How long has NICE taken to produce Technology Appraisal guidance? A retrospective study to estimate predictors of time to guidance.

OBJECTIVES: To assess how long the UK's National Institute for Health and Clinical Excellence's (NICE) Technology Appraisal Programme has taken to produce guidance and to determine independent predictors of time to guidance. DESIGN: Retrospective time to event (survival) analysis. SETTING: Technology Appraisal guidance produced by NICE. DATASOURCE: All appraisals referred to NICE by February 2010 were included, except those referred prior to 2001 and a number that were suspended. OUTCOME MEASURE: Duration from the start of an appraisal (when the scope document was released) until publication of guidance. RESULTS: Single Technology Appraisals (STAs) were published significantly faster than Multiple Technology Appraisals (MTAs) with median durations of 48.0 (IQR; 44.3-75.4) and 74.0 (IQR; 60.9-114.0) weeks, respectively (p <0.0001). Median time to publication exceeded published process timelines, even after adjusting for appeals. Results from the modelling suggest that STAs published guidance significantly faster than MTAs after adjusting for other covariates (by 36.2 weeks (95% CI -46.05 to -26.42 weeks)) and that appeals against provisional guidance significantly increased the time to publication (by 42.83 weeks (95% CI 35.50 to 50.17 weeks)). There was no evidence that STAs of cancer-related technologies took longer to complete compared with STAs of other technologies after adjusting for potentially confounding variables and only weak evidence suggesting that the time to produce guidance is increasing each year (by 1.40 weeks (95% CI -0.35 to 2.94 weeks)). CONCLUSIONS: The results from this study suggest that the STA process has resulted in significantly faster guidance compared with the MTA process irrespective of the topic, but that these gains are lost if appeals are made against provisional guidance. While NICE processes continue to evolve over time, a trade-off might be that decisions take longer but at present there is no evidence of a significant increase in duration

The economics of replacement therapy for individuals with bleeding disorders

Individuals with haemophilia are deficient in essential clotting factors resulting in an increased tendency to bleed. Repeated bleeding into joints may cause haemophilic arthritis (HA). However, there is considerable interest from providers of haemophilia care in treating some individuals on a prophylactic basis to prevent bleeds, and hence joint damage, from occurring in the first instance. Prophylaxis was first administered at the Katharine Dormandy Haemophilia Centre (KDHC) in the late 1970s to some individuals with severe haemophilia, although full-time regimes were not introduced until the early 1980s. Data from individuals with severe haemophilia who were registered for treatment at the KDHC showed that following prophylaxis, the median incidence of bleeding had decreased significantly from 23.5 bleeds (range 1–107) per year in 1980 to 14 bleeds (range 0–52) per year by 1995 (P<0.0001). This said, however, individuals with severe haemophilia still recorded lower levels of health-related quality-of-life (HR-QoL) than individuals with mild / moderate haemophilia or the general UK male population even after adjusting for differences in age. Thus, significant scope exists for HR-QoL to be improved further. Using a unit clotting factor cost of 32.5 p/iu, a cost-utility analysis (CUA) showed that it cost an additional £46,500 per quality-adjusted life-year (QALY) and £8,600 per QALY to treat individuals with severe haemophilia A / vWD and severe haemophilia B with primary prophylaxis instead of on-demand respectively. However, the results from the CUA were not robust and both incremental cost-effectiveness ratios were found to be highly sensitive to a number of parameters including the unit clotting factor cost, the time between maintenance clotting factor infusions and the decision to discount future QALYs. Thus, further research over longer time periods is required to provide more accurate estimates of cost-effectiveness

Electromagnetic reflections inside ice sheets

When radio echo sounding polar ice sheets weak stratified reflections are visible deep inside the ice sheets. These reflections are often called internal layers. Previously it has been suggested as a result of glacier flow models that these reflections can be treated as surfaces of equal age. In order for a reflection to be related to a single age feature in an ice sheet a one dimensional wave model must be adequate to model the propagation of a wavelet down to the feature and back to the surface. In this thesis four different one dimensional models are constructed each including different physics. It is shown that for the frequencies of interest to radio echo sounding it is sufficient to use the non-dispersive high frequency values of permittivity and conductivity for the ice in the models. The models are used on data from two drill sites. The first site is Berkner Island where I constructed an instrument to measure the electrical conductivity of the 181 metre long ice core. The second site is the Greenland Ice Core Project (GRIP) site at Summit of length 3028 metres. For both sites permittivity and conductivity profiles inside the ice sheet are calculated and put into the models with an estimate of the transmitted wavelet to produce expected radio echo profiles at the sites. For Berkner despite altering many parameters no match between model result and radar data was obtained. For GRIP a satisfactory match was obtained between model result and radar data. It is concluded that the weak, specular (plane like), st Ratified reflections at depth can be treated as isochrones. The strong reflections at shallow depths are a result of a combination of spherical reflection surfaces and interference between many closely spaced layers and cannot necessarily be treated as isochrones

"A man of extremes - w.g. ward as a member of the church of England"

The purpose of this thesis is to examine the role of W.G. Ward in the Oxford Movement, with specific reference to his series of Articles in the British Critic and his book 'The Ideal, of a Christian Church.' In the Introduction we examine Ward's family background, and his early education. We also consider the influence of Thomas Arnold, and Ward's 'conversion' to the new Movement through the influence of J.H. Newman. Chapter One deals with Tract Ninety and Ward's defence of it. Chapter Two contains Ward's explanation of his ideas to Pusey, and extracts from the correspondence of Newman and Pusey. In Chapter Three we examine in detail each of Ward's eight Articles in the British Critic. Chapter Four describes the embarrassment that Ward and his group had caused to other members of the Movement, and outlines specifically William Palmer's criticism. In Chapter Five we see Ward's reply in the form of his book 'The Ideal of a Christian Church,' which was largely a development of the ideas expressed in the British Critic Articles. In the final Chapter, we see reactions to Ward's book from different quarters, the disciplinary measures taken against him and his departure from the Church of England to the Church of Rome in 1845

Testing for sexually transmitted infections among students: a discrete choice experiment of service preferences

Objectives To assess preferences among students for sexually transmitted infection (STI) testing services, with a view to establishing strength of preference for different service attributes. Design Online discrete choice experiment (DCE) questionnaire. Setting South East of England. Participants A convenience sample of 233 students from two universities. Outcomes Adjusted ORs in relation to service characteristics. Results The study yielded 233 responses. Respondents’ ages ranged from 16 to 34 years with a mean age of 22 years. Among this sample, the respondents demonstrated strong preferences for a testing service which provided tests for all STIs including syphilis, herpes and HIV (OR 4.1; 95% CI 3.36 to 4.90) and centres staffed by a doctor or nurse with specialist knowledge of STIs (OR 2.1; 95% CI 1.78 to 2.37). Receiving all test results, whether positive or negative, was also significantly preferable to not being notified when tests were all negative (‘no news is good news’; OR 1.3; 95% CI 1.16 to 1.5). The length of time waiting for an appointment and the method by which results are received were not significant service characteristics in terms of preferences. Patient level characteristics such as age, sex and previous testing experience did not predict the likelihood of testing. Conclusions This study demonstrates that of the examined attributes, university students expressed the strongest preference for a comprehensive testing service. The next strongest preferences were for being tested by specialist STI staff and receiving negative as well as positive test results. However, it remains unclear how strong these preferences are in relation to characteristics which were not part of the study design and whether or not they are cost-effective

Understanding patient choices for attending sexually transmitted infection testing services: a qualitative study

Objectives: To establish which aspects of sexually transmitted infection (STI) testing services are important to STI testing service users. Methods: 10 focus groups consisting of previous or existing users of STI testing services were conducted in community settings in the south east of England. Groups were quota sampled based on age, gender and sexual orientation. Data were analysed using Framework Analysis. Results: 65 respondents (58% men) participated. Perceived expertise of staff was the key reason for attendance at genitourinary medicine services rather than general practice. Although some respondents voiced a willingness to test for STIs within general practice, the apparent limited range of tests available in general practice and the perceived lack of expertise around sexual health appeared to discourage attendance at general practice. The decision of where to test for STIs was also influenced by past experience of testing, existing relationships with general practice, method of receiving test results and whether the patient had other medical conditions such as HIV. Conclusions: No one type of STI testing service is suitable for all patients. This is recognised by policymakers, and it now requires commissioners and providers to make services outside of genitourinary medicine clinics more acceptable and attractive to patients, in particular to address the perceived lack of expertise and limited range of STIs tests available at alternative testing sites

Cerebrovascular disease in ageing and Alzheimer's disease

Cerebrovascular disease (CVD) and Alzheimer’s disease (AD) have more in common than their association with ageing. They share risk factors and overlap neuropathologically. Most patients with AD have Aβ amyloid angiopathy and degenerative changes affecting capillaries, and many have ischaemic parenchymal abnormalities. Structural vascular disease contributes to the ischaemic abnormalities in some patients with AD. However, the stereotyped progression of hypoperfusion in this disease, affecting first the precuneus and cingulate gyrus, then the frontal and temporal cortex and lastly the occipital cortex, suggests that other factors are more important, particularly in early disease. Whilst demand for oxygen and glucose falls in late disease, functional MRI, near infrared spectroscopy to measure the saturation of haemoglobin by oxygen, and biochemical analysis of myelin proteins with differential susceptibility to reduced oxygenation have all shown that the reduction in blood flow in AD is primarily a problem of inadequate blood supply, not reduced metabolic demand. Increasing evidence points to non-structural vascular dysfunction rather than structural abnormalities of vessel walls as the main cause of cerebral hypoperfusion in AD. Several mediators are probably responsible. One that is emerging as a major contributor is the vasoconstrictor endothelin-1 (EDN1). Whilst there is clearly an additive component to the clinical and pathological effects of hypoperfusion and AD, experimental and clinical observations suggest that the disease processes also interact mechanistically at a cellular level in a manner that exacerbates both. The elucidation of some of the mechanisms responsible for hypoperfusion in AD and for the interactions between CVD and AD has led to the identification of several novel therapeutic approaches that have the potential to ameliorate ischaemic damage and slow the progression of neurodegenerative disease

Cost-effectiveness of HCV case-finding for people who inject drugs via dried blood spot testing in specialist addiction services and prisons

ObjectivesPeople who inject drugs (PWID) are at high risk for acquiring hepatitis C virus (HCV), but many are unaware of their infection. HCV dried blood spot (DBS) testing increases case-finding in addiction services and prisons. We determine the cost-effectiveness of increasing HCV case-finding among PWID by offering DBS testing in specialist addiction services or prisons as compared to using venepuncture.DesignCost-utility analysis using a dynamic HCV transmission model among PWID, including: disease progression, diagnosis, treatment, injecting status, incarceration and addition services contact.Setting uk interventionDBS testing in specialist addiction services or prisons. Intervention impact was determined by a meta-analysis of primary data.Primary and secondary outcome measuresCosts (in UK £, £1=US$1.60) and utilities (quality-adjusted life years, QALYs) were attached to each state and the incremental cost effectiveness ratio (ICER) determined. Multivariate uncertainty and one-way sensitivity analyses were performed.ResultsFor a £20 000 per QALY gained willingness-to-pay threshold, DBS testing in addiction services is cost-effective (ICER of £14 600 per QALY gained). Under the base-case assumption of no continuity of treatment/care when exiting/entering prison, DBS testing in prisons is not cost-effective (ICER of £59 400 per QALY gained). Results are robust to changes in HCV prevalence; increasing PWID treatment rates to those for ex-PWID considerably reduces ICER (£4500 and £30 000 per QALY gained for addiction services and prison, respectively). If continuity of care is &gt;40%, the prison DBS ICER falls below £20 000 per QALY gained.ConclusionsDespite low PWID treatment rates, increasing case-finding can be cost-effective in specialist addiction services, and in prisons if continuity of treatment/care is ensured