Overview

The PEM technique is most applicable for new drugs intended for long term widespread use. PEM is a hypothesis generating technique, however, the large database with data on 900,000 patients can be used for hypothesis testing.

Introduction

The thalidomide disaster of the early 1960s produced an estimated 10,000 deformed babies in the countries in which the drug was widely used in early pregnancy. This disaster led directly to the establishment in Europe of the modern drug regulatory mechanisms. In the UK these mechanisms were first enacted into law by the Medicines Act, 1968. Even before this Act was implemented it was officially recognised that no drug which is pharmacologically effective is entirely without hazard and not all hazards can be known before a drug is marketed.

Thus, post-marketing surveillance (PMS) of new drugs is imperative to quantify common adverse drug reactions (ADRs) and to identify rare adverse reactions. In the UK the only form of PMS which prompts all doctors using new drugs to report the events which follow their use is Prescription-Event Monitoring (PEM). This method of pharmacovigilance is undertaken by the Drug Safety Research Unit (DSRU) at Southampton to examine the safety of new drugs intended for widespread use in primary care.

At the time when a new drug is marketed the clinical safety database is very limited and comprises a rather small number of patients. By contrast, computerised clinical data are available from PEM concerning 88 newly marketed medicines and these studies have an average cohort size of 10,942 patients. PEM therefore substantially enlarges the clinical safety database and in many cases provides almost a tenfold increase in size of these safety data. It is of importance that the PEM data represent the ‘real world’ use of the newly marketed medicines in the age and sex distribution and with the concurrent medication that typifies everyday practical clinical use of the new drug.

PEM is a non-interventional observational cohort technique. It is non-interventional in the sense that nothing happens to interfere with the doctor’s decision regarding which drug to prescribe for each individual patient. The technique relies upon the collection of individual prescriptions once these have been issued to the patients and dispensed by pharmacists. The DSRU collects details of the prescriptions for the drugs it is monitoring and thereby records information on the first 20,000-50,000 patients given the new drug. This information provides the exposure data. After a suitable interval the doctors who prescribed the drug being monitored are sent green form questionnaires on which they are asked to record events reported by the patient subsequent to the prescription. The information on these green forms provides the outcome data.

Objectives

PEM seeks to identify the events recorded following the use of newly marketed drugs selected for monitoring by the DSRU. These event data are assembled from large cohorts of patients and are used to identify suspected adverse drug reactions.