Potential Clinical and Economic Impact of Nonadherence with Osteoporosis Medications

This study aims to estimate the potential clinical and economic implications of therapeutic adherence to bisphosphonate therapy. A validated Markov microsimulation model was used to estimate the impact of varying adherence to bisphosphonate therapy on outcomes (the number of fractures and the quality-adjusted life-years [QALYs]), health-care costs, and the cost-effectiveness of therapy compared with no treatment. Adherence was divided into persistence and compliance, and multiple scenarios were considered for both concepts. Analyses were performed for women aged 65 years with a bone mineral density T-score of −2.5. Health outcomes and the cost-effectiveness of therapy improved significantly with increasing compliance and/or persistence. In the case of real-world persistence and with a medical possession ratio (MPR; i.e., the number of doses taken divided by the number of doses prescribed) of 100%, the QALY gain and the number of fractures prevented represented only 48 and 42% of the values estimated assuming full persistence, respectively. These proportions fell to 27 and 23% with an MPR value of 80%. The costs per QALY gained, for branded bisphosphonates (and generic alendronate), were estimated at €19,069 (€4,871), €32,278 (€11,985), and €64,052 (€30,181) for MPR values of 100, 80, and 60%, respectively, assuming real-world persistence. These values were €16,997 (€2,215), €24,401 (€6,179), and €51,750 (€20,569), respectively, assuming full persistence. In conclusion, poor compliance and failure to persist with osteoporosis medications results not only in deteriorating health outcomes, but also in a decreased cost-effectiveness of drug therapy. Adherence therefore remains an important challenge for health-care professionals treating osteoporosis.     

Models for Assessing the Cost-Effectiveness of the Treatment and Prevention of Osteoporosis

Received: 6 May 2002 / Accepted: 7 May 2002 Correspondence and offprint requests to: Niklas Zethraeus, Centre for Health Economics, Stockholm School of Economics, PO Box 6501, S-113 83 Stockholm, Sweden. Tel: +46 8 7369640. Fax: +46 8 302115. e-mail: henz@hhs.se     

Cost–Effectiveness of Osteoporosis Screening Followed by Treatment: The Impact of Medication Adherence

ObjectiveTo estimate the impact of medication adherence on the cost–effectiveness of mass-screening by bone densitometry followed by alendronate therapy for women diagnosed with osteoporosis.MethodsA validated Markov microsimulation model with a Belgian health-care payer perspective and a lifetime horizon was used to assess the cost per quality-adjusted life year (QALY) gained of the screening/treatment strategy compared with no intervention. Real-world adherence to alendronate therapy and full adherence over 5 years were both investigated. The real-world adherence scenario employed adherence data from published observational studies, and medication adherence was divided into persistence, compliance, and primary adherence. Uncertainty was investigated using one-way and probabilistic sensitivity analyses.ResultsAt 65 years of age, the costs per QALY gained because of the screening/treatment strategy versus no intervention are €32,008 and €16,918 in the real-world adherence and full adherence scenarios, respectively. The equivalent values are €80,836 and €40,462 at the age of 55 years, and they decrease to €10,600 and €1229 at the age of 75 years. Sensitivity analyses show that the presence of the upfront cost of case finding has a substantial role in the impact of medication adherence on cost–effectiveness.ConclusionThis study indicates that nonadherence with osteoporosis medications substantially increases the incremental cost–effectiveness ratio of osteoporosis screening strategies. All aspects of medication adherence (i.e., compliance, persistence, and primary adherence) should therefore be reported and included in pharmacoeconomic analyses, and especially in the presence of the upfront cost of case finding (such as screening cost).     

Lifetime absolute risk of hip and other osteoporotic fracture in Belgian women

ObjectivesTo estimate the lifetime absolute risks of hip and other osteoporotic fracture in Belgian women aged 60 years and to examine the effect of changes in baseline population fracture risk and changes in life expectancy.Materials and methodsEstimates were performed using a Markov microsimulation model and were based on the incidence of first fracture as well as life expectancy. Baseline scenario included projected mortality rates and increasing fracture incidence by 1% per year. Alternative scenarios were performed on age, life expectancy and trends in fracture incidence. Lifetime fracture risk for osteoporotic population (T-score ≤ − 2.5) was also estimated.ResultsIn the baseline scenario, lifetime absolute risks of hip fracture and of any major osteoporotic fracture (hip, clinical vertebral or wrist) were respectively 24.8% and 44.3%. Alternative scenarios showed that when assuming no change of age-specific fracture rates over time, these lifetime risks were 18.3% and 35.2%, while these values were 20.0% and 38.3% assuming no future mortality reductions. For osteoporotic women, these values were respectively 34.5% and 51.5%.ConclusionWe conclude that absolute lifetime fracture risks are substantial and that trends in fracture incidence and changes in life expectancy have a marked impact on absolute lifetime fracture risks.     

Development and Validation of a Markov Microsimulation Model for the Economic Evaluation of Treatments in Osteoporosis

Objective:  Markov models are increasingly used in economic evaluations of treatments for osteoporosis. Most of the existing evaluations are cohort-based Markov models missing comprehensive memory management and versatility. In this article, we describe and validate an original Markov microsimulation model to accurately assess the cost-effectiveness of prevention and treatment of osteoporosis.
Methods:  We developed a Markov microsimulation model with a lifetime horizon and a direct health-care cost perspective. The patient history was recorded and was used in calculations of transition probabilities, utilities, and costs. To test the internal consistency of the model, we carried out an example calculation for alendronate therapy. Then, external consistency was investigated by comparing absolute lifetime risk of fracture estimates with epidemiologic data.
Results:  For women at age 70 years, with a twofold increase in the fracture risk of the average population, the costs per quality-adjusted life-year gained for alendronate therapy versus no treatment were estimated at €9105 and €15,325, respectively, under full and realistic adherence assumptions. All the sensitivity analyses in terms of model parameters and modeling assumptions were coherent with expected conclusions and absolute lifetime risk of fracture estimates were within the range of previous estimates, which confirmed both internal and external consistency of the model.
Conclusion:  Microsimulation models present some major advantages over cohort-based models, increasing the reliability of the results and being largely compatible with the existing state of the art, evidence-based literature. The developed model appears to be a valid model for use in economic evaluations in osteoporosis.