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- Dahal, Prabin, et al.
(author)
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Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
- 2019
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In: Malaria Journal. - : BMC. - 1475-2875. ; 18
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Journal article (peer-reviewed)abstract
- Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
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| 2. |
- Engert, Andreas, et al.
(author)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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In: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Journal article (peer-reviewed)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 3. |
- Wagner, Michelle, et al.
(author)
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ORAMA Project - D6-6 Technical Final Report and Recommendations
- 2019
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Reports (other academic/artistic)abstract
- Securing the sustainable access to and supply of raw materials, and particularly of Critical Raw Materials (CRM), is of high importance for the European economy. Complex primary and secondary resources contain many different raw materials. The inability to easily produce reliable statistics about reserves, resources, stocks, and flows of raw materials limits the understanding of global trends in resource availability and hampers formulation of mineral and waste policies. This ultimately affects supply chain security and strategic decisions by industry. Hence, it is an issue of great concern for the European Commission (EC) and many other stakeholders. The ORAMA project (Optimising quality of information in RAw MAterial data collection across Europe) seeks to contribute to better supply of raw materials by improving the quality of harmonised raw materials data collection and information sharing among the different levels within the European Union (EU). Data collection practices for primary and secondary raw materials (PRM and SRM) face specific challenges in EU Member States (MS). For PRM data, the main concerns are related to data availability, geographical coverage, accessibility, harmonisation, interoperability, quality, and thematic coverage. The reporting of primary mineral resources and reserves statistics is currently carried out by a wide variety of systems, standards or codes which are not directly comparable. Hence, it is currently impossible to produce reliable pan-European figures for resources for any mineral commodity. ORAMA addresses these issues by recommending a single standard for reporting of resource data, the United Nations Framework Classification (UNFC), a framework for reporting mineral resource data developed by the UN. To enable and encourage data providers to adopt this standard for European PRM data, the ORAMA project has developed resources in the form of a range of training materials and good practice examples. The ORAMA project demonstrates that the analysis of various classifications and reporting systems that sit within the INSPIRE (Infrastructure for Spatial Information in the European Community) concept and data services, are not opposing but rather integral elements of the proper European level data collection and production of information for PRM and SRM. The use of UNFC/UNRMS (United Nations Resource Management System) in the framework of the INSPIRE compliant data service can significantly contribute to sustainable resource management taking into account not only geological knowledge and raw materials potential but also environmental and social issues, based on using the national/regional legislative elements for exploration and exploitation as well. In the case of SRM, the challenges are somewhat different. Regarding mining waste (MIN), the lack of information on deposit characteristics (composition, volumes, and suitable processing technology) is a huge barrier in the identification of recovery potential of the valuable materials that remain in the waste. Furthermore, the lack of a single reporting standard commonly accepted at EU level has created a dispersion of existing information in various systems and project deliverables. In the case of electrical and electronic equipment (EEE) and batteries, beyond the lack of harmonisation, substantial data gaps exist for the market inputs, materials consumption and stocks, and for waste electrical and electronic equipment (WEEE) for unaccounted flows ending up being scavenged, metal scrap and export channels. For vehicles, huge amounts of data, both on stocks and flows and on composition, are systematically collected by authorities and the manufacturing industry, but are only publicly available in a somewhat too aggregated form (placed on market (POM), stock, waste flows) or not at all (composition data). Even when collected, the reporting of the composition of these flows on a product, component and materials level are currently poorly described across all MS, and when actually ending up in recycling processes, the recovery efficiency for all elements and CRMs, in particular, is disappointing. In order to improve the data collection and reporting practices for SRM a structured review and inventory were made followed by a data gap analysis which resulted in the developments of recommendations and subsequently the selection of 6 case studies. The SRM case studies tackle the main data gaps encountered in the analysis and developed tools that will enable the improvement and harmonisation of collection and reporting practices in MS, treatment facilities, data providers, academia among others. The ORAMA project recommends to establish more structured and continuous funding for realising and maintaining a European data infrastructure for tracking both PRM and SRM. The current project-by-project based financing is insufficient and not sustainable to properly track and understand Europe’s strengths and weaknesses in the early resource intensive stages of global supply chains.
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