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Efficacy and side-effects of cyclosporine dose monitoring with levels 6 h after the morning dose in heart transplant patients |
Cantarovich M, Besner J G, Fitchett D H, Latter D A |
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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 Cyclosporine dose (CsA) monitoring with trough levels (T0) versus levels obtained 6 hours after the morning dose (T6) in heart transplant patients. Oral CsA was started at a dosage of 2 mg/kg/day, 1-4 days after transplantation. The target range for either T0 or T6 was 150 to 250 ng/ml, respectively. The CsA dose was increased or decreased by 0.5-1 mg/kg/day if the measured level was outside the target range.
Economic study type Cost-effectiveness analysis.
Study population Adult male and female consecutive heart transplant patients were included in the analysis.
Setting Hospital. The economic study was carried out in Montreal, Quebec, Canada.
Dates to which data relate The main effectiveness data were derived from a single study conducted between May 1994 and January 1996. Resource and cost data were obtained from 1994-1996 sources. The price year was not stated.
Source of effectiveness data The estimates of incidence of acute rejection,left ventricular ejection fraction and serum creatinine, maximal, minimal, current and cumulative doses were obtained from a single study.
Link between effectiveness and cost data The costing was undertaken prospectively on the same patient sample as that used in the effectiveness analysis.
Study sample Twenty consecutive adult heart transplant patients were randomised into CsA monitoring with either T0 (group I, female/male: 1/9, age: 53 +/-8 years) or T6 (group II, female/male:0/10, age:58 +/- 4 years). Power calculations to determine the sample size were not undertaken.
Study design The study was a randomized controlled trial. The duration of follow-up was 11 (+/- 2) months for group 1 and 10 (+/- 3) months for group 2. The loss to follow-up was not reported.
Analysis of effectiveness The basis for the analysis of effectiveness was not specifically stated but is likely to have been treatment completers only. The primary health outcomes were the incidence of acute rejection,left ventricular ejection fraction and serum creatinine, maximal, minimal, current and cumulative doses. No significant differences were recorded in terms of demographic data for the two groups.
Effectiveness results The incidence of acute rejection was 50% in each group. The left ventricular ejection fraction and serum creatinine were similar in both groups at 1 month and at the end of the follow-up.
The doses of CsA (mg/kg/day) were:
maximal: 3.8 (+/- 1) versus 5 (+/- 0.6), (P=0.002);
minimal: 2.2 (+/- 0.7) versus 3.4 (+/- 0.8), (P=0.003);
current: 2.6 (+/- 0.6) versus 3.5 (+/- 1), (P=0.02);
cumulative (mg): 61,790 (+/- 19,754) versus 88,524 (+/- 18,082), (P=0.005).
Clinical conclusions CsA dose monitoring with T6 was associated with a 30% lower CsA dose compared to T0 with the same effectiveness in the prevention of acute rejection and similar cardiac and renal function.
Measure of benefits used in the economic analysis No summary benefit measure was used in the analysis and as such the benefits are considered to be the same as the outcome measures. The principal benefit was therefore the reduction in dose of CsA and the attendant reductions in cost.
Direct costs CsA dose costs (based on the price of 100 mg tablets) were included in the analysis. Discounting was not undertaken due to the limited period of follow-up (less than one year). The quantities were reported separately from the prices. The quantity/cost boundary adopted was the hospital. The price year was not stated.
Statistical analysis of costs Fisher's exact test and Mann-Whitney U-test were used. However, whether these have been used for an analysis of costs was not clearly stated.
Sensitivity analysis No sensitivity analysis was performed.
Estimated benefits used in the economic analysis The incidence of acute rejection was 50% in each group. The left ventricular ejection fraction and serum creatinine were similar in both groups at 1 month and at the end of the follow-up.
The doses of CsA (mg/kg/day) were:
maximal: 3.8 (+/- 1) versus 5 (+/- 0.6), (P=0.002);
minimal: 2.2 (+/- 0.7) versus 3.4 (+/- 0.8), (P=0.003);
current: 2.6 (+/- 0.6) versus 3.5 (+/- 1), (P=0.02);
cumulative (mg): 61,790 (+/- 19,754) versus 88,524 (+/- 18,082), (P=0.005).
Cost results The total CsA cost was Can$5,106 (+/- 1,045) and Can$3,589 (+/-1,116), (P =0.005).
Synthesis of costs and benefits Costs and benefits were not combined.
Authors' conclusions CsA dose monitoring with T6 was associated with a 30% lower CsA dose and cost compared to T0 with the same effectiveness in the prevention of acute rejection and similar cardiac and renal functions.
CRD COMMENTARY - Selection of comparators The reason for the choice of the comparator is clear. CsA dose has been progressively decreased since its introduction into clinical practice as side-effects such as hypertension and renal dysfunction were frequently reported after heart transplantation. You, as a user of this database, should consider whether this is a widely used health technology in your own setting.
Validity of estimate of measure of benefit No summary benefit measure was used in the analysis and as such the principal benefits centred around reductions in dose and therefore cost. The data have not been used selectively but a full economic evaluation using a single benefit measure would assure greater validity in terms of economic evaluation.
Validity of estimate of costs Resource quantities were reported separately from the prices. Adequate details of methods of quantity/cost estimation were given. Important cost items do not appear to have been omitted.
Other issues The authors' conclusions are likely to be internally valid given the uncertainties in the data. The issue of generalisability to other settings or countries was not addressed, however, appropriate comparisons were made with other studies in terms of effects of different doses on the incidence of acute and chronic rejection. The results do not appear to have been presented selectively although a longer period of follow-up was identified as a requirement for future research.
Implications of the study Further research is required in analysing a longer follow-up period to assess if the lower CsA dose used in patients monitored with T6 will be associated with a higher incidence of accelerated graft atherosclerosis after heart transplantation.
Bibliographic details Cantarovich M, Besner J G, Fitchett D H, Latter D A. Efficacy and side-effects of cyclosporine dose monitoring with levels 6 h after the morning dose in heart transplant patients. Clinical Transplantation 1997; 11(5 Part 1): 399-405 Indexing Status Subject indexing assigned by NLM MeSH Acute Disease; Administration, Oral; Adult; Blood Pressure /drug effects; Creatinine /blood; Cyclosporine /administration & Drug Administration Schedule; Drug Costs; Drug Monitoring; Enzyme Multiplied Immunoassay Technique; Female; Follow-Up Studies; Graft Rejection /etiology /prevention & Heart Transplantation /physiology; Humans; Immunosuppressive Agents /administration & Incidence; Kidney /drug effects; Male; Middle Aged; Prospective Studies; Stroke Volume /drug effects; Ventricular Function, Left /drug effects; control; dosage /adverse effects /blood /economics; dosage /adverse effects /blood /economics AccessionNumber 21997001469 Date bibliographic record published 30/04/1999 Date abstract record published 30/04/1999 |
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