Background: A number of new antiepileptic agents have been introduced within a short period of time. Direct comparisons are not available, and information about the balance between costs and effects for these new therapies is lacking.
Objective: To introduce a first approximation of the cost effectiveness of the new therapeutic agents (topiramate and lamotrigine) for epilepsy that have been assessed in clinical trials against placebo.
Methods: Without head to head comparative data no formal methods are available to assess the relative cost effectiveness of two products; therefore, a Bayesian approach was developed. The approach starts with the ‘proportionality assumption’ saying that the differences in healthcare expenditure (less the direct cost of therapy) are directly proportional to the differences in effectiveness. Given this assumption, a therapy that is x times as expensive as an alternative therapy has an equivalent cost-effectiveness profile if the acquisition cost is x times as high. Moreover, simple formulas can be derived to calculate the probabilities that a therapy is dominant (more effective and less expensive) and that it is weakly dominant (more effective and a better cost-effectiveness profile). The approach is applied to data from published fixed dosage, parallel-design studies comparing both topiramate and lamotrigine with placebo.
Results: Assuming that the ‘proportionality assumption’ holds for the medical treatment of epilepsy, and disregarding uncertainties, it is estimated that topiramate may be priced more than 2.2 times its current acquisition cost and still be more cost effective than lamotrigine. Taking uncertainties into account, it is estimated that lamotrigine 500 mg/day is dominated by topiramate 200 mg/day with a probability of 0.875 and by topiramate 400 mg/day with a probability of 0.986.
Conclusions: A simple method can be applied to assess the relative cost effectiveness of two therapies in the absence of direct comparative data. Applying this method to compare topiramate and lamotrigine leads to a strong preference for topiramate. However, to be able to draw this conclusion, some heroic assumptions need to be made. As such the method as developed here only reflects a first approximation. It needs to be used with care and is not intended to replace good comparative research.
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This study was supported by a grant from Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, New Jersey, USA. D.D. Gagnon and P. McNulty are employees and shareholders of Johnson & Johnson. B.A. van Hout and A. O’Hagan are consultants to Johnson & Johnson.
Marson AG, Kadit ZA, Hutton JL, et al. The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Epilepsia 1997; 38 (8): 859–80PubMedCrossRefGoogle Scholar
Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant partial epilepsy. Available from The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 3. Oxford: Update Software, 2001: CD001909Google Scholar
Stinnett AA, Mullahy J. Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis. Med Decis Making 1998; 18 Suppl. 2: S68–80PubMedCrossRefGoogle Scholar
Cooper H, Hedges LV, editors. The handbook of research synthesis. New York: Russel Sage Foundation, 1994Google Scholar
Guberman A, Neto W, Gassmann-Mayer C, the EPAJ-119 Study Group. Low-dose topiramate in adults with treatment-resistant partial-onset seizures. Acta Neurol Scand 2002; 106 (4); 183–9PubMedCrossRefGoogle Scholar
Whitehead A, Whitehead J. A general parametric approach to the meta-analysis of randomized clinical trials. Stat Med 1991; 10: 1677CrossRefGoogle Scholar
Sachdeo R, Kramer LD, Rosenberg A, et al. Felbamate monotherapy: controlled trial in patients with partial onset seizures. Ann Neurol 1992; 32 (3): 386–92PubMedCrossRefGoogle Scholar
Chiron C, Dumas C, Dulac O. Vigabatrin versus hydrocortisone as first-line monotherapy in infantile spasms due to tuberous sclerosis. Epilepsia 1995; 36 Suppl. 3: S265Google Scholar
Spilker B, Segreti A. Validation of the phenomenon of regression of seizure frequency in epilepsy. Epilepsia 1984; 25 (4): 443–9PubMedCrossRefGoogle Scholar
Willmore JL. Depakote adjunctive therapy in the treatment of partial seizures. Epilepsia 1995; 36 Suppl. 3: S66Google Scholar
Pocock SJ. Clinical trials: a practical approach. New York: John Wiley, 1983Google Scholar
Brodie MJ, Richens A, Yuen AWC. Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 1995; 345 (8948): 476–9PubMedCrossRefGoogle Scholar
Binnie CD, Debets RM, Engelsman M, et al. Double blind cross-over trial of lamotrigine (Lamictal) as add on therapy in intractable epilepsy. Epilepsy Res 1989; 4 (3): 222–9PubMedCrossRefGoogle Scholar
Boas J, Dam M, Friis ML, et al. Controlled trial of lamotrigine (Lamictal®) for treatment-resistant partial seizures. Acta Neurol Scand 1996; 94: 247–52PubMedCrossRefGoogle Scholar
Jawad S, Richens A, Goodwin G, et al. Controlled trial of lamotrigine (Lamictal) for refractory partial seizures. Epilepsia 1989; 30 (3): 356–63PubMedCrossRefGoogle Scholar
Loiseau P, Yuen AW, Duche B, et al. A randomised double blind placebo controlled cross-over add on trial of lamotrigine in patients with treatment resistant partial seizures. Epilepsy Res 1990; 7 (2): 136–45PubMedCrossRefGoogle Scholar
Messenheimer J, Ramsey RE, Willmore LJ, et al. Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial. Epilepsia 1994; 35 (1): 113–21PubMedCrossRefGoogle Scholar
Schapel GJ, Beran RG, Vajda FJ, et al. Double blind, placebo controlled, cross-over study of lamotrigine in treatment resistant partial seizures. J Neurol Neurosurg Psychiatry 1993; 56 (5): 448–53PubMedCrossRefGoogle Scholar
Schmidt D, Jacob R, Loiseau P. Zonisamide for add on treatment of refractory partial epilepsy: a European double blind trial. Epilepsy Res 1993; 15 (1): 67–73PubMedCrossRefGoogle Scholar
Smith D, Baker G, Davies G, et al. Outcomes of add on treatment with lamotrigine in partial epilepsy. Epilepsia 1993; 34 (2): 312–22PubMedCrossRefGoogle Scholar
Matsuo F, Bergen D, Faught E, et al. Placebo-controlled study of the efficacy and safety of lamotrigine in patients with partial seizures: U.S. Lamotrigine Protocol 0.5 Clinical Trial Group. Neurology 1993; 43 (11): 2284–91PubMedCrossRefGoogle Scholar
Elterman RD, Glauser TA, Wyllie E, et al. A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children: Topiramate YP Study Group. Neurology 1999; 52: 1338–44PubMedCrossRefGoogle Scholar
Sachdeo RC, Glauser TA, Ritter F, et al. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome: Topiramate YL Study Group. Neurology 1999; 52: 1882–7PubMedCrossRefGoogle Scholar
Reife R, Pledger G, Wu SC. Topiramate as add-on therapy: pooled analysis of randomized controlled trials in adults. Epilepsia 2000; 41 Suppl. 1: S66–71PubMedCrossRefGoogle Scholar
Kamin M, Kraut L, Olson WH. Tolerability and safety of topiramate (TPM) in a community based study (TRAITS) of adults with partial-onset seizures [abstract]. Epilepsia 1999; 40 Suppl. 7: 5Google Scholar
Pellock J, Kamin M, Kraut L, et al. Adverse events (AEs) when topiramate is titrated to effect: results from an open-label, in-practice study with 800+ patients [abstract]. Epilepsia 2000; 41 Suppl. 7: 105Google Scholar
Chadwick DW, Marson T, Kadir Z. Clinical administration of new antiepileptic drugs: an overview of safety and efficacy. Epilepsia 1996; 37 Suppl. 6: S17–22PubMedCrossRefGoogle Scholar
Jette NJ, Marson AG, Kadir ZA, et al. Topiramate for drug-resistant partial epilepsy. Available from The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 3. Oxford: Update Software, 2001: CD001417Google Scholar
Sander JW. Practical aspects of the use of topiramate in patients with epilepsy. Epilepsia 1997; 38 Suppl. 1: S56–8PubMedCrossRefGoogle Scholar
Shorvon SD. Safety of topiramate: adverse events and relationships to dosing. Epilepsia 1996; 37 Suppl. 2: S18–22PubMedCrossRefGoogle Scholar
Peeters K, Adrianssen I, Wapenaar R, et al. A pooled analysis of adjunctive topiramate in refractory partial epilepsy. Acta Neurol Scand. In pressGoogle Scholar
Begley CE, Lairson DR, Reynolds TF, et al. Early treatment cost in epilepsy and how it varies with seizure type and frequency. Epilepsy Res 2001; 47: 205–15PubMedCrossRefGoogle Scholar
de Zelicourt M, Buteau L, Fagnani F, et al. The contributing factors to medical cost of epilepsy: an estimation based on a French prospective cohort study of patients with newly diagnosed epileptic seizures (the CAROLE study). Seizure 2000; 9: 88–95PubMedCrossRefGoogle Scholar
Jacoby A, Buck D, Baker G, et al. Uptake and costs of care for epilepsy: findings from a UK regional study. Epilepsia 1998; 39 Suppl. 7: 776–86PubMedCrossRefGoogle Scholar
Van Hout BA, Gagnon D, McNulty P. An economic evaluation of topiramate versus placebo, gabapentin, and lamotrigine [abstract]. Neurology 1997; 48 Suppl. 3: A170Google Scholar
Van Hout B, Gagnon D, Souetre E, et al. Relationship between seizure frequency and costs and quality of life of outpatients with partial epilepsy in France, Germany, and the United Kingdom. Epilepsia 1997; 38: 1221–6PubMedCrossRefGoogle Scholar
Haymarket Medical Ltd. eMIMS: the definitive prescribing information system [online]. Available from URL: http://www.emims.net [Accessed 2001 Oct 15]
O’Hagan A, Stevens JW, Montmartin J. Inference for the cost-effectiveness acceptability curve and cost-effectiveness ratio. Pharmacoeconomics 2000; 17 (4): 339–49PubMedCrossRefGoogle Scholar
Jones DA. A Bayesian approach to the economic evaluation of health care technologies. In: Spilker B, editor. Quality of life and pharmacoeconomics in clinical trials. 2nd ed. Philadelphia (PA): Lippincott-Raven, 1996: 1189–96Google Scholar
Lilford RJ, Braunholtz D. The statistical basis of public policy: a paradigm shift is overdue. BMJ 1996; 313: 603–7PubMedCrossRefGoogle Scholar