Cross-country Variation in Medicines Use. A Pharmaceutical System Perspective
(2013; 218 pages)

Thesis Utrecht University - with ref. - with summary in Dutch. The research presented in this PhD thesis was conducted under the umbrella of the Utrecht World Health Organization (WHO) Collaborating Centre for Pharmaceutical Policy and Regulation, which is based at the Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, the Netherlands. The Collaborating Centre aims to develop new methods for independent pharmaceutical policy research, evidence-based policy analysis and conceptual innovation in the area of policy making and evaluation in general. The research in this thesis was performed in collaboration with the Netherlands Institute for Health Services Research (NIVEL), Utrecht, the Netherlands.


Ensuring access to medical care is a challenge for governments and health care systems across the world. Choices need to be made about which medicine can be used and in what quantity because there are many (effective) medicines available on the market, but resources are limited. These choices may differ among countries and may be influenced by a (large) number of factors. In addition, it is likely that any given level of use of a specific medicine in one country is determined by a set of factors that might vary in another country. In the last decade an interest has arisen in studying the variation in medicines use in an integrated way, i.e. by including relevant pharmaceutical system parameters, to enhance our understanding of causes and consequences of this variation. This thesis includes studies on cross-national variation in medicines use from a pharmaceutical system perspective. The level of medicines use in various countries and across multiple medical conditions is measured, while also taking into account pharmaceutical system factors. An overview of national medicines policies and a global view on outpatient pharmaceutical consumption is followed by five comparative studies in Europe; two with regard to TNF alpha inhibitors (biologicals for the treatment of rheumatoid arthritis), two with regard to psychotropic medicines and one on time to market in relation to national participation to the European regulatory activity. These studies address the importance of the quality of data collection, and equal access to new medicines (TNFalpha inhibitors), the impact of cultural diversity and the impact of reimbursement delay and restrictions on medicines use (psychotropic medicines), and the contribution of EU member states to the regulatory process in light of the availability and uptake of medicines that received a granting of the market authorization in 2004. Finally, two studies focus on the impact of a single policy: the delisting of benzodiazepines in the Netherlands in 2009. One study describes the impact on volume of use in patients newly diagnosed with anxiety and or sleeping disorder, and one assesses the importance of information services for patients in the context of this policy intervention. The thesis identified two critical factors for performing a successful study on the extent and causes of cross-national variation in medicines use from a pharmaceutical perspective;

  1. to improve data harmonization and combine data(sources) and
  2. to have adequate information on the environmental context.

By comparing and combining datasets researchers may detect more subtle and complex associations among variables, which in the end may improve the interpretation of variation caused by historical and societal developments – the contextual environment. Furthermore, it is essential to hypothesize why certain pharmaceutical system factors may influence medicines use, and by which mechanisms. Finally, the studies in this thesis have shown that the currently available databases and epidemiological methods provide ample opportunities for studying cross-national variation in medicines use from a pharmaceutical system perspective.

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