Health-Economic Analysis of Alternative Bypassing Agents in Haemophilia Complicated by an Inhibitor - the FEIBA® NovoSeven® Comparative Study (FENOC).
Authors: Carlsson Katarina Steen , Astermark Jan , Donfield Sharyne M. , Berntorp Erik 
Published: April 2020

Abstract
BACKGROUND: The development of inhibitory antibodies to factor VIII is a serious complication in haemophilia. Two haemostatic agents with different bypassing mechanisms have been used in the treatment of patients with inhibitors: activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa). To date, published analyses on costs and outcomes in inhibitor treatment have been based on comparatively small samples and on expert opinion. Existing comparisons have used decision-analytic modelling.
DATA: The FENOC study used a prospective, crossover design where each patient used activated prothrombin complex concentrate (FEIBA®) at one bleed and recombinant factor VIIa (NovoSeven®) at another bleed. The order of bypassing agents was randomised. The resource use and haemostatic efficacy was recorded at 2, 6, 12, 24, 36 and 48 hours following treatment. Time until bleeding had stopped was also evaluated. Forty-eight pairs (96 bleeding episodes) were included in the analysis.
METHODS: Two types of health-economic analysis were performed: cost analysis identifying the determinants of cost using regression methods, and cost-effectiveness analysis to relate resource use to three measures of outcome; patient perception of treatment efficacy (defined as effective and/or partially effective), whether the bleeding had stopped and reduction in patient-perceived pain on a Visual Analogue Scale from start of treatment. Confidence intervals (CI) of the incremental cost-effectiveness ratios were calculated by bootstrap. The sensitivity of results were tested using the different relative prices in the US (Red Book AWP) and Sweden (national negotiated prices from the Swedish Pharmaceutical Benefits Board).
RESULTS: Key determinants of cost were prescribed dose per kg bodyweight, weighing relatively more than persons of the same age and treatment in addition to protocol. FEIBA® cost on average less (p&lt;0.0001) than NovoSeven® at all measurement points during 48h while it had slightly higher (but not significantly) percentages of efficacy measured by patient perception of treatment and whether the bleeding had stopped at all but one time point. A slightly higher proportion considered NovoSeven® effective/partially effective at 12 hours after treatment start. The incremental cost-effectiveness ratios were negative with wide, but negative, CIs. The same analysis measuring outcome by reduction in pain from start of treatment gave less clear results due to a considerable variation at the individual level. By 48h after start of treatment, more than half of the patients reported significantly better results with one of the products. However, this group was evenly divided between the two bypassing agents. The different relative prices in the US and Sweden mattered, but did not reverse the main results.
CONCLUSIONS: Health-economic analysis from the FENOC study indicated that FEIBA® was a dominant strategy having on average lower cost and slightly higher percentages of patient-stated efficacy. The large variation at the individual level of the two bypassing agents’ effect on reduction of pain supports
1) decisions that take the individual patient’s experience into account, 2) decisions that make trade-offs between cost and reduction in pain rather than focusing on cost only, 3) further research on the underlying causes of differences in reduction of pain.