A modeling approach to evaluate long-term outcome of prophylactic and on demand treatment strategies for severe hemophilia A

Abstract

The online version of this article has a Supplementary Appendix. BackgroundSevere hemophilia requires life-long treatment with expensive clotting factor concentrates; studies comparing effects of different therapeutic strategies over decades are very difficult to perform. A simulation model was developed to evaluate the long-term outcome of on demand, prophylactic and mixed treatment strategies for patients with severe hemophilia A. Design and MethodsA computer model was developed based on individual patients' data from a Dutch cohort study in which intermediate dose prophylaxis was used and a French cohort study in which on demand treatment was used, and multivariate regression analyses. This model simulated individual patients' life expectancy, onset of bleeding, life-time joint bleeds, radiological outcome and concentrate use according to the different treatment strategies. ResultsAccording to the model, life-time on demand treatment would result in an average of 1,494 joint bleeds during the hemophiliac's life, and consumption of 4.9 million IU of factor VIII concentrate. In contrast, life-time intermediate dose prophylaxis resulted in a mean of 357 joint bleeds and factor consumption of 8.3 million IU. A multiple switch strategy (between prophylactic and on demand treatment based on bleeding pattern) resulted in a mean number of 395 joint bleeds and factor consumption of 6.6 million IU. The estimated proportion of patients with Pettersson scores over 28 points was 32% for both the prophylactic and the multiple switching strategies, compared to 76% for continuous on demand treatment. ConclusionsThe present model allows evaluation of the impact of various treatment strategies on patients' joint bleeds and clotting factor consumption. It may be expanded with additional data to allow more precise estimates and include economic evaluations of treatment strategies.Key words: hemophilia, prophylaxis, on demand, arthropathy, cost, outcome.Citation: Fischer K, Pouw ME, Lewandowski D, Janssen MP, van den Berg HM, and van Hout BA. A modeling approach to evaluate long-term outcome of prophylactic and on demand treatment strategies for severe hemophilia A. Haematologica 2011;96(5):738-743. doi:10.3324/haematol.2010 A modeling approach to evaluate long-term outcome of prophylactic and on demand treatment strategies for severe hemophilia A

The Relationship of Frequency and Intensity of Bleeding with Hemophilic Arthropathy in Hemophilia Patients, Radiological Assesment and Socio-Economic Impacts of the Arthropathy

“…These findings are compatible with the results of prior studies demonstrating that factor level is proportionate with the frequency and the intensity of bleeding. 17 Gilbert's 11 article evaluating hemarthrosis reported a weak association between clinical and radiologic scores and stated that a treatment based solely on radiologic findings will therefore be inappropriate.…”

Modelling lifelong effects of different prophylactic treatment strategies for severe haemophilia A

“…Details on the structure and operation of the previous model for simulating haemophilia treatment strategies were described elsewhere [17]. In short, based on distributions of actual data, the model assigns a random age of first joint bleed, adult weight, life expectancy and baseline bleeding frequency to each patient entering the cohort.…”

“…The present model is the first to confirm this hypothesis. So far, several other groups have simulated life-long haemophilia treatment using computer models [13][14][15][16][17]. However, most of them used Markov modelling, and all were focused on economic evaluations, using cost per QALY as outcome parameters.…”

“…Studies modelling patient treatment and outcome are a method used to circumvent this problem [13][14][15][16]. Our group designed a micro simulation model based on data from existing cohorts [17]. The model allows comparing on-demand treatment, intermediate-dose prophylaxis, and various strategies switching between these two for treatment of severe haemophilia A.…”

An innovative outcome-based care and procurement model of hemophilia management

“…However, it also imposes a barrier to health systems and payers, which need to record and justify drivers of treatment costs, and thereby to control costs and predict future procurement needs [66][67][68]. Accurate, real-time, patient-level cumulative data also facilitates benchmarking within a single patient over time and among patients, facilitating comparisons of outcomes between different geographies, hemophilia care centers, treatment regimens, or physician practices [69].…”