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Economic analysis of epilepsy treatment: a cost minimization analysis comparing carbamazepine and lamotrigine in the UK |
Shakespeare A, Simeon G |
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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 Anti-epileptic drugs used in the treatment of partial or general tonic-clonic seizures.
Economic study type Cost-effectiveness analysis.
Study population Patients, at least 13 years of age, with newly diagnosed cases of epilepsy. Patients had previously not received treatment with an anti-epileptic drug.
Setting Hospital. The economic analysis was conducted in London, UK.
Dates to which data relate Data on effectiveness were taken from a randomised controlled trial published in 1995. Resource use data were determined both from expert opinion and from literature published in 1994 - 1995. 1994/1995 price years were used.
Source of effectiveness data Effectiveness data were derived from a single study.
Link between effectiveness and cost data Costing was not undertaken on the same patient sample as that used in the effectiveness analysis.
Study sample 260 patients were randomised to receive either CBZ 600mg per day or LTG 150mg per day monotherapy. After randomisation there were 131 patients in the LTG group and 129 in the CBZ group. Power calculations were used in determining the sample size: power of 70% to show a maximum difference between the drugs of 20% in terms of seizure-free patients.
Study design This was a multi-centre double blind randomised controlled trial. The method of randomisation used was not stated. The duration of follow up was the 48 week study period of the trial.
Analysis of effectiveness The analysis of effectiveness was based on intention to treat. The primary clinical outcomes were the number of patients maintained seizure-free during the trial, the incidence of adverse events and withdrawal as a result of adverse events. The authors considered that both patient groups were well matched although those randomised to LTG had reported more seizures prior to receiving treatment.
Effectiveness results There were no significant differences between the number of patients maintained seizure-free in the two groups. Adverse events rates also did not significantly differ with the exception of sleepiness, which was experienced by 12% of patients in the LTG group compared with 22% in the CBZ group, (P<0.05). The rates of withdrawal due to adverse events in the LTG and CBZ groups were 15% (19 patients) and 27% (35 patients) respectively. This difference was significant in favour of LTG (hazard ratio 1.57, 95% CI: 1.07 - 2.31)
Clinical conclusions LTG and CBZ have demonstrated similar rates of efficacy in the prevention of partial onset seizures and primary generalised tonic-clonic seizures in newly diagnosed epilepsy. LTG had better tolerability than CBZ and patients are therefore more likely to continue treatment than if they receive CBZ.
Modelling A decision analysis model was used to estimate the total annual costs of therapy using either drug, including costs associated with adverse events.
Measure of benefits used in the economic analysis Since the effectiveness analysis did not demonstrate any difference in efficacy between the intervention and the comparator, the economic analysis was based on the differences in costs only.
Direct costs Costs of care (excluding routine care costs) were estimated. These included medical consultations, acquisition costs for CBZ, LTG and switch therapy and adverse event treatment. Quantities and patterns of resources used were estimated by a Delphi panel consisting of four hospital specialists in epilepsy care. Unit cost estimates for specialist medical consultations were taken from the CIPFA database of NHS costs and GP consultations from the Personal Social Services Research Unit's Annual Costs of Community Care. Costs of drug therapies were taken from the British National Formulary 1995. Costs of tests were taken from a 1994 study and also from a pathology service. Costs of brain imaging were obtained from a NHS hospital trust. The cost of treating adverse events was assumed to be the same in both groups and all events were assumed to be mutually exclusive. All costs were estimated from the perspective of the NHS. Costs were not discounted as the study ran for less than one year and 1994/95 prices were used. Cost estimates were inflated using the 1995 Hospital and Community Health Services Inflation Index where necessary.
Sensitivity analysis One way sensitivity analyses were conducted. Costs using UK physician recommended daily dosages of 800 mg CBZ and 250 mg for LTG were estimated. The rate of withdrawal of treatment was varied to a rate reported in literature of 10% and 4.5% for CBZ and LTG. Mean time at which drug therapy was switched was varied between 1 and 6 months. The impact on cost of patients on CBZ switching to LTG rather than sodium valproate were also examined.
Estimated benefits used in the economic analysis Cost results Overall average costs per patient for the first year of treatment in the CBZ group were estimated to be 179.34 compared with 521.74 in the LTG group. Specifically these costs included: drug costs 71.66 (CBZ) and 430.34 (LTG); adverse events 88.15 and 80.95 and switching (consultation) 19.54 and 10.44. The average costs per annum for successfully treated patients were 145.63 for the CBZ group and 564.44 for the LTG group. Average costs for patients in the CBZ and LTG groups who switched treatment were 269.86 and 269.99 respectively.
Synthesis of costs and benefits Authors' conclusions CBZ monotherapy for patients with newly diagnosed epilepsy is cost saving compared with LTG. In the analysis average costs per patient, including the costs of switching therapy, were 34% of the average costs of LTG therapy. The results of the study are, however, derived from limited data and need to be validated by well designed trials. The analysis did not consider quality of life considerations, which could have an impact on results, but insufficient information was available to examine this. The findings of the study are similar to those reported in a 1993 US analysis.
CRD COMMENTARY - Selection of comparators A justification was given for the comparators used as both drugs had been demonstrated, in a clinical trial using newly diagnosed patients, to have similar rates of efficacy. In addition, the comparator, LTG, is a well recognised drug treatment for these seizures. However, it would also have been useful to compare both drugs with sodium valproate as the main therapy (the switch therapy for patients in the CBZ group) as this treatment was assumed by the authors to have similar rates of efficacy and incidence of adverse events
Validity of estimate of measure of benefit The estimates of efficacy and tolerability were taken from a single randomised controlled trial and, as noted by the authors, may not be representative of clinical practice in the UK. As noted by the authors quality of life outcomes were not considered due to a lack of information on severity of adverse events in the two groups. These quality of life measures, however, may identify whether the improved tolerability of LTG is also reflected in improved quality of life for patients.
Validity of estimate of costs Sufficient information was provided on the source of costs used in the analysis. However, estimates of resources used in the treatment of adverse events were based on expert opinion rather than on prospective studies, and costs to others in society, such as patients and caregivers, were not included due to a lack of data.
Other issues The results of this study may not be generalisable outside the UK although similar conclusions on the cost saving potential of CBZ were reported in the United States. Well designed prospective economic evaluations are required to examine further the conclusions reached in this study.
Implications of the study Further prospective studies are required to confirm the conclusions of clinical analysis and to generate more information on the use of resources.
Bibliographic details Shakespeare A, Simeon G. Economic analysis of epilepsy treatment: a cost minimization analysis comparing carbamazepine and lamotrigine in the UK. Seizure 1998; 7(2): 119-125 Other publications of related interest Brodie M J, Richens A and Yuen A W C. Double blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 1995;345:476-479.
Navarro R P and Ashraf T. Cost analysis of carbamazepine, phenytoin, and valproate for use in complex partial seizures. Medical Interface 1993:113-118.
Indexing Status Subject indexing assigned by NLM MeSH Anticonvulsants /adverse effects /economics /therapeutic use; Carbamazepine /adverse effects /economics /therapeutic use; Cost Control; Decision Support Techniques; Drug Costs /statistics & Epilepsies, Partial /drug therapy /economics; Epilepsy /drug therapy /economics; Epilepsy, Generalized /drug therapy /economics; Epilepsy, Tonic-Clonic /drug therapy /economics; Great Britain; Health Resources /economics; Humans; State Medicine /economics; Triazines /adverse effects /economics /therapeutic use; numerical data AccessionNumber 21998000769 Date bibliographic record published 29/02/2000 Date abstract record published 29/02/2000 |
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