Prescription-event monitoring--recent progress and future horizons.

Abstract

Post-marketing surveillance (PMS) is essential because the safety database on newly licensed drugs is limited by both the number and characteristics of the patients involved. In the UK, for example, successful applications for product licences for medicines containing new active substances include, as a safety database, information on a median number of 1480 (range 129–9400) patients [1]. Most of these patients will have been carefully chosen to have only one disease being treated with one drug. Few, if any of them, will be typical of the patients likely to receive the drug once it has been marketed. The identification of uncommon, even if serious or lethal, adverse reactions from such a small number of highly selected patients is unlikely. This led the Committee on Safety of Drugs (the forerunner of today's Committee on Safety of Medicines) to conclude that ‘It is well recognised that no drug which is pharmacologically effective is without hazard. Furthermore not all hazards can be known before a drug is marketed: neither tests in animals nor clinical trials in patients will always reveal all the possible side effects of a drug. These may only be known when the drug has been administered to large numbers of patients over considerable periods of time’. The Committee on Safety of Drugs Annual Report [2] which contained these remarkable conclusions was for 1969/1970. Thus, for almost 30 years it has been recognised that drug safety in clinical practice cannot depend solely upon pre-marketing data. The backbone of the post-marketing techniques that have been developed to survey the use of newly marketed drugs in large populations is provided by the hypothesis-generating methods, including spontaneous adverse drug reaction (ADR) reporting and prescription-event monitoring (PEM). The findings of such studies can be confirmed or refuted by hypothesis-testing techniques, such as case-control or cohort studies or randomised controlled clinical trials. Computerised clinical data are currently available from completed PEM studies of 58 newly marketed medicines and, as shown in Table 1, these studies have an average cohort size of 10 624 (median 11 081; range 1371–17 329) patients. Thus, PEM frequently enlarges the available safety database on newly marketed medicines. It also provides information on the ‘real-world’ use of these medicines: the data show the age, sex and geographical distribution that typifies the everyday clinical use of these drugs in general medical practice. Table 1 Details of 58 complete PEM studies. This paper briefly reviews the methodology of PEM and the current and planned activities that relate to this technique.