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Cost-efficacy of oral triptans in the treatment of acute migraine |
Slof J, Badia X, Magaz S, Lainez M J, Galvan J, Heras J |
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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 The study compared different oral triptans at different doses for the treatment of acute migraine. The treatments compared were:
almotriptan 12.5 mg,
eletriptan 40 and 80 mg,
naratriptan 2.5 mg,
rizatriptan 10 mg,
sumatriptan 50 and 100 mg, and
zolmitriptan 2.5 and 5 mg.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of people with migraine (18 - 65 years of age) defined according to the International Headache Society criteria.
Setting The study setting would appear to be primary care. The economic study was carried out in Spain.
Dates to which data relate The effectiveness data were derived from a meta-analysis, the results of which were published in 2001 and 2002. The price year was 2002.
Source of effectiveness data The effectiveness data were derived from a meta-analysis undertaken by Ferrari et al. (2001 and 2002, see 'Other Publications of Related Interest' below for bibliographic details).
Modelling A decision analytic tree model was used to assess the cost-effectiveness of the different treatments being used.
Outcomes assessed in the review The outcomes assessed in the meta-analysis were:
the rate of patients experiencing pain relief by 2 hours post dose;
the rate of patients becoming pain free within 2 hours post dose; and
the rate of sustained pain-free patients.
Study designs and other criteria for inclusion in the review For inclusion in the meta-analysis the trials had to meet the following entry criteria:
double-blind, randomised, controlled clinical trial (RCT);
treatment of moderate or severe migraine attacks within 8 hours of onset;
people with migraine (18 - 65 years of age) defined according to the International Headache Society criteria;
treatment with an oral triptan at a recommended clinical dose; and
measurement of the headache on a 4-point pain scale.
Sources searched to identify primary studies The authors did not report the sources searched for the primary studies in the meta-analysis undertaken by Ferrari et al. (2001 and 2002).
Criteria used to ensure the validity of primary studies The authors did not report the criteria used to ensure the validity of primary studies in the meta-analysis undertaken by Ferrari et al. (2001 and 2002).
Methods used to judge relevance and validity, and for extracting data The authors did not report the methods used to judge the relevance and validity of primary studies, or the methods used to extract the data in the meta-analysis undertaken by Ferrari et al. (2001 and 2002).
Number of primary studies included Fifty-three studies were included in the meta-analysis undertaken by Ferrari et al. (2001 and 2002).
Methods of combining primary studies The primary studies were combined in a meta-analysis. More than 24,000 patients were included in the analysis.
Investigation of differences between primary studies The authors did not report whether differences between the primary studies were investigated in the meta-analysis undertaken by Ferrari et al. (2001 and 2002).
Results of the review The authors only provided results from the meta-analysis for one of the three clinical end points used to compare treatment efficacy.
The proportion of sustained pain-free patients for each triptan was:
20.0% with sumatriptan 100 mg,
19.8% with sumatriptan 50 mg,
19.0% with zolmitriptan 2.5 mg,
21.9% with zolmitriptan 5 mg,
15.9% with naratriptan 2.5 mg;
25.3% with rizatriptan 10 mg,
20.9% with eletriptan 40 mg,
25.0% with eletriptan 80 mg, and
25.9% with almotriptan 12.5 mg.
Measure of benefits used in the economic analysis The measure of benefit used was the rate of sustained pain-free patients. Sustained pain-free was defined as being pain free by 2 hours post dose and not experiencing recurrence of moderate or severe headache, nor using rescue headache medication 2 to 24 hours post dose. The authors used this measure of benefit as it is currently considered to be the most demanding efficacy parameter for migraine drugs.
Direct costs The direct costs included in the analysis were those of the health service. The costs included were for the study drugs and the resources used in the treatment of adverse events. The main adverse events considered were chest related and central nervous system (CNS) related. The former covered chest pressure, chest pain, radiating pain in arm, other chest feelings, heavy arms, shortness of breath, palpitations and anxiety. The latter covered asthenia, abnormal dreams, agitation, aphasia, ataxia, confusion, dizziness, somnolence, speech disorder, thinking abnormally, tremor, vertigo and other focal neurological symptoms. The information on the proportion of patients experiencing these adverse events was taken from the meta-analysis. Information on healthcare resource use in the treatment of these events was collected from a panel of six neurologists with extensive experience in migraine treatment. The resources potentially consumed were general practitioners, neurologists, emergency departments, and diagnostic tests (electrocardiograms, cardiac enzymes, chest radiography).
The drugs were valued according to their official retail prices. As the Spanish National Health System only reimburses 60% of the retail price, a 40% co-payment was subtracted. All other unit costs were obtained from a national database of healthcare resource costs. The costs were not discounted as the time horizon for an episode of migraine was short. The average costs were reported. The price year was 2002.
Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic).
Indirect Costs The indirect costs were not included.
Sensitivity analysis Sensitivity analyses were performed to evaluate the potential impact of uncertainty surrounding the model parameters on the model outcomes. Two alternative scenarios, which reflected the two opposite extreme scenarios for adverse events, were developed. The first, low-cost scenario assumed that there were no costs associated with the treatment of adverse events, or that patients did not seek medical attention at all. The second, high-cost scenario, assumed the highest proportion of patients seeking medical attention and the most resource-intensive management pattern imaginable by the expert panel.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The mean costs per patient for each treatment were as follows:
sumatriptan 100 mg, EUR 8.67;
sumatriptan 50 mg, EUR 4.54;
zolmitriptan 2.5 mg, EUR 4.85;
zolmitriptan 5 mg, EUR 9.09;
naratriptan 2.5 mg, EUR 3.64;
rizatriptan 10 mg, EUR 5.53;
eletriptan 40 mg, EUR 5.40;
eletriptan 80 mg, EUR 10.92; and
almotriptan 12.5 mg, EUR 5.17.
Synthesis of costs and benefits The costs and benefits were combined using an incremental cost-effectiveness ratio (i.e. the additional cost per sustained pain-free patient gained). In the incremental analysis, starting from the less costly treatment option, the additional cost of using the next best alternative was divided by the additional efficacy achieved. Sumatriptan 100 mg, zolmitriptan 2.5 and 5 mg, rizatriptan 10 mg, and eletriptan 40 and 80 mg were found to be dominated (i.e. there were other treatments that were both more effective and less costly). When compared with naratriptan 2.5 mg, the incremental cost-effectiveness ratio of sumatriptan 50 mg was EUR 23.09 per sustained pain-free patient. When compared with sumatriptan 50 mg, the additional cost per sustained pain-free patient of almotriptan was EUR 10.45.
The results of the sensitivity analyses showed that, in the low-cost scenario, sumatriptan 100 mg, zolmitriptan 5 mg, and eletriptan 40 and 80 mg were still dominated. Under the high-cost scenario, naratriptan 2.5 mg and almotriptan 12.5 mg were the only two interventions that were not dominated by another treatment option. When compared with naratriptan 2.5 mg, the additional cost per sustained pain-free patient was EUR 7.59.
Authors' conclusions Rizatriptan 10 mg and, particularly, almotriptan 12.5 mg were the most appealing triptans in Spain, after combining clinical and economic considerations.
CRD COMMENTARY - Selection of comparators The authors compared different triptans for the treatment of acute migraine. The authors reported that only triptans currently in use in Spain were compared in their study. You should decide if these interventions represent current practice in your own settings.
Validity of estimate of measure of effectiveness The effectiveness estimates for each intervention were derived from a meta-analysis of 53 RCTs involving over 24,000 patients. Although the authors did not report many details of this meta-analysis, which was published elsewhere, the large number of patients and the fact that only RCTs were included (the 'gold'-standard study design when comparing health interventions' would suggest that the results of the analysis were internally valid.
Validity of estimate of measure of benefit The estimation of benefits was obtained directly from the meta-analysis. Consequently, these estimates are very likely to be internally valid. However, the outcome measure used in the economic analysis (i.e. sustained pain-free patients) would appear not to be generalisable and to be difficult to compare with the outcomes from other interventions. Further, when the authors derived incremental cost-effectiveness ratios, it was not possible to determine which of the treatments was the most cost-effective, as it was difficult to value what the cost-effectiveness threshold was for an additional sustained pain-free patient. Ideally, the authors should have translated this outcome measure into a more generalisable outcome measure such as quality-adjusted life-years.
Validity of estimate of costs All the categories of cost relevant to the health service perspective adopted were included in the analysis. A group of experts was asked to determine the resource categories in the treatment of acute migraine. Consequently, it appears that all the major relevant costs have been included in the analysis. The authors reported that the costs of treating some adverse events were not included, either because they were assumed equal between treatments or because they were not associated with significant costs. The costs and the quantities were reported separately, which will increase the generalisability of the authors' results. The proportions of patients suffering chest and CNS-related adverse events were derived from the meta-analysis. The resources used to treat these events were then derived using expert opinion. The unit costs were derived from national sources. A very limited sensitivity analysis was undertaken using two extreme scenarios, a low-cost one (where there were no costs in treating adverse events) and a high-cost one (where the upper values given by the experts on the resources needed to treat such adverse events were used). Since all the costs were incurred during a short time, discounting was unnecessary. The price year was reported, which will aid any future inflation exercises.
Other issues The authors made appropriate comparisons of their findings with numerous other studies. In particular, the authors compared their results with a similar US study that had also used data from the meta-analysis undertaken by Ferrari et al. The results of this study showed that the lowest cost per sustained pain-free patient was almotriptan 12.5 mg, while the costs of the other oral triptans were between 1.5 and 2.7 times higher. The issue of generalisability to other settings was addressed. The authors do not appear to have presented their results selectively. The authors reported a number of further limitations to their study. First, the results are based on a Spanish context, and cannot be extrapolated straightforwardly to other healthcare systems. Second, the authors would have preferred to obtain clinical data from a simultaneous head-to-head trial of all treatments. However, they acknowledged that undertaking such a trial would be unlikely. Finally, the resource use data had to be derived using expert opinion.
Implications of the study The authors would appear to recommend the use of rizatriptan 10 mg and, particularly, almotriptan 12.5 mg.
Source of funding Sponsored by Almirall Prodesfarma, Barcelona, Spain.
Bibliographic details Slof J, Badia X, Magaz S, Lainez M J, Galvan J, Heras J. Cost-efficacy of oral triptans in the treatment of acute migraine. Journal of Medical Economics 2005; 8: 27-43 Other publications of related interest Ferrari MD, Roon KI, Lipton RB, et al. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001;358:1668-75.
Reeder CE, Steadman S, Goldfarb SD. Economic comparison of oral triptans for management of acute migraine: implications for managed care. Am J Manag Care 2002;8:S80-4.
Wang JT, Barr CE, Torigoe Y, et al. Cost savings in migraine associated with less chest pain on new triptan therapy. Am J Manag Care 2002;8:S102-7.
Belsey JD. The clinical and financial impact of oral triptans - an updated meta-analysis. J Med Econ 2002;5:79-89.
Indexing Status Subject indexing assigned by CRD MeSH Clinical Trials as Topic; Cost of Illness; Costs and Cost Analysis; Drug Costs; Meta-Analysis; Migraine Disorders /complications /prevention & Spain; Sumatriptan /adverse effects /administration & Tryptamines; control /drug therapy; dosage /therapeutic use /economics AccessionNumber 22005008113 Date bibliographic record published 31/05/2006 Date abstract record published 31/05/2006 |
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