured: 
- Reasons for consultations during primary care treatment - Dose and duration of treatment - Demographics of patients using alendronic acid (70mg once weekly) - Prior medical history (reasons for consultations)

Professor Saad Shakir - Chief Investigator - Drug Safety Research Unit
Dr Debabrata Roy - Corresponding Applicant - Drug Safety Research Unit
Dr Elizabeth Lynn - Collaborator - Drug Safety Research Unit
Dr Vicki Osborne - Collaborator - Drug Safety Research Unit