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A model analysis of costs of blood pressure destabilization and edema associated with rofecoxib and celecoxib among older patients with osteoarthritis and hypertension in a Medicare choice population |
Becker R V, Burke T A, McCoy M A, Trotter J P |
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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 two alternative cyclooxygenase-specific inhibitors, oral celecoxib (Celebrex, Pharmacia Corporation) and oral rofecoxib (Vioxx, Merck & Co., Inc.), for the treatment of osteoarthritis (OA) in hypertensive patients aged 65 years or older. Celecoxib was administered at 200 mg/day and rofecoxib at 25 mg/day.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients aged 65 years or older who had OA and hypertension, and who were members of a Medicare Choice Plan.
Setting The setting was primary care. The economic study was performed in the USA.
Dates to which data relate The effectiveness data were collected from studies published between 1997 and 2002. The cost data were estimated from studies published between 1997 and 2002. The price year was 2000.
Source of effectiveness data The effectiveness data were derived from a non-systematic review of published studies.
Modelling A decision analysis model was used to estimate the costs associated with the use of either celecoxib or rofecoxib. A 6-week period was considered for the cost estimation. From a hypothetical cohort of 100,000 Medicare Choice members, the authors estimated that 25,630 would have OA and hypertension, and 5,126 would use either celecoxib or rofecoxib. The costs were estimated for a hypothetical cohort of 5,126 individuals.
Outcomes assessed in the review The outcomes assessed were:
the percentage of patients experiencing clinically significant oedema only, destabilised systolic BP only, and both oedema and destabilised systolic BP; and
the overall percentage of patients experiencing these events when treated with celecoxib or rofecoxib.
Some data concerning the prevalence of OA and hypertension were also reviewed. The percentages of patients with oedema who discontinued treatment with celecoxib or rofecoxib were reported.
Study designs and other criteria for inclusion in the review The authors did not state that they used any criteria to include studies in the review. Three randomised double-blind controlled studies and some prevalence studies were included.
Sources searched to identify primary studies Criteria used to ensure the validity of primary studies The criteria used to ensure the validity of the primary studies were not reported. However, the fact that two multi-centre, double-blind randomised controlled trials (RCTs) were pooled to estimate the effectiveness results increases the validity of the included studies (see Other Publications of Related Interest).
Methods used to judge relevance and validity, and for extracting data Number of primary studies included At least 3 double-blind RCTs and some results from 2 published health surveys were included in the review.
Methods of combining primary studies The results from two of the RCTs included in the review were pooled. The authors did not report the method used to combine the results of the other studies.
Investigation of differences between primary studies No tests of homogeneity or differences between the individual studies were reported. The authors stated that this was because the study designs and the study populations of the pooled RCTs were similar, and they presented comparable data collection and outcome measures.
Results of the review After pooling the data from the two RCTs, the results showed that, overall, the use of rofecoxib resulted in a significantly higher incidence of both oedema and BP destabilisation. The incidence of oedema was 8.5% in rofecoxib-treated patients versus 4.8% in celecoxib-treated patients, (p<0.001). BP destabilisation occurred in 15.6% (rofecoxib) and 8.7% (celecoxib) of the patients, respectively, (p<0.001).
Compared with patients receiving celecoxib, a significantly higher proportion of patients receiving rofecoxib had clinically significant oedema only or destabilised systolic BP only. Clinically significant oedema alone was experienced by 6.3% of rofecoxib-treated patients versus 4.2% of celecoxib-treated patients, (p=0.001). Destabilised BP alone occurred in 13.4% (rofecoxib) versus 8.1% (celecoxib) of the patients, respectively, (p<0.001).
There were no statistically significant differences between the proportion of patients treated either with rofecoxib or celecoxib that experienced both oedema and destabilised systolic BP (2.2% versus 0.6%; p-value not reported).
In total, 49.4% of the patients with oedema who were treated with celecoxib, and 47.1% of those treated with rofecoxib, discontinued treatment, (p-value not reported).
Methods used to derive estimates of effectiveness The authors made assumptions to derive some of the estimates of effectiveness.
Estimates of effectiveness and key assumptions The authors assumed that the efficacy of celecoxib and rofecoxib was similar for treating OA. Therefore, it was assumed that discontinuation due to lack of efficacy was the same for both treatments.
Measure of benefits used in the economic analysis The intermediate model outcomes reported were the number of patients in each cohort (either celecoxib or rofecoxib) who experienced oedema alone, destabilised BP alone, or both oedema and destabilised BP. The time considered was 6 weeks.
Direct costs The resource quantities and the costs were not reported separately, although some percentages of the distribution of health care utilisation and some daily costs were reported independently. The direct costs considered in the economic analysis were those of the Medicare Choice Plan. These were physician visits and medication. The costs of physician visits were for family practice, internal medicine, orthopaedics and rheumatology. The medication costs were for celecoxib, rofecoxib and additional medications that could be administered to the patients, such as non-steroidal anti-inflammatory drugs (NSAIDs). The costs associated with BP destabilisation and oedemas were also included.
For the estimation of health care utilisation, the direct costs came from published studies and experts' opinions derived from a published survey. For the imputation of costs, average wholesale prices were used. Therefore, the costs were estimated from actual data. The price year was 2000. Discounting was not performed, which was appropriate given the short study period. The costs reported were the total costs for the whole cohort of patients during the study period, and the monthly and daily average costs per patient.
Statistical analysis of costs No statistical analyses of the costs were reported.
Indirect Costs No indirect costs were estimated.
Sensitivity analysis Sensitivity analyses were performed to assess the robustness of the study findings. One-way sensitivity analyses were performed on all variables, while multi-way sensitivity analyses were performed on the most sensitive variables. The area of uncertainty investigated was, therefore, variability in the data.
Estimated benefits used in the economic analysis Two hundred and fifteen celecoxib-treated patients and 323 rofecoxib-treated patients experienced oedema alone.
Four hundred and fifteen celecoxib-treated patients and 689 rofecoxib-treated patients experienced destabilised BP alone.
Thirty-one celecoxib-treated patients and 113 rofecoxib-treated patients experienced both oedema and destabilised BP.
Cost results The total costs were $547,873 when the cohort of patients was treated with celecoxib and $581,811 when the cohort of patients was treated with rofecoxib. The incremental cost-difference against rofecoxib was $33,938.
The average monthly cost per patient was $77.36 with celecoxib versus $82.15 with rofecoxib. The incremental monthly cost per patient was $4.79 against rofecoxib.
The average daily cost per patient was $2.54 with celecoxib versus $2.70 with rofecoxib. The incremental daily cost per patient was $0.16 when using rofecoxib.
One-way sensitivity analyses did not show relevant changes that made celecoxib more costly than rofecoxib. The results from the multi-way sensitivity analyses showed that the most sensitive combination was the costs of the cyclooxygenase-specific inhibitors and the physician visits. These could make the celecoxib costs slightly higher ($0.01 higher per patient per day) than those associated with rofecoxib.
Synthesis of costs and benefits The health benefits and costs were not combined.
Authors' conclusions The results suggested that celecoxib was a lower cost alternative to rofecoxib when treating osteoarthritis (OA) patients with hypertension, primarily because of the lower costs of managing oedema and destabilised BP.
CRD COMMENTARY - Selection of comparators Celecoxib and rofecoxib were chosen as the health technologies to be compared in this effectiveness analysis because they are cyclooxygenase-specific inhibitors, which are recommended for the treatment of OA patients besides NSAIDs. NSAIDs appear not to have been considered since they are associated with increases in BP and the study population comprised OA patients with hypertension. You should decide what treatment is most used in your own setting for treating OA patients with hypertension.
Validity of estimate of measure of effectiveness The authors did not report that a systematic review of the literature was undertaken. Some effectiveness estimates were combined by pooling the results from two RCTs. The rest of the effectiveness estimates may have been combined using narrative methods. The authors assumed that both celecoxib and rofecoxib had similar effectiveness in treating OA. Consequently, the effectiveness of the treatments was evaluated based on the adverse events that these treatments could cause, not on their real effectiveness in the treatment of OA. The authors justified this and other assumptions with reference to the medical literature. The authors reported that one of the limitations was the short study period considered at analysis. This was justified because effectiveness data were available for this period and, as the authors stated, extrapolating the results to a longer period may be less reliable. The fact that they obtained the main effectiveness estimates from two pooled RCTs with similar designs and results enhances the validity of the effectiveness results. However, due to the overall ad hoc nature of the review and synthesis, the validity is still likely to have been quite low.
Validity of estimate of measure of benefit The estimation of benefits was modelled. The decision analysis model used appears to have been appropriate, although only oedema and destabilised BP associated with the treatments were considered as measures of health benefit. Nevertheless, there are other associated health outcomes associated, such as pain and stiffness, that were not considered. The authors stated that the inclusion of these benefits would not change the effectiveness results. In addition, measures of health benefit such as quality-adjusted life-years were not considered. This means that it would be difficult to compare the results of this study with those from studies of different interventions.
Validity of estimate of costs The perspective adopted was that of the Medicare Choice plan. The authors stated that this is similar to the perspective of the health service since it considers the total costs of providing care. All the costs relevant to this perspective appear to have been considered. Resource use was estimated using experts' opinions obtained from surveys, which may not reflect real behaviours. However, sensitivity analyses were performed to test for variability in the cost data and the results were found to be robust. Charges were used instead of costs, which may not reflect the true opportunity costs of the treatments. No adjustments were made to approximate these charges to costs. The price year was reported and discounting, which was not appropriate due to the short time considered for the analysis, was not performed.
Other issues The authors did not make appropriate comparisons of their findings with those from other studies. The issue of the generalisability of the results to other settings was not addressed. The conclusions of the study reflected the scope of the analysis.
Implications of the study The authors stated that further research is needed to validate the results obtained in this study. Such research should compare not only celecoxib and rofecoxib, but also the use of NSAIDs as another alternative treatment.
Bibliographic details Becker R V, Burke T A, McCoy M A, Trotter J P. A model analysis of costs of blood pressure destabilization and edema associated with rofecoxib and celecoxib among older patients with osteoarthritis and hypertension in a Medicare choice population. Clinical Therapeutics 2003; 25(2): 647-662 Other publications of related interest Whelton A, White WB, Bello AE, et al. Effects of celecoxib and rofecoxib on blood pressure and edema in patients > 65 years of age with systemic hypertension and osteoarthritis. American Journal of Cardiology 2002;90:959-63.
Whelton A, Fort JG, Puma JA, et al. Cyclooxygenase-2-specific inhibitors and cardiorenal function: a randomised, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. American Journal of Therapeutics 2001;8:85-95.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Anti-Inflammatory Agents, Non-Steroidal /adverse effects /economics /therapeutic use; Blood Pressure /drug effects; Celecoxib; Costs and Cost Analysis; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors /adverse effects /economics /therapeutic use; Data Collection; Double-Blind Method; Edema /chemically induced; Female; Humans; Hypertension /complications /physiopathology /prevention & Isoenzymes /antagonists & Lactones /adverse effects /economics /therapeutic use; Male; Medicare; Membrane Proteins; Osteoarthritis /complications /drug therapy; Practice Patterns, Physicians' /statistics & Prostaglandin-Endoperoxide Synthases; Pyrazoles; Randomized Controlled Trials as Topic; Sulfonamides /adverse effects /economics /therapeutic use; Sulfones; control; inhibitors; numerical data AccessionNumber 22003008078 Date bibliographic record published 31/07/2004 Date abstract record published 31/07/2004 |
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