|Cost-containment strategies in transplantation: the utility of cyclosporine-ketoconazole combination therapy
|Odocha O, Kelly B, Trimble S, Murigande C, Toussaint R M, Callender C O
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.
Cyclosporine-ketoconazole (CyA-KCZ) combination therapy in kidney and liver transplantation.
Type of intervention
Secondary prevention and treatment.
Economic study type
Patients with kidney and liver transplants.
Hospital. The economic study was carried out in Washington, DC, USA.
Dates to which data relate
The data for the effectiveness and resource use corresponded to patients transplanted between May 1984 and December 1993. The price date was not reported.
Source of effectiveness data
Effectiveness data were derived from a single study.
Link between effectiveness and cost data
The costing was retrospectively undertaken on the same patient sample as that used in the effectiveness analysis.
Power calculations were not used to determine the sample size. A total of 17 patients with a mean age of 42 years (range: 15 - 57) was included in the study. Of those, 10 had undergone kidney transplant, and 7 had undergone a liver transplant. 12 patients were male and 5 were female.
A before-and-after study design was used and the study was carried out in a single centre. The duration of follow-up was 12 weeks. No loss to follow-up was reported.
Analysis of effectiveness
The principle (intention to treat or treatment completers only) used in the analysis of effectiveness was not explicitly specified. The primary health outcomes used in the analysis were the serum creatinine level and the platelet count. These outcome measures were obtained before and at 1, 4, 8 and 12 weeks following CyA-KCZ therapy.
For liver transplant patients, the mean serum creatinine levels (mg/dL) were 1.43 before the intervention, 1.43 at 1 week, 1.5 at 4 weeks, 1.4 at 8 weeks, and 1.57 at 12 weeks. For kidney transplant patients, the mean serum creatinine levels (mg/dL) were 4.1 (before intervention), 2.6 (1 week), 2.2 (4 weeks), 2.1 (8 weeks), and 2.0(12 weeks). At the same time intervals, the platelet count (x1000cells/cc) for the liver transplantation group had mean values of 162,232, 216, 195, and 179. The corresponding mean values (x1000cells/cc) for the platelet count measurement for kidney transplant patients were 251, 306, 262, 276, and 297. The p values for the differences corresponding to the values before and after the intervention were all equal to or greater than 0.05.
The authors observed no clinical toxic side effects. For instance, new-onset pruritus, fever and chills, dizziness or somnolence, hepatotoxicity (known to occur in up to 1:10,000 exposed patients), and CyA-induced hepatic dysfunction were not noted.
Measure of benefits used in the economic analysis
No summary benefit measure was identified in the economic analysis, and only separate clinical outcomes were reported.
Due to the short time frame of the study discounting of costs was not required. The resource quantities were reported separately from theprices. The costs measured were related only to drug use (CyA andKCZ). The calculations corresponded to the period of 12 weeks after the start of the intervention. The cost boundary adopted was patient or third-party payer. The estimation of costs was based on actual data. The resource use corresponded to transplants conducted between May 1984 and December 1993. The price date used in the analysis was not reported. All other costs associated with complications, laboratory testing, overheads etc., were excluded from the analysis, while the authors thought some of these components were common to both modalities studied.
No sensitivity analysis was conducted.
Estimated benefits used in the economic analysis
The costs saving after the onset of the intervention was $320 per patient. Savings from the reduction in CyA use amounted to $700 per patient, whereas the additional cost of KCZ was $380 per patient.
Synthesis of costs and benefits
Costs and benefits were not combined since the use of combined CyA-KCZ regimen was the weakly dominant strategy (with equal efficacy and lower costs).
A combined CyA-KCZ regimen can significantly reduce the mean cyclosporine dose by approximately 70% at the end of the 8th and 12th weeks of therapy without significant toxic side effects. In three patients who developed acute cellular rejection (ACR), no clear relation with the intervention (CyA-KCZ) was found.
CRD COMMENTARY - Selection of comparators
No specific justification was given for the choice of the comparator (CyA therapy alone).
Validity of estimate of measure of benefit
The study results may not be internally valid, due to the biases arising from the study design used, the small sample size, and the lack of identification of additional prognostic or demographic characteristics which might have influenced the results.
Validity of estimate of costs
The quantities of resource use were reported separately from the prices, but this analysis was restricted to drug costs as charged to the patients. The price date was not reported. Some important cost items appear to have been omitted from the analysis. The study lacked a prospective cost analysis.
The conclusions reached in the study may not be fully justified, given the uncertainties inherent in the study results. The issue of generalisability to other settings or countries was not addressed. The results were not presented selectively.
Odocha O, Kelly B, Trimble S, Murigande C, Toussaint R M, Callender C O. Cost-containment strategies in transplantation: the utility of cyclosporine-ketoconazole combination therapy. Transplantation Proceedings 1996; 28(2): 907-909
Subject indexing assigned by NLM
Adolescent; Adult; Alanine Transaminase /blood; Cost Control; Creatinine /blood; Cyclosporine /economics /therapeutic use; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents /economics /therapeutic use; Ketoconazole /economics /therapeutic use; Kidney Transplantation /economics /immunology /physiology; Liver Function Tests; Liver Transplantation /economics /immunology /physiology; Male; Middle Aged; Platelet Count
Date bibliographic record published
Date abstract record published