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Cost-effectiveness of treatment strategies for osteoarthritis of the knee in Taiwan |
Yen Z S, Lai M S, Wang C T, Chen L S, Chen S C, Chen W J, Hou S M |
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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 Three treatment strategies for osteoarthritis (OA) of the knee were studied:
250 mg naproxen, 3 times daily for 26 weeks;
100 mg celecoxib, twice daily for 26 weeks; and
25 mg hyaluronan (HA) by intraarticular injection, once weekly for 5 weeks, followed by conventional outpatient treatment for 21 weeks.
Conventional treatment may include non-pharmacologic therapies, calcium supplements, muscle relaxants, topical analgesics and acetaminophen.
Study population The base-case was a hypothetical 60-year-old woman who had symptomatic and radiologically verified OA of the right knee. She was working full time. Her knee pain after a 50-foot walk was 50 mm on a 100-mm visual analogue scale (VAS). Global assessment of her right knee on a scale of 1 (very poor) to 5 (very good) was 2 (poor). She declined surgical intervention.
Setting The setting was secondary care. The economic study was carried out in Taiwan.
Dates to which data relate The effectiveness evidence was taken from studies published between 1989 and 2000 and valued on the advice of an expert panel apparently convened in 2002. Estimates of resource use related to the period from July 2001 to February 2002. The price year was 2002.
Source of effectiveness data The effectiveness data were derived from a review or synthesis of completed studies.
Modelling A decision analytic model was developed in order to simulate possible outcomes of OA of the knee using treatment with naproxen, celecoxib or OA. The time horizon was 26 weeks.
Outcomes assessed in the review The outcomes equate to input parameters in the decision model. These included:
the probability of improvement of knee OA with naproxen, celecoxib or HA, that is, an improvement of at least 20 mm on the VAS or at least 2 grades on global assessment;
the probability of serious gastrointestinal (GI) complications in 26 weeks with naproxen or celecoxib;
the probability of local injection pain from HA; and
the probability of mortality from serious GI complications.
Study designs and other criteria for inclusion in the review Although not explicitly stated, all of the studies included in the review appear to have been clinical trials.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data For each variable, a base-case estimate was determined if the authors considered the study authoritative or most similar to their clinical practice.
Number of primary studies included The authors reported 13 primary studies or references as sources of effectiveness evidence.
Methods of combining primary studies The primary studies were not combined.
Investigation of differences between primary studies To represent uncertainty, a plausible range for each input parameter estimate was determined using other studies of similar topics that were not considered authoritative. These ranges were applied in a sensitivity analysis. However, no explanation of the differences was provided.
Results of the review The base-case probability of improvement of knee OA was 0.31 (range: 0.2 - 0.6) with naproxen, 0.35 (range: 0.2 - 0.6) with celecoxib and 0.36 (range: 0.2 - 0.6) with HA.
The base-case probability of serious GI complications in 26 weeks was 0.0037 (range: 0.001 - 0.05) with naproxen and 0.0000075 (range: 0 - 0.0001) with celecoxib.
The base-case probability of mortality from a serious GI complication was 0.0006 (range: 0.001 - 0.0006).
The base-case probability of local injection pain from HA was 0.021 (range: 0.01 - 0.10).
Measure of benefits used in the economic analysis The outcome measure used in the economic analysis was QALYs. No data existed on the health utilities related to knee OA in Taiwan. An expert panel consisting of 2 orthopaedic physicians, 2 emergency physicians and 1 internist with extensive experience in the treatment of knee OA participated in a standard gamble to determine quality of life adjustments for certain clinical outcomes. More specifically, OA with or without improvement, OA with serious GI complications and OA with local injection pain from HA treatment.
Direct costs Discounting was not carried out, which was appropriate as it would not have been relevant given the 26-week timeframe. The quantities and the costs were analysed separately, but were not reported in full. The quantities were estimated using data for 300 OA patients selected randomly from the database of the National Taiwan University Hospital. The costs were represented by the reimbursement prices paid for resources by Taiwan's compulsory National Health Insurance (NHI) between July 2001 and February 2002. Weekly outpatient treatment costs were calculated and reported for naproxen, celecoxib, HA, conventional treatment and GI complications. These included the unit costs of medication, administrative fees per outpatient visit and physician fees per outpatient visit. The weekly inpatient cost of serious GI complications was also reported. Over-the-counter medication is not covered by NHI and was not included in the cost of conventional therapy.
Statistical analysis of costs The costs were treated deterministically. The ranges for the cost estimates represented +/- 30% of the baseline estimates.
Indirect Costs Time lost from work was based on 0.5 days per outpatient visit, where the quantity of outpatient visits was estimated in the valuation of direct costs. Loss of productivity was valued using the average Taiwanese industrial weekly wage of US$239.37/week in 2003.
Currency US dollars ($). These were converted from New Taiwan dollars (NT$) using the rate NT$34.96 = $117.
Sensitivity analysis One-way sensitivity analyses were carried out on all input parameters, using the ranges described already.
Estimated benefits used in the economic analysis The expected QALYs per patient were 0.4357 with naproxen, 0.4380 with celecoxib and 0.4411 with HA.
Thus, celecoxib gained 0.0023 incremental QALYs over naproxen, while HA gained 0.0031 incremental QALYs over celecoxib.
Adverse events were considered in the analysis. A patient in perfect health would have sustained 0.5 QALYs over the model period of 26 weeks.
Cost results The total expected costs per patient for 26 weeks were $498.98 with naproxen, $547.80 with celecoxib and $678.00 with HA.
The incremental cost of celecoxib over naproxen was $48.82, while the incremental cost of HA over celecoxib was $130.20.
The cost of adverse events were considered in the analysis.
Synthesis of costs and benefits The estimated benefits and costs were combined into incremental cost-effectiveness ratios (ICERs).
The ICER of the celecoxib strategy compared with the naproxen strategy was $21,226 per QALY gained.
The ICER of the HA strategy compared with the celecoxib strategy was $42,000 per QALY gained.
The ICER of celecoxib versus naproxen decreased to $3,170 per QALY gained if the probability of serious GI complications with naproxen increased to 0.037, and became dominant for probabilities over 0.0464.
The ICER of HA versus celecoxib was very sensitive to changes in the improvement probability of HA such that, if this value was 0.60 the ICER decreased to $8,900 per QALY gained.
The ICER of HA versus celecoxib decreased to about $25,000 per QALY gained if the weekly treatment cost of HA was decreased from $41.84 to $31.
The results were insensitive to the cost of time lost from work and the costs of outpatient and inpatient GI complications.
Authors' conclusions Valuable clinical outcomes are obtained under all three treatment strategies, but only naproxen and celecoxib treatments result in reasonable cost-effectiveness in Taiwan.
CRD COMMENTARY - Selection of comparators The authors justified the comparators based on normal clinical practice in Taiwan. You should decide if these are widely used health technologies in your setting, bearing in mind that celecoxib has since been withdrawn from the market by its manufacturer.
Validity of estimate of measure of effectiveness Although some kind of review of the literature was undertaken, the authors did not state that it was systematic. The authors used data from the available studies selectively, subjectively choosing those that were "authoritative" or "closest to their clinical practice". They did not consider the impact of differences between the primary studies when estimating the effectiveness inputs. This method of incorporating effectiveness data from several studies casts doubt on the validity of the data and the generalisability of the results to other settings.
Validity of estimate of measure of benefit The estimation of benefits was modelled. The standard gamble instrument used to elicit the measure of benefit (utility) was appropriate, though it would have been preferable to have elicited population responses, rather than clinician responses, in view of the societal perspective of the analysis.
Validity of estimate of costs All the categories of cost relevant to the perspective adopted were included. Over-the-counter medications were excluded on the basis that they were not reimbursed by the NHI, but this does not accord with a societal perspective. The indirect costs were assumed to apply only on days of inpatient stays or outpatient visits, but it may be appropriate to investigate possible further impact of OA on productivity. However, these exclusions are unlikely to have affected the incremental calculations and hence the authors' conclusions. The costs of serious adverse events were included. The costs and the quantities were not reported separately, thus making it more difficult to replicate the study in another setting. A sensitivity analysis of the quantities was not conducted, which may limit the interpretation of the study's findings. The prices were based on national insurance reimbursement charges. A sensitivity analysis of the prices found that the results were sensitive to HA medication cost. The authors performed appropriate currency conversions and discounting was unnecessary.
Other issues The authors did not compare their findings with those of other studies. They also did not address the issue of generalisability to other settings. The authors did not present their results selectively and confined their conclusions to the scope of the study (older patients with knee OA in Taiwan). Several limitations of the study were reported. For example, the uncertainty around effectiveness estimates and the lack of community preference data for quality of life.
Implications of the study The authors recommended that celecoxib be used in elderly patients and those with a high risk of GI bleeding, owing to similar efficacy to naproxen in the treatment of OA but favourable cost-effectiveness given the threat of GI complications. They also stated that HA treatment does not appear to be a cost-effective alternative in Taiwan. However, the probability of improvement with HA has varied in clinical trials and this treatment could become cost-effective if a higher improvement probability is proven. The authors suggested that future studies should involve large-scale, multi-centre, prospective, randomised controlled analyses to assess the validity of the costs and benefits estimated here.
Source of funding Supported by the Bureau of National Health Insurance, Taiwan.
Bibliographic details Yen Z S, Lai M S, Wang C T, Chen L S, Chen S C, Chen W J, Hou S M. Cost-effectiveness of treatment strategies for osteoarthritis of the knee in Taiwan. Journal of Rheumatology 2004; 31(9): 1797-1803 Indexing Status Subject indexing assigned by NLM MeSH Adjuvants, Immunologic /economics /therapeutic use; Anti-Inflammatory Agents, Non-Steroidal /economics /therapeutic use; Celecoxib; Cost-Benefit Analysis; Female; Humans; Hyaluronic Acid /economics /therapeutic use; Middle Aged; Naproxen /economics /therapeutic use; Osteoarthritis, Knee /drug therapy /economics; Pyrazoles; Sensitivity and Specificity; Sulfonamides /economics /therapeutic use; Taiwan AccessionNumber 22004001246 Date bibliographic record published 30/11/2005 Date abstract record published 30/11/2005 |
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