(2003; 49 pages)
1.1. Definition and domains
Drug utilization; pharmacoepidemiology; pharmacosurveillance; pharmacovigilance
• Drug utilization research was defined by WHO in 1977 as «the marketing, distribution, prescription, and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences». Since then, a number of other terms have come into use and it is important to understand the interrelationships of the different domains.
• Epidemiology has been defined as «the study of the distribution and determinants of health-related states and events in the population, and the application of this study to control of health problems».
• Pharmacoepidemiology applies epidemiological methods to studies of the clinical use of drugs in populations. A modern definition of pharmacoepidemiology is: «the study of the use and effects/side-effects of drugs in large numbers of people with the purpose of supporting the rational and cost-effective use of drugs in the population thereby improving health outcomes».
• Pharmacosurveillance and pharmacovigilance are terms used to refer to the monitoring of drug safety, for example, by means of spontaneous adverse-effect reporting systems, case-control and cohort studies.
Pharmacoepidemiology may be drug-oriented, emphasizing the safety and effectiveness of individual drugs or groups of drugs, or utilization-oriented aiming to improve the quality of drug therapy through pedagogic (educational) intervention. Drug utilization research may also be divided into descriptive and analytical studies. The emphasis of the former has been to describe patterns of drug utilization and to identify problems deserving more detailed studies.
Analytical studies try to link data on drug utilization to figures on morbidity, outcome of treatment and quality of care with the ultimate goal of assessing whether drug therapy is rational or not. Sophisticated utilization-oriented pharmacoepidemiology may focus on the drug (e.g. dose-effect and concentration-effect relationships), the prescriber (e.g. quality indices of the prescription),or the patient (e.g. selection of drug and dose, and comparisons of kidney function, drug metabolic phenotype/genotype, age, etc.).
Drug utilization research is thus an essential part of pharmacoepidemiology as it describes the extent, nature and determinants of drug exposure. Over time, the distinction between these two terms has become less sharp, and they are sometimes used interchangeably. However, while drug utilization studies often employ various sources of information that focus on drugs (e.g. aggregate data from wholesale and prescription registers) the term epidemiology implies defined populations in which drug use can be expressed in terms of incidence and prevalence (see chapter 1.2.1).
Together, drug utilization research and pharmacoepidemiology may provide insights into the following aspects of drug use and drug prescribing.
• Pattern of use: This covers the extent and profiles of drug use and the trends in drug use and costs over time.
• Quality of use: This is determined using audits to compare actual use to national prescription guidelines or local drug formularies.1 Indices of quality of drug use may include the choice of drug (compliance with recommended assortment), drug cost (compliance with budgetary recommendations), drug dosage (awareness of inter-individual variations in dose requirements and age-dependence), awareness of drug interactions and adverse drug reactions, and the proportion of patients who are aware of or unaware of the costs and benefits of the treatment.
1 An audit in drug use was defined by Crooks (1979) as an examination of the way in which drugs are used in clinical practice carried out at intervals frequent enough to maintain a generally accepted standard of prescribing.
• Determinants of use: These include user characteristics (e.g. sociodemographic parameters and attitudes towards drugs), prescriber characteristics (e.g. speciality, education and factors influencing therapeutic decisions) and drug characteristics (e.g. therapeutic properties and affordability).
• Outcomes of use: These are the health out comes (i.e. the benefits and adverse effects) and the economic consequences.
The initial focus of pharmacoepidemiology was on the safety of individual drug products (pharmacosurveillance), but it now also includes studies of their beneficial effects. The driving force behind this development was a growing awareness that the health outcomes of drug use in the rigorous setting of randomized clinical trials are not necessarily the same as the health outcomes of drug use in everyday practice. The clinical trials needed to obtain marketing authorization for new drugs involve limited numbers of carefully selected patients, who are treated and followed-up for a relatively short time in strictly controlled conditions. As a result, such trials do not accurately reflect how drug use will affect health outcomes in everyday practice under everyday circumstances. Pharmacoepidemiological studies often make useful contributions to our knowledge about effectiveness and safety, because, unlike clinical trials, they assess drug effects in large, heterogeneous populations of patients over longer periods.
Drug utilization research also provides insight into the efficiency of drug use, i.e. whether a certain drug therapy provides value for money and the results of such research can be used to help to set priorities for the rational allocation of health care budgets.