Olaparib versus Placebo in Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer: A Cost-Utility Analysis from the Canadian Public Payer's Perspective.

Pancreatic cancer has an annual incidence of 2/10,000 in Canada, with a one-year mortality rate greater than 80%. In the absence of a cost-effectiveness analysis in Canada, this study's objective was to assess the cost-effectiveness of olaparib versus a placebo in adult patients with deleterious or suspected deleterious BRCA metastatic pancreatic adenocarcinoma, who did not show any progression for at least 16 weeks with first-line platinum-based chemotherapy. A partitioned survival model with a 5-year time horizon was adopted to estimate the costs and effectiveness. All of the costs were extracted from the public payer's available resources, effectiveness data were obtained from the POLO trial, and Canadian studies were used for utility inputs. Probabilistic sensitivity analyses and scenario analyses were performed. The total costs of olaparib and the placebo over five years were CAD 179,477 and CAD 68,569, with overall quality-adjusted life-years (QALYs) of 1.70 and 1.36, respectively. The incremental cost-effectiveness ratio (ICER) of the olaparib group compared with the placebo was CAD 329,517 per QALY. With a commonly cited willingness to pay (WTP) threshold of CAD 50,000 per QALY, the drug does not achieve acceptable cost-effectiveness mainly due to the high price of the medication and insufficient impact on the overall survival of patients with metastatic pancreatic cancer.

Is Total Hip Arthroplasty a Cost-Effective Option for Management of Displaced Femoral Neck Fractures? A Trial-Based Analysis of the HEALTH Study.

BACKGROUND: Displaced femoral neck fractures are a significant source of morbidity and mortality and can be treated with either hemiarthroplasty (HA) or total hip arthroplasty (THA). Proponents of THA have argued THA offers lower risk of revision, with improved functional outcomes when compared to HA. To evaluate cost effectiveness of THA compared with HA, a trial-based economic analysis of the HEALTH study was undertaken. METHODS: Health care resource utilization (HRU) and health-related quality of life (HRQoL) data were collected postoperatively and costed using publicly available databases. Using EuroQol-5 Dimensions (EQ-5D) scores, we derived quality adjusted life years (QALYs). A 1.5% discount rate to both costs and QALYs was applied. Age analyses per age group were conducted. All costs are reported in 2019 Canadian dollars. RESULTS: When compared with HA, THA was not cost-effective for all patients with displaced femoral neck fractures ($150,000/QALY gained). If decision makers were willing to spend $50,000 or $100,000 to gain one QALY, the probability of THA being cost-effective was 12.8% and 32.8%, respectively. In a subgroup of patients younger than 73 (first quartile), THA was both more effective and less costly. Otherwise, THA was more expensive and yielded marginal HRQoL gains. CONCLUSIONS: Our results suggest that for most patients, THA is not a cost-effective treatment for displaced femoral neck fracture management versus HA. However, THA may be cost effective for younger patients. These patients experience more meaningful improvements in quality of life with less associated cost because of shorter hospital stay and fewer postoperative complications. LEVEL OF EVIDENCE: Economic Level II. See Instructions for Authors for a complete description of levels of evidence.

A Canadian cost-effectiveness analysis of SAPIEN 3 transcatheter aortic valve implantation compared with surgery, in intermediate and high-risk severe aortic stenosis patients.

Background and objectives: The treatment of severe aortic stenosis requires replacement of the defective native valve. Traditionally, this has been done via surgery, but in the last 10 years, transcatheter techniques have emerged. Transcatheter aortic valve implantation (TAVI) is a less invasive option compared to surgical aortic valve replacement (SAVR), and this study evaluates the cost-effectiveness of TAVI versus SAVR in intermediate and high surgical risk patients in Canada. Methods: A Markov model was used to project the costs and quality-adjusted life years (QALYs) gained for TAVI using the SAPIEN 3 valve and SAVR over a 15-year time horizon. The PARTNER I and II studies were used to populate the model in terms of survival, clinical event rates and quality of life over time. The costs of TAVI with SAPIEN 3 and SAVR as well as the costs associated with events included in the model were derived from Canadian administrative and literature data. Costs were expressed in 2018 Canadian dollars and all future costs and QALYs were discounted at a rate of 1.5% annually. Probabilistic and one-way sensitivity analyses were conducted. Results: The incremental cost-effectiveness ratios of TAVI using the SAPIEN 3 valve compared to surgery were $28,154 per QALY gained in intermediate risk patients and $17,237 per QALY gained in high-risk patients. The results of the probabilistic analyses indicated that at willingness-to-pay threshold of $50,000 per QALY gained, the probability of TAVI to be cost-effective was greater than 0.9 in both intermediate-risk and high-risk patients. Sensitivity analyses showed the results were most sensitive to the time horizon used. Conclusion: TAVI using the SAPIEN 3 valve is highly likely to be cost-effective in Canadian patients with severe aortic stenosis who are at intermediate and high surgical risk.

Screening for atrial fibrillation in Canadian pharmacies: an economic evaluation.

BACKGROUND: Screening for undiagnosed atrial fibrillation may lead to treatment with oral anticoagulation therapy, which can decrease the risk of ischemic stroke. The objective of this study was to conduct an economic evaluation of the Program for the Identification of 'Actionable' Atrial Fibrillation in the Pharmacy Setting (PIAAF-Pharmacy), which screened 1145 participants aged 65 years or more at 30 community pharmacies in Ontario and Alberta between October 2014 and April 2015. METHODS: We used a 2-part decision model to evaluate the short- and long-term costs and quality-adjusted life-years (QALYs) of a pharmacy screening program for atrial fibrillation compared to no screening. Data from the PIAAF-Pharmacy study were used for the short-term model, and the relevant literature was used to extrapolate the benefits of the PIAAF-Pharmacy study in the long-term model. Costs and QALYs were calculated from a payer perspective over a lifetime horizon and were discounted at 1.5%/year. RESULTS: Screening for atrial fibrillation in pharmacies was associated with higher costs ($26) and more QALYs (0.0035) compared to no screening, yielding an incremental cost per QALY gained of $7480. Univariate and probabilistic sensitivity analyses confirmed that screening for atrial fibrillation in a pharmacy setting was a cost-effective strategy. INTERPRETATION: Our results support screening for atrial fibrillation in Canadian pharmacies. Given this finding, efforts should be made by provincial governments and pharmacies to implement such programs in Canada. The addition of atrial fibrillation screening alongside screening and management of other cardiovascular conditions may help to reduce the burden of stroke.

Economic evaluation of an influenza immunization strategy of healthy children.

OBJECTIVES: Vaccinating healthy children is proposed as a strategy to produce a herd effect and protect vulnerable groups. The Hutterite Influenza Prevention Study investigated this strategy, comparing communities with or without childhood influenza immunization programs. There are costs associated with vaccination therefore there may be a trade-off between these costs and the benefits of avoiding influenza cases. This evaluation estimates the cost-effectiveness of immunizing only healthy children in preventing cases of influenza within entire communities. METHODS: Effect data and resource utilization were collected during the trial. Cost data were collected from payer, literature and Internet sources. A two-stage bootstrap (TSB) with shrinkage correction was used to estimate average costs and effects. The incremental cost effectiveness ratio (ICER) and sample uncertainty around this estimate were calculated from the TSB results. RESULTS: Mean costs per patient for the treatment and control arms were $69.07 and $32.66 (difference $36.41). Mean number of influenza cases for the treatment and control arms were 0.04 and 0.27 (difference 0.23). ICER was $164.12 ($28.38, $2767.75) per case of influenza averted. CONCLUSIONS: Immunizing healthy children for influenza is more costly, yet more effective than no immunization in preventing cases in the sample. At a cost of $164.12 to prevent a case of influenza, immunizing healthy children to protect all community members may be considered costeffective. Estimated results are conservative as the influenza season was mild and the sample population was healthy. In a more severe season with a less healthy population the ICER is expected to decrease.

Cost-effectiveness of a shared computerized decision support system for diabetes linked to electronic medical records.

BACKGROUND: Computerized decision support systems (CDSSs) are believed to enhance patient care and reduce healthcare costs; however the current evidence is limited and the cost-effectiveness remains unknown. OBJECTIVE: To estimate the long-term cost-effectiveness of a CDSS linked to evidence-based treatment recommendations for type 2 diabetes. METHODS: Using the Ontario Diabetes Economic Model, changes in factors (eg, HbA1c) from a randomized controlled trial were used to estimate cost-effectiveness. The cost of implementation, development, and maintenance of the core dataset, and projected diabetes-related complications were included. The base case assumed a 1-year treatment effect, 5% discount rate, and 40-year time horizon. Univariate, one-way sensitivity analyses were carried out by altering different parameter values. The perspective was the Ontario Ministry of Health and costs were in 2010 Canadian dollars. RESULTS: The cost of implementing the intervention was $483,699. The one-year intervention reduced HbA1c by 0.2 and systolic blood pressure by 3.95 mm Hg, but increased body mass index by 0.02 kg/m², resulting in a relative risk reduction of 14% in the occurrence of amputation. The model estimated that the intervention resulted in an additional 0.0117 quality-adjusted life year; the incremental cost-effectiveness ratio was $160,845 per quality-adjusted life-year. CONCLUSION: The web-based prototype decision support system slightly improved short-term risk factors. The model predicted moderate improvements in long-term health outcomes. This disease management program will need to develop considerable efficiencies in terms of costs and processes or improved effectiveness to be considered a cost-effective intervention for treating patients with type 2 diabetes.

Economic evaluation of reamed versus unreamed intramedullary nailing in patients with closed and open tibial fractures: results from the study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures (SPRINT).

INTRODUCTION: Recently, results from the large, randomized study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures (SPRINT) trial suggested a benefit for reamed intramedullary nail insertion in patients with closed tibial shaft fractures largely based on cost-neutral autodynamizations and a potential advantage for unreamed intramedullary nailing in open fractures. We performed an economic evaluation to compare resource use and effectiveness of reamed and unreamed intramedullary nailing using a cost-utility analysis. METHODS: We calculated quality-adjusted life years (QALYs) for each patient from a self-administered health utility index 3 questionnaire for the first 12 months following the intramedullary nailing. A convenience sample of 235 SPRINT patients provided data on costs associated with health care resource utilization. All costs are reported in Canadian dollars for the 2008 financial year. RESULTS: We found incremental effects of -0.017 (95% confidence interval [CI] -0.021-0.058) and -0.002 (95% CI -0.060-0.062) QALYs for patients treated with reamed compared with unreamed intramedullary nails in closed and open fractures, respectively. The incremental costs for reamed compared with unreamed intramedullary nailing were $51 Canadian dollars (95% CI -$2298-$2400) in closed tibial fractures and $2546 Canadian dollars (95%CI -$1773-$6864) in open tibial fractures. Unreamed nailing dominated reamed nailing for both closed and open tibial fractures; however, the cost and the utility results had high variability. CONCLUSION: Our economic analysis from a governmental perspective suggests small differences in both cost and effectiveness with large uncertainty between reamed and unreamed intramedullary nailing.

General population versus disease-specific event rate and cost estimates: potential bias for economic appraisals.

Economic appraisals are increasingly being used for reimbursement decision making. Differences exist in the population data sources used in different studies and these differences may result in errors or biased estimates. A review of the literature suggests that very little has been written on this topic and guidelines and good practice documents are silent on the issue. Using illustrative examples, it was found that the population chosen for event/complication costing did not have a large impact on a cost-effectiveness analysis; however, the choice of population did have a large impact for cost-of-illness (COI) estimation. It was found that not controlling for event/complication rates in a nondiseased population resulted in a 15% inflated COI estimate and using event costs from the general population underestimated COI by 20-32%. Our analysis suggests that using event costs from the general population instead of a diseased population may not have a significant impact on cost-effectiveness estimates; however, COI studies should only use excess event/complication rates and should also only use event costs from populations with the disease.

Assessing the impact of censoring of costs and effects on health-care decision-making: an example using the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

OBJECTIVES: Losses to follow-up and administrative censoring can cloud the interpretation of trial-based economic evaluations. A number of investigators have examined the impact of different levels of adjustment for censoring, including nonadjustment, adjustment of effects only, and adjustment for both costs and effects. Nevertheless, there is a lack of research on the impact of censoring on decision-making. The objective of this study was to estimate the impact of adjustment for censoring on the interpretation of cost-effectiveness results and expected value of perfect information (EVPI), using a trial-based analysis that compared rate- and rhythm-control treatments for persons with atrial fibrillation. METHODS: Three different levels of adjustment for censoring were examined: no censoring of cost and effects, censoring of effects only, and censoring of both costs and effects. In each case, bootstrapping was used to estimate the uncertainty incosts and effects, and the EVPI was calculated to determine the potential worth of further research. RESULTS: Censoring did not impact the adoption decision. Nevertheless, this was not the case for the decision uncertainty or the EVPI. For a threshold of $50,000 per life-year, the EVPI varied between $626,000 (partial censoring) to $117 million (full censoring) for the eligible US population. CONCLUSIONS: The level of adjustment for censoring in trial-based cost-effectiveness analyses can impact on the decisions to fund a new technology and to devote resources for further research. Only when censoring is taken into account for both costs and effects are these decisions appropriately addressed.

Economics methods in the Clinical Outcomes Utilizing percutaneous coronary Revascularization and Aggressive Guideline-driven drug Evaluation (COURAGE) trial.

Percutaneous coronary intervention (PCI) remains a major therapeutic option for the treatment of chronic coronary artery disease. In the COURAGE trial, 2287 patients with chronic coronary disease were randomized between PCI with medical management and medical management alone. Embedded within the COURAGE trial is a detailed economic analysis being conducted in three health care systems: the US Veterans Administration (VA), Canada, and the US non-VA. Resource use and costs are being collected for each system and overall. Survival is assessed internally in the trial with mean follow-up of 4.5 years. Long-term mean survival will be estimated by projecting survival beyond the trial period by extrapolating the in-trial hazard rates. Utility is being assessed at baseline and at 1, 3, and 6 months and annually thereafter, using a computer-administered standard gamble. Quality-adjusted life years are calculated by multiplying survival by utility. The incremental cost-effectiveness ratio of PCI will be defined as the additional cost of PCI divided by the gain in life years and quality-adjusted life years. The 95% confidence regions of efficacy and costs will be determined by bootstrap over a range of acceptability thresholds, which will then be displayed in the cost-effectiveness plane and as a cost-effectiveness acceptability curve. A multilevel regression model will assess cost-effectiveness from a net benefit perspective. These approaches should provide the most detailed assessment available of the cost-effectiveness of PCI for coronary artery disease.

Economic evaluation of rivastigmine in patients with Parkinson's disease dementia.

BACKGROUND: The positive results of a randomised clinical trial of rivastigmine in patients with dementia associated with Parkinson's disease have been published recently. Patient-level healthcare utilisation data were also collected, and this report is the economic evaluation based on these data. OBJECTIVE: To determine the cost effectiveness of rivastigmine 3-12 mg/day in patients in whom mild to moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease. METHODS: A cost-effectiveness analysis was performed by applying Canadian and UK cost weights (year 2004 values) to healthcare utilisation data collected prospectively during a randomised, double-blind, multinational, 24-week trial of rivastigmine 3-12 mg/day (n = 362) versus placebo (n = 179). Patients were > or =50 years of age, had a Mini-Mental State Examination (MMSE) score of between 20 and 24 and had contact with a responsible caregiver at least 3 days a week.Quality-adjusted survival time, transformed from MMSE scores, was the measure of effectiveness. Caregiver costs included paid and unpaid time, and direct costs included concomitant medications, outpatient care, hospitalisations, long-term care and study medications. Analysis was conducted from a societal perspective with a time horizon of 24 weeks. RESULTS: Consistent with the improvement in clinical outcomes, there was an observed increase in quality-adjusted survival time in the rivastigmine arm of 2.81 quality-adjusted life-days (two-sided p-value 0.13 [90% CI -0.243, 5.86]). Using Canadian price weights, there was an observed increase in cost in the rivastigmine arm of Can 55.76 dollars(two-sided p-value 0.98 [90% CI -3431, 3543]), with a resulting incremental cost-effectiveness ratio of Can 7429 dollars per QALY. Using UK price weights, there was an observed decrease in cost in the rivastigmine arm of pound 26.18 (two-sided p-value 0.99 [90% CI -2407, 2355]). CONCLUSION: Although no between-treatment differences in cost were seen, the small sample size, highly variable cost distributions and short time horizon prevent us from making strong conclusions with regard to the effect of rivastigmine on total costs and, by inference, on cost effectiveness.

Cost-effectiveness of physiologic pacing: results of the Canadian Health Economic Assessment of Physiologic Pacing.

OBJECTIVES: The purpose of this study was to determine the cost-effectiveness of physiologic pacemakers. BACKGROUND: The Canadian Trial of Physiologic Pacing (CTOPP) was a large randomized trial that evaluated the efficacy of physiologic pacing compared with ventricular pacing. CTOPP also included a prospective cost-effectiveness substudy. METHODS: Resource usage and costs were collected from a subset of 472 patients (of 1,094) who received a physiologic pacemaker and 586 (of 1,474) who received a ventricular pacemaker. Costs included initial pacemaker implantation and all health care follow-up costs over a follow-up of 5.2 years. Costs are reported in 2004 Canadian dollars (1 Canadian dollar = 0.76 US dollars), with adjustments for censoring. Incremental cost-effectiveness was estimated as the ratio of the difference (treatment-control) in mean cost to the difference in life expectancy (mean survival), with costs and effects discounted at 3% per year. RESULTS: Over a mean follow-up of 3.1 years, physiologic pacing was associated with a gain of 0.01 life-years. This benefit increases to 0.25 life-years in the subgroup of patients with an intrinsic (unpaced) heart rate < or =60 bpm. Physiologic pacing was more expensive than ventricular (16,833 Canadian dollars vs 13,857 US dollars), largely because of the increased cost of dual-chamber devices. Among all substudy patients, the incremental cost-effectiveness of physiologic pacing is 297,600 Canadian dollars per life-year gained; however, this value falls to 16,343 Canadian dollars in patients with an intrinsic heart rate >60. CONCLUSIONS: In the short term, a strategy of routine implantation of physiologic pacemakers is not cost-effective by currently accepted standards. The selective use of these devices in patients likely to be pacemaker dependent appears to be cost-effective. Further studies with longer follow-up and which consider the benefit of reducing nonfatal cardiac events would be valuable.

Cost-effectiveness of rhythm versus rate control in atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common type of sustained cardiac arrhythmia, but recent trials have identified no clear advantage of rhythm control over rate control. Consequently, economic factors often play a role in guiding treatment selection. OBJECTIVE: To estimate the cost-effectiveness of rhythm-control versus rate-control strategies for atrial fibrillation in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM). DESIGN: Retrospective economic evaluation. Nonparametric bootstrapping was used to estimate the distribution of incremental costs and effects on the cost-effectiveness plane. DATA SOURCES: Data on survival and use of health care resources were obtained for all 4060 AFFIRM participants. Unit costs were estimated from various U.S. databases. TARGET POPULATION: Patients with atrial fibrillation who were 65 years of age or who had other risk factors for stroke or death, similar to those enrolled in AFFIRM. TIME HORIZON: Mean follow-up of 3.5 years. PERSPECTIVE: Third-party payer. INTERVENTIONS: Management of patients with atrial fibrillation with antiarrhythmic drugs (rhythm control) compared with drugs that control heart rate (rate control). OUTCOME MEASURES: Mean survival, resource use, costs, and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: A mean survival gain of 0.08 year (P = 0.10) was observed for rate control. Patients in the rate-control group used fewer resources (hospital days, pacemaker procedures, cardioversions, and short-stay and emergency department visits). Rate control costs 5077 dollars less per person than rhythm control. RESULTS OF SENSITIVITY ANALYSIS: Cost savings ranged from 2189 dollars o 5481 dollars per person. Rhythm control was more costly and less effective than rate control in 95% of the bootstrap replicates over a wide range of cost assumptions. LIMITATIONS: Resource use was limited to key items collected in AFFIRM, and the results are generalizable only to similar patient populations with atrial fibrillation. CONCLUSION: Rate control is a cost-effective approach to the management of atrial fibrillation compared with maintenance of sinus rhythm in patients with atrial fibrillation similar to those enrolled in AFFIRM.

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.

Oseltamivir for treatment of influenza in healthy adults: pooled trial evidence and cost-effectiveness model for Canada.

BACKGROUND: Influenza is a common viral respiratory infection that is associated with significant morbidity. Oseltamivir (Tamiflu) is a neuraminidase inhibitor-a new class of antiviral treatment for influenza where efficacy and safety has been established but cost-effectiveness is unknown. METHODS: A decision analytic model was used to estimate the costs and effectiveness of two treatment scenarios for empiric management of otherwise healthy nonelderly patients, presenting with influenza-like illness (ILI) to primary care physicians in Canada: 1) where oseltamivir is reimbursed and on formulary for prescription; and 2) where oseltamivir is not on formulary. Outcomes are influenza-days averted and quality-adjusted life-years (QALYs) gained. Effectiveness, utility, and pneumonia complication risk estimates are by pooled analysis of patient-level data from four clinical trials. Unit cost information (Canadian dollars) was obtained from published sources in Ontario. Probabilistic sensitivity analysis was conducted using Monte Carlo simulation. RESULTS: Of 2288 patients randomized, influenza was confirmed in 1575 (69%) and oseltamivir treatment reduced the mean time to symptom alleviation by 1.08 days (95% confidence interval CI] 0.58-1.59). Infected patients treated with oseltamivir had higher utility scores (quality of life) than placebo patients over the 7 days of follow-up (P <.05). Cost per influenza-day averted with oseltamivir on formulary is 49 US dollars (95% CI 31-107) and the cost per QALY is 57,863 US dollars (95% CI 48,919- 70,149 US dollars). Results are sensitive to the percentage of patients presenting to their physician beyond 48 hours from symptom onset who get oseltamivir and the prevalence of influenza among patients presenting with ILI. CONCLUSIONS: Oseltamivir for treatment of patients with ILI is potentially cost-effective if clinical diagnostic specificity for influenza observed in clinical trials is applicable to routine practice. More population-based information on the prevalence of influenza among early (<48 hours) presenters with ILI would be valuable.

Cost-effectiveness and cost-utility of long-term management strategies for heartburn.

OBJECTIVES: To compare the expected costs and outcomes of seven alternative long-term primary care strategies for the management of patients with moderate-to-severe heartburn over a 1-year period. METHODS: A decision-analytic model was developed to estimate costs and effects (weeks with heartburn symptoms and quality adjusted life years [QALYs]) for each strategy. Meta-analyses were used to synthesize acute treatment and maintenance studies and physician surveys to collect information on patient management. The impact of uncertainty on the base case results was assessed using probabilistic sensitivity analysis. Probability distributions were defined for key model parameters and techniques of Monte Carlo simulation were used to draw values from these distributions. Cost-effectiveness acceptability curves (CEACs) conditional on the monetary value decision makers are willing to pay for a symptom-free day or QALY were created for each strategy. RESULTS: In the base case, no strategy was strictly dominated by any other strategy. However, two strategies (maintenance H2-receptor antagonists H2RA] and step-down proton pump inhibitor PPI]) were dominated through principles of extended dominance. The least costly and least effective strategy was intermittent H2RA, while maintenance PPI was the most costly and most effective. CONCLUSIONS: This analysis showed that the best way of managing patients with heartburn depends on how much society is willing to pay to achieve health improvements. Based on the commonly quoted threshold of US 50,000 dollars per QALY, the optimal primary care strategy for managing patients with moderate-to-severe heartburn symptoms is to treat the symptoms with a PPI followed by maintenance therapy with an H2RA to prevent symptomatic recurrence.

A note on the estimation of confidence intervals for cost-effectiveness when costs and effects are censored.

BACKGROUND: The relation between methodological advances in estimation of confidence intervals (CIs) for incremental cost-effectiveness ratios (ICER) and estimation of cost effectiveness in the presence of censoring has not been explored. The authors address the joint problem of estimating ICER precision in the presence of censoring. METHODS: Using patient-level data (n = 168) on cost and survival from a published placebo-controlled trial, the authors compared 2 methods of measuring uncertainty with censored data: 1) Bootstrap with censor adjustment (BCA); 2) Fieller's method with censor adjustment (FCA). The authors estimate the FCA over all possible values for the correlation (rho) between costs and effects (range = -1 to + 1) and also examine the use of the correlation between cases without censoring adjustment (i.e., simple time-on-study) for costs and effects as an approximation for rho. RESULTS: Using time-on-study, which considers all censored observations as responders (deaths), yields 0.64 life-years gained at an additional cost of 87.9 for a cost per life-year of 137 (95% CI by bootstrap -5.9 to 392). Censoring adjustment corrects for the bias in the time-on-study approach and reduces the cost per life-year estimate to 132 (=72/0.54). Confidence intervals with censor adjustment were approximately 40% wider than the base-case without adjustment. Using the Fieller method with an approximation of rho based on the uncensored cost and effect correlation provides a 95% CI of (-48 to 529), which is very close to the BCA interval of (-52 to 504). CONCLUSIONS: Adjustment for censoring is necessary in cost-effectiveness studies to obtain unbiased estimates of ICER with appropriate uncertainty limits. In this study, BCA and FCA methods, the latter with approximated covariance, are simple to compute and give similar confidence intervals.

Thinking outside the box: recent advances in the analysis and presentation of uncertainty in cost-effectiveness studies.

As many more clinical trials collect economic information within their study design, so health economics analysts are increasingly working with patient-level data on both costs and effects. In this paper, we review recent advances in the use of statistical methods for economic analysis of information collected alongside clinical trials. In particular, we focus on the handling and presentation of uncertainty, including the importance of estimation rather than hypothesis testing, the use of the net-benefit statistic, and the presentation of cost-effectiveness acceptability curves. We also discuss the appropriate sample size calculations for cost-effectiveness analysis at the design stage of a study. Finally, we outline some of the challenges for future research in this area-particularly in relation to the appropriate use of Bayesian methods and methods for analyzing costs that are typically skewed and often incomplete.