Modelling therapeutic strategies in the treatment of osteoarthritis: an economic evaluation of meloxicam versus diclofenac and piroxicam Tavakoli M 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 meloxicam, a cyclo-oxygenase (COX)-2 selective inhibitor, versus diclofenac modified-release and piroxicam for 4 weeks, in the treatment of patients with osteoarthritis. The doses studied were 7.5 mg meloxicam once daily, 100 mg diclofenac modified-release once daily, and 20 mg piroxicam once daily. Type of intervention Treatment. Economic study type Cost-effectiveness analysis. Study population The study population comprised a hypothetical cohort of patients diagnosed with osteoarthritis. Setting The study setting was unclear, but it appears to have been the community and secondary care. The economic analysis was conducted in the UK. Dates to which data relate The effectiveness data were derived from studies published between 1997 and 1998. The resource use data were derived from studies published between 1997 and 1999. The price year was 1998 (2000 for drug costs). Source of effectiveness data The effectiveness data were derived from a review of published studies. Modelling A decision model was developed to compare the economic efficiency of meloxicam with traditional drugs (diclofenac or piroxicam) in patients with osteoarthritis. The time horizon was 4 weeks. Outcomes assessed in the review The outcomes assessed in the review and used as model inputs were the rates of adverse events, such as: gastrointestinal (GI) adverse events with and without perforation, ulcers and bleeds; renal adverse events; Page: 1 / 5
hepatic adverse events; cardiovascular adverse events; and other adverse events. Study designs and other criteria for inclusion in the review Two large-scale trials, the Meloxicam Large-scale International Study Safety Assessment (MELISSA) and the Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) were used to estimate the outcomes (see Other Publications of Related Interest). The clinical information was supplemented with case narratives from the original trial reports. The two trials were of a randomised, double-blind, prospective and parallel-group design, and were conducted in several countries. Sources searched to identify primary studies Not reported. Criteria used to ensure the validity of primary studies The author reported that the inclusion and exclusion criteria of the two trials reflected prescribing recommendations for nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, all serious adverse events were closely examined and their possible relationship to the trial drug was assessed. Methods used to judge relevance and validity, and for extracting data Not specified. Number of primary studies included Two trials and data on file (published in 1997) were included in the review. Methods of combining primary studies Not reported. Investigation of differences between primary studies The author noted that the two trials were identical in terms of design, clinical protocol, assessment of safety, tolerability and efficacy, and statistical methods. Results of the review The rate of GI adverse events with meloxicam was 0.11845. The rate of GI adverse events requiring treatment was 0.3478, and the rate of GI adverse events with perforation, ulcers or bleeds was 0.0325. The rate of GI adverse events with piroxicam was 0.1538. The rate of GI adverse events requiring treatment was 0.4213 and the rate of GI adverse events with perforation, ulcers or bleeds was 0.0569. The rate of GI adverse events with diclofenac was 0.1871. The rate of GI adverse events requiring treatment was 0.325 and the rate of GI adverse events with perforation, ulcers or bleeds was 0.02105. The rate of renal adverse events was 0.00972 with meloxicam, 0.01084 with piroxicam, and 0.01195 with diclofenac. The rate of hepatic adverse events was 0.002122 with meloxicam, 0.00323 with piroxicam, and 0.0064 with diclofenac. Page: 2 / 5
The rate of cardiovascular adverse events was 0.0133 with meloxicam, 0.01776 with piroxicam, and 0.01386 with diclofenac. The rate of other adverse events was 0.1066 with meloxicam, 0.09363 with piroxicam, and 0.0996 with diclofenac. Measure of benefits used in the economic analysis The author reported that the efficacy of meloxicam had been shown to be equivalent to that of piroxicam and diclofenac in the two large clinical trials. Therefore, the author conducted a cost-minimisation analysis. Direct costs The perspective of the NHS was adopted. The direct costs included the costs of visits, NSAIDs, ulcer-healing drugs, pain medication, diagnosis and secondary investigation, and hospitalisation. The resource quantities were given separately from the costs. The mean costs were derived from various sources, such as published studies, a monthly index of medical specialties and the Department of Health (for drug tariff). The quantities were derived from the Tayside Medicines Monitoring Unit (MEMO) database, expert opinion and existing medical literature. The duration of hospitalisation was derived from the two large trials. Discounting was not performed because of the relatively short treatment period (4 weeks). With the exception of drug costs, which were in 2000 values, all of the costs were adjusted to 1998 values. The total costs per patient were reported. Statistical analysis of costs No statistical analysis of the costs was performed. Indirect Costs The indirect costs were not included. Currency UK pounds sterling (). Sensitivity analysis One-way sensitivity analyses were performed on the resource costs, using a range either derived from the MEMO database or calculated using +/- 20%. In addition, a probabilistic sensitivity analysis was performed in which probability distributions were assigned to the point estimates of all key variables. A Monte Carlo simulation was performed using 4,000 samples. Estimated benefits used in the economic analysis Not relevant since a cost-minimisation analysis was conducted. Cost results Meloxicam had the lowest cost per patient, 30 versus 35 for piroxicam and 51 for diclofenac. Synthesis of costs and benefits A synthesis of the costs and benefits was not relevant as a cost-minimisation analysis was carried out. The Monte Carlo simulation suggested that meloxicam was the optimal strategy in the drug treatment of patients with osteoarthritis compared with nonselective NSAIDs (piroxicam and diclofenac), both individually and as a group. Page: 3 / 5
Switching patients from piroxicam and diclofenac to meloxicam would indicate a cost-saving of over 25 million per annum. Authors' conclusions Based on a 4-week trial period, compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) such as piroxicam and diclofenac, meloxicam was predicted to be the lowest cost drug therapy, and thus the optimal drug therapy, in the management of patients with osteoarthritis. CRD COMMENTARY - Selection of comparators The selection of the comparators was implicitly justified since they represented nonselective NSAIDs for the treatment of osteoarthritis. The author reported that other comparators, such as rofecoxib, celecoxib and etodolac, could not be included in the model because no head-to-head comparable patient data were available from either US Food and Drug Administration reports or other published sources. You should consider whether any of the comparators used in the analysis represent widely used health technologies in your own setting. Validity of estimate of measure of effectiveness The author did not state that a systematic review of the literature had been carried out. Data from the available studies were used selectively. Since the methods used to find and select the primary studies and to extract the data were unclear, it is difficult to assess the validity of the estimates. There may be relevant studies that were not included. The author reported that the efficacy of the various treatment strategies were similar. However, the author did not report any of these results, reporting instead the number of adverse events. Therefore, this omission introduced uncertainty into the effectiveness results. Validity of estimate of measure of benefit The author acknowledged that the impact of adverse events on the patient's quality of life was an important issue. However, he noted that there were no data available to carry out a cost-utility analysis. Therefore, no measure of benefit was used. A cost-minimisation analysis was conducted on the basis of the efficacy equivalence of the strategies. Validity of estimate of costs The perspective of the study was explicitly stated and was that of the NHS. All the categories of cost relevant to this perspective were included in the analysis. The costs and the quantities were reported separately, which will help the generalisability of the author's results. Statistical tests were not carried out and the costs were treated deterministically. A sensitivity analysis of the costs was undertaken, based on a range of values which were mostly justified (derived from the MEMO). There was some confusion about the price year finally considered for the cost estimation (either 1998 or 2000). However, the price years used were reported, which will aid any possible inflation exercises. Since the treatment costs were incurred during less than two years, discounting was appropriately not undertaken. Other issues The author stated that their results agreed with those obtained in other studies in that meloxicam was the lowest cost therapy. However, the author noted that his study differed from these other studies by considering both GI and non-gi adverse events. The issue of generalisability to other settings was partially addressed in the sensitivity analysis. The results of the analysis were reported in full and the author's conclusions reflected the scope of the analysis. The author reported further limitations of the study. First, comparable data on the patient's probability and resource use were not available directly from the trials. Second, the long-term toxicity issues could not be considered because of the short duration of the clinical trial period. Finally, the dosages used in the model might not have been equivalent. Implications of the study The author did not make any recommendations for changes in practice. However, it was suggested that longer-term Page: 4 / 5
Powered by TCPDF (www.tcpdf.org) clinical trial or post-marketing surveillance data will be needed to validate the results. Source of funding None stated. Bibliographic details Tavakoli M. Modelling therapeutic strategies in the treatment of osteoarthritis: an economic evaluation of meloxicam versus diclofenac and piroxicam. PharmacoEconomics 2003; 21(6): 443-454 PubMedID 12678570 Other publications of related interest Hawkey C, Kahan A, Steinbruck K, et al. Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. British Journal of Rheumatology 1998;37:937-45. Dequeker J, Hawkey C, Kahan A, et al. Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the safety and efficacy large-scale evaluation of COX-inhibiting therapies (SELECT) trial in osteoarthritis. British Journal of Rheumatology 1998;37:946-51. Jansen RB, Capri S, Nuitjen MJ, et al. Economic evaluation of meloxicam (7.5 mg) versus sustained release diclofenac (100 mg) treatment for osteoarthritis: a cross- national assessment for France, Italy and the UK. British Journal of Medical Economics 1997;11:9-22. Jansen R B, Burrell A, Nuitjen MJ, et al. An economic evaluation of meloxicam 7.5 mg versus diclofenac 100 mg retard in the treatment of osteoarthritis in the UK: a decision analysis model based on gastrointestinal complications. British Journal of Medical Economics 1996;10:247-62. Indexing Status Subject indexing assigned by NLM MeSH Anti-Inflammatory Agents, Non-Steroidal /adverse effects /economics /therapeutic use; Clinical Trials as Topic; Decision Support Techniques; Diclofenac /adverse effects /economics /therapeutic use; Humans; Monte Carlo Method; Osteoarthritis /drug therapy /economics; Piroxicam /adverse effects /economics /therapeutic use; Thiazines /adverse effects /economics /therapeutic use; Thiazoles /adverse effects /economics /therapeutic use AccessionNumber 22003008127 Date bibliographic record published 31/07/2005 Date abstract record published 31/07/2005 Page: 5 / 5