European collaboration on relative effectiveness assessments: What is needed to be successful?

OBJECTIVE: The objective of this study is to identify the possible barriers and critical success factors for the implementation of European collaboration in the field of relative effectiveness assessment (REA) of drugs. METHODS: Data were gathered through semi-structured interviews with representatives from eight European health technology assessment (HTA) organisations involved in assessment of drugs for coverage decision-making (AAZ, AIFA, AHTAPol, HAS, HVB, IQWIG, NICE and ZiN). RESULTS: Potential barriers identified mainly relate to methodology, resources and challenges with implementation in the respective national processes (e.g. legal restrictions). The most critical success factors for production of cross-border assessments were the continuous cooperation of competent partners, and the quality and timely availability of the assessment. CONCLUSION: Further adaptation of the process and methods is required for optimal collaboration. In the near future it can be expected that cross-border assessments will meet in particular the needs of smaller/middle-sized European countries and also European countries with less developed HTA systems as the potential efficiency/quality gains are the highest for these countries. Therefore, national implementation of cross-border assessments is especially likely in these countries in the coming years. Once more experience is gained with cross-border assessments, and successes become more evident, efficiency/quality gains may also be likely for some larger countries with well established processes.

Relative effectiveness assessment of pharmaceuticals: similarities and differences in 29 jurisdictions.

OBJECTIVE: Assessment of the effectiveness compared with alternative treatment(s) plays an important role in many jurisdictions in determining the reimbursement status of pharmaceuticals. This type of assessment is often referred to as a relative effectiveness assessment (REA) and is carried out by many jurisdictions. Increased sharing of information across jurisdictions may save costs and reduce duplication. The objective of this study was to explore the main similarities and differences in the major methodological aspects of REA in multiple jurisdictions. METHODS: Data were gathered with a standardized data extraction form by searching publicly available information and by eliciting information from representatives at relevant organizations. RESULTS: Of the initially included 35 jurisdictions, data were gathered for 29 jurisdictions. There seem to be substantial similarities on the choice of the comparator, the role of indirect comparisons, and preferred end points in REAs (except for the use of health state utilities). Jurisdictions, however, differ in whether effectiveness (usual circumstances of health care practice) is estimated in case no (comparative) effectiveness data are available and how this is done. CONCLUSION: Some important methodological aspects for REA are approached in a similar way in many jurisdictions, indicating that collaboration on assessments may be feasible. Enhanced collaboration in the development of methods and best practices for REA between jurisdictions will be a necessary first step. Important topics for developing best practice are indirect comparisons and how to handle the gap between efficacy and effectiveness data in case good quality comparative effectiveness data are not yet available at the time of reimbursement decisions.

Lipoteichoic acids selectively stimulate rat mast cells to cysteinyl leukotriene generation and affect mast cell migration after tumor necrosis factor (TNF)-priming.

It is well established that mast cells play a critical role in the host defense against bacteria. Upon stimulation with bacteria and their antigens, mast cells release various mediators and cytokines that promote the development of inflammation at the site of infection. In the present study, we examined the ability of lipoteichoic acids (LTAs), some of the major components of cell walls of most gram-positive bacteria, to stimulate mast cell degranulation and histamine release as well as to generate of cysteinyl leukotrienes (LTs). We also studied the influence of LTAs on mast cell migration. Experiments were done on rat peritoneal mast cells and LTA from Staphyloccocus aureus and LTA from Bacillus subtilis were used. We have stated that neither S. aureus LTA nor B. subtilis LTA used at a wide range of concentrations (from 10(-4) to 10(5)ng/mL) induced mast cell degranulation and histamine release. However, stimulation of mast cells with both LTAs resulted in generation and release of significant levels of LTs. We have also documented that none of the LTAs stimulated rat mast cell migration, even in the presence of laminin. IL-6 priming did not influence mast cell migration towards LTAs, whereas, pretreatment of mast cells with TNF caused time-dependent mast cell migration in response to LTAs stimulation. Pretreatment of mast cells with anti-TNFR1 antibodies completely inhibited LTA-induced migratory response of TNF-primed mast cells. Our results showed that LTAs might be among important bacterial antigens involved in mast cell activation during bacterial infections.

[Lipopolysaccharides and lipoteichoic acids stimulate rat mast cells to cysteinyl leukotriene synthesis]. / Lipopolisacharydy i kwasy lipotejchojowe stymuluja komórki tuczne szczura do syntezy leukotrienów cysteinowych.

We have investigated the ability of lipopolysaccharides (LPS) and lipoteichoic acids (LTA) to induce rat peritoneal mast cells to degranulation and histamine release, and to cysteinyl leukotriene (LT) generation. We have stated that LPS Salmonella Enteritidis, LPS Escherichia coli O111:B4 and LPS E. coli O55:B5 did not activate rat mast cells to degranulation and histamine release. However, LPSs induced LT synthesis and secretion; the strongest stimulant to generation of LT was LPS E. coli O55:B5 (concentration of LT in supernatant was 830.5 +/-15.2 pg/ml). We have also observed that LTA Staphylococcus aureus and LTA Bacillus subtilis stimulated rat mast cells to degranulation and histamine secretion, even though the percentage of the releases histamine was relatively low (10.0 +/- 1.4 and 10.4 +/- 5.4 at antigen concentration, respectively). At the same time, LTA of both of the bacterial species strongly activate LT generation by mast cells (concentrations of LT in supernatants were 777.9 +/- 11.2 pg/ml and 734.0 +/- 38.3 pg/ml, respectively, at the antigen concentration 50 ng/ml). Our results have shown that LPS oraz LTA activate rat mast cells to secretion of proinflammatory mediators.

[The role of mast cells in innate immunity in antibacterial defense]. / Rola komórek tucznych w nieswoistej obronie przeciwbakteryjnej.

Nowadays it is well documented that bacteria and/or their products directly or indirectly activate mast cells to secrete mediators and cytokines. These mediators and cytokines induce various effects leading to the development of local inflammation. Moreover, mast cells have the capacity to bind and phagocytose bacteria. What is more, these cells have the capacity to kill bacteria. Thus, mast cells play a pivotal role in host defense, especially in natural immunity, during bacterial infection.

[The mast cells phagocytose bacteria]. / Komórki tuczne fagocytuja bakterie.

In the last years there has been a growing number of reports concerning the role of mast cells in host defense against bacteria. The mast cell membrane is replete with many receptors/molecules, including those that promote the recognition and binding of bacteria. Mast cells exhibit two basic mechanisms of microbial recognition: opsonin-dependent (via Fc and C3 receptors) and opsonin-independent (via integrins, CD48 molecule and Toll-like receptors). Moreover, mast cells phagocytose and kill adherent bacteria. Phagocytosis of bacteria results in the presentation of bacterial antigens for MHC class I to T cells.