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

Environmental Constraints on the Mechanics of Crawling and Burrowing Using Hydrostatic Skeletons

Mechanics, kinematics, and energetics of crawling and burrowing by limbless organisms using hydrostatic skeletons depend on the medium and mode in which the organism is moving. Whether the animal is moving over or through a solid has long been considered important enough to distinguish crawling and burrowing as different terms, and in fact the mechanics are very different. Crawlers use mechanisms to increase friction to generate thrust while reducing resistive friction. Burrowers in elastic muds extend their burrows by fracture, whereas sands are fluidized by burrowers much larger than grain sizes and smaller burrowers displace individual grains. Gravitational forces depend on how closely the density of the organism matches that of its fluid surroundings, therefore frictional forces depend on whether the organism is moving through air or water and fluidization on whether sands are saturated or unsaturated

Medicines use reviews: a potential resource or lost opportunity for general practice?

Background: Patient non-adherence to medicines represents a significant waste of health resource and lost opportunity for health gain. Medicine management services are a key health policy strategy to encourage patients to take medicines as they are prescribed. One such service is the English Medicines Use Review (MUR) which is an NHS-funded community pharmacy service involving a patient-pharmacist consultation aiming to improve patients’ knowledge of medicines and their use. To date the evidence for MURs to improve patient health outcomes is equivocal and GPs are reported to be sceptical about the value of the service. This paper presents the patient’s perspective of the MUR service and focuses on the importance of GP-pharmacist collaboration for patient care. Suggestions on how MURs may have value to GPs through the delivery of increased patient benefit are discussed. Method: A qualitative study involving ten weeks of ethnographic observations in two English community pharmacies. Observations were made of all pharmacy activities including patient-pharmacist MUR consultations. Subsequent interviews with these patients were conducted to explore their experience of the service. Interviews with the pharmacy staff were conducted after the period of observations. A thematic approach was used to analyse the data. Results: Fifty-four patients agreed to have their MUR observed of which thirty-four were interviewed. Seventeen pharmacy staff were also interviewed. Patients reported positive views about MURs. However, there was little evidence suggesting that pharmacists and GPs were working collaboratively or communicating outcomes resulting from MURs. MURs were conducted in isolation from other aspects of patient care. Patients considered GPs to have authority over medicines making a few wary that MURs had the potential to cause tensions between these professionals and possibly adversely affect their own relationship with their doctor. Conclusions: This study reveals the potential for effective GP-pharmacist collaboration to improve the capacity of the MUR service to support patient medicine taking. Closer collaboration between GPs and pharmacists could potentially improve patients’ use of medicines and associated health care outcomes. The current lack of such collaboration constitutes a missed opportunity for pharmacists and GPs to work together with patients to improve effective prescribing and optimise patient use of medicines

A real world example of coverage with evidence development in Australia - ipilimumab for the treatment of metastatic melanoma

Abstract Background Australian Government subsidisation of ipilimumab for the treatment of patients with metastatic melanoma was conditional on the sponsor entering a ‘managed entry scheme’ to assess the 2-year overall survival rate in metastatic melanoma patients who received ipilimumab in the first year of Pharmaceutical Benefits Scheme listing. Methods All unresectable stage IIIc / IV metastatic melanoma patients treated with at least one dose of ipilimumab therapy in Australia from the PBS listing date to a time point 12 months later (i.e. from 1-Aug-2013 to 31-Jul-2014) were invited to participate. Overall survival at 2 years post treatment initiation was measured, with Cox regression analysis used to examine the relationship between survival and patient baseline characteristics. Results The evaluable population (910 patients) was on average 63.3 years old, male (70.1%) and treated in a public hospital (64.4%) in an urban area (76.5%). The majority of patients were treatment naïve (63.3%), did not have brain metastases (71.1%), and were classified as ECOG performance status 0 or 1 (90.4%). The 2 year overall survival rate was conservatively calculated to be at least 23.9% and potentially as high as 34.2%. A significant difference in overall survival at 2 years was demonstrated across the categories of ECOG performance status (p < 0.0001), M-status (p = 0.0005) and treatment status (p = 0.0114). No statistical difference in survival rate was observed when examining brain metastases vs no brain metastases (p = 0.2622), treatment at private vs public hospitals (p = 0.7601) nor treatment in the urban vs rural setting (p = 0.5048). Conclusions The 2 year overall survival rate for all patients receiving PBS subsidised ipilimumab in Australia from the first year Pharmaceutical Benefits Scheme cohort is estimated to be between 23.9% and 34.2%, which is higher than the 23.5% observed in the key ipilimumab registrational trial. Results and learnings from the ipilimumab ‘managed entry scheme’ illustrate that early access with the promise of future evidence to confirm a medicine’s cost-effectiveness can work, but needs to be carefully considered, constructed and managed