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PubMed1998

Modelling the potential economic impact of viral load-driven triple drug combination antiretroviral therapy.

The purpose of this study is to model the potential economic impact of viral load-driven triple drug combination (including a protease inhibitor) antiretroviral therapy on incremental drug and hospitalisation costs among individuals with HIV disease. Individuals included in the study were HIV-positive men and women from the province of British Columbia, Canada, who were aged 18 years or older and had given consent to access their medical records. The study employed pharmacoeconomic modelling of drug- and hospital-utilisation patterns among a population-based cohort with free access to antiretroviral therapy. Protease inhibitor use and associated costs based on actual use in a subsequent period was modelled upon men and women who were able to maintain stable CD4+ cell counts (slope > or = 0) for at least 6 months (baseline period) with an average follow-up period of 30 months (protease-like group). A control was modelled upon individuals with declining CD4+ cell counts (slope < 0) during similar baseline and follow-up periods. The primary outcome measure was average annual incremental cost of triple drug therapy net of hospitalisation and testing costs in 1996 Canadian dollars ($Can). The utilisation pattern of drugs and hospitals was modelled from actual use among a total of 1271 individuals who were eligible for this analysis. Programme participants who gave consent to access their medical records were more likely to be men (p < 0.001), older (p < 0.020), and on antiretroviral therapy (p < 0.001) than programme participants who did not give consent. No differences were observed between the protease-like and comparison groups with respect to age (p = 0.65) and CD4+ cell count (p = 0.30) at study entry. Over a period of 1 year, the protease-like group was shown to spend less time in hospital (2.7 vs 6.6 days; p < 0.001). This difference in hospitalisation remained in multivariate models, adjusting for prior AIDS-defining illnesses and gender. The average annual incremental cost of adding a protease inhibitor to a 2-drug antiretroviral regimen was estimated to be $Can2318 per person. The cost implications of hospital stay while using a protease inhibitor drug and 2 nucleosides translated into an average annual incremental cost (savings if negative) of between -$Can4798 and -$Can2227 per person. The overall average annual incremental cost impact per person associated with triple drug therapy with a protease inhibitor varied between -$Can2288 to $Can283. Negative incremental costs imply overall savings from adopting triple combination therapy. This modelling exercise demonstrated that the cost of triple drug combination antiretroviral therapy with a protease inhibitor among HIV-positive men and women was considerably less than the expected acquisition cost of the drug alone due to hospitalisation savings in the province of British Columbia.

Adult↗
PubMed2003

The role of modelling in prioritising and planning clinical trials.

OBJECTIVES: To identify the role of modelling in planning and prioritising trials. The review focuses on modelling methods used in the construction of disease models and on methods for their analysis and interpretation. DATA SOURCES: Searches were initially developed in MEDLINE and then translated into other databases. REVIEW METHODS: Systematic reviews of the methodological and case study literature were undertaken. Search strategies focused on the intersection between three domains: modelling, health technology assessment and prioritisation. RESULTS: The review found that modelling can extend the validity of trials by: generalising from trial populations to specific target groups; generalising to other settings and countries; extrapolating trial outcomes to the longer term; linking intermediate outcome measures to final outcomes; extending analysis to the relevant comparators; adjusting for prognostic factors in trials; and synthesising research results. The review suggested that modelling may offer greatest benefits where the impact of a technology occurs over a long duration, where disease/technology characteristics are not observable, where there are long lead times in research, or for rapidly changing technologies. It was also found that modelling can inform the key parameters for research: sample size, trial duration and population characteristics. One-way, multi-way and threshold sensitivity analysis have been used in informing these aspects but are flawed. The payback approach has been piloted and while there have been weaknesses in its implementation, the approach does have potential. Expected value of information analysis is the only existing methodology that has been applied in practice and can address all these issues. The potential benefit of this methodology is that the value of research is directly related to its impact on technology commissioning decisions, and is demonstrated in real and absolute rather than relative terms; it assesses the technical efficiency of different types of research. Modelling is not a substitute for data collection. However, modelling can identify trial designs of low priority in informing health technology commissioning decisions. CONCLUSIONS: Good practice in undertaking and reporting economic modelling studies requires further dissemination and support, specifically in sensitivity analyses, model validation and the reporting of assumptions. Case studies of the payback approach using stochastic sensitivity analyses should be developed. Use of overall expected value of perfect information should be encouraged in modelling studies seeking to inform prioritisation and planning of health technology assessments. Research is required to assess if the potential benefits of value of information analysis can be realised in practice; on the definition of an adequate objective function; on methods for analysing computationally expensive models; and on methods for updating prior probability distributions.

Clinical Trials as Topic↗
PubMed2001

Efavirenz: a pharmacoeconomic review of its use in HIV infection.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of patients with HIV infection. Both US and British treatment guidelines for HIV infection recommend NNRTI- or protease inhibitor-based combinations [i.e. with nucleoside reverse transcriptase inhibitors (NRTIs)] as first-line treatmentoptions in the management of HIV disease. Results of a pivotal randomised study (DMP 266-006) comparing efavirenz- versus indinavir-based triple combination therapy in patients with HIV infection (the majority of whom were antiretroviral therapy-naive) showed the efavirenz-based regimen was better tolerated and had greater success in achieving reductions in viral load below the limit of detection. These and other clinical data were incorporated into economic models in 2 analyses, one conducted in the US and the other in Canada. The US analysis examined long term clinical and economic outcomes predicted on the basis of response (viral load and CD4+ cell counts), tolerability and willingness to adhere to therapy. The efavirenz-based regimen was the dominant treatment strategy as it was predicted to improve survival and reduce direct medical costs in the US healthcare system. Compared with the indinavir-containing regimen, survival was increased by 11% (absolute difference) and cumulative costs were reduced by $US10,326 per patient (1998 discounted costs) at 5 years after starting treatment with efavirenz-based therapy. The Canadian analysis was conducted from the perspective of the Ontario healthcare system. This study did not consider differences in clinical efficacy between treatment groups, costs of study medication or outcomes beyond 1 year--all factors that would have favoured the efavirenz-based regimen. Of the 2 treatment options, the efavirenz-based regimen was associated with 7.4% lower average annual medical care costs, primarily because of greater costs associated with adverse clinical events with the indinavir-based regimen. In conclusion, current treatment guidelines for HIV infection recognise efavirenz-based combination regimens as a first-line treatment option. A pivotal comparative clinical trial (DMP 266-006) showed a significantly greater virological response to efavirenz- than indinavir-based triple combination therapy, and the efavirenz-based regimen was better tolerated. These clinical data are supported by pharmacoeconomic analyses conducted in the US and Canada, both of which showed lower medical care costs with the efavirenz-based regimen. The US analysis also predicted long term health benefits, such as improved survival, with efavirenz- versus indinavir-based triple combination therapy. These results must be weighed against the inherent difficulties of predicting long term treatment failure rates from short term data, and the limited number of pharmacoeconomic analyses conducted with efavirenz to date.

Alkynes↗
PubMed1999

Pharmacoeconomic evaluation of new treatments: efficacy versus effectiveness studies?

The juxtaposition of economic and clinical evaluation raises new issues in the design of clinical trials. Recent pharmacoeconomic guidelines provide some direction, but do not deal with the appropriate timing of economic evaluations in the drug developmental process. Ideally, pharmacoeconomic data should be available at the time of the regulatory and formulary decision making. Current pivotal phase III trials do not provide these data; they are designed to test safety and efficacy (does the drug work under optimal circumstances?) and not to answer questions about the effectiveness of a drug, the more relevant question for economic analysis (does the drug work in usual care?). The use of more "naturalistic" designs for some phase III randomised trials has been suggested. These so called "effectiveness trials" more closely reflect routine clinical practice. They use a more flexible dosage regimen, and a "usual care" instead of a placebo comparator. Patients randomised are more representative of actual practice and outcomes include quality of life and utility measures. They are more suited to provide the data needed to estimate the real benefit of the treatment in actual care. When costs are applied and compared with these benefits, you can estimate the efficiency of allocating resources to this new drug. Increasing the use of effectiveness trials in phase III would decrease the need for economic modelling.

Antirheumatic Agents↗
PubMed2006

Socio-economic pathways to diet: modelling the association between socio-economic position and food purchasing behaviour.

OBJECTIVES: To examine the association between education level and food purchasing behaviour and the contribution of dietary knowledge to this relationship; and the association between household income and purchasing behaviour and the contribution made by subjective perceptions about the cost of healthy food. DESIGN AND SETTING: The study was conducted in Brisbane City (Australia) in 2000. The sample was selected using a stratified two-stage cluster design. Data were collected by face-to-face interview from residents of private dwellings (n=1003), and the response rate was 66.4%. Dietary knowledge was measured using a 20-item index that assessed general knowledge about food, nutrition, health and their interrelationships. Food-cost concern was measured using a three-item scale derived from principal components analysis (alpha=0.647). Food purchasing was measured using a 16-item index that reflected a household's purchase of grocery items that were consistent (or otherwise) with dietary guideline recommendations. Associations among the variables were analysed using linear regression with adjustment for age and sex. RESULTS: Significant associations were found between education, household income and food purchasing behaviour. Food shoppers with low levels of education, and those residing in low-income households, were least likely to purchase foods that were comparatively high in fibre and low in fat, salt and sugar. Socio-economic differences in dietary knowledge represented part of the pathway through which educational attainment exerts an influence on diet; and food purchasing differences by household income were related to diet in part via food-cost concern. CONCLUSIONS: Our findings suggest that socio-economic differences in food purchasing behaviour may contribute to the relationship between socio-economic position and food and nutrient intakes, and, by extension, to socio-economic health inequalities for diet-related disease. Further, socio-economic differences in dietary knowledge and concerns about the cost of healthy food play an important role in these relationships and hence should form the focus of future health promotion efforts directed at reducing health inequalities and encouraging the general population to improve their diets.

Adult↗
PubMedDate not supplied

Views on visualization.

The field of visualization is maturing. Many problems have been solved and new directions are sought. In order to make good choices, an understanding of the purpose and meaning of visualization is needed. In this paper, visualization is considered from multiple points of view. First, a technological viewpoint is adopted, where the value of visualization is measured based on effectiveness and efficiency. An economic model of visualization is presented and benefits and costs are established. Next, consequences and limitations of visualization are discussed (including the use of alternative methods, high initial costs, subjectiveness, and the role of interaction). Example uses of the model for the judgment of existing classes of methods are given to understand why they are or are not used in practice. However, such an economic view is too restrictive. Alternative views on visualization are presented and discussed: visualization as an art, visualization as design and, finally, visualization as a scientific discipline.

Computer Graphics↗
PubMed2004

Teratogenic evaluation of metronidazole and ornidazole using Drosophila melanogaster as an experimental model.

BACKGROUND: Drosophila and vertebrates show similarities that suggest that the mechanisms involved in the induction of developmental defects may be similar in both. Therefore, Drosophila has been proposed as a useful, rapid, and economical model in the preliminary screening for teratology studies. The objective of the present study was to investigate the effect of metronidazole (MTZ) and ornidazole (ONZ) on the developmental stages of Drosophila melanogaster. METHODS: Samarkand wild-type females were allowed to lay eggs for 24 hr in media containing MTZ or ONZ at concentrations of 0, 500, 1000, and 2000 microg/ml. When larvae completed their development, the emerging flies were counted and examined for morphological abnormalities. RESULTS: After the analysis of 400-1000 flies for each concentration, ONZ-treated flies did not show an incidence of malformations above control values, although a significant high number of individuals with reduced body size was observed (p < 0.005, chi2 test). On the other hand, the 1000- and 2000-microg/ml MTZ-treated series presented higher frequencies of total abnormalities than did concurrent and historic controls (p < 0.05, chi2 test), indicating an MTZ effect during developmental morphogenesis. CONCLUSIONS: These findings contribute to the characterization of both nitroimidazoles, which are widely used, especially in underdeveloped countries. At the same time, this Drosophila bioassay is sensitive enough to detect differential effects of MTZ and ONZ (abnormalities vs. growth effects), showing specificity and selectivity.

Abdomen↗
PubMedDate not supplied

Impact of generic drug entry on cost-effectiveness analysis.

The market share of generic drugs has grown substantially since the passage of the Waxman-Hatch Act, increasing from 19% in 1984 to 50% in 2001. At entry, the generic drugs typically are priced lower than brand-name drugs; thus, incorporating the impact of the generic drug entry introduces an additional source of uncertainty in economic models as both the timing of entry and the level of generic drug pricing are subject to variation. In this article, the authors explored the impact of generic drug entry on cost-effectiveness analyses of new or brand-name drugs. Using a mathematical model, they argue that failure to incorporate the impact of generic drug entry will underestimate the incremental cost-effectiveness ratio (ICER) and, thus, overstate the economic benefit of the new product. The authors provide 2 examples to illustrate such impact on short-term and long-term cost-effectiveness analyses. To better assess the uncertainty associated with the impact of generic drug entry, in addition to a deterministic analysis, they also employed a Bayesian probabilistic approach to analyze these examples and presented the results using cost-effectiveness acceptability curves. They conclude that incorporating generic drug entry into pharmacoeconomic models will yield more accurate projections of the ICER and lead to better decision making.

Bayes Theorem↗
PubMed2004

An economic analysis of life expectancy by gender with application to the United States.

This paper presents an economic model to explain the behavior of life expectancy of both sexes. It explicitly examines the relationship between the gender gap in life expectancy and the gender gap in pay. It shows that as the latter narrows over the course of economic development, the former may initially expand but will eventually shrink. Simulation results from our model accord with the behavior of life expectancy for both sexes since the 1940s in the United States.

Female↗
PubMed2005

Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy.

BACKGROUND: Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy. METHODS: A global economic model was adapted to the UK National Health Service (NHS), with primary outcomes of direct healthcare costs and quality-adjusted life years (QALYs). Efficacy, measured as relative risk reduction of skeletal-related events (SREs), was obtained from clinical trials. Resource use data for i.v. bisphosphonates and the cost of managing SREs were obtained from published studies. Hospital management and SRE treatment costs were taken from unit cost databases. Monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with/without an SRE to adjust survival for quality of life. Model design and inputs were validated through expert UK clinician review. RESULTS: Total cost, including drug acquisition, was pound 386 less per patient with oral ibandronate vs. i.v. zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate, respectively, making it the economically dominant option. At a threshold of pound 30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85% of simulations and vs. pamidronate in 79%. CONCLUSIONS: Oral ibandronate is a cost-effective treatment for metastatic bone disease from breast cancer due to reduced SREs, bone pain, and cost savings from avoidance of resource use commonly associated with bisphosphonate infusions.

Administration, Oral↗
PubMedDate not supplied

Is vaccination against hepatitis B efficient? A review of world literature.

We report on the result of a study aimed at assessing the variability of assumptions upon which economic models for the introduction of vaccination against Hepatitis B are based, the conclusions reached and define a minimum set of methodological standards upon which future economic studies on vaccines should be based. We identified 116 published and unpublished works by Medline literature searches, consulting private databases and corresponding with all authors and researchers active in economic evaluation of vaccines. All works were assessed but we included in our review only those which were original economic analyses (90 studies). Principal epidemiological and economic variables were extracted and compared where possible. Rough manipulations were carried out to make the data comparable. We found profound variability on the main parameters of the efficiency equation (disease incidence, costing methods, use of marginal theory, discounting and study time-span, sensitivity analysis and reporting methods). We also found inconsistencies in definition and study design in 38% of a subset of studies. Although we found scarce decision-making impact, we believe that due to uncertain or unclear methodology, few studies reach valid conclusions. In future decisions may be based on biased evidence and scarce resources committed to untested programmes. There is an urgent need to standardise study methods and define a common set of procedures.

Cost-Benefit Analysis↗
PubMed2006

From the simple to the sublime: incorporating surgical models into your surgical curriculum.

Financial and time constraints have limited graduating residents' operative experience, making the use of models a necessary adjunct to a complete surgical curriculum. Models are useful tools to teaching surgical skills outside the operating room. They can be very realistic and complex, or they can be simple and economical. Models are developed to represent the anatomic arrangements seen in human patients, and to reproduce the biomechanical tasks necessary to complete a surgical case. Bench model laboratories are well-received by trainees and steepen the learning curve in the operating room.

Female↗
PubMed2006

Treatment intensity and provider remuneration: dentists in the British National Health Service.

Dental service providers in the British National Health Service (NHS) operate under a number of remuneration arrangements that give rise to different incentives. Using data derived from the Scottish dental system, we examine the relationships between remuneration, patient exemption status and treatment intensity. After controlling for differences in patient need and dentist-specific preferences, we find that self-employed dentists treat patients who are exempt from payment more intensively than their salaried counterparts. The results imply that changes in remuneration can have a large effect on the distribution of treatments. More generally, our results provide support for economic models that view financial incentives as important determinants of physician behaviour.

Dental Care↗
PubMed1986

A utility maximization model of driver traffic safety behavior.

A simple utility maximization model is presented to illustrate that risk compensation is a natural part of human behavior when individuals pursue multiple goals with limited resources. In this positive economic model driver safety effort is determined by a balance between reduced risk and increased disutility cost. Changes which affect the balance induce drivers to change their own safety efforts. Under plausible conditions a change in exogenous safety, which is beyond driver control, causes a compensatory change in driver effort in the opposite direction. A sample of special seat belt use studies illustratively indicates the usefulness of the model.

Accidents, Traffic↗
PubMed2005

Prospect theory on the brain? Toward a cognitive neuroscience of decision under risk.

Most decisions must be made without advance knowledge of their consequences. Economists and psychologists have devoted much attention to modeling decisions made under conditions of risk in which options can be characterized by a known probability distribution over possible outcomes. The descriptive shortcomings of classical economic models motivated the development of prospect theory (D. Kahneman, A. Tversky, Prospect theory: An analysis of decision under risk. Econometrica, 4 (1979) 263-291; A. Tversky, D. Kahneman, Advances in prospect theory: Cumulative representation of uncertainty. Journal of Risk and Uncertainty, 5 (4) (1992) 297-323) the most successful behavioral model of decision under risk. In the prospect theory, subjective value is modeled by a value function that is concave for gains, convex for losses, and steeper for losses than for gains; the impact of probabilities are characterized by a weighting function that overweights low probabilities and underweights moderate to high probabilities. We outline the possible neural bases of the components of prospect theory, surveying evidence from human imaging, lesion, and neuropharmacology studies as well as animal neurophysiology studies. These results provide preliminary suggestions concerning the neural bases of prospect theory that include a broad set of brain regions and neuromodulatory systems. These data suggest that focused studies of decision making in the context of quantitative models may provide substantial leverage towards a fuller understanding of the cognitive neuroscience of decision making.

Animals↗
PubMed1997

Is medical treatment for angina the most cost-effective option?

A meta-analysis of the benefits of coronary artery bypass graft (CABG) surgery has been used as the basis of a model for comparing the costs and benefits of surgical and medical treatment of angina pectoris. In order to allow for the results of recent research, the economic model included the addition of aspirin and aspirin plus an HMG-CoA reductase inhibitor (statin) to medical management. The analysis indicates that in unselected patients the cost-effectiveness of CABG vs initial standard medical therapy over 5 years is towards the upper limit of what can be considered a cost-effective treatment both in terms of its effect on mortality (life-years gained) and morbidity (quality adjusted life-years). Addition of a statin to medical therapy reduced mortality and made coronary artery bypass graft surgery an expensive option in terms of improvement of quality of life. In patients with three-vessel disease or left ventricular dysfunction surgery appears fairly cost-effective in comparison with standard medical therapy but becomes relatively expensive when the benefits of aspirin or lipid-lowering therapy are added to medical treatment.

Angina Pectoris↗
PubMed2005

Chayanov revisited: a model for the economics of complex kin units.

Chayanov's model of the peasant economy is based on autarkic nuclear family households. Expansion to the more complex households and kin groups common in peasant societies shows that the sharp changes Chayanov observed in the consumer/producer ratio over the domestic cycle are smoothed by the intergenerational structure of complex households and extended kin groups. This amelioration may be retarded by competition between constituent units. Understanding the dynamics of the developmental cycle and micropolitics of domestic groups is a useful correction to Chayanov's widely used formulation, especially in developing countries where complex kin structures are common.

Journal Article↗