Coverage with evidence development: applications and issues

Copyright © Cambridge University Press, 2010OBJECTIVES: The aim of this study was to describe the current issues surrounding Coverage with Evidence Development (CED). CED is characterized by restricted coverage for a new technology in parallel with targeted research when the stated goal of the research or data collection is to provide definitive evidence for the clinical or cost-effectiveness impact of the new technology. METHODS: Presented here is information summarized and interpreted from presentations and discussions at the 2008 Health Technology Assessment International (HTAi) meeting and additional information from the medical literature. This study describes the differences between CED and other conditional coverage agreements, provides a brief history of CED, describes real-world examples of CED, describes the areas of consensus between the stakeholders, discusses the areas for future negotiation between stakeholders, and proposes criteria to assist stakeholders in determining when CED could be appropriate. RESULTS: Payers could interpret the evidence obtained from a CED program either positively or negatively, and a range of possible changes to the reimbursement status of the new technology may result. Striking an appropriate balance between the demands for prompt access to new technology and acknowledging that some degree of uncertainty will always exist is a critical challenge to the uptake of this innovative form of conditional coverage. CONCLUSIONS: When used selectively for innovative procedures, pharmaceuticals, or devices in the appropriate disease areas, CED may provide patients access to promising medicines or technologies while data to minimize uncertainty are collected.The development of the manuscript was funded by Medicines Australi

Locations of marine animals revealed by carbon isotopes

Knowing the distribution of marine animals is central to understanding climatic and other environmental influences on population ecology. This information has proven difficult to gain through capture-based methods biased by capture location. Here we show that marine location can be inferred from animal tissues. As the carbon isotope composition of animal tissues varies with sea surface temperature, marine location can be identified by matching time series of carbon isotopes measured in tissues to sea surface temperature records. Applying this technique to populations of Atlantic salmon (Salmo salar L.) produces isotopically-derived maps of oceanic feeding grounds, consistent with the current understanding of salmon migrations, that additionally reveal geographic segregation in feeding grounds between individual philopatric populations and age-classes. Carbon isotope ratios can be used to identify the location of open ocean feeding grounds for any pelagic animals for which tissue archives and matching records of sea surface temperature are available

Asymptotics of Feynman Diagrams and The Mellin-Barnes Representation

It is shown that the integral representation of Feynman diagrams in terms of the traditional Feynman parameters, when combined with properties of the Mellin--Barnes representation and the so called {\it converse mapping theorem}, provide a very simple and efficient way to obtain the analytic asymptotic behaviours in both the large and small ratios of mass scales.Comment: References added. This is the version published in Physics Letters

Lickometry: A novel and sensitive method for assessing functional deficits in rats after stroke

The need for sensitive, easy to administer assessments of long-term functional deficits is crucial in pre-clinical stroke research. In the present study, we introduce lickometry (lick microstructure analysis) as a precise method to assess sensorimotor deficits up to 40 days after middle cerebral artery occlusion in rats. Impairments in drinking efficiency compared to controls, and a compensatory increase in the number of drinking clusters were observed. This highlights the utility of this easy to administer task in assessing subtle, long-term deficits, which could be likened to oral deficits in patients

DNA barcoding identifies a cosmopolitan diet in the ocean sunfish

The ocean sunfish (Mola mola) is the world’s heaviest bony fish reaching a body mass of up to 2.3 tonnes. However, the prey M. mola consumes to fuel this prodigious growth remains poorly known. Sunfish were thought to be obligate gelatinous plankton feeders, but recent studies suggest a more generalist diet. In this study, through molecular barcoding and for the first time, the diet of sunfish in the north-east Atlantic Ocean was characterised. Overall, DNA from the diet content of 57 individuals was successfully amplified, identifying 41 different prey items. Sunfish fed mainly on crustaceans and teleosts, with cnidarians comprising only 16% of the consumed prey. Although no adult fishes were sampled, we found evidence for an ontogenetic shift in the diet, with smaller individuals feeding mainly on small crustaceans and teleost fish, whereas the diet of larger fish included more cnidarian species. Our results confirm that smaller sunfish feed predominantly on benthic and on coastal pelagic species, whereas larger fish depend on pelagic prey. Therefore, sunfish is a generalist predator with a greater diversity of links in coastal food webs than previously realised. Its removal as fisheries’ bycatch may have wider reaching ecological consequences, potentially disrupting coastal trophic interactions

Gear error induced impact in a multiple take-off textile drive system operating under light loading

A combined theoretical and experimental investigation is made into the causes of premature gear failures which had occurred in the complex and lighly loaded gear trains of an industrial textile machine. A comprehensive review of previous relevant work identifies the problem as one of torsional vibratory impact excited by gear transmission errors. An extension of the dynamic stiffness method is developed for the analysis of forced vibration response due to relative displacement, harmonic excitation imparted by transmission error components. The technique is then applied to a generalised mathematical model of the complete machine in which typical production distributions of gear error magnitude and relative phasing are inserted. Gear-tooth dynamic loads are computed at every mesh for a number of different machine configurations over the operating speed range. The influence of selected inertia, flexibility and damping elements is demonstrated. A novel technique employing magnetic drums is devised and evaluated for the direct measurement of-relative motions in a meshed pair of oscillating gears. Automatic compensation is provided for transmission error and mounting eccentricity. A further direct technique is reported for the detection of tooth impacts and is based on the change in electrical resistance between meshing teeth as the contact pressure varies. Measurements in a multi-gearbox experimental rig demonstrated that the gears described non-linear motions, involving excursions through the backlash and heavy impacts on both drive and reverse faces. Theoretical predictibns of dynamic loading distribution within machines show reasonable compatibility with patterns of gear failure recorded in service, even though the analysis does not allow for system non-linearities. Machine design considerations are examined in retrospect from a dynamics standpoint. Past and present designs are appraised and possible alternatives to these are briefly discussed. Finally, the salient factors identified in the investigation are summarised and recommendations made for future work

Systematic and detailed analysis of behavioural tests in the rat Middle Cerebral Artery Occlusion (MCAO) model of stroke: tests for long-term assessment

In order to test therapeutics, functional assessments are required. In pre-clinical stroke research, there is little consensus regarding the most appropriate behavioural tasks to assess deficits; especially when testing over extended times in milder models with short occlusion times and small lesion volumes. In this study we comprehensively assessed 16 different behavioural tests, with the aim of identifying those that show robust, reliable and stable deficits for up to 2 months. These tasks are regularly used in stroke research, as well as being useful for examining striatal dysfunction in models of Huntington’s and Parkinson’s disease. Two cohorts of male Wistar rats underwent the intraluminal filament model of MCAO (30min) and were imaged 24hrs later. This resulted in primarily subcortical infarcts, with a small amount of cortical damage. Animals were tested, along with sham and naïve groups at 24hrs, 7 days, and 1 and 2 months. Following behavioural testing, brains were processed and striatal neuronal counts were performed alongside measurements of total brain and white matter atrophy. The staircase, adjusting steps, rotarod and apomorphine induced rotations were the most reliable for assessing long-term deficits in the 30 min transient MCAO model of stroke

Corymbia torelliana hybrids for hardwood forestry - without the weediness!

Corymbia torelliana hybrids have great potential for sustainable plantation forestry in many areas of tropical Australia. The species as a parent in hybrid breeding programs confers benefits such as resistance to Ramularia shoot blight, environmental plasticity, effective site capture and good rooting ability for clonal forestry. C. torelliana occurs naturally in rainforests and rainforest margins in the wet tropics region of Far North Qld between Shiptons’ Flat, near Cooktown and Mt Fox, near Ingham. The species has a tendency to become a weed where it is planted in areas outside of the wet tropics. Consequently, it is now listed as a noxious weed by many local councils between Grafton and Mackay and there are bans on selling, propagating and distributing the species. C. torelliana has a unique seed dispersal syndrome that may contribute to its weediness in areas where it has been introduced. Seeds are dispersed by bees, sometimes up to 300 m from the parent tree (Wallace and Trueman 1995). Native stingless bees of the genus Trigona build their nests from plant resins, and T. carbonaria forages for resin inside the mature capsules of C. torelliana. When the bees forage for resin, C. torelliana seeds become attached to the resin droplets carried by bees. The bees eventually discard the seeds outside their nests. Seeds dispersed by bees are almost all viable, and abundant germination and establishment occurs around hives and wild nests. Some beekeepers claim that C. torelliana is harmful to stingless bees. Claims are that the seed “clogs” the nest and prevents bee movement, and that the resin from C. torelliana, when used in nest structures, tends to collapse, causing death of the colony. In spite of no scientific study on the weediness of C. torelliana or the effect on stingless bees, C. torelliana has been banned from new plantings and actively removed by local councils from amenity plantings. In this study, we examined the interaction between stingless bees and C. torelliana and its hybrids in the natural range of C. torelliana in the Wet Tropics . Here we report the structure of hybrid capsules and their attractiveness to stingless bees

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified