A cost minimization model for the treatment of minor bleeding episodes in patients with haemophilia A and high-titre inhibitors.

Treatment of acute bleeding episodes in patients with haemophilia A and inhibitory antibodies 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 complete 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). Consensus 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 dollars, compared with 33 400 dollars for initial treatment 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.

The economic impact of factor VIII inhibitors in patients with haemophilia.

The impact on the cost of care for haemophilia patients with inhibitors is not well defined. To quantify the effect on health care expenditures associated with inhibitors to factor VIII (FVIII) or FIX, we conducted a retrospective cohort study examining product use and outcomes in adult and paediatric haemophilia patients with and without inhibitors. Twelve patients with inhibitors to FVIII or FIX (cases) identified in the haemophilia surveillance system (HSS) at two centres were matched on age, severity of haemophilia, and treatment centre to haemophilia patients without inhibitors. Patients with HIV or significant liver disease were excluded from the study. All eligible non-inhibitor control patients were selected for inclusion in the study, resulting in a total of 28 controls. We then tracked product usage and hospitalizations from programme entry until 1998 or loss to follow-up, producing a total database of 184 person-years of experience. A descriptive matched analysis was conducted to examine annual differences in the cost of product used and hospitalizations. We found that the median cost for factor products among haemophilia patients with inhibitors was $55,853/year, $2,760 less than comparable haemophilia patients without inhibitors. The median number of hospitalizations per year was 1.0 for both inhibitor and non-inhibitor patients and the median number of days hospitalized was virtually the same. Although these findings do not appear to support the belief that there is a substantial increase in the cost of care for haemophilia patients with inhibitors, it does document that a few outlier patients can drive the cost of treatment for this disease. As the largest component of the cost of care is that of factor concentrate, it becomes imperative in the current health care environment to better define the true costs and benefits of treatments designed to eradicate or manage inhibitors. A careful cost accounting of immune tolerance induction (ITI) and other therapeutic strategies, taking into account successes and failures and duration and intensity of therapy, should help to better define the costs and benefits of such approaches. Methods to identify high cost inhibitor patients should be developed so that these strategies may be targeted to appropriate candidates.

Porcine factor VIII: pharmacoeconomics of inhibitor therapy.

The treatment of acquired haemophilia is characteristically exceedingly expensive and thus a cost-benefit analysis of the several available treatment strategies is urgently needed. To address this issue, decision-analysis techniques were used to construct a cost-minimization model to compare the cost of treatment with porcine factor VIII (pFVIII), human FVIII (hFVIII) or an activated prothrombin complex concentrate (APCC). This model was based upon the results of a comprehensive literature search of all relevant clinical studies and case series. To supplement these data, a panel of haemophilia specialists was presented with a clinical scenario describing an acquired haemophilia patient with an acute haemorrhage in whom the human and porcine inhibitor titres were initially unknown. Based on this scenario and on their own clinical experience, the expert panel assessed the applicability of the model as initially constructed, assigned probabilities of success to each treatment and recommended appropriate initial dosing and follow-up regimens. This information was incorporated into the model and a simulation was conducted from which the costs of care were calculated. Sensitivity analyses were then conducted on all parameters. The results of the model show that treatment initiated with pFVIII would be more cost effective compared with treatment sequences initiated with an APCC or hFVIII, respectively. The model indicates that initial treatment with pFVIII in this scenario may be the preferred strategy clinically, as well as on economic grounds.