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Biomedical subjects

J Hutton

Publications and source records attributed to J Hutton.

At least 19 recordsLinked to original sources
PubMed2002

Cost effectiveness of eptifibatide in acute coronary syndromes; an economic analysis of Western European patients enrolled in the PURSUIT trial. The Platelet IIa/IIb in unstable Angina: Receptor Suppression Using Integrilin Therapy.

AIMS: To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infarction without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial. METHODS AND RESULTS: Health care resources were collected for the Western European PURSUIT trial patients (n=3697). Unit costs for major resources were developed within six countries using a consistent bottom-up methodology. Resource consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial. Eptifibatide was estimated to cost 524 Euros per treatment. Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios. Additionally, cost per death and non-fatal myocardial infarction at 30 days was calculated. Sensitivity analyses were conducted on the discount rate and resource consumption. Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3% discount. Using resource consumption based on countries with low coronary arteriography rates, the cost per year of life saved was between 3329 Euros and 10 079 Euros. Using resource consumption based on high coronary arteriography rate countries, the cost per year of life saved was between 17 089 Euros and 24 099 Euros. Assuming no difference in treatment costs except for the addition of eptifibatide, the incremental cost per year of life saved was 23 818 Euros. CONCLUSIONS: Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infarction at 30 days, which was sustained at 6 months. Long-term projections indicate a modest increase in survival in eptifibatide patients. These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use.

Acute Disease↗
PubMed2001

A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma.

BACKGROUND: Endoscopic ultrasound (EUS) may be used for preoperative staging of gastro-oesophageal carcinoma but performance values given in the literature differ. AIMS: To identify and synthesise findings from all articles on the performance of EUS in tumour, node, metastasis (TNM) staging of gastro-oesophageal carcinoma. SOURCE: Published and unpublished English language literature, 1981-1996. METHODS: Data on the staging performance of EUS were retrieved and evaluated. Summary receiver operator characteristic methodology was used for synthesis, and a summary estimate of performance, Q*, obtained. Multiple regression analysis was used to assess study validity and investigate reasons for differences in performance. RESULTS: Twenty seven primary articles were assessed in detail. Thirteen supplied results for staging oesophageal cancer, 13 for gastric cancer, and four for cancers at the gastro-oesophageal junction. For gastric T staging, Q*=0.93 (95% confidence interval (CI) 0.91-0.95) and for oesophageal T staging, Q*=0.89 (95% CI 0.88-0.92). For gastro-oesophageal T staging, including cancers at the gastro-oesophageal junction, Q*=0.91 (95% CI 0.89-0.93). Inclusion of cases with non-traversable stenosis was found to slightly reduce staging performance. For N staging, Q*=0.79 (95% CI 0.75-0.83). In articles that compared EUS directly with incremental computed tomography, EUS performed better. None of the variables assessed in the regression analysis was significant using a Bonferroni correction. Three variables (anatomical location, traversability, and blinding) showed strong relationships for future research and validation. CONCLUSIONS: EUS is highly effective for discrimination of stages T1 and T2 from stages T3 and T4 for primary gastro-oesophageal carcinomas. The failure rate of EUS from non-traversability of a stenotic cancer may be a limitation in some patient groups.

Confidence Intervals↗
PubMed2001

Treatment pathways, resource use and costs in the management of small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) represents about 20% of primary lung tumours and the costs associated with the management of SCLC can be significant. The main objective of this study was to obtain information on current patterns of care and associated resource use and costs for patients with SCLC from initial diagnosis and treatment phase, throughout disease progression and terminal care. METHODS: A 4 year retrospective patient chart analysis (1994-7) was conducted on a consecutive series of 109 patients diagnosed with SCLC in two Newcastle hospitals. For this consecutive series of patients all details about care received including tests and procedures, treatment, and medication from diagnosis till death were recorded. Pathways of care and forms were designed to enable resource use to be captured for different disease phases. Unit costs were determined from a variety of sources including the Newcastle Hospitals NHS Trust Finance Department and the British National Formulary. RESULTS: The average total cost per patient calculated for the full cohort of 109 patients was pound 11,556. Initial treatment was the most resource use intensive constituting 48.2% of the total cost. The major cost element throughout all disease phases was hospitalisation. Twenty eight percent of the total costs of care occur after recurrence of the disease until death, of which 73% are generated by terminal care. CONCLUSION: The results of this retrospective medical chart analysis show that the costs of care of SCLC are considerable, although the variability between patients in terms of the type and quantity of resource use is very high. Analyses such as this provide a useful insight into resources used in actual clinical practice.

Aged↗
PubMed2001

A comparison of the costs and survival of hospital-admitted stroke patients across Europe.

BACKGROUND AND PURPOSE: Policy makers require evidence on the costs and outcomes of different ways of organizing stroke care. This study compared the costs and survival of different ways of providing stroke care. METHODS: Hospitalized stroke patients from 13 European centers were included, with demographic, case-mix, and resource use variables measured for each patient. Unit costs were collected and converted into US dollars using the purchasing power parity (PPP) index. Cox and linear regression analyses were used to compare survival and costs between the centers adjusting for case mix. RESULTS: A total of 1847 patients were included in the study. After case-mix adjustment, the mean predicted costs ranged from $466 [95% CI 181 to 751] in Riga (Latvia) to $8512 [7696 to 9328] in Copenhagen (Denmark), which reflected differences in unit costs, and resource use. The mean length of hospitalization ranged from 8.3 days in Menorca (Spain) to 36.8 days in Turku B (Finland). In the 3 Finnish centers at least 80% of patients were admitted to wards providing organized stroke care, which was not provided at the centers in Almada (Portugal), Menorca, or Riga. Patients in Turku A and Turku B were less likely to die than those in Riga, Warsaw (Poland), or Menorca. The adjusted hazard ratios were 0.18 [0.10 to 0.32] for Turku A, 0.18 [0.10 to 0.32] for Turku B, 0.68 [0.48 to 0.96] for Warsaw, and 0.56 [0.33 to 0.96] for Menorca, all compared with Riga. CONCLUSIONS: The cost of stroke care varies across Europe because of differences in unit costs, and resource use. Further research is needed to assess which ways of organizing stroke care are the most cost-effective.

Aged↗
PubMed2001

Developing guidance for budget impact analysis.

The role of economic evaluation in the efficient allocation of healthcare resources has been widely debated. Whilst economic evidence is undoubtedly useful to purchasers, it does not address the issue of affordability which is an increasing concern. Healthcare purchasers are concerned not just with maximising efficiency but also with the more simplistic goal of remaining within their annual budgets. These two objectives are not necessarily consistent. This paper examines the issue of affordability, the relationship between affordability and efficiency and builds the case for why there is a growing need for budget impact models to complement economic evaluation. Guidance currently available for such models is also examined and it is concluded that this guidance is currently insufficient. Some of these insufficiencies are addressed and some thoughts on what constitutes best practice in budget impact modelling are suggested. These suggestions include consideration of transparency, clarity of perspective, reliability of data sources, the relationship between intermediate and final end-points and rates of adoption of new therapies. They also include the impact of intervention by population subgroups or indications, reporting of results, probability of re-deploying resources, the time horizon, exploring uncertainty and sensitivity analysis, and decision-maker access to the model. Due to the nature of budget impact models, the paper does not deliver stringent methodological guidance on modelling. The intention was to provide some suggestions of best practice in addition to some foundations upon which future research can build.

Budgets↗
PubMed2001

Cost effectiveness of treatment options in advanced breast cancer in the UK.

OBJECTIVE: To compare clinical and economic study data for docetaxel, paclitaxel and vinorelbine in the treatment of anthracycline-resistant advanced breast cancer. STUDY DESIGN AND METHODS: A Markov decision-analysis model to simulate the clinical course of a 'typical' patient with advanced breast cancer during salvage chemotherapy was updated with response rates and adverse effect rates from phase III clinical trial data for docetaxel, paclitaxel and vinorelbine. Costs were taken from UK national databases and hospitals. Utilities were estimated from 30 oncology nurses in the UK using the standard gamble method. PERSPECTIVE: National Health Service. RESULTS: When compared with other chemotherapeutic agents, docetaxel has been shown to increase response rate, time to progression and survival in patients with advanced breast cancer. In the base-case analysis, the incremental cost-utility ratio for docetaxel versus paclitaxel was pound1995 per quality-adjusted life year (QALY) gained (1998 values). The incremental cost-utility ratio for docetaxel versus vinorelbine was pound14 055 per QALY gained. In the comparison with vinorelbine, docetaxel provided the equivalent of an additional 92 days of perfect health. Sensitivity analyses confirmed the robustness of the model and the validity of the base-case analysis results. Even in the worst case scenarios, docetaxel remained cost effective compared with paclitaxel and vinorelbine. CONCLUSIONS: These findings support the use of the taxoids, notably docetaxel, in the management of advanced breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen.

Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells in genetically susceptible individuals. Growing evidence suggests that genetically determined variation in the expression of self-antigens in thymus may affect the shaping of the T-cell repertoire and susceptibility to autoimmunity. For example, both allelic variation and parent-of-origin effects influence the thymic expression of insulin (a known type 1 diabetes autoantigen), and insulin gene transcription levels in thymus inversely correlate with susceptibility in both humans and transgenic models. It is unclear why patients lose tolerance to IA-2 (insulinoma-associated tyrosine phosphatase-like protein, or islet cell antigen 512 [ICA512]), especially because IA-2 polymorphisms are not associated with type 1 diabetes. We report that alternative splicing determines differential IA-2 expression in islets compared with thymus and spleen. Islets express full-length mRNA and two alternatively spliced transcripts, whereas thymus and spleen exclusively express an alternatively spliced transcript lacking exon 13. This encodes for the transmembrane (TM) and juxta-membrane (JM) domains that comprise several type 1 diabetes target epitopes, supporting the concept that tolerance to IA-2 epitopes not expressed in lymphoid organs may not be achieved. We propose differential splicing as a regulatory mechanism of gene expression playing a permissive role in the development of autoimmune responses to IA-2. Our findings also show that candidate gene expression studies can help in dissecting the complex genetic determinants of a multifactorial disease such as type 1 diabetes.

Adult↗
PubMed2000

Identifying studies for systematic reviews. An example from medical imaging.

OBJECTIVES: To determine if published figures on the proportion of articles included in systematic reviews and identified in electronic databases are applicable to an example from medical imaging. METHODS: A systematic review was performed. Additionally, sensitivity and precision of a MEDLINE search were compared with values from three published searches, each customized for a specific field. RESULTS: All articles included in the systematic review were in electronic databases. The MEDLINE search had low precision compared with searches in other fields. CONCLUSIONS: In a specific area of medical imaging, electronic databases, including MEDLINE, are reliable sources of articles.

Bibliometrics↗
PubMed2000

A comparison of the cost-effectiveness of stroke care provided in London and Copenhagen.

OBJECTIVES: This study compared the relative cost-effectiveness of stroke care provided in London and Copenhagen. METHODS: Hospitalized stroke patients at centers in London (1995-96) and Copenhagen (1994-95) were included. Each patient's use of hospital and community health services was recorded for 1 year after stroke. Center-specific unit costs were collected and converted into dollars using the Purchasing Power Parity Index. An incremental cost-effectiveness ratio (ICER) was calculated comparing a Copenhagen model of stroke care to a London model, using regression analysis to adjust for case-mix differences. RESULTS: A total of 625 patients (297 in Copenhagen, 328 in London) were included in the analysis. Most patients in London (85%) were admitted to general medical wards, with 26% subsequently transferred to a stroke unit. In Copenhagen, 57% of patients were directly admitted to a stroke or neurology unit, with 23% then transferred to a separate rehabilitation hospital. The average length of total hospital stay was 11 days longer in Copenhagen. Patients in Copenhagen were less likely to die than those in London; for patients with cerebral infarction the hazard ratio after case-mix adjustment was 0.53 (95% CI from 0.35 to 0.80). However, a lower proportion of patients with hemorrhagic stroke died in London. The ICER of using the Copenhagen compared with the London model of care ranged from $21,579 to $37,444 per life-year gained for patients with cerebral infarctions. CONCLUSIONS: The ICERs of the Copenhagen compared with the London model of care were within a range generally regarded as cost-effective.

Aged↗
PubMed2000

Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

BACKGROUND: Intravascular ultrasound (IVUS) is the generic name for any ultrasound technology used in vivo within the blood vessels. More specifically, intracoronary ultrasound enables imaging of the coronary arteries from within the lumen. This review concentrates on the role of intracoronary ultrasound as an adjunct to interventional cardiology. OBJECTIVES: (1) To identify the literature on IVUS for guiding coronary interventions, and to synthesise evidence about outcomes compared with outcomes when IVUS guidance has not been used. (2) To use this evidence, together with other information about costs and outcomes, to model the cost effectiveness of IVUS guidance. (3) To synthesise the evidence on the reproducibility of measurements of cross-sectional area made using IVUS. METHODS DATA SOURCES: (1) Electronic searches of MEDLINE, EMBASE, Science Citation Index, Index to Scientific and Technical Proceedings, Engineering Compendex, Engineering Page One, Cochrane Library, Inside (British Library), 1990-98. (2) Contacting experts and centres of expertise, 1990-99. (3) Internet search, 1990-99. METHODS STUDY SELECTION: Studies of IVUS-guided coronary interventions performed on humans were included in the review. Non-English language studies were also included when they covered IVUS-guided stenting or angioplasty. Control evidence regarding outcomes without IVUS guidance was sought only from randomised controlled trials (RCTs). Studies investigating the reproducibility of measurements of cross-sectional area were included only if the results were expressed in terms of the mean and standard deviation of paired differences. METHODS DATA EXTRACTION: Checklists that covered study details, patient characteristics and results were completed independently by three reviewers. Consensus was reached on any disagreements. Local data were gathered on the costs of IVUS-guided stenting. METHODS DATA SYNTHESIS: Overall event rates were calculated by pooling patient results from the included studies. A decision-analytic model was used to combine information from the literature with cost estimates, in order to predict cost-effectiveness in terms of cost per restenosis event avoided by the use of IVUS guidance. The analysis was performed from the perspective of the healthcare provider. Sensitivity analysis was undertaken. A simple extrapolation was made to long-term outcome so that cost-utility (using quality-adjusted life years (QALYs)) could be estimated. The minimum detectable change in cross-sectional area was estimated from the reproducibility results. RESULTS: Only one study on IVUS-guided angioplasty satisfied the inclusion criteria, and there were no studies on IVUS-guided atherectomy or other IVUS-guided interventions that satisfied the inclusion criteria. Of the 15 articles on IVUS-guided stenting that satisfied the inclusion criteria, seven presented data on outcomes at 6 months post-intervention. The angiographic restenosis rate was 16 +/- 1%. This compared with 24 +/- 2% derived from five articles on stenting without IVUS guidance. Data for follow-up periods longer than 6 months were presented in only two studies. Data from a total of five studies were included in the decision-analytic model. The cost per restenosis event avoided was 1545 pound sterling. After extrapolation to long-term outcome, the calculated cost per QALY was 6438 pound sterling. The baseline QALY gain was only 0.03 years. Sensitivity analysis resulted in large differences between the best- and worst-case scenarios, for example, from a saving of 5000 pound sterling to a cost of 24,000 pound sterling restenosis event avoided. The smallest changes in cross-sectional area that could be measured were 1.6 mm2 by a single observer and 1.9 mm2 by different observers. CONCLUSIONS: Implications for healthcare: The evidence available is too weak for there to be any reliable implications for clinical practice. (ABSTRACT TRUNCATED)

Algorithms↗
PubMed1999

The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials.

Recent cases of fraud in clinical trials have attracted considerable media attention, but relatively little reaction from the biostatistical community. In this paper we argue that biostatisticians should be involved in preventing fraud (as well as unintentional errors), detecting it, and quantifying its impact on the outcome of clinical trials. We use the term 'fraud' specifically to refer to data fabrication (making up data values) and falsification (changing data values). Reported cases of such fraud involve cheating on inclusion criteria so that ineligible patients can enter the trial, and fabricating data so that no requested data are missing. Such types of fraud are partially preventable through a simplification of the eligibility criteria and through a reduction in the amount of data requested. These two measures are feasible and desirable in a surprisingly large number of clinical trials, and neither of them in any way jeopardizes the validity of the trial results. With regards to detection of fraud, a brute force approach has traditionally been used, whereby the participating centres undergo extensive monitoring involving up to 100 per cent verification of their case records. The cost-effectiveness of this approach seems highly debatable, since one could implement quality control through random sampling schemes, as is done in fields other than clinical medicine. Moreover, there are statistical techniques available (but insufficiently used) to detect 'strange' patterns in the data including, but no limited to, techniques for studying outliers, inliers, overdispersion, underdispersion and correlations or lack thereof. These techniques all rest upon the premise that it is quite difficult to invent plausible data, particularly highly dimensional multivariate data. The multicentric nature of clinical trials also offers an opportunity to check the plausibility of the data submitted by one centre by comparing them with the data from all other centres. Finally, with fraud detected, it is essential to quantify its likely impact upon the outcome of the clinical trial. Many instances of fraud in clinical trials, although morally reprehensible, have a negligible impact on the trial's scientific conclusions.

Biometry↗
PubMed1999

Assessing the potential cost effectiveness of pneumococcal vaccines in the US: methodological issues and current evidence.

Pneumococcal disease imposes a notable burden on society, particularly in the elderly and those at high risk of complications. Preventive strategies, especially vaccines, are possibly the best way to minimise such a burden. We report on the conduct and results of a preliminary exploratory review of the economics of pneumococcal vaccines in the elderly population in the US. After extensive electronic and manual searches, we identified 5 economic evaluations that fulfilled our study criteria. From these we extracted key economic variables and assessed the quality of the studies against the criteria in the checklist for authors and peer reviewers of economic submissions to the British Medical Journal. We found variation of quality of study design such as a lack of clarity in the treatment of indirect costs and a failure to present the data on resource use and costs separately. We carried out supplementary searches to assess the quality of the epidemiological and efficacy evidence upon which the economic models were based and found contradictory evidence of effects of the vaccines, which included the results of 2 meta-analyses. One of these meta-analyses reported that retrospective studies, especially case-control studies, tended to underestimate the protective efficacy of the vaccine by as much as 20%. We believe that a well resourced Cochrane review of the clinical evidence of the effects of the vaccines should be carried out before any further economic studies. No more economic modelling should take place before such a review is undertaken.

Bacterial Vaccines↗
PubMed1999

Cost-effectiveness analysis of antiplatelet therapy in the prevention of recurrent stroke in the UK. Aspirin, dipyridamole and aspirin-dipyridamole.

OBJECTIVES: To evaluate the cost effectiveness from a UK health and social services perspective of antiplatelet therapies tested in the Second European Stroke Prevention Study (ESPS-2) in preventing recurrent stroke. To demonstrate the value of modelling studies in this area. DESIGN AND SETTING: A decision-analytic model was developed to evaluate health outcomes and associated costs. Sources of data for efficacy, adverse events, background event risks, disability and mortality were ESPS-2, the Oxfordshire Community Stroke Project and UK national statistics. Published national unit costs were applied to clinician panel estimates of resource use for acute stroke, rehabilitation and long term care. Outcome measures were strokes or disabled life-years averted, and disability-free, stroke-free or quality-adjusted life-years gained. PATIENTS AND INTERVENTIONS: 30-day survivors of ischaemic stroke treated with low dose aspirin, modified-release dipyridamole; the coformulation of low dose aspirin plus modified-release dipyridamole, or no antiplatelet therapy. MAIN OUTCOME MEASURES AND RESULTS: The model predicted that over 5 years the coformulation prevented 29 more strokes than aspirin alone per 1000 patients, at an additional cost of 1900 Pounds per stroke averted (1996 values). Over 5 years, each antiplatelet therapy was cost saving compared with no therapy. Results were sensitive to the cost of acute care, the cost of long term care of disabled stroke survivors, the effectiveness of therapy and the background risk of recurrent stroke. In sensitivity analyses, the cost effectiveness did not exceed 7000 Pounds per stroke averted or 11,000 Pounds per quality-adjusted life-year (QALY) gained, except when varying the effectiveness parameter. CONCLUSIONS: Application of a decision-analytic model to the results of ESPS-2 indicated that first-line therapy with the coformulation of modified-release dipyridamole and low dose aspirin to patients with a previous ischaemic stroke is likely to generate significant health benefits at modest extra costs to health and social services. The extra costs of treatment are balanced by the savings in future costs of acute care and long term care of the disabled. Future economic evaluations in this area should pay particular attention to the cost perspective, the duration of analysis, the selection of trials from which effectiveness data are derived, and the impact of the pooling of outcome events with potentially different economic consequences.

Aged↗