A systematic review of the cost-effectiveness of rFVIIa and APCC in the treatment of minor/moderate bleeding episodes for haemophilia patients with inhibitors
The clinical, humanistic and economic consequences associated with haemophilia and inhibitors are considerable. Primary treatment for mild-to-moderate bleeding disorders in such patients is recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (APCC). The aims of this study were to identify, review and evaluate the quality of the published literature on the relative cost-effectiveness of rFVIIa and APCC in treating haemophilia patients with inhibitors. The review concentrates on model type, design and assumptions, and results. The results of this study suggest that rFVIIa may be the cost-effective alternative to treatment with APCC. In seven out of the nine studies, rFVIIa had the lower average treatment cost. The difference in average treatment cost to resolve a bleed, between rFVIIa and APCC in these seven studies, ranged from $3000 to $17 000. The adapted modelling framework is similar in all the economic models reviewed, suggesting clinical acceptability of the approach used. The estimates of efficacy varied between the models, especially for APCC. The efficacy for APCC derived from retrospective studies was lower than reported in the literature. Sensitivity analysis was undertaken in the majority of the economic analyses and the results were found to be robust to realistic parameter variations. Only one of the studies was a cost-utility study, showing the lack of measuring health status within this area. This systematic review showed that models based on different sources of data produced fairly similar robust results despite differences in the estimates of efficacy, average dosage required, and unit costs. However, ideally there should be a systematic approach to identifying the relevant data.
Systematic review of efficacy of rFVIIa and aPCC treatment for hemophilia patients with inhibitors
Advances in Therapy. 2009;26((1):):68-88.
INTRODUCTION The primary treatment for mild-to-moderate bleeding disorders in hemophilia is either recombinant activated factor VII (rFVIIa) or activated prothrombin complex concentrate (aPCC). The efficacy of both products has been evaluated in individual studies; however, there has not been an overall review to compare the efficacy from these individual studies of rFVIIa and aPCC. Our aim is to establish robust estimates of the efficacy, speed of bleed resolution, and adverse event profile of both rFVIIa and aPCC. METHODS A systematic review was conducted of the relevant literature. RESULTS We identified 11 open-label cohort studies, six randomized clinical trials, including two head-to-head clinical trials, and a meta-analysis. The definition of efficacy varies between these studies, but is usually a composite measure of definite pain relief, reduction in the size of the hemorrhage, and cessation of bleeding. The individual making the interpretation of efficacy and the time from treatment initiation to recording the efficacy endpoint also varies across the studies. Overall, estimates of efficacy from randomized clinical trials using dosing regimens in line with the guidelines are higher for rFVIIa (81%-91%) than for aPCC (64%-80%). Conclusions from a meta-analysis suggest that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than aPCC due to higher efficacy levels at different time points. The results from a comparative trial support the improved efficacy rates associated with rFVIIa compared with aPCC. CONCLUSION The wide variations in definitions of efficacy and study methods make comparison of results across studies difficult. Further head-to-head trials should incorporate a standardized measurement for defining efficacy.