Mart P. Janssen

The PROTON study: profiles of blood product transfusion recipients in the Netherlands

Background  Transfusion recipient data are needed for correct estimation of cost‐effectiveness in terms of recipient outcomes after transfusion. Also, such data are essential for monitoring blood use, estimation of future blood use and benchmarking.

Carotid stenting versus carotid endarterectomy: evidence basis and cost implications.

OBJECTIVE Carotid Angioplasty combined with Stenting (CAS) is increasingly performed because of its presumed benefits. A study was performed to identify key factors that determine the cost-effectiveness as compared to conventional carotid endarterectomy (CEA). METHODS The incremental cost-effectiveness of CAS over CEA for different scenarios was estimated using a modeling approach. Treatment costs were based on actual costs of successful procedures whereas costs of complications were taken from the literature. Patient survival was modeled using the endarterectomy patients from the ECST trial. RESULTS Procedural costs of CAS are higher than those of CEA, mainly as a result of the high material costs. Cost-effectiveness of CAS primarily depends on major stroke rates. One percent increase in the peri-operative major stroke rate causes a cost increase of 1051 euros and a loss of 0.06 quality adjusted life years. CONCLUSIONS At present CAS is at best non-inferior to CEA in terms of clinical outcome. Cost savings due to shorter admission are offset by the high costs associated with catheter-based interventions. At present CAS should be restricted to controlled settings until clinical trials have shown a substantial clinical benefit.

Costs and benefits of bacterial culturing and pathogen reduction in the Netherlands

BACKGROUND:  Bacterial contamination is a life‐threatening risk of blood transfusion, especially with platelet (PLT) transfusions. Bacterial culturing (BCU) of PLTs as well as pathogen reduction (PRT) reduce the likelihood of such contamination. The cost‐effectiveness (CE) of these interventions was analyzed after the introduction of the diversion pouch during blood collection.

Demographic changes and predicting blood supply and demand in the Netherlands.

BACKGROUND: Concerns have been raised that aging of the general population will increase the demand for blood products. Modeling can be applied to assess trends in blood demand and supply and predict how these will develop over time.

Cost-effectiveness of additional blood screening tests in the Netherlands

BACKGROUND: During the past decade, blood screening tests such as triplex nucleic acid amplification testing (NAT) and human T‐cell lymphotropic virus type I or I (HTLV‐I/II) antibody testing were added to existing serologic testing for hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV). In some low‐prevalence regions these additional tests yielded disputable benefits that can be valuated by cost‐effectiveness analyses (CEAs). CEAs are used to support decision making on implementation of medical technology. We present CEAs of selected additional screening tests that are not uniformly implemented in the EU.

Modeling the transmission risk of emerging infectious diseases through blood transfusion

A timely risk assessment is desired to guide decisions on preventive transfusion safety measures during emerging infectious disease (EID) outbreaks. The European Up‐Front Risk Assessment Tool (EUFRAT) model was developed to provide quantitative transmission risk estimates of EIDs through blood transfusion.

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

Background Severe 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 Methods A 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. Results According 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. Conclusions The 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.

Cost-effectiveness of additional hepatitis B virus nucleic acid testing of individual donations or minipools of six donations in the Netherlands

BACKGROUND: To further reduce the risk of hepatitis B virus (HBV) transmission by blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this study is to estimate the incremental cost‐effectiveness ratio (ICER) in the Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection in individual donations (ID‐NAT) or in minipools of 6 donations (MP‐6‐NAT), compared to a triplex NAT assay in minipools of 24 donations (MP‐24‐NAT).

Health economics and outcomes methods in risk‐based decision‐making for blood safety

Analytical methods appropriate for health economic assessments of transfusion safety interventions have not previously been described in ways that facilitate their use. Within the context of risk‐based decision‐making (RBDM), health economics can be important for optimizing decisions among competing interventions. The objective of this review is to address key considerations and limitations of current methods as they apply to blood safety. Because a voluntary blood supply is an example of a public good, analyses should be conducted from the societal perspective when possible. Two primary study designs are recommended for most blood safety intervention assessments: budget impact analysis (BIA), which measures the cost to implement an intervention both to the blood operator but also in a broader context, and cost‐utility analysis (CUA), which measures the ratio between costs and health gain achieved, in terms of reduced morbidity and mortality, by use of an intervention. These analyses often have important limitations because data that reflect specific aspects, for example, blood recipient population characteristics or complication rates, are not available. Sensitivity analyses play an important role. The impact of various uncertain factors can be studied conjointly in probabilistic sensitivity analyses. The use of BIA and CUA together provides a comprehensive assessment of the costs and benefits from implementing (or not) specific interventions. RBDM is multifaceted and impacts a broad spectrum of stakeholders. Gathering and analyzing health economic evidence as part of the RBDM process enhances the quality, completeness, and transparency of decision‐making.

Validity of assessing inhibitor development in haemophilia PUPs using registry data: the EUHASS project

Summary.  Inhibitory antibodies to exogenous FVIII/FIX are a major complication of haemophilia treatment. Up to 30% of previously untreated patients (PUPs) with severe haemophilia A develop inhibitors, most likely during the initial 50 exposure days to concentrate. In addition to classical cohort studies, a European monitoring system (EUHASS) has been set up to evaluate inhibitor development in PUPs. The present study addresses the reliability of estimating the cumulative incidence of inhibitor development in this registry. Data from the retrospective CANAL cohort study, including 288 PUPs with severe haemophilia A and complete treatment records until the 50th exposure to FVIII, were used to simulate the consequences of several cross‐sectional sampling techniques on the estimated incidence of inhibitors. Both mathematical calculus and computer modelling were applied to study the effects of sample size and the introduction of a new product. For existing concentrates, both longitudinal cohort study methods and the EUHASS method yielded similar estimates of the cumulative incidence of inhibitor cases over a 5‐year time period: 27.9% (95% CI: 21–36) vs. 29.4% (22–38). For a newly introduced concentrate, a reliable estimate of inhibitor incidence with the EUHASS method could only be made after 3–4 years, even in large datasets. The results from EUHASS in inhibitor incidence in PUPs are expected to be valid. After introduction of a new concentrate, the inhibitor incidence on this concentrate can only be reliably determined after an observation period of several years.