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Cost effectiveness of low dose corticosteroids versus non steroidal anti inflammatory drugs and COX 2 specific inhibitors in the long term treatment of rheumatoid arthritis |
Bae S C, Corzillius M, Kuntz K M, Liang M H |
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Record Status 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. Health technology The use of low dose (less than 10 mg/day prednisone) corticosteroids for the treatment of rheumatoid arthritis (RA) was examined.
Study population The hypothetical study population comprised males and females aged 50 years who were diagnosed with RA. The population had a female-to-male ratio of 2.5:1.
Setting The setting was the community. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data related to 1986 to 2000. The cost data related to 1983 to 1998. The price year was 1999.
Source of effectiveness data The effectiveness data were derived from a review of completed studies.
Modelling A Markov model was used to calculate the number of adverse events and the costs associated with each treatment group. The model followed the hypothetical cohort until death. A diagram of the model structure was not provided, but the health states included complications from corticosteroids, complications from NSAIDs and death. Adverse events were temporary states. Treatment was assumed to discontinue following an adverse event, and to be resumed the next year. Patients who failed to recover from disability or fractures were assumed to require permanent nursing home care. The model included states for post fracture and post gastrointestinal (GI) complications, to account for increased risk of further events or increased costs following a fracture or GI complication.
Outcomes assessed in the review The review assessed the probability of:
adverse events such as fracture, diabetes mellitus, cataracts glaucoma or infection for corticosteroids; and
adverse events such as dyspepsia, GI complications, and hepatic or renal failure for NSAIDs.
The effectiveness of corticosteroids and NSAIDs was presumed to be equal for controlling RA.
Study designs and other criteria for inclusion in the review The review assessed studies from 1966 to 1999 that contained the keywords "corticosteroid, prednisone, prednisolone, glucocorticoid, steroid, NSAID, COX 2 inhibitor, rheumatoid arthritis". The authors stated that the study population had to be similar to the hypothetical cohort used in the decision model. No other inclusion or exclusion criteria were provided.
Sources searched to identify primary studies MEDLINE was searched from 1966 to 1999. The bibliographies of included studies were also searched for relevant papers.
Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included The review included approximately 16 studies.
Methods of combining primary studies The authors stated that no attempt was made to combine data from multiple studies.
Investigation of differences between primary studies Results of the review The response rate to corticosteroids, NSAIDs and COX 2 inhibitors was estimated to be 60%.
While on corticosteroids, the annual probabilities of fracture, diabetes mellitus and cataract were 0.0098, 0.0043 and 0.0114, respectively.
While on NSAIDs, the annual probabilities of dyspepsia and serious GI complications were 0.29 and 0.0190, respectively.
The annually probability of a recurrent GI complication was 0.0281.
Measure of benefits used in the economic analysis The economic analysis was based on quality adjusted life years (QALYs). The utility decrement associated with discontinuation of treatment was based on the Health Utilities Index II. The other utility estimates were predominantly based on studies using time trade off or standard gamble techniques, but further information was not provided.
Direct costs The resource use quantities were not reported. Only cost estimates were provided. The direct costs appear to be for the perspective of a third party payer. The direct costs included the costs of treatment for RA, fracture, osteoporosis, diabetes, glaucoma, infection and dyspepsia. They also included the costs of nursing home care, operations for cataracts, hospital treatment for GI complications, and treatment for acute hepatic or renal failure. The cost estimates were taken from completed studies. The costs were discounted at a rate of 3% per year. The costs were inflated to the year 1999 using the medical care component of the Consumer Price Index.
Statistical analysis of costs The costs were not derived from individual patient level data, so a statistical analysis was not possible.
Indirect Costs The indirect costs were not included in the analysis.
Sensitivity analysis Several one way sensitivity analyses were undertaken to explore the robustness of the results to variation in the main parameters. The sensitivity analysis included best case scenarios (0.5 times the adverse event rate) and worst case scenarios (1.5 times the adverse event rate).
Estimated benefits used in the economic analysis Treatment with corticosteroids was estimated to result in 11.67 QALYs over a lifetime, compared with 11.46 for NSAIDs. Adverse events were the primary health outcomes in the model as each treatment was assumed equally effective for RA.
Cost results The lifetime cost of treatment was $43,800 with corticosteroids versus $44,900 with NSAIDs. The costs were discounted at a rate of 3% per annum. The costs of adverse events were the main costs included in the model.
Synthesis of costs and benefits The benefits and costs were combined to calculate the incremental cost per QALY. Corticosteroids were found to be more effective and less costly in the base-case analysis. The results were sensitive to the adverse event rate of corticosteroids being increased by 1.5 times the base-case rate, and to increases in the cost of nursing home care.
Authors' conclusions Corticosteroids may be a cost effective treatment, compared with non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo oxygenase 2 (COX 2) inhibitors, in the treatment of long term rheumatoid arthritis (RA).
CRD COMMENTARY - Selection of comparators The choice of NSAIDs and COX 2 inhibitors as the comparators was justified as they are common therapies for RA in the study setting. The authors indicated that the effectiveness of these alternatives is similar, but there is concern about the side effect profile of each approach to treating long term RA. You should decide if these technologies are relevant to your own context.
Validity of estimate of measure of effectiveness The authors stated that a detailed review of the literature had been undertaken. However, it was unclear if the review was undertaken systematically to identify relevant research and minimise biases. The authors did not attempt to combine the results from multiple studies, thus indicating that they might have been selective in their use of the study evidence. The authors tried to select studies that matched the hypothetical cohort for the model. Variability in the data was, however, assessed in the sensitivity analyses and this increases the validity of the results.
Validity of estimate of measure of benefit The estimation of QALYs was modelled using a Markov state transition model. The utility effects of the adverse events included in the analysis were based on several different studies, which made use of standard gamble and time trade-off techniques and the Health Utility Index II. These different instruments can give different utility values for the same health state. Hence, combining estimates from each instrument can make the model inconsistent in its ranking of adverse events. The effect of two or more events associated with a utility decrement was assumed to be additive, as estimates for combined states were not available. The authors acknowledge this as a limitation of their study.
Validity of estimate of costs The authors did not state the cost perspective adopted, so it is not possible to judge which costs should have been included. The costs and the quantities were not reported separately. The authors did not investigate differences between the primary studies used to provide the cost estimates. The source of the prices was unclear as different sources might have been used in each of the primary studies. The authors stated that the lack of more appropriate cost data was a limitation of the study. The costs were discounted as appropriate, and the price year and adjustments for inflation were reported.
Other issues The authors made appropriate comparisons of their findings with those from other studies. The issue of generalisability to other study populations, but not to other settings, was addressed. The authors did not present their results selectively and their conclusions reflected the scope of the analysis. The authors discussed a number of limitations. For example, the fact that the model omitted alternative strategies for treating adverse events and other complications from treatment, for which there were little data.
Implications of the study In terms of clinical practice, the findings of the present study tended to support the use of low dose corticosteroids in the treatment of patients with long term RA. The authors, however, recommended that further research be undertaken on adverse events associated with the use of low dose corticosteroids, as current research on the use of corticosteroids for the treatment of RA is limited.
Source of funding Supported in part by the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (grant 01 PJ1 PG1 01CH10 0007), NIH (grant #AR36308), and an Arthritis Foundation Clinical Science Grant.
Bibliographic details Bae S C, Corzillius M, Kuntz K M, Liang M H. Cost effectiveness of low dose corticosteroids versus non steroidal anti inflammatory drugs and COX 2 specific inhibitors in the long term treatment of rheumatoid arthritis. Rheumatology 2003; 42(1): 46 53 Indexing Status Subject indexing assigned by NLM MeSH Adult; Age Factors; Anti-Inflammatory Agents, Non-Steroidal /adverse effects /economics /therapeutic use; Anti-Ulcer Agents /therapeutic use; Arthritis, Rheumatoid /drug therapy; Cohort Studies; Cost-Benefit Analysis; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors /adverse effects /economics /therapeutic use; Drug Costs; Female; Glucocorticoids /adverse effects /economics /therapeutic use; Humans; Isoenzymes /antagonists & Male; Markov Chains; Membrane Proteins; Middle Aged; Prednisolone /adverse effects /economics /therapeutic use; Prostaglandin-Endoperoxide Synthases; Quality-Adjusted Life Years; inhibitors AccessionNumber 22003000309 Date bibliographic record published 31/08/2005 Date abstract record published 31/08/2005 |
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