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- Malmström, Rickard E., et al.
(författare)
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Dabigatran - a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs
- 2013
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Ingår i: Frontiers in Pharmacology. - : FRONTIERS RESEARCH FOUNDATION. - 1663-9812. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. Objective: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups. Methodology: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. Results: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, pen-, and post-launch activities. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.
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- Godman, Brian, et al.
(författare)
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Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs
- 2014
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, pen-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.
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- Rossignoli, Araceli E., et al.
(författare)
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Toxicity characterisation of Gambierdiscus species from the Canary Islands
- 2020
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Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- In the last decade, several outbreaks of ciguatera fish poisoning (CFP) have been reported in the Canary Islands (central northeast Atlantic Ocean), confirming ciguatera as an emerging alimentary risk in this region. Five Gambierdiscus species, G. australes, G. excentricus, G. silvae, G. carolinianus and G. caribaeus, have been detected in macrophytes from this area and are known to produce the ciguatoxins (CTXs) that cause CFP. A characterization of the toxicity of these species is the first step in identifying locations in the Canary Islands at risk of CFP. Therefore, in this study the toxicity of 63 strains of these five Gambierdiscus species were analysed using the erythrocyte lysis assay to evaluate their maitotoxin (MTX) content. In addition, 20 of the strains were also analysed in a neuroblastoma Neuro-2a (N2a) cytotoxicity assay to determine their CTX-like toxicity. The results allowed the different species to be grouped according to their ratios of CTX-like and MTX-like toxicity. MTX-like toxicity was especially high in G. excentricus and G. australes but much lower in the other species and lowest in G. silvae. CTX-like toxicity was highest in G. excentricus, which produced the toxin in amounts ranging between 128.2 ± 25.68 and 510.6 ± 134.2 fg CTX1B equivalents (eq) cell-1 (mean ± SD). In the other species, CTX concentrations were as follows: G. carolinianus (100.84 ± 18.05 fg CTX1B eq cell-1), G. australes (31.1 ± 0.56 to 107.16 ± 21.88 fg CTX1B eq cell-1), G. silvae (12.19 ± 0.62 to 76.79 ± 4.97 fg CTX1B eq cell-1) and G. caribaeus (
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