A cost minimization model for the treatment of minor bleeding episodes in patients with haemophilia A and high-titre inhibitors K. G. PUTNAM, R. L. BOHN, B. M. EWENSTEIN, W. C. WINKELMAYER and J. AVORN Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School; and Division of Hematology, Harvard Medical School, Boston, MA, USA Summary. Treatment of acute bleeding episodes in patients with haemophilia A and inhibitory antibod- ies to factor VIII (FVIII) most often involves the use of bypassing haemostatic agents, such as activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa (rFVIIa). We constructed a cost minimization model to compare the costs of initial treatment with aPCC vs. rFVIIa in the home treatment of minor bleeding episodes. We developed a clinical scenario describing such a case and presented it to a panel of US haemophilia specialists. For each product class, we asked panellists to provide dosing regimens required to achieve com- plete resolution of a minor haemarthrosis in a child with high-titre inhibitors, and for the probabilities of success at two time points (8–12 and 24 h). Consen- sus among the panellists was refined by a second round of the process, and the median values resulting were used as inputs to a decision analysis model. Sensitivity analyses were conducted to determine threshold values for key variables. The base case model found that initial treatment with aPCC would result in a mean cost per episode of $21 000, compared with $33 400 for initial treat- ment with rFVIIa. Sensitivity analyses over a range of clinically plausible values for cost, dosing, and efficacy did not change the selection of aPCC as the dominant strategy. Keywords: activated prothrombin complex com- plexes, Costs and cost analysis, decision analysis, factor VIIa, factor VIII, hemophilia, inhibitors Introduction For patients with haemophilia A, the development of inhibitors to factor VIII (FVIII), especially at high titre, is a serious event associated with increased morbidity and mortality. Treatment of minor bleed- ing episodes in such patients typically requires the use of ÔbypassingÕ agents, including an activated prothrombin complex concentrates (aPCC) or recombinant activated factor VII (rFVIIa). Porcine FVIII, which is currently virtually unobtainable, is often reserved for major bleeding episodes. Several alternative therapeutic strategies are presently in use, but there is a lack of consensus concerning which bypassing agent should be considered first- line therapy [1]. No randomized controlled trial data are available from studies that compared these agents with one another with respect to their relative efficacy, safety and cost. Minor bleeding episodes in selected patients may be initially treated at home using either rFVIIa or aPCC. In selecting a regimen, the treating physician must consider competing benefits, risks and costs. These include inhibitor titre, inhibitor responsive- ness, time to resolution, overall duration of treat- ment, infectious and thrombotic complications, and, in an environment of limited health care resources, the relative cost of each therapeutic strategy. With little consensus among clinicians, inad- equate comparative literature, and mounting cost considerations, there is a need for further study of the optimal strategy for treating high-titre inhibitor A preliminary version of this paper was presented orally at the 44th Annual Meeting of the American Society of Hematology, Philadelphia, PA, 10 December 2002. Correspondence: Jerry Avorn, MD, Division of Pharmacoepide- miology and Pharmacoeconomics, 1620 Tremont St., Boston, MA 02120, USA. Tel.: (617) 278 0930; fax: (617) 232 8602; email: javorn@rics.bwh.harvard.edu Accepted after revision 29 March 2005 Haemophilia (2005), 11, 261–269 DOI: 10.1111/j.1365-2516.2005.01098.x Ó 2005 Blackwell Publishing Ltd 261