|Incorporating adherence into health economic modelling of osteoporosis
|Strom O, Borgstrom F, Kanis JA, Jonsson B
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
The objective was to examine the impact of adherence on the cost-effectiveness of drugs for patients with osteoporosis. The authors concluded that improved adherence led to relevant benefits, but that these might be offset by increased intervention costs. The study appears to have been based on valid methodology, but the data sources were only partially reported. In general, the authors’ conclusions appear to be valid.
Type of economic evaluation
The objective was to examine the impact of adherence on the cost-effectiveness of drugs for patients with osteoporosis.
The comparators were two hypothetical medications, one of which conferred optimal or full adherence and was 50% more costly, while the other conferred partial adherence. In full adherence, patients stayed on the treatment for as long as it was intended and received the full anti-fracture effect. In partial adherence, patients were at risk of dropping out of treatment and had a fraction of the benefit that a fully compliant patient would have. Both treatments were administered for five years. A third strategy of no treatment, with an intake of calcium and vitamin D, was also considered.
Sweden/primary and secondary care.
This economic evaluation was based on an individual state transition model. The time horizon was 30 years or until death, whichever came first. The authors stated that a societal perspective was adopted.
The clinical data came from a selection of known, relevant studies, which appear to have been selected by the authors. Little information on the data sources was provided. The risk of dropping out within the first three years was derived from a large US health care claims database. The epidemiological data and risk of fracture for osteoporotic patients were taken from Swedish data, including registries and databases. The treatment effect was based on a hypothetical risk reduction of 50%. A key clinical endpoint was the treatment efficacy duration after discontinuation, for which some assumptions were made.
Monetary benefit and utility valuations:
The utility values associated with fractures came from the KOFOR study (Borgstrom et al 2006, see 'Other Publications of Related Interest' below for bibliographic details).
Measure of benefit:
Quality-adjusted life-years (QALYs) were the summary benefit measure and were discounted at 3% per annum. Life-years (LYs) and the number of hip fractures were also reported, but were not combined with costs.
The economic analysis included the costs of the intervention (medication with full or partial adherence), health care, informal care, and loss of productivity associated with fractures. The resources and costs related to the intervention appear to have been derived from authors’ opinions based on the approximate cost of oral treatment in Sweden. All costs and quantities were derived from the KOFOR study (Borgstrom et al 2006, see 'Other Publications of Related Interest' below for bibliographic details) and were adjusted to fit the decision model. All costs were estimated in Swedish kronor and then converted to Euros (EUR). The price year was 2005 and future costs were discounted at 3% per annum.
Analysis of uncertainty:
The uncertainty in the model was investigated by means of 30,000 first-order simulations that generated stable incremental cost-utility ratios. The variable-dependent elasticity was determined to identify the variables that had the greatest impact on the cost-utility ratios. The model inputs examined were fraction of benefit, drug efficacy, duration of treatment, dropout rate, primary non-adherence, offset time, discount rates, cost of fractures, and pre-treatment fracture risk.
The expected total costs were EUR 14,626 without treatment, EUR 15,123 with partial adherence, and EUR 15,835 with full adherence. The QALYs were 7.7588 without treatment, 7.7739 with partial adherence, and 7.8118 with full adherence.
The incremental cost per QALY gained with partial adherence versus no treatment was EUR 32,914 and the incremental cost per QALY gained with full versus partial adherence was EUR 18,809.
In general, the cost-effectiveness of the full adherence strategy improved in high-risk individuals and with increasing age. When the drug costs were assumed to be the same for both partial and full adherence, full adherence was cost saving. The sensitivity analysis showed that offset time was an influential model input. The variable-dependent elasticity analysis showed that the cost-effectiveness of adherence was affected by changes in fraction of benefit, drug effect, offset time, risk of fractures, and drug cost.
The authors concluded that improved adherence led to benefits, but that these might be partially offset by increased intervention costs. The cost-effectiveness of treatments with high adherence depended on the offset time and drug effect reductions from poor compliance.
The comparators were selected to include two generic drugs rather than specific medications as the focus of the analysis was on adherence. Conventional drug treatment associated with suboptimal adherence was compared with a hypothetical fully adherent regimen. The authors noted that a fully compliant population does not exist.
The clinical analysis was not reported in detail and the approach used to identify the data sources was not described. Only a few details were provided of the studies and databases used to derive the clinical estimates. The use of Swedish registries for the epidemiology and risk of fracture was appropriate as these data reflected the national setting, but more information on these would have made the analysis more transparent. A similar method was used to derive the utility values for the calculation of QALYs. The benefit measure was appropriate given the impact of the treatment on both quality of life and survival. QALYs are also a generalisable benefit measure.
The analysis of costs included all the categories relevant to the perspective stated but the costs were presented as macro-categories and were not broken down into individual items. A clear description of the sources used was not given. The economic estimates were treated deterministically, and the key cost items were varied in the sensitivity analysis. Other information such as the price year and discounting was provided.
Analysis and results:
The costs and benefits were analysed using an incremental approach, which was appropriate. The findings were clearly reported. The issue of uncertainty was investigated using various approaches, which appear to have been appropriate for the objective of the study. The key features of the decision model were presented and extensive information was provided on the statistical approach used to identify the relevant drivers of the cost-effectiveness model. The authors noted some limitations of their analysis, such as the key role played by the assumptions made in the base case, which might have been only partially assessed by the changes made in the sensitivity analysis.
The study appears to have been based on valid methodology, but the data sources were only partially reported. In general, the authors’ conclusions appear to be valid.
Strom O, Borgstrom F, Kanis JA, Jonsson B. Incorporating adherence into health economic modelling of osteoporosis. Osteoporosis International 2009; 20(1): 23-34
Other publications of related interest
Seeman E, Compston J, Adachi J, Brandi ML, et al. Non-compliance: the Achilles’ heel of anti-fracture efficacy. Osteoporosis International 2007; 18: 711-719.
Stevenson M, Lloyd Jones M, De Nigris E, Brewer N, et al. A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis. Health Technology Assessment 2005; 9: 1-160.
Solomon DH, Avorn J, Katz JN, Finkelstein JS, et al. Compliance with osteoporosis medications. Archives of Internal Medicine 2005; 165: 2414-2419.
Borgstrom F, Jonsson B, Strom O, Kanis JA. An economic evaluation of strontium ranelate in the treatment of osteoporosis in a Swedish setting: based on the results of the SOTI and TROPOS trials. Osteoporosis International 2006; 17: 1781-1793.
Borgstrom F, Zethraeus N, Johnell O, Lidgren L et al. Costs and quality of life associated with osteoporosis-related fractures in
Sweden. Osteoporos Int 2006; 17(5): 637-650.
Subject indexing assigned by NLM
Aged; Aged, 80 and over; Colles' Fracture /economics /prevention & Cost-Benefit Analysis; Drug Costs; Female; Fractures, Bone /economics /prevention & Hip Fractures /economics /prevention & Humans; Medication Adherence; Models, Economic; Osteoporosis /drug therapy /economics; Spinal Fractures /economics /prevention & control; control; control; control
Date bibliographic record published
Date abstract record published