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Biomedical subjects

John Brazier

Publications and source records attributed to John Brazier.

At least 19 recordsLinked to original sources
PubMed2007

A comparison of patient and population values for health states in varicose veins patients.

Cost utility analyses typically incorporate preferences based upon the mean values for health states generated from a sample of the general population. The main argument for using general population values rests upon the premise that in a publicly funded health care system the main objective of the health care system is a societal one, namely to maximise health subject to equity concerns. Alternatively, it can be argued that patients themselves should be asked to value their own health state given that they have first hand experience of the state being valued. This paper investigates the relationship between patient and general population values within the context of a randomised controlled trial to compare alternative treatments for varicose veins. It was found that patients' own health valuations tended to be higher than those of the general population sample. The results from this study have important implications for economic evaluation. The incremental QALY gain for patients receiving treatment for moderate varicose veins would be almost halved if patients' own values were used to estimate QALYs in contrast to the general population values. The results also suggest that the variant of elicitation technique may be more important than the source of those values in revealing discrepancies.

Adult↗
PubMed2007

Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study.

UNLABELLED: A 3-year prospective, randomized, placebo-controlled trial of oral clodronate 800 mg showed that the incidence of clinical fractures was decreased by 20% in 5596 elderly women unselected for osteoporosis. The effect occurred in the absence of systematic calcium and vitamin D supplementation and was observed across a wide range of BMDs. INTRODUCTION: To date, most studies with bisphosphonates have reported on their use in individuals selected to be at high risk for fracture usually by the presence of low BMD or a prior fragility fracture, usually of the spine. We wished to determine the effect of the bisphosphonate, clodronate, on the rate of fractures in women > or =75 years of age living in the community. MATERIALS AND METHODS: Women > or =75 years of age living in the general community in South Yorkshire and North Derbyshire, identified from general practice registers, were recruited by letter of invitation to a randomized, double-blind, controlled trial of 800 mg oral clodronate (Bonefos) or matching placebo daily over 3 years. The main outcomes were the incidences of hip and any clinical fracture. RESULTS: Of the 5579 elderly women included in the intention-to-treat analysis of efficacy, 114 had a new hip fracture during the 3-year treatment phase: 56 (2.0%) women in the clodronate group and 58 (2.1%) women in the placebo group (hazard ration [HR], 1.02; 95% CI, 0.71-1.47). Clodronate did, however, decrease the incidence of any clinical fracture by 20% (264 women [9.5%] versus 337 [12.1%] in the placebo group; HR, 0.80; 95% CI, 0.68-0.94). The incidence of osteoporosis-associated nonhip fractures was also significantly decreased by 29% (5.2% versus 7.4%; HR, 0.71; 95% CI, 0.57-0.87). The ability of clodronate to reduce the risk of osteoporotic fracture was independent of baseline BMD, but the number needed-to-treat was lower in the presence of osteoporosis. CONCLUSIONS: Oral daily clodronate can prevent fractures without significant adverse effects in elderly women living in the general community. The effect on hip fracture risk is not significant, but an effect similar to that at other nonvertebral sites cannot be excluded. This study suggests that antiresorptive therapies can reduce fracture incidence in high-risk individuals even in the presence of a normal or osteopenic BMD.

Aged↗
PubMed2006

A pilot Internet "value of health" panel: recruitment, participation and compliance.

OBJECTIVES: To pilot using a panel of members of the public to provide preference data via the Internet METHODS: A stratified random sample of members of the general public was recruited and familiarized with the standard gamble procedure using an Internet based tool. Health states were periodically presented in "sets" corresponding to different conditions, during the study. The following were described: Recruitment (proportion of people approached who were trained); Participation (a) the proportion of people trained who provided any preferences and (b) the proportion of panel members who contributed to each "set" of values; and Compliance (the proportion, per participant, of preference tasks which were completed). The influence of covariates on these outcomes was investigated using univariate and multivariate analyses. RESULTS: A panel of 112 people was recruited. 23% of those approached (n = 5,320) responded to the invitation, and 24% of respondents (n = 1,215) were willing to participate (net = 5.5%). However, eventual recruitment rates, following training, were low (2.1% of those approached). Recruitment from areas of high socioeconomic deprivation and among ethnic minority communities was low. Eighteen sets of health state descriptions were considered over 14 months. 74% of panel members carried out at least one valuation task. People from areas of higher socioeconomic deprivation and unmarried people were less likely to participate. An average of 41% of panel members expressed preferences on each set of descriptions. Compliance ranged from 3% to 100%. CONCLUSION: It is feasible to establish a panel of members of the general public to express preferences on a wide range of health state descriptions using the Internet, although differential recruitment and attrition are important challenges. Particular attention to recruitment and retention in areas of high socioeconomic deprivation and among ethnic minority communities is necessary. Nevertheless, the panel approach to preference measurement using the Internet offers the potential to provide specific utility data in a responsive manner for use in economic evaluations and to address some of the outstanding methodological uncertainties in this field.

Adolescent↗
PubMed2006

Using rank data to estimate health state utility models.

In this paper we report the estimation of conditional logistic regression models for the Health Utilities Index Mark 2 and the SF-6D, using ordinal preference data. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using ordinal data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that ordinal data have the potential to provide useful insights into community health state preferences. However, important questions remain.

Health Status Indicators↗
PubMed2006

Does the whole equal the sum of the parts? Patient-assigned utility scores for IBS-related health states and profiles.

The quality-adjusted life year (QALY) assumes that the value of a health state is linearly related to the time spent in it, which implies that the value of a health state is independent of the states which precede or follow it. Irritable bowel syndrome (IBS) is a suitable condition to test this assumption since it is subject to considerable fluctuations over time. Forty-nine IBS patients were asked to rate their own health using generic measures of health and a condition specific classification. They were then asked to value five IBS states and four profiles using a self-completed version of the standard gamble technique. The implied value of each profile was estimated using the QALY assumption of linearity over time and compared with the direct profile valuations. The directly elicited profile values suggest that reductions in the duration of IBS symptoms has less of an impact on the value of quality of life than would be implied by the QALY assumption of linearity over time, though the differences were small. There are a number of competing explanations for this finding, including possible sequence effects, quantity effects or time preference, or it might be due to gestalt effects resulting in a neglect of time spent in symptomatic states of health.

Costs and Cost Analysis↗
PubMed2006

Discounting and cost-effectiveness in NICE - stepping back to sort out a confusion.

Brouwer and colleagues [1] argue that the reasons for specifying an equal discount rate for health outcomes and costs in the recent guidance on methods of technology appraisal issued by the National Institute for Clinical Excellence (NICE) [2] is both opaque and wrong. They argue that a lower rate should apply to health outcomes like QALYs. It is also claimed that the guidance on discounting represents a step backwards, that is both inconsistent with current theoretical insights and will prejudice the outcome of cost-effectiveness studies of preventive interventions.The reasoning behind the use of equal discount rates for costs and health outcomes is indeed not well developed in the published guidance. Nor does it reflect the debate that underpinned the guidance. We therefore welcome the opportunity to explain more completely the rationale in the minds of the principal authors of the current guidance.

Academies and Institutes↗
PubMed2005

Comparison of valuation methods used to generate the EQ-5D and the SF-6D value sets.

An interview study with 101 members of public compared the protocols used in valuation studies for EQ-5D (using ranking, visual analogue scale, and time trade-off), and SF-6D (using ranking and standard gamble). Respondents were given one of the two protocols and asked to value four states each from EQ-5D and SF-6D. VAS scores suggest the narrower range of SF-6D values is partly attributable to the descriptive system; TTO values for milder states were higher than SG values; and the mean value for EQ-5D pits using TTO and SF-6D pits using SG were closer than across the two original valuation studies.

Health Status Indicators↗
PubMed2005

Mechanism of the Escherichia coli DNA T:G-mismatch endonuclease (Vsr protein) probed with thiophosphate-containing oligodeoxynucleotides.

The mechanism of the Escherichia coli DNA T:G mismatch endonuclease (Vsr) has been investigated using oligodeoxynucleotides substituted, at the scissile phosphate, with isomeric phosphorothioates and a 3'-phosphorothiolate. Binding and kinetic data with the phosphorothioates/phosphorothiolate indicate that the two magnesium ions, which constitute essential co-factors, are required to stabilise the extra negative charge developed on the phosphate as the transition state is formed. Additionally one of the magnesium ions serves to activate the leaving group (the non-bridging 3'-oxygen atom of the scissile phosphate) during the hydrolysis reaction. Stereochemical analysis, using the R(p) phosphorothioate isomer, indicates that Vsr carries out a hydrolytic reaction with inversion of stereochemistry at phosphorus, compatible with an in-line attack of water and a pentacovalent transition state with trigonal bipyramidal geometry. In conjunction with structures of Vsr bound to its products, these data allow the reconstruction of the enzyme-substrate complex and a comprehensive description of the hydrolysis mechanism.

Base Pairing↗
PubMed2005

Health state values for the HUI 2 descriptive system: results from a UK survey.

This paper reports the results of a study to estimate a statistical health state valuation model for a revised version of the Health Utilities Index Mark 2, using Standard Gamble health state preference data. A sample of 51 health states were valued by a sample of the 198 members of the UK general population. Models are estimated for predicting health state valuations for all 8000 states defined by the revised HUI2. The recommended model produces logical and significant coefficients for all levels of all dimensions in the HUI2. These coefficients appear to be robust across model specifications. This model performs well in predicting the observed health state values within the valuation sample and for a separate validation sample of health states. However, there are concerns over large prediction errors for two health states in the valuation sample. These problems must be balanced against concerns over the validity of using the VAS based health state valuation data of the original HUI2 valuation model.

Data Collection↗
PubMed2005

Probabilistic sensitivity analysis for NICE technology assessment: not an optional extra.

Recently the National Institute for Clinical Excellence (NICE) updated its methods guidance for technology assessment. One aspect of the new guidance is to require the use of probabilistic sensitivity analysis with all cost-effectiveness models submitted to the Institute. The purpose of this paper is to place the NICE guidance on dealing with uncertainty into a broader context of the requirements for decision making; to explain the general approach that was taken in its development; and to address each of the issues which have been raised in the debate about the role of probabilistic sensitivity analysis in general. The most appropriate starting point for developing guidance is to establish what is required for decision making. On the basis of these requirements, the methods and framework of analysis which can best meet these needs can then be identified. It will be argued that the guidance on dealing with uncertainty and, in particular, the requirement for probabilistic sensitivity analysis, is justified by the requirements of the type of decisions that NICE is asked to make. Given this foundation, the main issues and criticisms raised during and after the consultation process are reviewed. Finally, some of the methodological challenges posed by the need fully to characterise decision uncertainty and to inform the research agenda will be identified and discussed.

Cost-Benefit Analysis↗
PubMed2005

Control of DNA conformation using 3'-S-phosphorothiolate-modified linkages.

An in-depth study into the incorporation of multiple 3-S-phosphorothiolate modifications into oligodeoxynucleotides (ODNs) and their subsequent effect on ODN/DNA and ODN/RNA duplex stability. 3-S-Phosphorothiolate linkages increase the stability of ODN/RNA duplexes and decrease the stability of ODN/DNA duplexes.

DNA↗
PubMed2005

Should patients have a greater role in valuing health states?

Currently, health state values are usually obtained from members of the general public trying to imagine what the state would be like rather than by patients who are actually in the various states of health. Valuations of a health state by patients tend to vary from those of the general population, and this seems to be due to a range of factors including errors in the descriptive system, adaptation to the state and changes in internal standards. The question of whose values are used in cost-effectiveness analysis is ultimately a normative one, but the decision should be informed by evidence on the reasons for the differences. There is a case for obtaining better informed general population preferences by providing more information on what it is like for patients (including the process of adaptation).

Adaptation, Psychological↗
PubMed2005

What value health?: A review of health state values used in early technology assessments for NICE.

The objective of this article was to review the methods used to obtain quality-of-life (utility) weights reported in assessments carried out for the National Institute for Health and Clinical Excellence (NICE).The design of the review was a cross-sectional survey. Health technology assessment (HTA) reports published on the NICE website up to May 2003 were reviewed. Data were extracted on the following: the approach to utility estimation (direct or indirect), how health states were described for indirect estimation, valuation techniques used (standard gamble [SG], time trade-off [TTO], visual analogue scale [VAS], etc.), whether uncertainty in utility estimates was explored in cost-utility analyses, and whether utility values were identified as a priority for further research by assessment authors.Fifty-six assessments were reviewed, of which 28 reported 45 cost-utility analyses. There was striking variation in the values used to describe different health states. Data from patients were used in 15 (33%) analyses, from the general public in 10 (22%) and from clinicians in 4 (9%). In 16 (36%) cases, the source for utility estimates was unclear. Health states were described using a range of generic and disease-specific measures, although the EQ-5D was used most frequently. In 25 analyses (56%), the valuation technique used was not reported. TTO was used in 11 (24%), SG in 3 (7%), magnitude estimation in 5 (11%) and VAS in 1 (2%). Sensitivity analyses based on utility values were reported in 25 cases (56%), more commonly in reports of analyses carried out by independent teams than technology sponsors although this may be subject to reporting bias. Further research into quality of life was recommended in 17 (61%) of the 28 assessment reports that contained at least one cost-utility analysis. Greater transparency and consistency are required in reporting the methods used to obtain quality-of-life weights in cost-utility analyses, and better sources of data are required. Methodological variation results in important differences in values. Therefore, caution must be exercised when comparing the results of different cost-utility analyses.

Academies and Institutes↗
PubMed2004

Quality of life and illness costs in irritable bowel syndrome.

Quality of life is reduced in patients with irritable bowel syndrome, and the costs for this disease are substantial to society. During a meeting in London, UK, the IBiS club reviewed the literature on these subjects. Drawbacks and advantages with existing instruments to assess quality of life and costs were discussed and the clinical and scientific relevance of the current knowledge was assessed. A summary from the meeting is presented in this paper.

Clinical Trials as Topic↗
PubMed2004

A comparison of the EQ-5D and SF-6D across seven patient groups.

As the number of preference-based instruments grows, it becomes increasingly important to compare different preference-based measures of health in order to inform an important debate on the choice of instrument. This paper presents a comparison of two of them, the EQ-5D and the SF-6D (recently developed from the SF-36) across seven patient/population groups (chronic obstructive airways disease, osteoarthritis, irritable bowel syndrome, lower back pain, leg ulcers, post menopausal women and elderly). The mean SF-6D index value was found to exceed the EQ-5D by 0.045 and the intraclass correlation coefficient between them was 0.51. Whilst this convergence lends some support for the validity of these measures, the modest difference at the aggregate level masks more significant differences in agreement across the patient groups and over severity of illness, with the SF-6D having a smaller range and lower variance in values. There is evidence for floor effects in the SF-6D and ceiling effects in the EQ-5D. These discrepancies arise from differences in their health state classifications and the methods used to value them. Further research is required to fully understand the respective roles of the descriptive systems and the valuation methods and to examine the implications for estimates of the impact of health care interventions.

Activities of Daily Living↗
PubMed2003

A view from the bridge: agreement between the SF-6D utility algorithm and the Health Utilities Index.

BACKGROUND: The SF-6D is a new health state classification and utility scoring system based on 6 dimensions ('6D') of the Short Form 36, and permits a "bridging" transformation between SF-36 responses and utilities. The Health Utilities Index, mark 3 (HUI3) is a valid and reliable multi-attribute health utility scale that is widely used. We assessed within-subject agreement between SF-6D utilities and those from HUI3. METHODS: Patients at increased risk of sudden cardiac death and participating in a randomized trial of implantable defibrillator therapy completed both instruments at baseline. Score distributions were inspected by scatterplot and histogram and mean score differences compared by paired t-test. Pearson correlation was computed between instrument scores and also between dimension scores within instruments. Between-instrument agreement was by intra-class correlation coefficient (ICC). RESULTS: SF-6D and HUI3 forms were available from 246 patients. Mean scores for HUI3 and SF-6D were 0.61 (95% CI 0.60-0.63) and 0.58 (95% CI 0.54-0.62) respectively; a difference of 0.03 (p<0.03). Score intervals for HUI3 and SF-6D were (-0.21 to 1.0) and (0.30-0.95). Correlation between the instrument scores was 0.58 (95% CI 0.48-0.68) and agreement by ICC was 0.42 (95% CI 0.31-0.52). Correlations between dimensions of SF-6D were higher than for HUI3. CONCLUSIONS: Our study casts doubt on the whether utilities and QALYs estimated via SF-6D are comparable with those from HUI3. Utility differences may be due to differences in underlying concepts of health being measured, or different measurement approaches, or both. No gold standard exists for utility measurement and the SF-6D is a valuable addition that permits SF-36 data to be transformed into utilities to estimate QALYs. The challenge is developing a better understanding as to why these classification-based utility instruments differ so markedly in their distributions and point estimates of derived utilities.

Algorithms↗