Adrian Bagust

Dynamics of bed use in accommodating emergency admissions: stochastic simulation model

Abstract Objective: To examine the daily bed requirements arising from the flow of emergency admissions to an acute hospital, to identify the implications of fluctuating and unpredictable demands for emergency admission for the management of hospital bed capacity, and to quantify the daily risk of insufficient capacity for patients requiring immediate admission. Design: Modelling of the dynamics of the hospital system, using a discrete-event stochastic simulation model, which reflects the relation between demand and available bed capacity. Setting: Hypothetical acute hospital in England. Subjects: Simulated emergency admissions of all types except mental disorder. Main outcome measures: The risk of having no bed available for any patient requiring immediate admission; the daily risk that there is no bed available for at least one patient requiring immediate admission; the mean bed occupancy rate. Results: Risks are discernible when average bed occupancy rates exceed about 85%, and an acute hospital can expect regular bed shortages and periodic bed crises if average bed occupancy rises to 90% or more. Conclusions: There are limits to the occupancy rates that can be achieved safely without considerable risk to patients and to the efficient delivery of emergency care. Spare bed capacity is therefore essential for the effective management of emergency admissions, and its cost should be borne by purchasers as an essential element of an acute hospital service. Key messages Acute hospitals which operate at bed occupancy levels of 90% or more face regular bed crises, with the associated risks to patients Management interventions should focus on measures with long term benefits to counteract the growth trend in demand for admission Many initiatives have only a short term effect; they briefly delay the worst effects but do not address the growing mismatch between supply and demand Evaluating management interventions year on year at a single hospital is futile—any effects are swamped by random variations

The projected health care burden of Type 2 diabetes in the UK from 2000 to 2060

Aims/hypothesis To predict the incidence and prevalence of Type 2 diabetes in the UK, the trends in the levels of diabetes‐related complications, and the associated health care costs for the period 2000–60.

The Average Body Surface Area of Adult Cancer Patients in the UK: A Multicentre Retrospective Study

The majority of chemotherapy drugs are dosed based on body surface area (BSA). No standard BSA values for patients being treated in the United Kingdom are available on which to base dose and cost calculations. We therefore retrospectively assessed the BSA of patients receiving chemotherapy treatment at three oncology centres in the UK between 1st January 2005 and 31st December 2005. A total of 3613 patients receiving chemotherapy for head and neck, ovarian, lung, upper GI/pancreas, breast or colorectal cancers were included. The overall mean BSA was 1.79 m2 (95% CI 1.78–1.80) with a mean BSA for men of 1.91 m2 (1.90–1.92) and 1.71 m2 (1.70–1.72) for women. Results were consistent across the three centres. No significant differences were noted between treatment in the adjuvant or palliative setting in patients with breast or colorectal cancer. However, statistically significant, albeit small, differences were detected between some tumour groups. In view of the consistency of results between three geographically distinct UK cancer centres, we believe the results of this study may be generalised and used in future costings and budgeting for new chemotherapy agents in the UK.

Accounting for Noncompliance in Pharmacoeconomic Evaluations

Noncompliance with prescribed drug regimens is a widespread phenomenon which results in decreased efficacy and is often associated with increased medical expenditures. Despite this, economic evaluations based on decision-analytic models rarely incorporate noncompliance to allow for the differences in compliance observed between controlled clinical trials and routine clinical practice.This review examines the issues relating to the measurement of noncompliance, and the clinical and economic consequences of noncompliant drug taking behaviour. In order to fully appreciate the clinical (and therefore the economic) consequences of noncompliance, a detailed understanding of the type of noncompliance, the pharmacokinetic and pharmacodynamic properties of the drug and the pathophysiological processes of the diseases being treated is required. These are described in detail, and a classification of drug-disease combinations according to the potential economic impact of the varying forms of noncompliance is set out.Issues are raised to highlight the need for improved modelling of the impact of noncompliance, and to this end, recommendations are made for future analyses. The main points are that compliance should be defined clearly, distinguishing between the various forms of noncompliance, that the assumptions relating to the health status of noncompliers should be explicit and robust, and that sensitivity analysis should be applied appropriately to ascertain the impact of noncompliance on the cost-effectiveness of drug therapies.

Evaluating the performance of the Framingham risk equations in a population with diabetes

Aims  The Framingham risk equations are widely used to estimate risk of coronary heart disease (CHD). The purpose of this study was to evaluate the reliability of these equations in predicting CHD risk in people with diabetes and the reliability of using imputed mean HDL‐cholesterol values.

Cost-effectiveness of flexible intensive insulin management to enable dietary freedom in people with Type 1 diabetes in the UK

Aims  To determine the cost‐effectiveness of a structured treatment and teaching programme (STTP) combining dietary freedom with insulin adjustment for Type 1 diabetes.

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

OBJECTIVE To determine whether testing for cytochrome P450 (CYP) polymorphisms in adults entering antipsychotic treatment for schizophrenia leads to improvement in outcomes, is useful in medical, personal or public health decision-making, and is a cost-effective use of health-care resources. DATA SOURCES The following electronic databases were searched for relevant published literature: Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA) Registry and the Centre for Health Economics website. In addition, publicly available information on various genotyping tests was sought from the internet and advisory panel members. REVIEW METHODS A systematic review of analytical validity, clinical validity and clinical utility of CYP testing was undertaken. Data were extracted into structured tables and narratively discussed, and meta-analysis was undertaken when possible. A review of economic evaluations of CYP testing in psychiatry and a review of economic models related to schizophrenia were also carried out. RESULTS For analytical validity, 46 studies of a range of different genotyping tests for 11 different CYP polymorphisms (most commonly CYP2D6) were included. Sensitivity and specificity were high (99-100%). For clinical validity, 51 studies were found. In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found. The only other significant finding linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the inclusion criteria for clinical utility. One economic evaluation assessing the costs and benefits of CYP testing for prescribing antidepressants and 28 economic models of schizophrenia were identified; none was suitable for developing a model to examine the cost-effectiveness of CYP testing. CONCLUSIONS Tests for determining genotypes appear to be accurate although not all aspects of analytical validity were reported. Given the absence of convincing evidence from clinical validity studies, the lack of clinical utility and economic studies, and the unsuitability of published schizophrenia models, no model was developed; instead key features and data requirements for economic modelling are presented. Recommendations for future research cover both aspects of research quality and data that will be required to inform the development of future economic models.

Erlotinib monotherapy for the maintenance treatment of non-small cell lung cancer after previous platinum-containing chemotherapy: a NICE single technology appraisal.

The UK National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of erlotinib (Roche) to submit evidence for the clinical and cost effectiveness of erlotinib as monotherapy for the maintenance treatment of patients with non-small cell lung cancer (NSCLC) and stable disease following previous treatment with four cycles of platinumcontaining therapy. The Liverpool Reviews and Implementation Group(LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal.The ERG reviewed the clinical- and cost-effectiveness evidence in two stages and in accordance with the decision problem defined by NICE. The analysis of the submitted models assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. Analysis also included reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to have substantial impact on the base-case cost-effectiveness results.Clinical evidence was derived from a multi-centre, double-blind, randomized, phase III study designed to address the overall population of NSCLC patients. Outcomes included progression-free survival (PFS) and overall survival (OS). The recruited population was mainly from outside of Western Europe and no patients in the pivotal trial had received pemetrexed as a firstline therapy, which is now accepted clinical practice in the UK. The evidence considered in this article includes only the population for whom marketing authorizations has been received–that is, patients with stable disease following first-line therapy.The trial reported a small but statistically significant increase in both PFS and OS in patients with stable disease receiving erlotinib compared with placebo. However, no significant difference was identified in OS when patients with non-squamous disease and stable disease were considered as a subgroup.The economic evidence was focussed on the ERG’s assessment of three economic models that related to patients with stable disease and compared erlotinib with placebo in the squamous and non-squamous populations and erlotinib with pemetrexed in the non-squamous population. The incremental cost-effectiveness ratios (ICERs) reported by the manufacturer were £39 936 per QALY gained (stable disease, all); £35 491 per QALY gained (stable disease, squamous); and £40 020 per QALY gained (stable disease, nonsquamous). In comparison with pemetrexed, in the cases where erlotinib was considered to be superior or equivalent, erlotinib dominated. In the cases where erlotinib was considered to be slightly inferior, then the ICERs ranged between £91 789 and £511 351 per QALY gained; these ICERs appear in the south-west corner of a cost-effectiveness plane, i.e. erlotinib is cheaper but less effective than pemetrexed.The ERG recalculated the base-case cost-effectiveness results in the manufacturer’s submission, considering nine key areas where corrections and/or adjustments were required, related to time horizon, discounting logic, costs of erlotinib and pemetrexed, cost of second-line chemotherapy, unit costs, utility values, PFS and OS. This resulted in ERG-revised ICERs for the stable disease squamous population of £44 812 per QALY gained, in the stable disease non-squamous population of £68 120 per QALY gained, and, when erlotinib was compared with pemetrexed, the result was £84 029 per QALY gained. All values were above NICE’s perceived willingness-to-pay threshold. After the second Appraisal Committee meeting, the Committee did not recommend the use of erlotinib in this patient population.

Cetuximab for Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck: A NICE Single Technology Appraisal

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of cetuximab (Merck Serono) to submit evidence for the clinical and cost effectiveness of cetuximab in combination with platinumbased chemotherapy (CTX) for the treatment of patients with recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN) according to the Institute’s Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG).This article summarizes the ERGs review of the evidence submitted by the manufacturer.Asummary of theAppraisal Committee (AC) decision is provided.The ERG reviewed the clinical evidence in accordance with the decision problem defined by NICE. The analysis of the submitted model assessed the appropriateness of the manufacturers approach to modelling the decision problem, the reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to impact substantially on the base-case cost-effectiveness results.Clinical-effectiveness evidence was derived from a single randomized controlled trial (RCT). Results presented for clinical outcomes were strongly supportive of benefits resulting from the use of cetuximab. Cetuximab + platinum-based CTX with 5 fluorouracil (5-FU) extended median overall survival (OS) from 7.4 months in the CTX group to 10.1 months in the cetuximab +CTX group. Median progression-free survival rose from 3.3months to 5.6 months, best overall response to therapy increased from 19.5% to 35.6%, disease control rate rose from60%to 81.1%andmedian time to treatment failure was 4.8 months compared with 3.0 months.Exploratory subgroup analyses indicated significant OS benefits in 11 of 16 pre-planned analyses.The ERG identified a number of issues relating to the clinical-effectiveness results: consideration was limited to first-line use of cetuximab; patients in the trial were younger and fitter than those presenting in UK clinical practice; there was no evidence of survival advantage for patients with metastatic disease; there was no evidence of effectiveness in patients not cetuximabnaive; and the quality-of-life data were poor.The submitted incremental cost-effectiveness ratio was considerably above the NICE threshold. The ERG questioned the submitted economic model on a number of grounds: the rationale for creating an economic model rather than direct analysis of trial data; the use of Weibull functions for survival models; inaccurate CTX costs; selection of health state utilities; inaccurate unit costs; and lack of mid-cycle correction. After amending the model, the ERG considered the use of cetuximab to be not cost effective for NICE at any price.The AC concluded that cetuximab in combination with platinum-based CTX should not be recommended for the treatment of patients with recurrent and/or metastatic SCCHN. Patients already receiving this treatment for this indication should have the option to continue treatment until they and their clinician consider it appropriate to stop. This was the first appraisal to consider the end-of-life medicines criteria introduced by NICE in January 2009.

Population screening for lung cancer using computed tomography, is there evidence of clinical effectiveness? A systematic review of the literature

Lung cancer is the leading cause of death among all cancer types in the UK, killing approximately 34 000 people per year. By the time symptoms develop, the tumour is often at an advanced stage and the prognosis is bleak. Treatment at a less advanced stage of disease by surgical resection has been shown to substantially reduce mortality. Screening would be attractive if it could detect presymptomatic lung cancer at a stage when surgical intervention is feasible but has been the subject of scientific debate for the past three decades. The aim of this review was to examine the current evidence on the clinical effectiveness of screening for lung cancer using computed tomography. A systematic literature review searching 15 electronic databases and Internet resources from 1994 until December 2004/January 2005 was carried out. Information was summarised narratively. A total of 12 studies of computed tomography screening for lung cancer were identified including two RCTs and 10 studies of screening without comparator groups. The two RCTs were of short duration (1 year). None examined the effect of screening on mortality compared with no screening. The proportion of people with abnormal computed tomography findings varied widely between studies (5–51%). The prevalence of lung cancer detected was between 0.4% and 3.2% (number needed to screen to detect one lung cancer  = 31 to 249). Incidence rates of lung cancer were lower (0.1–1%). Among the detected tumours, a high proportion were stage I or resectable tumours, 100% in some studies. Currently, there is insufficient evidence that computed tomography screening is clinically effective in reducing mortality from lung cancer.