Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration : A Novel Regression Analysis to Capture the Bilateral Nature of the Disease

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited

Six weeks of home enteral nutrition versus standard care after esophagectomy or total gastrectomy for cancer: study protocol for a randomized controlled trial

Background: Each year approximately 3000 patients in the United Kingdom undergo surgery for esophagogastric cancer. Jejunostomy feeding tubes, placed at the time of surgery for early postoperative nutrition, have been shown to have a positive impact on clinical outcomes in the short term. Whether feeding out of hospital is of benefit is unknown. Local experience has identified that between 15 and 20% of patients required ‘rescue’ jejunostomy feeding for nutritional problems and weight loss while at home. This weight loss and poor nutrition may contribute to the detrimental effect on the overall quality of life (QoL) reported in these patients. Methods/Design: This randomized pilot and feasibility study will provide preliminary information on the routine use of jejunostomy feeding after hospital discharge in terms of clinical benefits and QoL. Sixty participants undergoing esophagectomy or total gastrectomy will be randomized to receive either a planned program of six weeks of home jejunostomy feeding after discharge from hospital (intervention) or treatment-as-usual (control). The intention of this study is to inform a multi-centre randomized controlled trial. The primary outcome measures will be recruitment and retention rates at six weeks and six months. Secondary outcome measures will include disease specific and general QoL measures, nutritional parameters, total and oral nutritional intake, hospital readmission rates, and estimates of healthcare costs. Up to 20 participants will also be enrolled in a qualitative sub-study that will explore participants’ and carers’ experiences of home tube feeding. The results will be disseminated by presentation at surgical, gastroenterological and dietetic meetings and publication in appropriate peer review journals. A patient-friendly lay summary will be made available on the University of Leicester and the University Hospitals of Leicester NHS Trust websites. The study has full ethical and institutional approval and started recruitment in July 2012. Trial registration: UKClinical Research Network ID #12447 (Main study); UKCRN ID#13361 (Qualitative sub study); ClinicalTrials.gov #NCT01870817 (First registered 28 May 2013

A randomised controlled trial of six weeks of home enteral nutrition versus standard care after oesophagectomy or total gastrectomy for cancer: report on a pilot and feasibility study.

BACKGROUND: Poor nutrition in the first months after oesophago-gastric resection is a contributing factor to the reduced quality of life seen in these patients. The aim of this pilot and feasibility study was to ascertain the feasibility of conducting a multi-centre randomised controlled trial to evaluate routine home enteral nutrition in these patients. METHODS: Patients undergoing oesophagectomy or total gastrectomy were randomised to either six weeks of home feeding through a jejunostomy (intervention), or treatment as usual (control). Intervention comprised overnight feeding, providing 50 % of energy and protein requirements, in addition to usual oral intake. Primary outcome measures were recruitment and retention rates at six weeks and six months. Nutritional intake, nutritional parameters, quality of life and healthcare costs were also collected. Interviews were conducted with a sample of participants, to ascertain patient and carer experiences. RESULTS: Fifty-four of 112 (48 %) eligible patients participated in the study over the 20 months. Study retention at six weeks was 41/54 patients (76 %) and at six months was 36/54 (67 %). At six weeks, participants in the control group had lost on average 3.9 kg more than participants in the intervention group (95 % confidence interval [CI] 1.6 to 6.2). These differences remained evident at three months (mean difference 2.5 kg, 95 % CI -0.5 to 5.6) and at six months (mean difference 2.5 kg, 95 % CI -1.2 to 6.1). The mean values observed in the intervention group for mid arm circumference, mid arm muscle circumference, triceps skin fold thickness and right hand grip strength were greater than for the control group at all post hospital discharge time points. The economic evaluation suggested that it was feasible to collect resource use and EQ-5D data for a full cost-effectiveness analysis. Thematic analysis of 15 interviews identified three main themes related to the intervention and the trial: 1) a positive experience, 2) the reasons for taking part, and 3) uncertainty of the study process. CONCLUSIONS: This study demonstrated that home enteral feeding by jejunostomy was feasible, safe and acceptable to patients and their carers. Whether home enteral feeding as 'usual practice' is a cost-effective therapy would require confirmation in an appropriately powered, multi-centre study. TRIAL REGISTRATION: UK Clinical Research Network ID 12447 (main trial, first registered 30 May 2012); UK Clinical Research Network ID 13361 (qualitative substudy, first registered 30 May 2012); ClinicalTrials.gov NCT01870817 (first registered 28 May 2013)

Transmission of the biblical text in the Qumran scrolls The case of the large Isaiah scroll (1QIs&quot;a)

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN014439 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Has metal-on-metal resurfacing been a cost-effective intervention for health care providers? - a registry based study

Background: Total hip replacement for end stage arthritis of the hip is currently the most common elective surgical procedure. In 2007 about 7.5% of UK implants were metal-on-metal joint resurfacing (MoM RS) procedures. Due to poor revision performance and concerns about metal debris, the use of RS had declined by 2012 to about a 1% share of UK hip procedures. This study estimated the lifetime cost-effectiveness of metal-on-metal resurfacing (RS) procedures versus commonly employed total hip replacement (THR) methods. Methodology/Principal Findings: We performed a cost-utility analysis using a well-established multi-state semi-Markov model from an NHS and personal and social services perspective. We used individual patient data (IPD) from the National Joint Registry (NJR) for England and Wales on RS and THR surgery for osteoarthritis recorded from April 2003 to December 2012. We used flexible parametric modelling of NJR RS data to guide identification of patient subgroups and RS devices which delivered revision rates within the NICE 5% revision rate benchmark at 10 years. RS procedures overall have an estimated revision rate of 13% at 10 years, compared to <4% for most THR devices. New NICE guidance now recommends a revision rate benchmark of <5% at 10 years. 60% of RS implants in men and 2% in women were predicted to be within the revision benchmark. RS devices satisfying the 5% benchmark were unlikely to be cost-effective compared to THR at a standard UK willingness to pay of £20,000 per quality-adjusted life-year. However, the probability of cost effectiveness was sensitive to small changes in the costs of devices or in quality of life or revision rate estimates. Conclusion/Significance: Our results imply that in most cases RS has not been a cost-effective resource and should probably not be adopted by decision makers concerned with the cost effectiveness of hip replacement, or by patients concerned about the likelihood of revision, regardless of patient age or gender

Re : Mortality rates at 10 years after metal-on-metal hip resurfacing compared with total hip replacement in England : retrospective cohort analysis of hospital episode statistics

Two recent BMJ papers analyse mortality of recipients of hip replacements; they report strikingly superior survival for metal on metal resurfacing recipients relative to those getting cemented or un-cemented Total Hip Replacement (THR)1, 2. Both use observational data. In contrast, cost-effectiveness models of hip replacement, also based on observational data, have assumed that after surgical recovery the same mortality applies for all types of prosthesis, differences have been assumed or found to be attributable to age, gender and other population characteristics 3,4,5. We were interested to see if the new estimates published by McMinn et al1 and Kendal et al2 might be useful for cost-effectiveness comparisons in which lifetime models necessitate extrapolation beyond observed data in order to determine mean survival6

Cost-effectiveness of new left ventricular assist devices (LVADS) for patients with advanced heart failure : analysis of the UK NHS bridge to transplant (BTT) programme

Background: Public health measures aim to prevent people from reaching tertiary prevention or palliative or heroic care. Nevertheless these remain the only options for some people. There is an expanding population with very severe heart failure and although heart transplant is the optimal treatment, this option is dependent on a diminishing supply of donor hearts. For more than a decade, the NHS has supported the transplant programme for patients awaiting a donor heart with a ‘bridge to transplant’ programme - surgical implantation of a mechanical pump to support left ventricular function called a Left Ventricular Assist Device (LVAD). Alternatively individuals waiting for a heart receive medical management with drugs such as intravenous inotropes

Comparative cost-effectiveness of the HeartWare versus HeartMate II left ventricular assist devices used in the United Kingdom National Health Service bridge-to-transplant program for patients with heart failure

Background: Patients with advanced heart failure may receive a left ventricular assist device (LVAD) as part of a bridge-to-transplant (BTT) strategy. The United Kingdom National Health Service (UK NHS) has financed a BTT program in which the predominant LVADs used have been the HeartMate II (HM II; Thoratec, Pleasanton, CA) and HeartWare (HW; HeartWare International, Inc. Framingham, MA). We aimed to compare the cost-effectiveness of the use of these within the NHS program. Methods: Individual patient data from the UK NHS Blood and Transplant Data Base were analyzed with Kaplan-Meier and competing outcomes methodologies. Outcomes were time to death, time to heart transplant (HT), and cumulative incidences of HT, death on LVAD support, and LVAD explantation. A semi-Markov multistate economic model was built to assess cost-effectiveness. The perspective was from the NHS, discount rates were 3.5%. Outcomes were quality-adjusted life-years (QALYs) and incremental cost (2011 prices in GB£) per QALY (ICER) for HW vs HM II. Results: Survival was better with HW support than with HM II. Cumulative incidence of HT was low for both groups (11% at ~2 years). HW patients accrued 4.99 lifetime QALYs costing £258,913 ($410,970), HM II patients accrued 3.84 QALYs costing £231,871 ($368,048); deterministic and probabilistic ICERs for HW vs HM II were £23,530 ($37,349) and £20,799 ($33,014), respectively. Conclusions: Patients In the UK BTT program who received the HW LVAD had a better clinical outcome than those who received the HM II, and the HW was more cost-effective. This result needs to be reassessed in a randomized controlled trial comparing the 2 devices

Cost effectiveness of total hip arthroplasty in osteoarthritis : comparison of devices with differing bearing surfaces and modes of fixation

Many different designs of total hip arthroplasty (THA) with varying performance and cost are available. The identification of those which are the most cost-effective could allow significant cost-savings. We used an established Markov model to examine the cost effectiveness of five frequently used categories of THA which differed according to bearing surface and mode of fixation, using data from the National Joint Registry for England and Wales. Kaplan–Meier analyses of rates of revision for men and women were modelled with parametric distributions. Costs of devices were provided by the NHS Supply Chain and associated costs were taken from existing studies. Lifetime costs, lifetime quality-adjusted-life-years (QALYs) and the probability of a device being cost effective at a willingness to pay £20 000/QALY were included in the models. The differences in QALYs between different categories of implant were extremely small (< 0.0039 QALYs for men or women over the patient’s lifetime) and differences in cost were also marginal (£2500 to £3000 in the same time period). As a result, the probability of any particular device being the most cost effective was very sensitive to small, plausible changes in quality of life estimates and cost. Our results suggest that available evidence does not support recommending a particular device on cost effectiveness grounds alone. We would recommend that the choice of prosthesis should be determined by the rate of revision, local costs and the preferences of the surgeon and patient