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To establish how real-world evidence (RWE) has been used to inform single technology appraisals (STAs) of cancer drugs conducted by the National Institute for Health and Care Excellence (NICE).
STAs published by NICE from April 2011 to October 2018 that evaluated cancer treatments were reviewed. Information regarding the use of RWE to directly inform the company-submitted cost-effectiveness analysis was extracted and categorized by topic. Summary statistics were used to describe emergent themes, and a narrative summary was provided for key case studies.
Materials for a total of 113 relevant STAs were identified and analyzed, of which nearly all (96 percent) included some form of RWE within the company-submitted cost-effectiveness analysis. The most common categories of RWE use concerned the health-related quality of life of patients (71 percent), costs (46 percent), and medical resource utilization (40 percent). While sources of RWE were routinely criticized as part of the appraisal process, we identified only two cases where the use of RWE was overtly rejected; hence, in the majority of cases, RWE was accepted in cancer drug submissions to NICE.
RWE has been used extensively in cancer submissions to NICE. Key criticisms of RWE in submissions to NICE are seldom regarding the use of RWE in general; instead, these are typically concerned with specific data sources and the applicability of these to the decision problem. Within an appropriate context, RWE constitutes an extremely valuable source of information to inform decision making; yet the development of best practice guidelines may improve current reporting standards.
We examined demographic, clinical, and psychological characteristics of a large cohort (n = 368) of adults with dissociative seizures (DS) recruited to the CODES randomised controlled trial (RCT) and explored differences associated with age at onset of DS, gender, and DS semiology.
Prior to randomisation within the CODES RCT, we collected demographic and clinical data on 368 participants. We assessed psychiatric comorbidity using the Mini-International Neuropsychiatric Interview (M.I.N.I.) and a screening measure of personality disorder and measured anxiety, depression, psychological distress, somatic symptom burden, emotional expression, functional impact of DS, avoidance behaviour, and quality of life. We undertook comparisons based on reported age at DS onset (<40 v. ⩾40), gender (male v. female), and DS semiology (predominantly hyperkinetic v. hypokinetic).
Our cohort was predominantly female (72%) and characterised by high levels of socio-economic deprivation. Two-thirds had predominantly hyperkinetic DS. Of the total, 69% had ⩾1 comorbid M.I.N.I. diagnosis (median number = 2), with agoraphobia being the most common concurrent diagnosis. Clinical levels of distress were reported by 86% and characteristics associated with maladaptive personality traits by 60%. Moderate-to-severe functional impairment, high levels of somatic symptoms, and impaired quality of life were also reported. Women had a younger age at DS onset than men.
Our study highlights the burden of psychopathology and socio-economic deprivation in a large, heterogeneous cohort of patients with DS. The lack of clear differences based on gender, DS semiology and age at onset suggests these factors do not add substantially to the heterogeneity of the cohort.
We discuss the factors influencing the relationship between government policy-makers and scientists and how they affect the use of science in policy. We highlight issues related to context, values, culture, timeframes, communication and interpersonal relationships, providing insights from policy-makers and scientists. A spectrum of working strategies is given with examples of practical mechanisms that improve the effective use of science in policy. The shared governance model is a relatively mature approach with the potential to overcome many of the barriers discussed. At its core, shared governance, or co-production, invites policy-makers and scientists to develop and manage research priorities collaboratively. We explore the primary features of a successful shared governance arrangement, exemplified by the collaborative working model between the Australian Government Department of Agriculture and the Centre of Excellence for Biosecurity Risk Analysis. We conclude by outlining the advantages and disadvantages of the co-production of research priorities by scientists and policy-makers and present the learnings from its implementation in the biosecurity sector in Australia.
The Must Farm pile-dwelling site is an extraordinarily well-preserved Late Bronze Age settlement in Cambridgeshire, UK. The authors present the site's contextual setting, from its construction, occupation and subsequent destruction by fire in relatively quick succession. A slow-flowing watercourse beneath the pile-dwellings provided a benign burial environment for preserving the debris of construction, use and collapse, while the catastrophic manner of destruction introduced a definitive timeframe. The scale of its occupation speaks to the site's exceptional nature, enabling the authors to deduce the everyday flow and use of things in a prehistoric domestic setting.
We conduct a benefit-cost analysis of a package of early childhood interventions that can improve nutrition outcomes in Haiti. Using the Lives Saved Tool, we expect that this package can prevent approximately 55,000 cases of child stunting, 7,600 low-weight births and 28,000 cases of maternal anemia annually, if coverage reaches 90% of the target population. In addition, we expect these nutrition improvements will avoid 1,830 under-five deaths, 80 maternal deaths and 900,000 episodes of child illness every year. Those who avoid stunting will experience lifetime productivity benefits equivalent to five times gross national income per capita in present value terms, at a 5% discount rate. While previous benefit-cost analyses of this specific package have only estimated the lifetime productivity benefits of avoided stunting, this paper also accounts for reductions in fatal and non-fatal health risks. In the base case scenario, the annualized net benefits of the intervention equal Haitian gourdes 13.4 billion (USD 211 million) and the benefit-cost ratio (BCR) is 5.2. Despite these substantial benefits, the package may not be the most efficient use of a marginal dollar, with alternative interventions to improve human capital yielding BCRs approximately three to four times higher than the base estimate.
Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.
To investigate the potential association between clozapine and antibody deficiency.
Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.
Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31–27.44); IgA, OR = 16.75 (95% CI 2.18–128.60); and IgM, OR = 3.26 (95% CI 1.75–6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).
Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.
Declaration of interest
S.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.
Increasing longevity and the strain on state and occupational pensions have brought into question long-held assumptions about the age of retirement, and raised the prospect of a workplace populated by ageing workers. In the United Kingdom the default retirement age has gone, incremental increases in state pension age are being implemented and ageism has been added to workplace anti-discrimination laws. These changes are yet to bring about the anticipated transformation in workplace demographics, but it is coming, making it timely to ask if the workplace is ready for the ageing worker and how the extension of working life will be managed. We report findings from qualitative case studies of five large organisations located in the United Kingdom. Interviews and focus groups were conducted with employees, line managers, occupational health staff and human resources managers. Our findings reveal a high degree of uncertainty and ambivalence among workers and managers regarding the desirability and feasibility of extending working life; wide variations in how older workers are managed within workplaces; a gap between policies and practices; and evidence that while casualisation might be experienced negatively by younger workers, it may be viewed positively by financially secure older workers seeking flexibility. We conclude with a discussion of the challenges facing employers and policy makers in making the modern workplace fit for the ageing worker.
The promotion of extended working life has created a period of uncertainty between the ending of work and the beginning of retirement. This period of the life course is now ‘open-ended’ in respect of whether older workers decide to remain in employment or leave working. However, the choices available are framed within public policy and organisational contexts as well as personal circumstances. The study reviews the organisation of ‘work-ending’, the construction of age within organisations, and the influences on provision of support in late working life. The article concludes with a discussion on the range of pressures that might limit control over pathways through middle and late working careers.
Despite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.
Materials and methods
The modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation.
Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting.
Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.
Paramphistomosis, caused by Calicophoron daubneyi, is an emerging infection of ruminants throughout Western Europe. Despite its prevalence, many questions remain regarding the basic biology of this parasite and how it interacts with its host. Consequently, there is a need to develop methods to study C. daubneyi in vitro to improve our understanding of rumen fluke biology. Towards this, we aimed to identify a suitable protocol for in vitro excystment of C. daubneyi metacercariae. Six methods that have been used to excyst metacercariae from a number of trematode species were tested with C. daubneyi metacercariae. Three of these achieved an average of >50% excystment whilst one method, which included an acid-pepsin treatment, incubation in reducing conditions and an alkaline/bile salt solution to activate the larvae, consistently gave >80% excystment. The latter protocol also showed no detrimental effect on the motility of newly excysted juvenile (NEJ) parasites when observed for up to 24 h in RPMI 1640 medium post-excystment. The successful production of C. daubneyi NEJs in vitro is a significant step forward, and will enable the discovery of infective stage-specific parasite antigens and facilitate drug screening trials, to aid the development of much needed diagnostic and therapeutic options for paramphistomosis.
With climate change and increasing globalisation of trade and travel, the risks presented by invasive pests and pathogens to natural environments, agriculture and economies have never been greater, and are only increasing with time. Governments world-wide are responding to these increased threats by strengthening quarantine and biosecurity. This book presents a comprehensive review of risk-based techniques that help policy makers and regulators protect national interests from invasive pests and pathogens before, at, and inside national borders. Selected from the research corpus of the Centre of Excellence for Biosecurity Risk Analysis at the University of Melbourne, this book provides solutions that reflect scientific rigour coupled with practical, hands-on applications. Focusing on surveillance, stochastic modelling, intelligence gathering, decision making and risk communication, the contents combine the strengths of risk analysts, mathematicians, economists, biologists and statisticians. The book presents tested scientific solutions to the greatest challenges faced by quarantine and biosecurity policy makers and regulators today.
Excavations at Abreu Garcia provide a detailed case study of a mound and enclosure mortuary complex used by the southern proto-Jê in the southern Brazilian highlands. The recovery of 16 secondary cremation deposits within a single mound allows an in-depth discussion of spatial aspects of mortuary practices. A spatial division in the placement of the interments adds another level of duality to the mortuary landscape, which comprises: (1) paired mound and enclosures, (2) twin mounds within a mound and enclosure, and (3) the dual division in the mound interior. The multiple levels of nested asymmetric dualism evoke similarities to the moiety system that characterizes modern southern Jê groups, highlighting both the opposition and the complementarity of the social system. The findings offer deeper insight into fundamental aspects of southern proto-Jê social organization, including the dual nature of the community, the manifestation of social structure in the landscape, and its incorporation into mortuary ritual. The results have implications for research design and developing appropriate methodologies to answer culture-specific questions. Furthermore, the parallels among archaeology, ethnohistory, and ethnography enable an understanding of the foundation of modern descendent groups and an assessment of the continuity in indigenous culture beyond European contact.
As a discipline, design science has traditionally focused on designing products and associated technical processes to improve usability and performance. Although significant progress has been made in these areas, little research has yet examined the role of human behaviour in the design of socio-technical systems (e.g., organizations). Here, we argue that applying organizational psychology as a design science can address this omission and enhance the capability of both disciplines. Specifically, we propose a method to predict malfunctions in socio-technical systems (PreMiSTS), thereby enabling them to be designed out or mitigated. We introduce this method, describe its nine stages, and illustrate its application with reference to two high-profile case studies of such malfunctions: (1) the severe breakdowns in patient care at the UK’s Mid-Staffordshire NHS Foundation Trust hospital in the period 2005–2009, and (2) the fatal Grayrigg rail accident in Cumbria, UK, in 2007. Having first identified the socio-technical and behavioural antecedents of these malfunctions, we then consider how the PreMiSTS method could be used to predict and prevent future malfunctions of this nature. Finally, we evaluate the method, consider its advantages and disadvantages, and suggest where it can be most usefully applied.
While multiple studies have identified land managers’ preferences for agri-environmental schemes (AES), few approaches exist for integrating different understandings of landscape stewardship into the design of these measures. We compared and contrasted rural land managers’ attitudes toward AES and their preferences for AES design beyond 2020 across different understandings of landscape stewardship. Forty semi-structured interviews were conducted with similar proportions of small holders, medium holders and large holders in southwest Devon, UK. Overall, respondents most frequently cited concerns related to the reduced amount of funding available for entry-level and higher-level stewardship schemes in the UK since 2008, changing funding priorities, perceived overstrict compliance and lack of support for farm succession and new entrants into farming. However, there were differences in concerns across understandings of landscape stewardship, with production respondents citing that AES do not encourage food production, whereas environmental and holistic farmers citing that AES do not support the development of a local green food culture and associated social infrastructure. These differences also emerged in preferences for AES design beyond 2020. We adapted a collaborative and coordinated approach for designing AES to account for the differing interests of land managers based on their understanding of landscape stewardship. We discuss the implications of this approach for environmental policy design in the European Union and elsewhere.
We present an overview of the survey for radio emission from active stars that has been in progress for the last six years using the observatories at Fleurs, Molonglo, Parkes and Tidbinbilla. The role of complementary optical observations at the Anglo-Australian Observatory, Mount Burnett, Mount Stromlo and Siding Spring Observatories and Mount Tamborine are also outlined. We describe the different types of star that have been included in our survey and discuss some of the problems in making the radio observations.
The cave of Kayuko Naj Tunich is believed to have been the location of the accession ceremonies for the royal dynasty of the ancient Maya Uxbenká polity in southern Belize. Little is known, however, about the structures referred to as the Kayuko Mound Group that lie close to the cave. Excavations have now provided evidence for the date of this complex, and experimental research has estimated the labour costs involved in its construction. The results suggest that while both the mound group and the cave were involved in the celebration of royal accession, the former acted as a short-lived festival site in contrast to the enduring significance of Kayuko Naj Tunich.