Field testing of a multicriteria decision analysis (MCDA) framework for coverage of a screening test for cervical cancer in South Africa

<p>Abstract</p> <p>Background</p> <p>Systematic and transparent approaches to priority setting are needed, particularly in low-resource settings, to produce decisions that are sound and acceptable to stakeholders. The EVIDEM framework brings together Health Technology Assessment (HTA) and multi-criteria decision analysis (MCDA) by proposing a comprehensive set of decision criteria together with standardized processes to support decisionmaking. The objective of the study was to field test the framework for decisionmaking on a screening test by a private health plan in South Africa.</p> <p>Methods</p> <p>Liquid-based cytology (LBC) for cervical cancer screening was selected by the health plan for this field test. An HTA report structured by decision criterion (14 criteria organized in the MCDA matrix and 4 contextual criteria) was produced based on a literature review and input from the health plan. During workshop sessions, committee members 1) weighted each MCDA decision criterion to express their individual perspectives, and 2) to appraise LBC, assigned scores to each MCDA criterion on the basis of the by-criterion HTA report.</p> <p>Committee members then considered the potential impacts of four contextual criteria on the use of LBC in the context of their health plan. Feedback on the framework and process was collected through discussion and from a questionnaire.</p> <p>Results</p> <p>For 9 of the MCDA matrix decision criteria, 89% or more of committee members thought they should always be considered in decisionmaking. Greatest weights were given to the criteria "Budget impact", "Cost-effectiveness" and "Completeness and consistency of reporting evidence". When appraising LBC for cervical cancer screening, the committee assigned the highest scores to "Relevance and validity of evidence" and "Disease severity". Combination of weights and scores yielded a mean MCDA value estimate of 46% (SD 7%) of the potential maximum value. Overall, the committee felt the framework brought greater clarity to the decisionmaking process and was easily adaptable to different types of health interventions.</p> <p>Conclusions</p> <p>The EVIDEM framework was easily adapted to evaluating a screening technology in South Africa, thereby broadening its applicability in healthcare decision making.</p

Combining multicriteria decision analysis, ethics and health technology assessment: applying the EVIDEM decisionmaking framework to growth hormone for Turner syndrome patients

<p>Abstract</p> <p>Objectives</p> <p>To test and further develop a healthcare policy and clinical decision support framework using growth hormone (GH) for Turner syndrome (TS) as a complex case study.</p> <p>Methods</p> <p>The EVIDEM framework was further developed to complement the multicriteria decision analysis (MCDA) Value Matrix, that includes 15 quantifiable components of decision clustered in four domains (quality of evidence, disease, intervention and economics), with a qualitative tool including six ethical and health system-related components of decision. An extensive review of the literature was performed to develop a health technology assessment report (HTA) tailored to each component of decision, and content was validated by experts. A panel of representative stakeholders then estimated the MCDA value of GH for TS in Canada by assigning weights and scores to each MCDA component of decision and then considered the impact of non-quantifiable components of decision.</p> <p>Results</p> <p>Applying the framework revealed significant data gaps and the importance of aligning research questions with data needs to truly inform decision. Panelists estimated the value of GH for TS at 41% of maximum value on the MCDA scale, with good agreement at the individual level (retest value 40%; ICC: 0.687) and large variation across panelists. Main contributors to this panel specific value were "Improvement of efficacy", "Disease severity" and "Quality of evidence". Ethical considerations on utility, efficiency and fairness as well as potential misuse of GH had mixed effects on the perceived value of the treatment.</p> <p>Conclusions</p> <p>This framework is proposed as a pragmatic step beyond the current cost-effectiveness model, combining HTA, MCDA, values and ethics. It supports systematic consideration of all components of decision and available evidence for greater transparency. Further testing and validation is needed to build up MCDA approaches combined with pragmatic HTA in healthcare decisionmaking.</p

Evidence and Value: Impact on DEcisionMaking – the EVIDEM framework and potential applications

<p>Abstract</p> <p>Background</p> <p>Healthcare decisionmaking is a complex process relying on disparate types of evidence and value judgments. Our objectives for this study were to develop a practical framework to facilitate decisionmaking in terms of supporting the deliberative process, providing access to evidence, and enhancing the communication of decisions.</p> <p>Methods</p> <p>Extensive analyses of the literature and of documented decisionmaking processes around the globe were performed to explore what steps are currently used to make decisions with respect to context (from evidence generation to communication of decision) and thought process (conceptual components of decisions). Needs and methodologies available to support decisionmaking were identified to lay the groundwork for the EVIDEM framework.</p> <p>Results</p> <p>A framework was developed consisting of seven modules that can evolve over the life cycle of a healthcare intervention. Components of decision that could be quantified, i.e., intrinsic value of a healthcare intervention and quality of evidence available, were organized into matrices. A multicriteria decision analysis (MCDA) Value Matrix (VM) was developed to include the 15 quantifiable components that are currently considered in decisionmaking. A methodology to synthesize the evidence needed for each component of the VM was developed including electronic access to full text source documents. A Quality Matrix was designed to quantify three criteria of quality for the 12 types of evidence usually required by decisionmakers. An integrated system was developed to optimize data analysis, synthesis and validation by experts, compatible with a collaborative structure.</p> <p>Conclusion</p> <p>The EVIDEM framework promotes transparent and efficient healthcare decisionmaking through systematic assessment and dissemination of the evidence and values on which decisions are based. It provides a collaborative framework that could connect all stakeholders and serve the healthcare community at local, national and international levels by allowing sharing of data, resources and values. Validation and further development is needed to explore the full potential of this approach.</p

Antologia Bilíngue: Clássicos da Língua Italiana

Edição: 1.ª Ed. Editoria: Tubarão: Copiart, 2012. Páginas: 208 p. Língua da publicação: Português e italiano Tradução: Sergio Romanelli, Cecilia Casini & Patrizia Collina Bastianetto Língua do original: Italiano Comentários: Volume 1: Questione della Lingua - Leon Battista Alberti, Baldassar Castiglione, Nicolau Maquiavel. Edição bilíngue Referência ABNT: Romanelli, Sergio (Org.). Antologia Bilíngue: Clássicos da Língua Italiana. 1.ª Ed. Tubarão: Copiart, 2012. 208 p. [: Italiano]. Tradução de: Sergio Romanelli, Cecilia Casini & Patrizia Collina Bastianetto

The quail genome:insights into social behaviour, seasonal biology and infectious disease response

Background: The Japanese quail (Coturnix japonica) is a popular domestic poultry species and an increasingly significant model species in avian developmental, behavioural and disease research. Results: We have produced a high-quality quail genome sequence, spanning 0.93 Gb assigned to 33 chromosomes. In terms of contiguity, assembly statistics, gene content and chromosomal organisation, the quail genome shows high similarity to the chicken genome. We demonstrate the utility of this genome through three diverse applications. First, we identify selection signatures and candidate genes associated with social behaviour in the quail genome, an important agricultural and domestication trait. Second, we investigate the effects and interaction of photoperiod and temperature on the transcriptome of the quail medial basal hypothalamus, revealing key mechanisms of photoperiodism. Finally, we investigate the response of quail to H5N1 influenza infection. In quail lung, many critical immune genes and pathways were downregulated after H5N1 infection, and this may be key to the susceptibility of quail to H5N1. Conclusions: We have produced a high-quality genome of the quail which will facilitate further studies into diverse research questions using the quail as a model avian species

Burden of rotavirus gastroenteritis in the Middle Eastern and North African pediatric population

<p>Abstract</p> <p>Background</p> <p>Rotavirus gastroenteritis (RVGE) is the most common cause of severe childhood diarrhea worldwide. Objectives were to estimate the burden of RVGE among children less than five years old in the Middle East (Bahrain, Iran, Iraq, Israel, Jordan, Kuwait, Oman, Qatar, Saudi Arabia, Syria, UAE, Yemen), North Africa (Algeria, Egypt, Libya, Morocco, Tunisia) and Turkey.</p> <p>Methods</p> <p>A comprehensive literature search was conducted in major databases on the epidemiology and burden of rotavirus among children less than five years old between 1999 and 2009. Data from each country was extracted and compared.</p> <p>Results</p> <p>The search identified 43 studies. RVGE was identified in 16-61% of all cases of acute gastroenteritis, with a peak in the winter. RVGE-related hospitalization rates ranged from 14% to 45%, compared to 14%-28% for non-RVGE. Annually, RVGE caused up to 112 fatalities per 100,000 in certain countries in the region. Hospitalization costs ranged from $1.8 to$4.6 million annually, depending on the country. The most recent literature available showed that G1P[8] was the most prevalent genotype combination in 8 countries (range 23%-56%). G2P[4] was most prevalent in 4 countries (26%-48%). G9P[8] and G4P[8] were also frequently detected.</p> <p>Conclusions</p> <p>RVGE is a common disease associated with significant morbidity, mortality, and economic burden. Given the variety and diverse rotavirus types in the region, use of a vaccine with broad and consistent serotype coverage would be important to help decrease the burden of RVGE in the Middle East and North Africa.</p

Burden of community-acquired and nosocomial rotavirus gastroenteritis in the pediatric population of Western Europe: a scoping review

<p>Abstract</p> <p>Background</p> <p>Rotavirus affects 95% of children worldwide by age 5 years and is the leading cause of severe dehydrating diarrhea. The objective of this review was to estimate the burden of rotavirus gastroenteritis (RVGE) in the Western European pediatric population.</p> <p>Methods</p> <p>A comprehensive literature search (1999-2010) was conducted in PubMed and other sources (CDC; WHO, others). Data on the epidemiology and burden of RVGE among children < 5 years-old in Western Europe --including hospital-acquired disease--were extracted.</p> <p>Results</p> <p>76 studies from 16 countries were identified. The mean percentage of acute gastroenteritis (AGE) cases caused by rotavirus ranged from 25.3%-63.5% in children < 5 years of age, peaking during winter. Incidence rates of RVGE ranged from 1.33-4.96 cases/100 person- years. Hospitalization rates for RVGE ranged from 7% to 81% among infected children, depending on the country. Nosocomial RVGE accounted for 47%-69% of all hospital-acquired AGE and prolonged hospital stays by 4-12 days. Each year, RVGE incurred $0.54-$53.6 million in direct medical costs and $1.7-$22.4 million in indirect costs in the 16 countries studied. Full serotyping data was available for 8 countries. G1P[8], G2P[4], G9P[8], and G3P[8] were the most prevalent serotypes (cumulative frequency: 57.2%- 98.7%). Serotype distribution in nosocomial RVGE was similar.</p> <p>Conclusions</p> <p>This review confirms that RVGE is a common disease associated with significant morbidity and costs across Western Europe. A vaccine protecting against multiple serotypes may decrease the epidemiological and cost burden of RVGE in Western Europe.</p

Bridging health technology assessment (HTA) with multicriteria decision analyses (MCDA): field testing of the EVIDEM framework for coverage decisions by a public payer in Canada

<p>Abstract</p> <p>Background</p> <p>Consistent healthcare decisionmaking requires systematic consideration of decision criteria and evidence available to inform them. This can be tackled by combining multicriteria decision analysis (MCDA) and Health Technology Assessment (HTA). The objective of this study was to field-test a decision support framework (EVIDEM), explore its utility to a drug advisory committee and test its reliability over time.</p> <p>Methods</p> <p>Tramadol for chronic non-cancer pain was selected by the health plan as a case study relevant to their context. Based on extensive literature review, a by-criterion HTA report was developed to provide synthesized evidence for each criterion of the framework (14 criteria for the MCDA Core Model and 6 qualitative criteria for the Contextual Tool). During workshop sessions, committee members tested the framework in three steps by assigning: 1) weights to each criterion of the MCDA Core Model representing individual perspective; 2) scores for tramadol for each criterion of the MCDA Core Model using synthesized data; and 3) qualitative impacts of criteria of the Contextual Tool on the appraisal. Utility and reliability of the approach were explored through discussion, survey and test-retest. Agreement between test and retest data was analyzed by calculating intra-rater correlation coefficients (ICCs) for weights, scores and MCDA value estimates.</p> <p>Results</p> <p>The framework was found useful by the drug advisory committee in supporting systematic consideration of a broad range of criteria to promote a consistent approach to appraising healthcare interventions. Directly integrated in the framework as a "by-criterion" HTA report, synthesized evidence for each criterion facilitated its consideration, although this was sometimes limited by lack of relevant data. Test-retest analysis showed fair to good consistency of weights, scores and MCDA value estimates at the individual level (ICC ranging from 0.676 to 0.698), thus lending some support for the reliability of the approach. Overall, committee members endorsed the inclusion of most framework criteria and revealed important areas of discussion, clarification and adaptation of the framework to the needs of the committee.</p> <p>Conclusions</p> <p>By promoting systematic consideration of all decision criteria and the underlying evidence, the framework allows a consistent approach to appraising healthcare interventions. Further testing and validation are needed to advance MCDA approaches in healthcare decisionmaking.</p

Contrôle moléculaire de la transition endothélio-hématopoïétique

Hematopoietic Stem Cells (HSCs) are the basis of the regulated functioning of the hematopoietic system throughout the life of the individual. In adult amniotes, HSCs reside in the bone marrow but are produced very early during development, transiently and in small numbers, at the level the dorsal aorta from specialized Endothelial Cells (EC), termed Hemogenic Endothelial Cell (HEC), themselves derived from non-hemogenic ECs. HECs, under the influence of signals yet to be defined, lose their endothelial fate and acquire a hematopoietic identity through a mechanism designated as Endothelial-To-Hematopoietic transition (EHT). How HECs are specified and how EHT is fine-tuned remain unanswered questions but has major implication in regenerative medicine. We recently designed an ex vivo culture system, starting from the quail pre-somitic mesoderm, that mimics the steps occurring in the aorta to produce the first HSCs. We have exploited this system to isolate specific transcriptomic signatures for the passage from the mesoderm to ECs, from ECs to HECs and from HECs to HSCs. Using an ensemble of systems biology approaches; we have isolated specific molecular signatures for one or the other cell states and have emphasized on the identification of genes implicated in the specification of the hemogenic endothelium and the control of EHT. Two key signaling pathways (Wnt and Notch) and a specific gene (POFUT2) has been shown to play a crucial role in the EHT. Taken together our results should help to better define key steps in the commitment towards HSC to further produce safe and robust cells for therapeutic purposes.Les cellules souches hématopoïétiques (CSH) sont à la base du bon fonctionnement du système hématopoïétique tout au long de la vie de l'individu. Chez les amniotes, les CSHs résident dans la moelle osseuse mais sont produites très tôt au cours du développement, transitoirement et en petit nombre, au niveau de l'aorte dorsale à partir des Cellules Endothéliales (CE) spécialisées, appelées Cellules Endothéliales Hemogéniques (CEH), elles-mêmes dérivées de CE non hémogeniques. Les CEH, sous l'influence de signaux encore à définir, perdent leur identité endothéliale et acquièrent une identité hématopoïétique par un mécanisme désigné comme Transition Endothélio-Hématopoïétique (TEH). La façon dont les CEH sont spécifiés et comment la TEH est régulée restent des questions sans réponse, mais ont une implication majeure en biologie et en médecine régénérative. Nous avons récemment conçu un système de culture ex vivo, à partir du mésoderme pré-somitique de caille, qui mime les étapes se produisant dans l'aorte pour produire les premières CSH. Nous avons exploité ce système pour isoler des signatures transcriptomiques spécifiques pour les différentes étapes de la TEH. Un ensemble d'approches de biologie des systèmes nous a permis d'isoler des signatures moléculaires uniques en mettant l'accent sur la spécification de l'endothélium hémogénique et le contrôle de la TEH. Deux voies de signalisation clés (Wnt et Notch) et un gène spécifique (POFUT2) ont montré jouer un rôle crucial dans la TEH. Nos résultats devraient aider à mieux définir les étapes clés de l'engagement vers la production de CSH importante pour les thérapies

Synergy between HGF and ErbB2neu promotes epithelial cell invasion

The ErbB-2/neu receptor tyrosine kinase is involved in normal tissue development. However, this receptor has been implicated in the genesis of human breast and renal carcinomas, where ErbB2 is amplified in 20--30% of human breast cancers and correlates with poor prognosis. Using the non-transformed MDCK epithelial cell model, I have established that a deregulated activated ErbB2/Neu receptor (NeuNT) but not overexpression of the wild type (WT) receptor induces cell dispersal and motility, accompanied by the breakdown of cell-cell junctions and E-cadherin internalization, in addition to reorganization of the actin cytoskeleton. This phenotype can be reversed following treatment of the cells with a pharmacological inhibitor of MEK, indicating that MEK dependent pathways are involved in the NeuNT-induced remodeling of cell-cell junctions. In three-dimensional cultures of MDCK cells, NeuNT but not WT ErbB2 triggers a morphogenic response that correlates with recruitment and increased phosphorylation levels of the Shc adapter protein. This demonstrates that the deregulated ErbB2/NT receptor induces a distinct biological response when compared to the wild type receptor and induces the loss of epithelial architecture observed in carcinomas.Invasive morphogenesis downstream from the Met/HGF receptor is modulated through a sustained phosphorylation of the Gab1 docking protein and of downstream kinase (Erk). In contrast, a transient phosphorylation of Gab1 and Erk induced by EGF is not sufficient to promote a morphogenic response. In Chapter III, I demonstrate that NeuNT but not the WT ErbB2 receptor display elevated and sustained levels of Gab1 and Erk phosphorylation which correlates with their ability to promote invasive morphogenesis. In addition, co-immunoprecipitation analyses provide evidence for the recruitment of Gab1 to ErbB2/Neu in a Grb2-dependent and Grb2-independent manner.To identify physiologically relevant factors that synergize with ErbB2, I established that HGF, the Met receptor ligand, promotes the disruption and invasion of NeuNT-induced epithelial structures in three dimensional matrix cultures. Moreover HGF synergizes with NeuNT, enhancing the invasive potential of NeuNT expressing cells ten fold through Matrigel. HGF treatment of NeuNT expressing cells promotes a decrease in E-cadherin protein, and can be blocked or reversed by treatment with the MEK inhibitor, UO126, establishing the involvement of MEK-dependent pathways in this process. These results demonstrate that physiological signals downstream from HGF/Met cooperate with deregulated ErbB2/Neu to enhance the malignant phenotype promoting a more stable epithelial-mesenchymal transition and enhanced cell invasion