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Medico-economic analysis of diacerein with or without standard therapy in the treatment of osteoarthritis |
Fagnani F, Bouvenot G, Valat J, Bardin T, Berdah L, Lafuma A, Bone I, Eschwege E, Dresier R |
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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 Standard therapy with or without diacerein used in the treatment of osteoarthritis.
Economic study type Cost-effectiveness analysis.
Study population The study population was defined as outpatients, aged over 50 years, with radiologically confirmed osteoarthritis of the hip or knee existing for at least 3 months, who required treatment with NSAIDs, analgesics, or "slow-acting osteoarthritic" drugs.
Setting The study was conducted in the community, in 52 towns in France. The economic analysis was also carried out in France.
Dates to which data relate Effectiveness data were collected between March 1993 and April 1995. 1995 prices were used for drugs and other medical products; hydrotherapy was costed according to data published by the Department of Health Insurance in 1991; hip replacement costs were taken from the Diagnostic Related Groups.
Source of effectiveness data The source of effectiveness data was a single study.
Link between effectiveness and cost data Costing was undertaken on the same sample as that used in the effectiveness study. It is not clear whether costing was done prospectively.
Study sample Calculation of sample size was carried out after the first 50 subjects were enrolled. A gamma risk of 0.05, a change in Lequesne's function index of 1 point and a change of 100mg indomethacin were considered significant. Based on these assumptions, the sample size for each group should be 100. There were 109 patients in the diacerein group and 98 in the standard therapy group. The number of patients refusing to participate was not reported.
Study design This was a 'pragmatic' multicentre, randomized unblinded controlled trial. There were 68 rheumatologists at 52 sites. Patients were followed for 9 months. Diacerein was discontinued at 6 months. NSAIDs were discontinued at 6 months in both groups, unless needed for acute pain. An attempt was made to taper off NSAIDs and analgesics after 6 weeks in both groups. Randomization was stratified based on hip or knee involvement. A total of 39 patients withdrew from the study.24 in the diacerein group dropped out, over half of these due to adverse effects.15 in the standard therapy group dropped out, just over half for lack of efficacy.
Analysis of effectiveness It is not clear whether the analysis of effectiveness was based on intention to treat or on treatment completers. The primary health outcomes used in the analysis of effectiveness were NSAID and analgesic consumption, Lequesne's Functional Index, Pain evaluation (visual analogue scale method), Quality of Life as measured by the Arthritis Impact Measurement Scales Health Status Questionnaire (AIMS2) and the Nottingham Health Profile (NHP). The two groups were similar at baseline, with the exception of duration of disease and the average duration of monitoring in the trial. The standard therapy group had a longer duration of disease (on average 2.4 years longer) and also a longer duration of monitoring during the trial (an average of just over a month longer).
Effectiveness results NSAID use was reduced in both groups. The decrease at 9 months was 12% greater in the diacerein group, but was not statistically significant (p=0.70). Analgesic use was significantly lower in the diacerein group at the 6 month measurement (p=0.005). Lequesne's Functional Index was reduced by 2.2 points in the diacerein group and 1.2 points in the standard therapy group at 9 months (based on a "last observation carried forward" analysis). This difference was statistically significant, (p=0.001). Analysis of pain (as measured by visual analogue scale) was also based on a "last observation carried forward". The diacerein group had a reduction in pain of 27% versus a 16% reduction in the standard therapy group. The difference was statistically significant at 6 months (p<0.05) and 9 months (p=0.021). Quality of Life as measured by AIMS2 showed a trend towards greater improvement in the diacerein group, however the only statistically significant difference was in favour of the standard therapy group in the domain of symptoms (p<0.05). The Nottingham Health Profile (NHP) showed a statistically significant difference in favour of the diacerein group in 4 out of 6 domains.
Clinical conclusions Based on the parameters measured in this study, the addition of Diacerein to standard therapy is superior to standard therapy alone.
Measure of benefits used in the economic analysis Lequesne's Functional Index was the health outcome used in the economic analysis.
Direct costs The direct costs included were drug costs, visits to the doctor, intra-articular injections, x-rays, nursing care, hydrotherapy, and hospital admissions due to osteoarthritis. Discounting of costs was not necessary because the duration was less than 1 year. Cost and quantities were not reported separately. The estimation of quantities was based on actual data from all patients seen at day 15 in this study. The estimation of costs was based on reimbursement rates of the Social Security Health Insurance Scheme in France plus the portion the patient was responsible for paying. The quantity data refer to the period March 1993 - April 1995. Cost data refer to the reimbursement rates in 1995, with the exception of hydrotherapy, which was based on rates published in 1991 by the Department of Health Insurance.
Estimated benefits used in the economic analysis Lequesne's Functional Index was reduced by 2.2 points in the diacerein group and 1.2 points in the standard therapy group at 9 months (based on a "last observation carried forward" analysis). This difference was statistically significant, (p=0.001).
Cost results The mean outpatient cost was FF2,360 in the diacerein group and FF2,272 in the standard therapy group (extrapolated to 250 days).
Synthesis of costs and benefits The costs and benefits were combined by determining the cost of improving 1 point on Lequesne's Functional Index. The cost of improving 1 point in the diacerein group was FF1,072.90, while in the standard therapy group it was FF1,893.50. The incremental cost of adding diacerein to standard therapy was FF88.33 per 1 point on Lequesne's Functional Index (over 250 days).
Authors' conclusions Compared with standard therapy alone, the addition of diacerein achieves considerable medical benefit for negligible extra cost.
CRD COMMENTARY - Selection of comparators The selection of comparators was not justified, however, as a pragmatic study design, rheumatologists were allowed to use whatever therapies they chose to reflect usual practice. Specific drugs in the categories NSAIDs and analgesics were not defined. Other drugs in the same pharmacologic category as diacerein were allowed in the standard therapy group, however no data was given on the incidence of use, or the specific drugs being prescribed.
The protocol stated that an attempt was supposed to be made to taper NSAIDs and analgesics early in the study. Neither the reasons for this in a pragmatic study design, or the results of these attempts werereported.
The protocol also stated that NSAIDs had to be stopped after 6 months, unless needed for acute pain. This would seem to indicate that the comparison from 6 to 9 months was not truly standard therapy. The rate of success in discontinuing NSAIDs after 6 months was not reported. This strategy also seems to negate a pragmatic design.
Validity of estimate of measure of benefit The clinical significance of a 1-point change on Lequesne's Functional Index was not presented. Therefore, the usefulness of the results is unknown. A greater number of patients dropped out of the diacerein group. The "last observation carried forward" analysis may lead to bias in an unknown direction in this case, because there is more inference in the data for this group.
Validity of estimate of costs Cost data were based on extrapolation from patients seen on day 15. This may introduce bias in an unknown direction. No statistical analysis was carried out to exclude the role of chance.
Other issues The generalisability of the results of this study to other settings is questionable and was not addressed by the authors.
Implications of the study A blinded randomised controlled trialis needed to confirm the results of this study.
Source of funding Supported by an unrestricted grant from Laboratoires NEGMA, Magny les Hameaux, France.
Bibliographic details Fagnani F, Bouvenot G, Valat J, Bardin T, Berdah L, Lafuma A, Bone I, Eschwege E, Dresier R. Medico-economic analysis of diacerein with or without standard therapy in the treatment of osteoarthritis. PharmacoEconomics 1998; 13(1 Part 2): 135-146 Indexing Status Subject indexing assigned by NLM MeSH Aged; Anthraquinones /adverse effects /economics /therapeutic use; Anti-Inflammatory Agents, Non-Steroidal /adverse effects /economics /therapeutic use; Cost-Benefit Analysis; Diarrhea /chemically induced; Double-Blind Method; Female; France; Humans; Male; Middle Aged; Osteoarthritis /drug therapy /economics; Prospective Studies; Quality of Life AccessionNumber 21998008024 Date bibliographic record published 31/01/1999 Date abstract record published 31/01/1999 |
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