An evaluation of risk-based monitoring in pragmatic trials in UK Clinical Trials Units

Background Good Clinical Practice guidelines issued in 2016 encourage risk-based approaches to monitoring clinical trials. This study compared current risk assessment and monitoring approaches in UK Clinical Trials Units (CTUs) with the published guidance and makes recommendations for risk-based monitoring in pragmatic trials. Methods An online survey of UK Clinical Research Collaboration registered CTUs was administered via email invitation. Forty-nine units were invited, and 23 responded. Respondents were also invited to share copies of risk assessment templates. Results Most CTUs reported using remote combined with on-site monitoring. All reported undertaking a risk assessment for Clinical Trials of Investigational Medicinal Products (CTIMPs) and 21 units did so for non-CTIMPs. Most CTIMP risk assessments used MHRA (Medicines and Healthcare products Regulatory Agency) classifications, although some also employed staff judgement. Almost all units based their monitoring on perceived risk level; this number was higher for CTIMPs (n = 22) than for non-CTIMPs (n = 19). In most cases, monitoring plans were produced. More CTUs revisited risk assessments during trials in CTIMPs (n = 21) than in non-CTIMPs (n = 18). Small numbers of units reviewed the monitoring approach always (n = 4) or sometimes (n = 9) and few used the reflection to guide future monitoring. Conclusions A high proportion of UK CTUs are using risk-based monitoring in the UK, as recommended by guidelines, for both CTIMPs and non-CTIMPs. This has the potential to make trials more efficient and reduce costs. However, there appears to be a lack of reflection on the value of these revised approaches. There may be a benefit in CTUs collaborating nationally to improve processes for reflection and making changes during the life course of a trial

Adherence with NICE guidance on lifestyle advice for people with schizophrenia: a survey

Background Substantial weight gain is common in people taking antipsychotics. NICE recommends these patients are offered physical health screening and intervention. The STEPWISE trial is currently evaluating a lifestyle education programme in addition to usual care. However, it is difficult to define what constitutes “usual care”. Aims To define “usual care” for lifestyle management in people with schizophrenia, schizoaffective disorder and first episode psychosis in STEPWISE study sites. Method Ten NHS Mental Health Trusts participated in a bespoke survey based on NICE guidance. Results Eight trusts reported offering lifestyle education programmes. Nine Trusts reported offering smoking cessation support. Reported recording of biomedical measures varied. Conclusions No consistent lifestyle education programme is currently offered across UK NHS Mental Health Trusts. The survey benchmarks ‘usual care’ for the STEPWISE study on which changes can be measured

Enterprise Architecture Specification Case Study

A graduate course in enterprise architecture had a team project component in which a real-world business case, provided by an industry sponsor, formed the basis of the project charter and the architecture statement of work. The paper aims to share the team project experience on developing the architecture specifications based on the business case of an accountable health care organization. Students collaborated as a team in various roles to develop the architecture specifications for a new business initiative of the sponsoring organization, XYZ ACO. The teaching case describes the case study approach and the architecture approach adopted for the architecture process, and is accompanied by Teaching Case Notes which provide a selection of the models developed by members of the project team towards the architecture specifications. The course started with coverage of enterprise architecture theory, best practices and standards, and the team project gave students the opportunity to apply their theoretical knowledge and “learn by doing”. Students were challenged to interpret the business case, the project charter and project requirements, and each team member was allocated an architecture viewpoint and a role to play. The Teaching Case presents a summary of the team project and the lessons learned in performing the project

The fossil insect assemblage associated with the Toarcian (Lower Jurassic) oceanic anoxic event from Alderton Hill, Gloucestershire, UK

Extreme global warming and environmental changes associated with the Toarcian (Lower Jurassic) Oceanic Anoxic Event (T-OAE, ∼183 Mya) profoundly impacted marine organisms and terrestrial plants. Despite the exceptionally elevated abundances of fossil insects from strata of this age, only assemblages from Germany and Luxembourg have been studied in detail. Here, we focus on the insect assemblage found in strata recording the T-OAE at Alderton Hill, Gloucestershire, UK, where <15% of specimens have previously been described. We located all known fossil insects (n = 370) from Alderton Hill, and used these to create the first comprehensive taxonomic and taphonomic analysis of the entire assemblage. We show that a diverse palaeoentomofaunal assemblage is preserved, comprising 12 orders, 21 families, 23 genera and 21 species. Fossil disarticulation is consistent with insect decay studies. The number of orders is comparable with present-day assemblages from similar latitudes (30°-40°N), including the Azores, and suggests that the palaeoentomofauna reflects a life assemblage. At Alderton, Hemiptera, Coleoptera and Orthoptera are the commonest (56.1%) orders. The high abundance of Hemiptera (22.1%) and Orthoptera (13.4%) indicates well-vegetated islands, while floral changes related to the T-OAE may be responsible for hemipteran diversification. Predatory insects are relatively abundant (∼10% of the total assemblage) and we hypothesise that the co-occurrence of fish and insects within the T-OAE represents a jubilee-like event. The marginally higher proportion of sclerotised taxa compared to present-day insect assemblages possibly indicates adaptation to environmental conditions or taphonomic bias. The coeval palaeoentomofauna from Strawberry Bank, Somerset is less diverse (9 orders, 12 families, 6 genera, 3 species) and is taphonomically biased. The Alderton Hill palaeoentomofauna is interpreted to be the bestpreserved and most representative insect assemblage from Toarcian strata in the UK. This study provides an essential first step towards understanding the likely influence of the TOAE on insects

A new Liassophlebiidae (Odonata: Heterophlebioidea) from strata close to the Triassic-Jurassic boundary in Somerset, UK

Liassophlebiidae is an extinct family of damsel-dragonflies found in Upper Triassic and Lower Jurassic strata of Europe, Asia and Antarctica. Whilst Liassophlebiidae is well represented by Lower Jurassic fossils, their lowest occurrence in the Upper Triassic has hitherto only been suggested by three fragmentary specimens. These were originally ascribed to two species: Liassophlebia withersi and Liassophlebia batheri, but the latter is now considered nomen dubium. Here we describe a fourth, better preserved specimen that is likely to be Rhaetian (Late Triassic) in age. The specimen, BRSMG Cg3101 a+b, was collected from Bowdens Quarry, Somerset, UK, from the lower part of the White Lias Formation. The specimen comprises an incomplete forewing attributed to Liassophlebia due to: the small number of antenodals, antesubnodals and crossveins between RP and MA based RP3/4 in the base of RP2 opposite the subnodus; a straight and elongate secondary longitudinal vein in the postdiscoidal area; numerous cells and secondary veins in radial and median areas. The specimen is likely to represent a new species and provides stronger evidence than the previous three specimens of the presence of Liassophlebiidae during the late Rhaetian. Its stratigraphical position suggests that Liassophlebiidae arose in the immediate aftermath of the Triassic-Jurassic mass extinction

Pembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC): Post hoc analyses of treatment options from the phase III KEYNOTE-040 trial

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Design Study of CANGAROO-III, Stereoscopic Imaging Atmospheric Cherenkov Telescopes for sub-TeV Gamma-ray

CANGAROO-III is an Imaging Atmospheric Cherenkov Telescope (IACT) array of four 10 m telescopes for very high energy (sub-TeV) gamma-ray astronomy. A design study of the CANGAROO-III telescope system was carried out using the Monte Carlo technique in order to optimize the pixel size and the telescope spacing. Studies were also made of observations at low elevation angles.Comment: 17pages, 13 figures, elsart, to appear in Astro. Part. Phy

Search for TeV gamma-rays from SN 1987A in 2001

We searched for TeV gamma-rays from the remnant of SN 1987A around 5400 days after the supernova. The observations were carried out in 2001, from November 16 to December 11, using the CANGAROO-II Imaging Atmospheric Cherenkov Telescope. In total, 708 minutes of ON- and 1019 minutes of OFF-source data were obtained under good conditions. The detection threshold was estimated to be 1 TeV, due to the mean zenith angle of 39$^\circ$. The upper limits for the gamma-ray flux were obtained and compared with the previous observations and theoretical models. The observations indicate that the gamma-ray luminosity is lower than $1\times 10^{37}$ erg s$^{-1}$ at $\sim 10$ TeV.Comment: 8 pages, 3 figures, submitted for publication, style file adde