Health economic evaluation: a primer for the practicing rheumatologist.
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Arthritis, Rheumatoid↗
Biomedical subjects
Larry D Lynd
Publications and source records attributed to Larry D Lynd.
Cost-effectiveness of self-managed versus physician-managed oral anticoagulation therapy.
BACKGROUND: Patient self-management of long-term oral anticoagulation therapy is an effective strategy in a number of clinical situations, but it is currently not a funded option in the Canadian health care system. We sought to compare the incremental cost and health benefits of self-management with those of physician management from the perspective of the Canadian health care payer over a 5-year period. METHODS: We developed a Bayesian Markov model comparing the costs and quality-adjusted life years (QALYs) accrued to patients receiving oral anticoagulation therapy through self-management or physician management for atrial fibrillation or for a mechanical heart valve. Five health states were defined: no events, minor hemorrhagic events, major hemorrhagic events, thrombotic events and death. Data from published literature were used for transition probabilities. Canadian 2003 costs were used, and utility estimates were obtained from various published sources. RESULTS: Self-management resulted in 3.50 fewer thrombotic events, 0.78 fewer major hemorrhagic events and 0.12 fewer deaths per 100 patients than physician management. The average discounted incremental cost of self-management over physician management was found to be 989 dollars (95% confidence interval [CI] 310 dollars-1655 dollars) per patient and the incremental QALYs gained was 0.07 (95% CI 0.06-0.08). The cost-effectiveness of self-management was 14,129 dollars per QALY gained. There was a 95% chance that self-management would be cost-effective at a willingness to pay of 23,800 dollars per QALY. Results were robust in probabilistic and deterministic sensitivity analyses. INTERPRETATION: This model suggests that self-management is a cost-effective strategy for those receiving long-term oral anticoagulation therapy for atrial fibrillation or for a mechanical heart valve.
Administration, Oral↗
Approval process and access to prescription drugs in Canada.
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Canada↗
Prescription to over-the-counter deregulation in Canada: are we ready for it, or do we need to be?
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Canada↗
Antiviral agents for influenza: a comparison of cost-effectiveness data.
The economic burden of influenza-related illness has been estimated to be 71.3-166 billion US dollars in the US, the majority of which is attributable to indirect costs as a result of lost productivity. There are currently four antiviral drugs available for the treatment of influenza: two ion channel blockers, amantadine and rimantadine; and two neuraminidase inhibitors, zanamivir and oseltamivir. The objective of this paper was to review the studies evaluating the cost effectiveness of currently available antiviral treatment and prophylaxis management strategies for influenza. Published studies that reported both costs and effectiveness of influenza management were extracted using MEDLINE, pre-MEDLINE and EMBASE. To facilitate a broad comparison, all costs were inflated to 2003 US dollars. Fifteen studies met the inclusion criteria of the review, with 14 analyses based on decision-analytic modelling and one economic analysis performed alongside a clinical trial. Management strategies included antiviral influenza prophylaxis or vaccination, empiric treatment of suspected disease, or antiviral treatment following rapid influenza testing. Study populations included healthy adults, adults at risk of influenza-related adverse outcomes, institutionalised and non-institutionalised elderly, and children. The comparator in all studies was standard care (i.e. over-the-counter medications only), and analyses were carried out from both the societal and payer perspectives. The only dominant strategy relative to standard care was vaccination of the institutionalised elderly. All other strategies in all populations were both more costly and more effective than standard care. Depending on the population and the perspective, the incremental cost-effectiveness ratios (ICERs) for antiviral treatment strategies ranged from 5000 US dollars/QALY for amantadine in test-and-treat studies to >400,000 US dollars/QALY for zanamivir or oseltamivir treatment in children. Sensitivity analysis in all studies consistently reported a strong influence of the population prevalence or diagnostic accuracy of influenza on the cost effectiveness of all strategies. Baseline influenza prevalence varied widely between studies, ranging from 15% to 68%. There was also a wide variation in the assumption about the disutility of influenza (ranging from -0.137 to -0.983 for the elderly requiring hospitalisation), which also impacted the cost effectiveness. Given the variation in the ICERs of antiviral treatment and prophylaxis, the uncertainty around many model parameters, and the dynamic nature of influenza from year to year, one can only conclude that antiviral treatment or prophylaxis for influenza is likely to be more cost effective in specific populations at specific times during the influenza season, and during influenza seasons when the population prevalence reaches epidemic levels or there is mismatch between the vaccine and the circulating virus.
Adolescent↗
Advances in risk-benefit evaluation using probabilistic simulation methods: an application to the prophylaxis of deep vein thrombosis.
OBJECTIVE: To demonstrate the use of probabilistic simulation modeling to estimate the joint density of therapeutic risks and benefits. Published data are used to introduce the risk-benefit acceptability curve as a novel method of illustrating risk-benefit analysis. STUDY DESIGN AND SETTING: Using published data, we performed a second-order Monte Carlo simulation to estimate the joint density of major bleeding and deep vein thrombosis (DVT) secondary to enoxaparin or unfractionated heparin. Within a Bayesian framework, beta-distributions for the probabilities of experiencing a DVT and major bleed were derived from the clinical trial, and incremental probabilities were calculated. RESULTS: The incremental risk-benefit pairs from 3,000 simulations are presented on a risk-benefit plane. To accommodate different risk preferences, the results are also illustrated using a risk-benefit acceptability curve, which incorporates different risk-benefit acceptability thresholds (mu), or the number of major bleeds one is willing to accept in order to avert one DVT. Finally, a net-benefit curve is used to illustrate the risk-benefit ratio and the derivation of 95% confidence intervals around the ratio. CONCLUSION: Modern simulation methods permit the estimation of the joint density of risks and benefits with their associated uncertainty, and within a Bayesian framework, facilitate the estimation of the probability that a therapy is net-beneficial over different preference thresholds for risk-benefit trade-offs.
Anticoagulants↗
Using administrative healthcare data to recruit study subjects: experience with 'camouflaged sampling'.
PURPOSE: To recruit a sample of asthmatics heterogeneous for short-acting (SA) beta-agonist use while protecting their privacy, and to compare participants recruited via 'camouflaged sampling' to those recruited through media advertising. METHODS: Direct and indirect patient contact using camouflaged sampling was used to recruit a stratified random sample of asthmatics, identified based on their receipt of a prescription for a SA beta-agonist. Volunteers were recruited through media advertising. Recruitment rates were determined for both indirect and direct patient contact, and sampled participants were compared to volunteers recruited through media advertising for differences in SA beta-agonist use, demographic socioeconomic factors, and pulmonary function. RESULTS: 109 and 93 participants were recruited through camouflaged sampling and media advertising, respectively. Direct and indirect patient contact resulted in recruitment rates of 5 and 9%, respectively. Sampled participants were more heterogeneous for SA beta-agonist use, older, more likely to smoke or receive social assistance, and of lower socioeconomic status (SES) than volunteers. There was no difference in the association between SES and the magnitude of SA beta-agonist use between recruiting methods. CONCLUSIONS: Although recruitment rates were lower than anticipated, camouflaged sampling facilitated stratified sampling of a targeted population and resulted in a more heterogeneous sample while protecting patient privacy.
Adrenergic beta-Agonists↗
Reconcilable differences: a cross-sectional study of the relationship between socioeconomic status and the magnitude of short-acting beta-agonist use in asthma.
STUDY OBJECTIVE: To assess the association between socioeconomic status (SES) and short-acting (SA) beta-agonist use, controlling for asthma severity. DESIGN: Cross-sectional study. SETTING: Vancouver, BC, Canada. PARTICIPANTS: Two hundred two asthmatics between 19 years and 50 years of age and residing in the greater Vancouver regional district. MEASUREMENTS: The quantity of SA beta-agonist used in the previous year was collected by self-report; pulmonary function and beta-receptor genotype were measured on each participant. SES was measured at both the individual and population levels. Five methods of adjustment for asthma severity were used, as follows: the Canadian Asthma Consensus Guidelines, three previously developed asthma-severity scores, and forward stepwise multiple regression modeling. Polychotomous logistic regression was used to assess all relationships. RESULTS: Independent of the method used to measure SES or adjust for asthma severity, lower SES was consistently and significantly associated with the use of greater amounts of SA beta-agonist. Adjusting for severity using the multivariate model explained the most variance of SA beta-agonist use (R(2) adjusted, 0.35 to 0.37). In this model, social assistance recipients were more likely to use greater amounts of SA beta-agonist (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.7 to 6.5). An inverse relationship between SA beta-agonist use and both annual household income (> $50,000; OR, 0.28; 95% CI, 0.13 to 0.60; and $20,000 to $50,000; OR, 0.44; 95% CI, 0.21 to 0.96; relative to <$20,000) and education (completing a bachelor's degree vs no formal education; OR, 0.25; 95% CI, 0.14 to 0.71). Participants living in a neighborhood with higher median household income (OR, 0.91; 95% CI, 0.84 to 0.98 per $1,000 increase) or a higher prevalence of having attained a bachelor's degree (OR, 0.96; 95% CI, 0.84 to 0.98 per 1% increase) were also less likely use greater amounts of SA beta-agonist. Results were consistent for neighborhood unemployment rate. CONCLUSIONS: The social gradient in asthma-related outcomes may be at least partially attributable to poorer asthma control in lower-SES asthmatics.
Adrenergic beta-Agonists↗
The use of the osmole gap as a screening test for the presence of exogenous substances.
The rapid and accurate diagnosis of toxic alcohol poisoning due to methanol (methyl alcohol) [MeOH] and ethylene glycol (EG), is paramount in preventing serious adverse outcomes. The quantitative measurement of specific serum levels of these substances using gas chromatography is expensive, time consuming and generally only available at major tertiary-care facilities. Therefore, because these toxic substances are osmotically active and the measurement of serum osmolality is easily performed and more readily available, the presence of an osmole gap (OG) has been adopted as an alternative screening test. By definition, the OG is the difference between the measured serum osmolality determined using the freezing point depression (Osm(m)) and the calculated serum molarity (Mc), which is estimated from the known and readily measurable osmotically active substances in the serum, in particular sodium, urea, glucose, and potassium and ethanol (alcohol). Thus, the OG=Osm(m)-Mc, and an OG above a specific threshold (the threshold of positivity) suggests the presence of unmeasured osmotically active substances, which could be indicative of a toxic exposure. The objectives of this study were to review the principles of evaluating screening tests, the theory behind the OG as a screening test and the literature upon which the adoption of the OG as a screening test has been based. This review revealed that there have been numerous equations derived and proposed for the estimation of the Mc, with the objective of developing empirical evidence of the best equation for the determination of the OG and ultimately the utility of OG as a screening test. However, the methods and statistical analysis employed have generally been inconsistent with recommended guidelines for screening test evaluation and although many equations have been derived, they have not been appropriately validated. Specific evidence of the clinical utility of the OG requires that a threshold of positivity be definitively established, and the sensitivity and specificity of the OG in patients exposed to either EG or MeOH be measured. However, the majority of studies to date have only evaluated the relationship between the Osm(m) (mmol/kg H2O) and the Mc (mmol/L) in patients that have not been exposed to either MeOH or EG. While some studies have evaluated the relationship between the OG and serum ethanol concentration, these findings cannot be extrapolated to the use of the OG to screen for toxic alcohol exposure. This review shows that there has not been an appropriately designed empirical evaluation of the diagnostic utility of the OG and that its clinical utility remains hypothetical, having been theoretically extrapolated from the non-poisoned population.
Humans↗
The irrationality of the present use of the osmole gap: applicable physical chemistry principles and recommendations to improve the validity of current practices.
The present clinical use of serum osmometry is erroneous in two respects. The first, and the most important, is the incorrect assumption that serum behaves as a dilute 'ideal' solution and that the osmotic activity of a substance depends solely on the number of solute particles. The amount of variance from ideal behaviour of serum containing an exogenous substance is expressed by the osmotic coefficient (phi). We have calculated the osmotic coefficient for serum containing ethanol (alcohol) and recommend that the osmotic coefficient for serum containing other low molecular weight substances such as methanol (methyl alcohol), isopropyl alcohol and ethylene glycol also be calculated. This is necessary for the accurate calculation of the contribution of these substances to the serum osmolality.Secondly, the practice of subtracting the calculated serum molarity from measured serum osmolality is not valid since it represents a mathematically improper expression. The units of these two terms are different. The 'osmole gap' (OG) is typically viewed as the difference between serum osmolality determined by an osmometer and the estimated total molarity of solute in serum by directly measuring the concentration of several substances and then substituting them into a published formula. Some authors call this sum the calculated or estimated osmolarity but, because the concentrations are measured directly and not with an osmometer, the calculated term represents molarity. The units of osmolality are mmol/kg of H2O and the units of molarity are mmol/L. Therefore, the practice of subtracting calculated serum molarity from measured serum osmolality is not mathematically sound and is an oversimplification for ease of application. This mathematical transgression necessarily adds an error to the incorrectly calculated OG. Despite this, the OG is commonly used in clinical medicine. Serum osmolality can be converted to molarity provided the weight percentage and the density of the solution are known and thus, we recommend that this conversion be done prior to calculation of the gap. We recommend that the gap between measured serum osmolarity and calculated serum molarity be called the 'osmolar gap'. After having corrected for non-ideality for serum and for inconsistency of units, the standard value and reference range for this gap must be determined in an adequate number of patient populations and in a variety of clinical settings. An example of this determination, using data from a group of ethanol-poisoned patients is given. This correction should be applied before the evaluation of the osmolar gap as a screening test for other low molecular weight substances proceeds.
Chemical Phenomena↗
Cost-effectiveness of the implantable cardioverter defibrillator: a review of current evidence.
INTRODUCTION: Implantable cardioverter defibrillator (ICD) therapy is indicated for patients at risk for sudden cardiac death (SCD) due to ventricular tachycardia (VT) or ventricular fibrillation (VF). The high relative cost of therapy with the ICD versus antiarrhythmic drugs has raised questions regarding its cost-effectiveness. To address these questions, we review the literature on ICD cost-effectiveness. METHODS AND RESULTS: MEDLINE and other databases were searched for articles published since 1980 reporting original data on the cost-effectiveness of ICD versus drug therapy for patients at risk for SCD. Data on costs and life-years were abstracted and studies grouped into decision analysis models and trial-based analyses. Cost-effectiveness ratios were inflated to 2002 US dollars. Thirteen economic studies were included in this review: 6 decision-analytic models, 4 economic analysis alongside randomized controlled trials, and 1 observational study. Two additional studies evaluated the cost-effectiveness of ICDs stratified by mortality risk. Studies varied in time horizon, and in all but one study ICD therapy was more costly than drug therapy. Early models assumed larger survival benefits than were observed in subsequent trials; therefore, ICDs appeared to be more cost-effective (i.e., US dollars 28000-US dollars 60000 per life-year gained). Three large clinical trial-based studies estimated that the cost per life-year gained was between US dollars 30181 and US dollars 185000. Stratified analyses show that patients at higher risk for mortality due to structural heart disease (e.g., left ventricular ejection fraction <35%) benefit more from ICD therapy, resulting in lower cost-effectiveness ratios. CONCLUSION: ICD therapy continues to evolve with changing methods of implantation and improving technology. Current evidence suggests that ICDs may be a cost-effective option in patients at high risk for VT/VF. The cost-effectiveness of ICD therapy for primary and secondary prevention of SCD depends upon patient characteristics that influence their prior risk of mortality. Further research on patient selection criteria and the measurement of health-related quality of life is required.
Arrhythmias, Cardiac↗
Patterns of inhaled asthma medication use: a 3-year longitudinal analysis of prescription claims data from British Columbia, Canada.
STUDY OBJECTIVES: To assess trends in asthma management and to identify factors associated with increasing short-acting (SA) beta-agonist utilization in British Columbia using administrative prescription data. DESIGN: A retrospective cohort analysis. SETTING: All patients between 13 and 50 years of age who had received at least one prescription for a SA beta-agonist covered by BC Pharmacare between January 1, 1996, and December 31, 1998. METHODS: Cross-sectional analysis of all patients, and longitudinal analyses only of patients who had received at least one SA beta-agonist prescription in each of the 3 years. Trends in asthma medication use over time were evaluated using repeated-measures Mantel-Haenszel tests. Multiple logistic regression was used to identify factors associated with increasing SA beta-agonist use. RESULTS: A total of 78,758 patients were included in the cohort. No decrease in the annual prevalence of receiving more than four canisters per year of a SA beta-agonist was identified between 1996 and 1998. A total of 12,844 patients filled at least one SA beta-agonist prescription each year. Time-trend analysis showed an overall increasing probability of not receiving an inhaled corticosteroid (ICS) agent in this population (p = 0.002). In patients exhibiting low SA beta-agonist use, > 18 years of age (adjusted odds ratio [OR], 1.5), male gender (adjusted OR, 1.7), and in receipt of social assistance (adjusted OR, 2.3) were associated with receiving increasing amounts of SA beta-agonist agents over the 3 years. In patients with a high degree of use of SA beta-agonists, only the receipt of social assistance (adjusted OR, 1.3) was significantly associated with increasing use. CONCLUSIONS: Despite the development and dissemination of asthma management guidelines, there was no trend toward decreasing SA beta-agonist use. An unexpected trend toward decreasing ICS utilization was identified. Receiving social assistance was a risk factor for increasing SA beta-agonist use, independent of baseline utilization.
Administration, Inhalation↗