Economic evaluation in stratified medicine: Methodological issues and challenges

Background: Stratified Medicine (SM) is becoming a practical reality with the targeting of medicines by using a biomarker or genetic-based diagnostic to identify the eligible patient sub-population. Like any healthcare intervention, SM interventions have costs and consequences that must be considered by reimbursement authorities with limited resources. Methodological standards and guidelines exist for economic evaluations in clinical pharmacology and are an important component for health technology assessments (HTAs) in many countries. However, these guidelines have initially been developed for traditional pharmaceuticals and not for complex interventions with multiple components. This raises the issue as to whether these guidelines are adequate to SM interventions or whether new specific guidance and methodology is needed to avoid inconsistencies and contradictory findings when assessing economic value in SM. Objective: This article describes specific methodological challenges when conducting health economic (HE) evaluations for SM interventions and outlines potential modifications necessary to existing evaluation guidelines /principles that would promote consistent economic evaluations for SM. Results/Conclusions: Specific methodological aspects for SM comprise considerations on the choice of comparator, measuring effectiveness and outcomes, appropriate modeling structure and the scope of sensitivity analyses. Although current HE methodology can be applied for SM, greater complexity requires further methodology development and modifications in the guidelines

Workshop Report: Concepts and methods in the economics of nutrition - Gateways to better economic evaluation of nutrition interventions

Improving health through better nutrition of the population may contribute to enhanced efficiency and sustainability of healthcare systems. A recent expert meeting investigated in detail a number of methodological aspects related to the discipline of nutrition economics. The role of nutrition in health maintenance and in the prevention of non-communicable diseases is now generally recognised. However, the main scope of those seeking to contain healthcare expenditures tends to focus on the management of existing chronic diseases. Identifying additional relevant dimensions to measure and the context of use will become increasingly important in selecting and developing outcome measurements for nutrition interventions. The translation of nutrition-related research data into public health guidance raises the challenging issue of carrying out more pragmatic trials in many areas where these would generate the most useful evidence for health policy decision-making. Nutrition exemplifies all the types of interventions and policy which need evaluating across the health field. There is a need to start actively engaging key stakeholders in order to collect data and to widen health technology assessment approaches for achieving a policy shift from evidence-based medicine to evidence-based decision-making in the field of nutrition

The Economic Value of Enteral Medical Nutrition in the Management of Disease-Related Malnutrition: A Systematic Review

Economic evaluations for medical nutrition, such as oral nutritional supplements (ONS), are relatively uncommon compared with other health technologies, and represent an area that has not been reviewed so far. In this systematic review, economic evaluations of enteral medical nutrition in the management of disease-related malnutrition (DRM) were reviewed and qualified to estimate the economic value. Initially, 481 studies were found, of which 37 full-text articles were assessed for eligibility and were rated on their quality using the Quality of Health Economic Studies (QHES) instrument. The final review focused on the high QHES quality economic evaluation studies. As both the studied medical nutrition intervention and the form of the economic evaluation varied, a quantitative synthesis (meta-analysis) was not attempted but a critical analysis and comparison of the individual study results were performed. ONS was the most studied intervention, covering several patient populations and different health care settings. Outcomes included cost savings (n = 3), no significant extra costs per unit of clinical and/or functional improvement (n = 1), or significantly higher costs per unit of clinical and/or functional improvement but still cost-effective for the used threshold (n = 4). This review shows that the use of enteral medical nutrition in the management of DRM can be efficient from a health economic perspective

Cost-effectiveness in Clostridium difficile treatment decision-making.

To develop a framework for the clinical and health economic assessment for management of Clostridium difficile infection (CDI). CDI has vast economic consequences emphasizing the need for innovative and cost effective solutions, which were aim of this study. A guidance model was developed for coverage decisions and guideline development in CDI. The model included pharmacotherapy with oral metronidazole or oral vancomycin, which is the mainstay for pharmacological treatment of CDI and is recommended by most treatment guidelines. A design for a patient-based cost-effectiveness model was developed, which can be used to estimate the cost-effectiveness of current and future treatment strategies in CDI. Patient-based outcomes were extrapolated to the population by including factors like, e.g., person-to-person transmission, isolation precautions and closing and cleaning wards of hospitals. The proposed framework for a population-based CDI model may be used for clinical and health economic assessments of CDI guidelines and coverage decisions for emerging treatments for CD

Transcriptome Kuenenia stuttgartiensis bioreactor

Item does not contain fulltextAnaerobic ammonium-oxidising (anammox) bacteria, members of the ‘Candidatus Brocadiaceae’ family, play an important role in the nitrogen cycle and are estimated to be responsible for about half of the oceanic nitrogen loss to the atmosphere. Anammox bacteria combine ammonium with nitrite and produce dinitrogen gas via the intermediates nitric oxide and hydrazine (anammox reaction) while nitrate is formed as a by-product. These reactions take place in a specialized, membrane-bound compartment called the anammoxosome. Therefore, the substrates ammonium, nitrite and product nitrate have to cross the outer-, cytoplasmic- and anammoxosome membranes to enter or exit the anammoxosome. The genomes of all anammox species harbour multiple copies of ammonium-, nitrite- and nitrate transporter genes. Here we investigated how the distinct genes for ammonium-, nitrite- and nitrate- transport were expressed during substrate limitation in membrane bioreactors. Transcriptome analysis of Kuenenia stuttgartiensis planktonic cells under ammonium-limitation showed that three of the seven ammonium transporter genes and one of the six nitrite transporter genes were significantly upregulated, while another ammonium and nitrite transporter gene were downregulated in nitrite limited growth conditions. The two nitrate transporters were expressed to similar levels in both conditions. In addition, genes encoding enzymes involved in the anammox reaction were differentially expressed, with those using nitrite as a substrate being upregulated under nitrite limited growth and those using ammonium as a substrate being upregulated during ammonium limitation. Taken together, these results give a first insight in the potential role of the multiple nutrient transporters in regulating transport of substrates and products in and out of the compartmentalized anammox cell

Transcriptome Kuenenia stuttgartiensis bioreactor

Anaerobic ammonium-oxidising (anammox) bacteria, members of the ‘Candidatus Brocadiaceae’ family, play an important role in the nitrogen cycle and are estimated to be responsible for about half of the oceanic nitrogen loss to the atmosphere. Anammox bacteria combine ammonium with nitrite and produce dinitrogen gas via the intermediates nitric oxide and hydrazine (anammox reaction) while nitrate is formed as a by-product. These reactions take place in a specialized, membrane-bound compartment called the anammoxosome. Therefore, the substrates ammonium, nitrite and product nitrate have to cross the outer-, cytoplasmic- and anammoxosome membranes to enter or exit the anammoxosome. The genomes of all anammox species harbour multiple copies of ammonium-, nitrite- and nitrate transporter genes. Here we investigated how the distinct genes for ammonium-, nitrite- and nitrate- transport were expressed during substrate limitation in membrane bioreactors. Transcriptome analysis of Kuenenia stuttgartiensis planktonic cells under ammonium-limitation showed that three of the seven ammonium transporter genes and one of the six nitrite transporter genes were significantly upregulated, while another ammonium and nitrite transporter gene were downregulated in nitrite limited growth conditions. The two nitrate transporters were expressed to similar levels in both conditions. In addition, genes encoding enzymes involved in the anammox reaction were differentially expressed, with those using nitrite as a substrate being upregulated under nitrite limited growth and those using ammonium as a substrate being upregulated during ammonium limitation. Taken together, these results give a first insight in the potential role of the multiple nutrient transporters in regulating transport of substrates and products in and out of the compartmentalized anammox cell