This report explores the range of possible causes that might explain observed international variations in the usage of medicines for selected disease areas: dementia, osteoporosis, cancer, diabetes and hepatitis C. Commissioned by the UK Department of Health, through its Policy Research Programme, it complements a quantitative analysis of medicines uptake carried out by the Office for Health Economics (OHE) of medicines uptake across 16 classes of medicines in 13 high-income countries in 2012/13. Both studies build on an earlier study led by Professor Sir Mike Richards (UK) into the extent and causes of international variations in drug usage, published in 2010. Drawing on a rapid evidence assessment, we explore, for each of the five disease areas, epidemiological factors such as the disease burden and aspects of health system and service organisation that were shown to have a direct or indirect impact on drug usage, such as reimbursement mechanisms, access to diagnosis and treatment more broadly. We also provide a summary overview of key features of the health systems and of the principles of drug assessment or approval processes across the countries included in the OHE analysis. We find that a range of factors are likely to play a role in explaining international variation in medicines use, but their relative importance will vary depending on the disease area in question and the system context. Any given level of use of a given medicine in one country is likely determined by a set of factors the combination and the relative weight of which will be different in another country.