Fig. 5 Cost-effectiveness of an agent according to price for a woman from Sweden aged 65 years and a twofold increased risk of fracture. The shaded area approximates the willingness to pay by NICE in the UK. The lower slope (triangles) assumes no MG-132 concentration adverse effect of the agent on quality

of life, whereas the upper slope (squares) assumes a 1% decrease in quality of life due to adverse effects of the agent The impact of poor adherence (rather than side effects) on cost-effectiveness is a relatively recent field of health economics with the creation of models that capture the elements of adherence [22, 68]. Poor persistence results in lower costs and lower effectiveness so that the effects VX-770 Palbociclib ic50 move in the same direction and may have marginal impact on the ratio of cost with effectiveness. This, however, neglects the acquisition costs to identify the patient (BMD tests, visits to a physician, etc.) so that cost-effectiveness is adversely affected. The problem is compounded by poor compliance when patients may

take their bisphosphonate in a non-fasting state or with calcium-containing liquids. Under these circumstances, the cost remains the same (patients take the drug), but the effectiveness is reduced. When comparing full adherence with partial adherence, the variables that on average had the greatest beneficial effect on the incremental cost-effectiveness included the efficacy of the intervention, drug price, underlying very risk of fractures, the fraction of benefit assigned to partial adherence, and fracture-related costs. For example, a 1% increase in drug effect lowered the incremental cost-effectiveness ratio (ICER) by 2.2%, and a 1% increase in the drug price

of the high-adherence comparator increased the ICER by 2.7% [69]. The principal effect of poor adherence is that it leaves large groups of patients untreated, such that the public health objectives of fracture reduction are not met. Interventions that are associated with high adherence have a considerable impact on the number of avoided fractures—a feature that appears questionable in the case of generic bisphosphonates. Acknowledgements This review was developed following a meeting on generic bisphosphonates organised by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) in Paris, December 2010, the findings of which were reviewed at an ESCEO-FROMO Symposium of the IOF-ESCEO European Congress on Osteoporosis and Osteoarthritis in Valencia, March 2011.