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A H Briggs

Publications and source records attributed to A H Briggs.

At least 19 recordsLinked to original sources

Cost-effectiveness of asthma control: an economic appraisal of the GOAL study.

BACKGROUND: The Gaining Optimal Asthma ControL (GOAL) study has shown the superiority of a combination of salmeterol/fluticasone propionate (SFC) compared with fluticasone propionate alone (FP) in terms of improving guideline defined asthma control. METHODS: Clinical and economic data were taken from the GOAL study, supplemented with data on health related quality of life, in order to estimate the cost per quality adjusted life year (QALY) results for each of three strata (previously corticosteroid-free, low- and moderate-dose corticosteroid users). A series of statistical models of trial outcomes was used to construct cost effectiveness estimates across the strata of the multinational GOAL study including adjustment to the UK experience. Uncertainty was handled using the non-parametric bootstrap. Cost-effectiveness was compared with other treatments for chronic conditions. RESULT: Salmeterol/fluticasone propionate improved the proportion of patients achieving totally and well-controlled weeks resulting in a similar QALY gain across the three strata of GOAL. Additional costs of treatment were greatest in stratum 1 and least in stratum 3, with some of the costs offset by reduced health care resource use. Cost-effectiveness by stratum was 7600 pound (95% CI: 4800-10,700 pound) per QALY gained for stratum 3; 11,000 pound (8600-14,600 pound) per QALY gained for stratum 2; and 13,700 pound (11,000-18,300 pound) per QALY gained for stratum 1. CONCLUSION: The GOAL study previously demonstrated the improvement in total control associated with the use of SFC compared with FP alone. This study suggests that this improvement in control is associated with cost-per-QALY figures that compare favourably with other uses of scarce health care resources.

Albuterol↗

Analysis of uncertainty in health care cost-effectiveness studies: an introduction to statistical issues and methods.

Cost-effectiveness analysis is now an integral part of health technology assessment and addresses the question of whether a new treatment or other health care program offers good value for money. In this paper we introduce the basic framework for decision making with cost-effectiveness data and then review recent developments in statistical methods for analysis of uncertainty when cost-effectiveness estimates are based on observed data from a clinical trial. Although much research has focused on methods for calculating confidence intervals for cost-effectiveness ratios using bootstrapping or Fieller's method, these calculations can be problematic with a ratio-based statistic where numerator and/or denominator can be zero. We advocate plotting the joint density of cost and effect differences, together with cumulative density plots known as cost-effectiveness acceptability curves (CEACs) to summarize the overall value-for-money of interventions. We also outline the net-benefit formulation of the cost-effectiveness problem and show that it has particular advantages over the standard incremental cost-effectiveness ratio formulation.

Clinical Trials as Topic↗

The death of cost-minimization analysis?

Four different types of evaluation methods, cost-benefit analysis (CBA), cost-utility analysis (CUA), cost-effectiveness analysis (CEA) and cost-minimization analysis (CMA), are usually distinguished. In this note, we pronounce the (near) death of CMA by showing the rare circumstances under which CMA is an appropriate method of analysis. We argue that it is inappropriate for separate and sequential hypothesis tests on differences in effects and costs to determine whether incremental cost-effectiveness (or cost-utility) should be estimated. We further argue that the analytic focus should be on the estimation of the joint density of cost and effect differences, the quantification of uncertainty surrounding the incremental cost-effectiveness ratio and the presentation of such data as cost-effectiveness acceptability curves. Two examples from recently published CEA are employed to illustrate the issues. The first shows a situation where analysts might be tempted (inappropriately) to employ CMA rather than CEA. The second illustrates one of the rare circumstances in which CMA may be justified as a legitimate form of analysis.

Anticoagulants↗

Affordability and cost-effectiveness: decision-making on the cost-effectiveness plane.

Much recent research interest has focused on handling uncertainty in cost-effectiveness analysis and in particular the calculation of confidence intervals for incremental cost-effectiveness ratios (ICERs). Problems of interpretation when ICERs are negative have led to two important and related developments: the use of the net-benefit statistic and the presentation of uncertainty in cost-effectiveness analysis using acceptability curves. However, neither of these developments directly addresses the problem that decision-makers are constrained by a fixed-budget and may not be able to fund new, more expensive interventions, even if they have been shown to represent good value for money. In response to this limitation, the authors introduce the 'affordability curve' which reflects the probability that a programme is affordable for a wide range of threshold budgets. The authors argue that the joint probability an intervention is affordable and cost-effective is more useful for decision-making since it captures both dimensions of the decision problem faced by those responsible for health service budgets.

Budgets↗

A Bayesian approach to stochastic cost-effectiveness analysis. An illustration and application to blood pressure control in type 2 diabetes.

The aim of this paper is to discuss the use of Bayesian methods in cost-effectiveness analysis (CEA) and the common ground between Bayesian and traditional frequentist approaches. A further aim is to explore the use of the net benefit statistic and its advantages over the incremental cost-effectiveness ratio (ICER) statistic. In particular, the use of cost-effectiveness acceptability curves is examined as a device for presenting the implications of uncertainty in a CEA to decision makers. Although it is argued that the interpretation of such curves as the probability that an intervention is cost-effective given the data requires a Bayesian approach, this should generate no misgivings for the frequentist. Furthermore, cost-effectiveness acceptability curves estimated using the net benefit statistic are exactly equivalent to those estimated from an appropriate analysis of ICERs on the cost-effectiveness plane. The principles examined in this paper are illustrated by application to the cost-effectiveness of blood pressure control in the U.K. Prospective Diabetes Study (UKPDS 40). Due to a lack of good-quality prior information on the cost and effectiveness of blood pressure control in diabetes, a Bayesian analysis assuming an uninformative prior is argued to be most appropriate. This generates exactly the same cost-effectiveness results as a standard frequentist analysis.

Bayes Theorem↗

Cost-effectiveness of beta-blocker therapy with metoprolol or with carvedilol for treatment of heart failure in Canada.

OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness of beta-blocker therapy with either metoprolol or carvedilol in addition to conventional therapy for patients with heart failure (HF) in Canada. DESIGN: A Markov simulation was used to estimate the costs and life expectancy for treating patients with conventional therapy alone and with the addition of metoprolol or carvedilol. Although carvedilol has been marketed in Canada since 1999, metoprolol succinate has yet to be marketed there, so the price is unknown. Therefore we input a Canadian price based on the price ratio of the 2 drugs in the United States. RESULTS: For subjects aged 60 years at HF onset, the expected years of life are 4.53 years for those treated with conventional therapy alone, 5.70 years for those who receive conventional therapy plus metoprolol, and 6.21 years for those who receive conventional therapy plus carvedilol. The expected costs (in 1999 Canadian dollars) are $8,989, $13,833, and $18,114, respectively. This yields incremental cost-effectiveness ratios (ICERs) for metoprolol relative to conventional therapy alone of $4,140 per life-year gained, and for carvedilol relative to metoprolol, the ICER is $8,394 per life-year gained. CONCLUSIONS: In addition to conventional therapy with furosemide and angiotensin converting enzyme inhibitors, treatment with either metoprolol or carvedilol confers a survival benefit that is attractive from a cost-effectiveness point of view. Until better information becomes available, it is not possible to distinguish between the two beta-blockers on the basis of cost-effectiveness. This means that the choice of beta-blockers for HF should be based largely on clinical considerations because both beta-blockers prolong life at relatively low cost.

Adrenergic beta-Antagonists↗

Handling uncertainty in cost-effectiveness models.

The use of modelling in economic evaluation is widespread, and it most often involves synthesising data from a number of sources. However, even when economic evaluations are conducted alongside clinical trials, some form of modelling is usually essential. The aim of this article is to review the handling of uncertainty in the cost-effectiveness results that are generated by the use of decision-analytic-type modelling. The modelling process is split into a number of stages: (i) a set of methods to be employed in a study are defined, which should include a 'reference case' of agreed methods to enhance the comparability of results; (ii) the clinical and demographic characteristics of the patients the model relates to should be specified as carefully as in any experimental study; and (iii) the data requirements of the model should be estimated using the principles of Bayesian statistics, such that prior distributions are specified for unknown model parameters. Monte Carlo simulation can then be employed to sample from these prior distributions to obtain a distribution of the cost effectiveness of the intervention. Such probabilistic analyses are related to parameter uncertainty. In addition, modelling uncertainty is likely to add a further layer of uncertainty to the results of particular analyses.

Cost-Benefit Analysis↗

Management of urinary tract infection in general practice: a cost-effectiveness analysis.

BACKGROUND: Symptoms associated with urinary tract infection (UTI) are common in women in general practice and represent a significant burden for the National Health Service. There is considerable variation among general practitioners in the management of patients presenting with these symptoms. AIM: To identify the most appropriate patient management strategy given current information for non-pregnant, adult women presenting in general practice with symptoms of uncomplicated UTI. METHOD: A decision analytic model incorporating a variety of patient management strategies was constructed using available published information and expert opinion. This model was able to provide guidance on current best practice based upon cost-effectiveness (cost per symptom-free day). RESULTS: Empiric treatment was found to be the least costly strategy available. It saved two days of symptoms per episode of UTI at a cost of 14 Pounds. The empiric-and-laboratory strategy involves an incremental cost-effectiveness ratio of 215 Pounds per symptom day averted per episode of UTI. The remaining patient management strategies are never optimal. CONCLUSION: Empiric treatment of patients presenting with symptoms of UTI was found to be cost-effective under a range of assumptions for this patient group. However, recognition of the impact of this strategy upon antibiotic resistance may lead to the dipstick strategy being considered a superior strategy overall.

Adult↗

Constructing confidence intervals for cost-effectiveness ratios: an evaluation of parametric and non-parametric techniques using Monte Carlo simulation.

The statistic of interest in most health economic evaluations is the incremental cost-effectiveness ratio. Since the variance of a ratio estimator is intractable, the health economics literature has suggested a number of alternative approaches to estimating confidence intervals for the cost-effectiveness ratio. In this paper, Monte Carlo simulation techniques are employed to address the question of which of the proposed methods is most appropriate. By repeatedly sampling from a known distribution and applying the different methods of confidence interval estimation, it is possible to calculate the coverage properties of each method to see if these correspond to the chosen confidence level. As the results of a single Monte Carlo experiment would be valid only for that particular set of circumstances, a series of experiments was conducted in order to examine the performance of the different methods under a variety of conditions relating to the sample size, the coefficient of variation of the numerator and denominator of the ratio, and the covariance between costs and effects in the underlying data. Response surface analysis was used to analyse the results and substantial differences between the different methods of confidence interval estimation were identified. The methods, both parametric and non-parametric, which assume a normal sampling distribution performed poorly, as did the approach based on simply combining the separate intervals on costs and effects. The choice of method for confidence interval estimation can lead to large differences in the estimated confidence limits for cost-effectiveness ratios. The importance of such differences is an empirical question and will depend to a large extent on the role of hypothesis testing in economic appraisal. However, where it is suspected that the sampling distribution is skewed, normal approximation methods produce particularly poor results and should be avoided.

Computer Simulation↗

A Bayesian approach to stochastic cost-effectiveness analysis.

The aim of this paper is to briefly outline a Bayesian approach to cost-effectiveness analysis (CEA). Historically, frequentists have been cautious of Bayesian methodology, which is often held as synonymous with a subjective approach to statistical analysis. In this paper, the potential overlap between Bayesian and frequentist approaches to CEA is explored--the focus being on the empirical and uninformative prior-based approaches to Bayesian methods rather than the use of subjective beliefs. This approach emphasizes the advantage of a Bayesian interpretation for decision-making while retaining the robustness of the frequentist approach. In particular the use of cost-effectiveness acceptability curves is examined. A traditional frequentist approach is equivalent to a Bayesian approach assuming no prior information, while where there is pre-existing information available from which to construct a prior distribution, an empirical Bayes approach is equivalent to a frequentist approach based on pooling the available data. Cost-effectiveness acceptability curves directly address the decision-making problem in CEA. Although it is argued that their interpretation as the probability that an intervention is cost-effective given the data requires a Bayesian interpretation, this should generate no misgivings for the frequentist.

Bayes Theorem↗

Microtubule bending and breaking in living fibroblast cells.

Microtubules in living cells frequently bend and occasionally break, suggesting that relatively strong forces act on them. Bending implies an increase in microtubule lattice energy, which could in turn affect the kinetics and thermodynamics of microtubule-associated processes such as breaking. Here we show that the rate of microtubule breaking in fibroblast cells increases approximately 40-fold as the elastic energy stored in curved microtubules increases to > approximately 1 kT/tubulin dimer. In addition, the length-normalized breaking rate is sufficiently large (2.3 breaks x mm(-1) x minute(-1)) to infer that breaking is likely a major mechanism by which noncentrosomal microtubules are generated. Together the results suggest a physiologically important, microtubule-based mechanism for mechanochemical information processing in the cell.

3T3 Cells↗

Prevention of mother-to-child transmission of HIV-1 infection: alternative strategies and their cost-effectiveness.

OBJECTIVE: To estimate the cost-effectiveness of alternative interventions to reduce the risk of mother-to-child transmission of HIV. DESIGN: A model capturing the sequential nature of mother-to-child transmission in utero, at delivery and postnatally was used to determine how the effects of bottle-feeding, elective Cesarean section (CS) and zidovudine (ZDV) would combine to prevent mother-to-child HIV transmission. Parameter estimates were derived from the literature, UK health service costs applied, and incremental cost effectiveness ratios (ICER) estimated for alternative risk reduction strategies. Results can be transposed to other cost assumptions or currencies. RESULTS: In a woman who breast-feeds her baby, has a vaginal or emergency CS delivery and takes no ZDV, the estimated transmission risk is 31.6% (range, 23.7-38.1%), at a cost of 400 UK pound per woman; this falls to a risk of 3.7% (range, 1.7-6.9%) when bottle-feeding, ZDV therapy and elective CS are all implemented at a cost of 1968 UK pound per woman. From a public health perspective the ICER of ZDV and elective CS each depend on the acceptance rates of the other. In women counselled against breast-feeding, ZDV with 100% acceptance of elective CS has an ICER of 11 342 UK pound (95% confidence interval (CI), 7084-21 515 UK pound]. However, the ICER of CS ranges from 9248 UK pound (95% CI, 5072-46 913 pound sterling) at zero ZDV acceptance to 27 895 UK pound (95% CI, 10 018-154 462 pound sterling) at 100% ZDV acceptance. CONCLUSIONS: Considering the estimated cost of caring for an infected child, ZDV appears to be cost-effective under any of the circumstances examined. However, elective CS may not be cost-effective in populations where the uptake of ZDV is high, and a more precise estimate of its efficacy is required.

Anti-HIV Agents↗

Cost effectiveness of screening for and eradication of Helicobacter pylori in management of dyspeptic patients under 45 years of age.

OBJECTIVE: To assess the cost effectiveness of screening for and eradicating Helicobacter pylori in patients under 45 years of age presenting with dyspepsia. DESIGN: A decision analytic model composed of a decision tree to represent the epidemiology of dyspepsia and a Markov process to model the outcomes of treatment. PATIENTS: Patients under the age of 45 years presenting to their general practitioner with (peptic type) dyspepsia. INTERVENTIONS: Conventional empirical treatment with healing and maintenance doses of cimetidine v eradication treatment solely in patients with confirmed peptic ulcer; and conventional empirical treatment for all dyspeptic patients compared with the use of a serology test to identify patients with H pylori, who then receive endoscopy to investigate the presence of peptic ulcer disease and, when disease is found, are given eradication treatment with a breath test to confirm successful eradication. MAIN OUTCOME MEASURES: Expected cumulative costs over a period of 10 years. The proportion of time patients spend without a recurrent ulcer. RESULTS: After receiving eradication treatment, patients with confirmed ulcer spend an average of 99% of their time free from recurrent ulcer disease compared with 95% after treatment with cimetidine. Eradication treatment costs less than that with cimetidine. When the initial cost of identifying appropriate patients to receive eradication treatment is added to the analysis, however, these cost savings take almost eight years to accrue. CONCLUSIONS: Enthusiasm for introducing testing for and eradication of H pylori for dyspeptic patients in general practice should be tempered by an awareness that cost savings may take many years to realise.

Adult↗

Allelic association of human dopamine D2 receptor gene in alcoholism.

In a blinded experiment, we report the first allelic association of the dopamine D2 receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3' coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3' sequence of the human dopamine D2 receptor gene (lambda hD2G1). In the present samples, the presence of A1 allele of the dopamine D2 receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11.

Alcoholism↗

Ethanol ingestive behavior as a function of central neurotransmission.

Uncontrollable alcohol ingestive behavior has been linked to deficits of central neurotransmission. The pineal gland plays an important role in modulating ethanol intake in numerous animal species. The opioidergic (i.e. beta-endorphin, enkephalin, and dynorphin) system is involved in both the actions of alcohol and opiates, as well as craving and/or genetic predisposition towards abuse of these two agents. Furthermore, there is significant evidence to link ingestive behaviors with the ventral tegmental accumbens-hypothalamic axis, whereby the biogenic amines dopamine and serotonin are reciprocally involved. Evidence is presented which implicates the striatum and the hypothalamus as possible specific loci for regional differences between alcohol-preferring and alcohol-nonpreferring mice. We believe that photoperiod-induced alcohol ingestive behavior may involve alterations in both pineal and hypothalamic opioid peptides.

Alcoholism↗

Regional brain [Met]-enkephalin in alcohol-preferring and non-alcohol-preferring inbred strains of mice.

Scrutiny of the data from these studies reveals that the C58/J alcohol-preferring mice have significantly lower baseline methionine-enkephalin levels in both the corpus striatum and hypothalamus compared to C3H/CHRGL/2 non-alcohol-preferring mice. In other brain regions in these two strains, specifically, pituitary, amygdala, midbrain, and hippocampus, analysis of methionine-enkephalin levels did not show any significant differences. This suggests that the hypothalamus may indeed be a specific locus involved in the regulation of alcohol intake, via the molecular interaction between neuroamines, opioid peptides, as they are influenced by genetics and environment.

Alcohol Drinking↗