Quality-adjusted Life Years For Patients Research Articles

Cost-Effectiveness of the 21-Gene Assay for Guiding Adjuvant Chemotherapy Decisions in Early Breast Cancer

ObjectivesAdjuvant chemotherapy decisions in early breast cancer are complex. The 21-gene assay can potentially aid such decisions, but costs US $4175 per patient. Adjuvant! Online is a freely available decision aid. We evaluate the cost-effectiveness of using the 21-gene assay in conjunction with Adjuvant! Online, and of providing adjuvant chemotherapy conditional upon risk classification. MethodsA probabilistic Markov decision model simulated risk classification, treatment, and the natural history of breast cancer in a hypothetical cohort of 50-year-old women with lymph node–negative, estrogen receptor– and/or progesterone receptor–positive, human epidermal growth factor receptor 2/neu–negative early breast cancer. Cost-effectiveness was considered from an Ontario public-payer perspective by deriving the lifetime incremental cost (2012 Canadian dollars) per quality-adjusted life-year (QALY) for each strategy, and the probability each strategy is cost-effective, assuming a willingness-to-pay of $50,000 per QALY. ResultsThe 21-gene assay has an incremental cost per QALY in patients at low, intermediate, or high Adjuvant Online! risk of $22,440 (probability cost-effective 78.46%), $2,526 (99.40%), or $1,111 (99.82%), respectively. In patients at low (high) 21-gene assay risk, adjuvant chemotherapy increases (reduces) costs and worsens (improves) health outcomes. For patients at intermediate 21-gene assay risk and low, intermediate, or high Adjuvant! Online risk, chemotherapy has an incremental cost per QALY of $44,088 (50.59%), $1,776 (77.65%), or $1,778 (82.31%), respectively. ConclusionsThe 21-gene assay appears cost-effective, regardless of Adjuvant! Online risk. Adjuvant chemotherapy appears cost-effective for patients at intermediate or high 21-gene assay risk, although this finding is uncertain in patients at intermediate 21-gene assay and low Adjuvant! Online risk.

The Effect of Sacral Neuromodulation on Anticholinergic Use and Expenditures in a Privately Insured Population

Sacral neuromodulation is Food and Drug Administration approved for many types of voiding dysfunction. Goals of treatment often include cessation of anticholinergic therapy. With the goal of understanding the impact of sacral neuromodulation on anticholinergic use, we analyzed patterns of care using a national claims-based dataset. The Ingenix (i3) data base contains insurance claims, including utilization and cost data, for 75 large employers. De-identified patients who underwent sacral neuromodulation between 2002 and 2007 were identified by the unique current procedural terminology-4 procedure code for pulse generator implantation, code 64590. The number and costs of anticholinergic prescriptions were compared before and after treatment. There were 266 percutaneous and 794 two-staged procedures performed from 2002 to 2007 in the i3 dataset. A total of 484 pulse generator implantations were performed, representing 46% of the test procedures. During the year prior to pulse generator placement, each patient purchased an average of 2.1 prescriptions for an anticholinergic agent (SD 3.5). During the year after neuromodulation, each patient purchased an average of 1.0 prescription (SD 2.3, p < 0.0001 by t-test). Prescription charges were $241.31 per patient before and $103.52 after neuromodulation, a statistically significant cost difference (p < 0.0001 by t-test). During the year before the procedure, 50% of patients filled anticholinergic prescriptions. This decreased to 23% after the procedure (p < 0.0001 by chi-square test). Sacral neuromodulation was associated with a significant decrease in the use of anticholinergic medication. Cost-effectiveness analyses that take into account patient quality-adjusted life years are needed to determine the true cost-benefit ratio of sacral neuromodulation.

Economic Evaluation of 5-Grass Pollen Tablets Versus Placebo in the Treatment of Allergic Rhinitis in Adults

BackgroundAllergen immunotherapy (AIT) is aimed at modifying the immune response to a causative allergen, thereby reducing clinical symptoms and symptomatic medication intake and improving quality of life. Long-term AIT research has led to the development of 5-grass pollen tablets, currently indicated for the treatment of grass pollen-induced allergic rhinitis (AR).MethodsA post-hoc analysis was conducted using the Average Adjusted Symptom Score (AAdSS) to compare the effect of treatment of AR with 5-grass pollen tablets versus placebo treatment. Using the results of the VO34.04 and VO53.06 trials and economic data, cost-effectiveness analysis of 5-grass pollen tablet treatment was performed from the Italian third-party payer perspective with cost data derived from a study of 2008 updated to 2011. Also a societal perspective was considered by using the costs related to the losses of productivity by following the human capital approach. Using the results of the analysis, the estimated receiver-operating characteristic curve was plotted to evaluate medication effectiveness in terms of quality-adjusted life years (QALYs) and a decision tree constructed to model the possible outcomes and costs for adults and paediatric patients with a low, medium, and high AAdSS. Finally, probabilistic sensitivity analysis was conducted to test the robustness of the results as well as their consistency at an assumed cost-effectiveness threshold of € 30,000/QALY.ResultsThe results indicate that compared to the placebo, the 5-grass pollen tablet treatment provides a benefit of 0.127 QALYs in medium AAdSS patients and of 0.143 QALYs in high AAdSS patients. The 5-grass pollen tablet treatment was found to cost € 1,024/QALY for patients with a medium AAdSS and € 1,035/QALY for patients with a high AAdSS. Of all the simulations performed in the probabilistic sensitivity analysis, 99 % indicated that the incremental cost-effectiveness ratio of the 5-grass pollen tablet treatment was below the threshold of € 30,000/QALY in patients with medium and high AAdSS, whereas it was found to be dominated in 67 % of simulations related to patients with low AAdSS.ConclusionThe 5-grass pollen tablet is a cost-effective treatment for adult AR patients with a medium or high AAdSS. This finding should be carefully considered when deciding the management strategy for these patients.

Incidence, life expectancy and prognostic factors in cancer patients under prolonged mechanical ventilation: a nationwide analysis of 5,138 cases during 1998-2007.

IntroductionThis study is aimed at determining the incidence, survival rate, life expectancy, quality-adjusted life expectancy (QALE) and prognostic factors in patients with cancer in different organ systems undergoing prolonged mechanical ventilation (PMV).MethodsWe used data from the National Health Insurance Research Database of Taiwan from 1998 to 2007 and linked it with the National Mortality Registry to ascertain mortality. Subjects who received PMV, defined as having undergone mechanical ventilation continuously for longer than 21 days, were enrolled. The incidence of cancer patients requiring PMV was calculated, with the exception of patients with multiple cancers. The life expectancies and QALE of patients with different types of cancer were estimated. Quality-of-life data were taken from a sample of 142 patients who received PMV. A multivariable proportional hazards model was constructed to assess the effect of different prognostic factors, including age, gender, type of cancer, metastasis, comorbidities and hospital levels.ResultsAmong 9,011 cancer patients receiving mechanical ventilation for more than 7 days, 5,138 undergoing PMV had a median survival of 1.37 months (interquartile range [IQR], 0.50 to 4.57) and a 1-yr survival rate of 14.3% (95% confidence interval [CI], 13.3% to 15.3%). The incidence of PMV was 10.4 per 100 ICU admissions. Head and neck cancer patients seemed to survive the longest. The overall life expectancy was 1.21 years, with estimated QALE ranging from 0.17 to 0.37 quality-adjusted life years for patients with poor and partial cognition, respectively. Cancer of liver (hazard ratio [HR], 1.55; 95% CI, 1.34 to 1.78), lung (HR, 1.45; 95% CI, 1.30 to 1.41) and metastasis (HR, 1.53; 95% CI, 1.42 to 1.65) were found to predict shorter survival independently.ConclusionsCancer patients requiring PMV had poor long-term outcomes. Palliative care should be considered early in these patients, especially when metastasis has occurred.

Cost per QALY (Quality-Adjusted Life Year) and Lifetime Cost of Prolonged Mechanical Ventilation in Taiwan

IntroductionPatients who require prolonged mechanical ventilation (PMV) are increasing and producing financial burdens worldwide. This study determines the cost per QALY (quality-adjusted life year), out-of-pocket expenses, and lifetime costs for PMV patients stratified by underlying diseases and cognition levels.MethodsA nationwide sample of 50,481 patients with continual mechanical ventilation for more than 21 days was collected during 1997–2007. After stratifying the patients according to specific diagnoses, a latent class analysis (LCA) was performed to categorise PMV patients with multiple co-morbidities into several homogeneous groups. The survival functions were estimated for individual groups using the Kaplan-Meier method and extrapolated to 300 months through a semi-parametric method. The survival functions were adjusted using an EQ-5D utility value derived from a convenience sample of 142 PMV patients to estimate quality-adjusted life expectancies (QALE). Another convenience sample of 165 patients was used to estimate the out-of-pocket expenses. The lifetime expenditures paid by the single-payer National Health Insurance (NHI) system and patients' families were estimated by multiplying average monthly expenditures by the survival probabilities and summing the values over lifetime.ResultsPMV therapy costs more than 100,000 U.S. dollars (USD) per QALY for all patients with poor cognition. For patients with partial cognition, PMV therapy costs less than 56,000 USD per QALY for those with liver cirrhosis, intracranial or spinal cord injuries, and 57,000–69,000 USD for patients with multiple co-morbidities under age of 65. The average lifetime cost of PMV was usually below 56,000 USD. The out-of-pocket expenses were often more than one-third of the total cost of treatment.ConclusionsPMV treatment for patients with poor cognition would cost more than 5 times Taiwan's GDP (gross domestic products), or less cost-effective. The out-of-pocket expenses for PMV provision should also be considered in policy decision.

Comparative effectiveness of donation after cardiac death versus donation after brain death liver transplantation: Recognizing who can benefit

Due to organ scarcity and wait-list mortality, transplantation of donation after cardiac death (DCD) livers has increased. However, the group of patients benefiting from DCD liver transplantation is unknown. We studied the comparative effectiveness of DCD versus donation after brain death (DBD) liver transplantation. A Markov model was constructed to compare undergoing DCD transplantation with remaining on the wait-list until death or DBD liver transplantation. Differences in life years, quality-adjusted life years (QALYs), and costs according to candidate Model for End-Stage Liver Disease (MELD) score were considered. A separate model for hepatocellular carcinoma (HCC) patients with and without MELD exception points was constructed. For patients with a MELD score <15, DCD transplantation resulted in greater costs and reduced effectiveness. Patients with a MELD score of 15 to 20 experienced an improvement in effectiveness (0.07 QALYs) with DCD liver transplantation, but the incremental cost-effectiveness ratio (ICER) was >$2,000,000/QALY. Patients with MELD scores of 21 to 30 (0.25 QALYs) and >30 (0.83 QALYs) also benefited from DCD transplantation with ICERs of $478,222/QALY and $120,144/QALY, respectively. Sensitivity analyses demonstrated stable results for MELD scores <15 and >20, but the preferred strategy for the MELD 15 to 20 category was uncertain. DCD transplantation was associated with increased costs and reduced survival for HCC patients with exception points but led to improved survival (0.26 QALYs) at a cost of $392,067/QALY for patients without exception points. In conclusion, DCD liver transplantation results in inferior survival for patients with a MELD score <15 and HCC patients receiving MELD exception points, but provides a survival benefit to patients with a MELD score >20 and to HCC patients without MELD exception points.

The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: a European analysis

It remains unclear whether primary prophylactic implantable cardioverter-defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy' in the European health care setting. We performed a cost-effectiveness analysis for a cohort of patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease. A Markov decision analytic model was used to evaluate long-term survival, quality-adjusted life years (QALYs), and lifetime costs for a cohort of patients with a reduced left ventricular function without previous arrhythmias, managed with a prophylactic ICD. Input data on effectiveness were derived from a meta-analysis of primary prophylactic ICD-only therapy randomized trials, from a prospective cohort study of ICD patients, from a health care utilization survey, and from the literature. Input data on costs were derived from a micro-cost analysis. Data on quality-of-life were derived from the literature. Deterministic and probabilistic sensitivity analysis was performed to assess the uncertainty. Probabilistic sensitivity analysis demonstrated a mean lifetime cost of €50 685 ± €4604 and 6.26 ± 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD strategy' accumulated €86 759 ± €3343 and an effectiveness of 7.08 ± 0.71 QALYs yielding an incremental cost-effectiveness ratio of €43 993/QALY gained compared with the 'no ICD strategy'. The probability that ICD therapy is cost-effective was 65% at a willingness-to-pay threshold of €80 000/QALY. Our results suggest that primary prophylactic ICD therapy in patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease is cost-effective in the European setting.

Is Early Surgical Decompression for Traumatic Cervical Spinal Cord Injury (SCI) Feasible and Cost-Effective? (S47.003)

Objective: This study compares early (≤24 hours since SCI) versus later surgical decompression of spinal cord in order to determine which approach is more cost effective in the management of patients with acute cervical SCI and to examine the potential barriers and ideal timelines for each step to early surgical decompression. Background Pre-clinical and clinical studies suggest that early surgery is potentially beneficial. Design/Methods: A cost-utility analysis was performed using data for the first year after cervical SCI. The perspective of a public health care insurer was adopted. Utilities are from the Surgical Trial in Acute SCI Study. The reasons for delays in the management steps were classified into: (a) healthcare-related (“extrinsic”) and (b) patient-related (“intrinsic”) factors. Results: When considering the late decompression as the baseline strategy, the incremental cost-effectiveness ratio is US$8,523,852 per quality-adjusted life year (QALY) for patients with complete SCI and US$275,390/QALY for patients with incomplete SCI. The probabilistic analysis indicated that there is no clearly dominant strategy. While patients who underwent early surgery had a significantly shorter time period associated with extrinsic factors than individuals who underwent later surgery (19.16 versus 71.28 hours), both groups were comparable regarding time periods related to intrinsic factors. Conclusions: The results of our economic analysis suggests that, although no strategy is clearly superior to the other, early decompression of spinal cord can be more cost effective than delayed surgery in approximately one quarter of the patients with complete SCI and one third of the individuals with incomplete SCI. Our benchmarking analysis suggests that health-related factors are key determinants of the timing from SCI to spinal cord decompression. Time in the general hospital and time of waiting for surgical decision were the most important causes of delays for surgery. Early surgery is feasible in the vast majority of the cases. Supported by: Funded by the Rick Hansen Foundation. Disclosure: Dr. Furlan has nothing to disclose. Dr. Fehlings has received personal compensation for activities with Depuy Spine as a consultant.

The structure of optimal statin initiation policies for patients with Type 2 diabetes

Lipid abnormalities increase the risk of coronary heart disease (CHD) and stroke in patients with Type 2 diabetes. Statins can be used to treat these abnormalities, but may have adverse side effects. In this article, we consider the optimal timing of statin initiation for patients with Type 2 diabetes. We formulate an infinite-horizon Markov decision process to maximize the patient's quality-adjusted life years (QALYs) prior to the occurrence of the first CHD or stroke event. We describe the state of the process by the patient's lipid ratio levels, and derive structural properties of the resulting optimal stopping time model, including sufficient conditions for the optimality of control-limit policies with respect to patient's lipid ratio levels and age. We use a large clinical data set to parameterize our model and compute optimal treatment policies to demonstrate the clinical implications of our results. We illustrate the importance of individualized treatment factors by estimating the patients’ QALY gains using our customized policies rather than current U.S. guidelines.

472 Interaction of ephrinB2 with its receptors EphB4 and EphB6 – potential impact on tumour-associated inflammation in human melanoma

The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation–positive NSCLCs. Afatinib and gefitinib costs and patients’ outcomes in France were assessed.A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation–positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted.For all EGFR mutation–positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations.First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation–positive NSCLCs.

Cost-effectiveness Analysis of Office vs. Home Biofeedback in the Treatment of Dyssynergic Defecation (DD)

Purpose: Biofeedback therapy has been shown to be effective for DD. Aim: We examined, whether, from a societal perspective, home biofeedback is cost-effective when compared to the standard office biofeedback therapy. Methods: This is an economic evaluation alongside a RCT. Costs related to both biofeedback programs were estimated from hospital financial records, study questionnaires and electronic medical records. A conversion algorithm, developed by Brazier, was used to calculate the patient's QALY (quality-adjusted life years) from SF-36 version 1 patient responses. Assessments were conducted at baseline and at 3 months when treatment was completed. Differences between costs and QALYs were evaluated using Wilcoxon rank sum test. Cost-effectiveness was expressed as incremental costs per QALY between treatment arms. Results: 81 patients (F/M 77/4) with DD participated (44 office and 37 home biofeedback). The median estimated cost per patient was $1,943 (Q1 $1622, Q3 $2369) for the office biofeedback and $ 1,082 (Q1 $ 795, Q3 1,400) for the home biofeedback arm. There was a significant cost difference of $861.00 (p<0.01). The median QALY gained during the trial period was 0.03 for office biofeedback and 0.07 for home biofeedback group, and the difference was not significant. The incremental cost effectiveness ratio was estimated to be $21,525 in favor of home biofeedback group. Conclusion: Home biofeedback is a cost-effective, alternative method of providing biofeedback therapy for dyssynergic defecation. It offers the potential of treating many more patients in the community, outside of hospitals or offices, and at a lower cost. Acknowledgement: NIH Grant- R01. This research was supported by a grant from NIH Grant R01.

Estimating a Preference-Based Single Index from the Overactive Bladder Questionnaire

Objectives The aim of the study is to estimate a preference-based single index for calculating quality-adjusted life years for patients with overactive bladder (OAB), based on a survey of the UK general population using the 5-dimensional health classification system OAB-5D, derived from the validated Overactive Bladder Questionnaire (OAB-q). Methods An interview valuation survey of members of public in the South Yorkshire, UK was undertaken using the time-trade-off method. Each respondent was randomly allocated to one of 14 blocks, and valued seven states each plus the “pits” state, so that a total of 99 states were valued. A number of multivariate regression models were estimated for predicting a total of 3125 health state values defined by the classification. Models were compared and selected using a set of criteria, including overall diagnosis by adjusted R-squared, the sign and significance of individual parameter estimates, the relative size of coefficients within a given dimension and predictive ability. Results The mean model was recommended for use in economic evaluation. Conclusion This will permit the cost-effectiveness of new interventions to be assessed in patients with OAB using existing and future OAB-q data sets.

Diagnostic Ascertainment of Suspicious Pancreatic Mass: A Threshold Analysis

It is frequently difficult to differentiate between a benign and malignant pancreatic mass. The aim of this study was to assess the parameters that affect the decision to perform surgery on a suspicious pancreatic head lesion. A cost-benefit analysis, using decision tree and threshold analysis, accumulates costs and quality-adjusted life years in patients undergoing pancreaticoduodenectomy or expectant management. The threshold value is defined as the diagnostic probability for pancreatic cancer when the cost-benefit relationships of pancreaticoduodenectomy or expectant management are equal. For a localized pancreatic head lesion, the threshold probability of cancer is 43%. Any higher probability of pancreatic cancer makes pancreaticoduodenectomy the preferred treatment option. Within a range of $20,000 to $80,000 spent on surgery, the threshold in favor of Whipple procedure remains relatively low at 40% to 65%. A reduced quality of life after surgery weighs against surgery and raises its threshold. Varying quality of life between 100% and 80% changes the threshold between 31% and 67%. The threshold also is increased in younger patients because of the potentially more dire consequences of unnecessary surgery in instances of long life expectancy. Even if diagnostic certainty cannot be achieved, it frequently is beneficial to perform surgery despite the risk of subjecting the occasional patient with benign pancreatic head lesion to an unnecessary pancreaticoduodenectomy.

Adalimumab Maintenance Therapy Is Cost Effective for Maintaining Remission in Patients with Crohnʼs Disease

Purpose: Adalimumab, a fully human monoclonal antibody targeting tumor necrosis factor, is approved for treatment of adults with moderate severe Crohn's disease (CD). CLASSIC I and CHARM are two Phase III studies of the effectiveness of adalimumab in inducing and maintaining remission, respectively, in patients with moderate to severe CD. Methods: The objective of this analysis was to evaluate the cost-effectiveness of adalimumab compared to nonbiologic therapies in the maintenance treatment of CD. A cost-utility model compared these strategies from the perspective of the UK National Health Service over 1-year and lifetime horizons. Patients were modeled in four disease states based on their Crohn's Disease Activity Index (CDAI) scores. CHARM data were directly used to estimate adalimumab arm efficacy. A regression model using CLASSIC I data was used to similarly predict the CDAI state of patients who received standard of care. Hospitalizations for both arms were modeled using the clinical trials data. Utilization of other medical resources was based on CDAI states. The cost of adalimumab was £357.50 per 40 mg vial, and the cost of standard care drugs was assumed to be zero. Costs of hospitalization and other medical resources were taken from Bassi et al., 2004. All costs were inflated to 2006 British Pounds (GBP) based on the annual UK health price index. Health utility inputs were sourced from Gregor et al., 1997. Univariate and probabilistic sensitivity analyses were conducted. Results: Compared with nonbiologic therapy, adalimumab appeared to be cost-effective in the treatment of patients with both severe CD and moderate to severe CD, with a 56-week incremental cost effectiveness ratio (ICER) of £16,064/quality-adjusted life-year (QALY) and £33,731/QALY, respectively. Sensitivity analyses demonstrated that the findings were robust. In the treatment of patients over their lifetimes, the ICERs were £5,479/QALY for patients with severe CD and £16,065/QALY for patients with moderate to severe CD. Sensitivity analyses demonstrated the robustness of the base case analysis. Conclusion: Adalimumab maintenance therapy for CD was cost-effective when compared to conventional nonbiological management. This research was funded by Abbott Laboratories, Abbott Park, IL.

Effectiveness and costs of screening for aneurysms every 5 years after subarachnoid hemorrhage

Patients who survive after subarachnoid hemorrhage (SAH) are at risk for a recurrence despite successful treatment of the ruptured aneurysm and may therefore benefit from screening for new aneurysms. We screened 610 patients with SAH with CT angiography 2-18 years after clipping of the aneurysms. Results of screening were used as input for a Markov decision model. We compared the expected number of recurrent hemorrhages, life expectancy, quality-adjusted life-years (QALYs), and costs associated with the strategies "screening every 5 years" and "no screening." Screening individuals with previous SAH prevented almost half of the recurrences, slightly increased life expectancy (from 21.06 to 21.08 years), but reduced QALYs (from 12.18 to 12.04) and increased costs (from $2,750 to $4,165 per patient). Screening was cost-saving without increasing QALYs in patients with a more than twofold risk above baseline of both aneurysm formation and rupture and it was cost-saving while increasing QALYs if both risks were at least 4.5 times higher. In patients with reduced quality of life because of fear for a recurrence, screening increased QALYs at a maximum cost of $17,422 per QALY. In general, screening patients with previous subarachnoid hemorrhage (SAH) cannot be recommended. Screening can save costs and increase quality-adjusted life-years (QALYs) in patients with a relatively high risk of both aneurysm formation and rupture, and increases QALYs at acceptable costs in patients with fear for a recurrence. More data are needed on risk factors for aneurysm formation and rupture in patients with previous SAH and on management of fear for a recurrence to identify patients who can benefit from screening.

Projecting the Long-Term Quality-Adjusted Survival of Patients with Imatinib-Resistant Chronic Myelogenous Leukemia in Chronic Phase Receiving Nilotinib, Dasatinib, Dose Escalation Imatinib, or Palliative Care: An Essential Element for Cost-Effectiveness Analysis.

Background: Imatinib is the mainstay in the treatment of chronic phase CML (CML-CP). However, in a minority of patients, resistance to imatinib is observed. Until recently, these patients underwent dose-escalation with imatinib (DEI) or stopped therapy and received no further tyrosine kinase inhibitors (TKIs). Recent evidence suggests that the new-generation TKIs nilotinib and dasatinib may provide an alternative for these patients. This study modeled the quality-adjusted life years (QALYs) of nilotinib, dasatinib, DEI, or no additional TKI (i.e., palliative care) in imatinib-resistant CML-CP patients, with the aim of using these estimates in cost effectiveness analyses.Methods: A Markov model linking major cytogenetic response (MCyR) at 6 months to long-term survival was developed to project disease progression and estimate QALYs associated with each treatment option for a CML-CP patient (male, age 56 years old). The 6-month MCyR was used as it was the furthest assessment time common across all treatment options. The fundamental tenet of the model was that imatinib-resistant patients achieving a MCyR at 6 months on any option live longer than those who do not. The proportions of patients achieving a MCyR at 6 months were derived from separate single-arm registration trials and epidemiologic studies of each option. The duration of survival for patients achieving/not achieving a MCyR at 6 months was determined by estimating the areas under the Kaplan-Meier survival curves of CML-CP patients with documented resistance to regular-dose imatinib who were receiving DEI (based on a subgroup analysis of patients enrolled in the IRIS study who underwent dose escalation) or no additional TKI. Duration of survival for responders/non responders was further divided into time spent in chronic phase (CP), accelerated phase (AP), and blast crisis (BC). The time spent in AP and BC was assumed independent of the treatment option received and was estimated using the literature. Thus, patients with MCyR were projected to live longer, spend more time in CP, and progressed more slowly compared to AP, BC, and ultimately CML-related death than patients without MCyR. Assumptions regarding the quality of life impacts of CML and the adverse events of the treatments were obtained from the literature.Results: Patients achieving and not achieving a MCyR at 6 months were projected to live 12.78 and 6.14 years, respectively. The proportion of patients achieving a MCyR at 6 months was 51% for nilotinib, 31% for dasatinib, 25% for DEI, and 2.5% for no additional TKI. Total survival and QALY were projected at 6.31 years and 4.62 QALYs for patients not receiving additional TKI therapy. Compared to these patients, those treated with nilotinib, dasatinib, DEI lived an additional 3.22, 1.89, and 1.49 years, respectively. Corresponding QALY gains were estimated to be 2.80, 1.62, and 1.30, respectively.Conclusion: This analysis suggests that nilotinib may be superior to dasatinib, followed by DEI, and no additional TKI in terms of projected survival and QALYs. These findings reflect the MCyR for each option observed at 6 months and are based on modeling and indirect comparisons. As such, they require confirmation through comparative studies but can nevertheless serve as a starting point for cost effectiveness analyses.

Life expectancy gains and cost-effectiveness of implantable cardioverter/defibrillators for the primary prevention of sudden cardiac death in patients with hypertrophic cardiomyopathy

Sudden cardiac death (SCD) is a devastating complication of hypertrophic cardiomyopathy (HCM). The optimal strategy for the primary prevention of SCD in HCM remains controversial. Using a Markov model, we compared the health benefits and cost-effectiveness of 3 strategies for the primary prevention of SCD: implantable cardioverter/defibrillator (ICD) insertion, amiodarone therapy, or no therapy. We modeled hypothetical cohorts of 45-year-old patients with HCM with no history of cardiac arrest but at significant risk of SCD (3%/y). Over a lifetime, compared with no therapy, ICD therapy increased quality-adjusted survival by 4.7 quality-adjusted life years (QALYs) at an additional cost of $142,800 ($30,000 per QALY), whereas amiodarone increased quality-adjusted survival by 2.8 QALYs at an additional cost of $104,900 ($37,300 per QALY). Compared with no therapy, ICD therapy would cost < $50,000 per QALY for patients (i) aged 25, with > or = 1 risk factors for SCD, and (ii) aged 45 or 65, with > or = 2 risk factors for SCD. An ICD strategy is projected to yield the greatest increase in quality-adjusted life expectancy of the 3 treatment strategies evaluated. Combined consideration of age and the number of risk factors for SCD may allow more precise tailoring of ICD therapy to its expected benefits.

Cost-effectiveness of pegaptanib compared to photodynamic therapy with verteporfin and to standard care in the treatment of subfoveal wet age-related macular degeneration in Canada

Background: Age-related macular degeneration (AMD) is characterized by loss of central vision and is the leading cause of blindness among persons over the age of 50 years in Canada. The wet form of AMD has 3 subtypes—occult, minimally classic, and predominantly classic. Photodynamic therapy (PDT) with verteporfin is indicated only for the category of predominantly classic wet AMD. Currently, there are no treatments available for the other AMD subtypes. Pegaptanib sodium was the first pharmacologic therapy approved in Canada for the treatment of subfoveal wet AMD regardless of subtype. Objective: The aim of this study was to examine the cost-effectiveness of pegaptanib versus PDT with verteporfin and versus standard care for the treatment of subfoveal wet AMD in patients aged ⁥65 years in Canada. Methods: A Markov model based on visual acuity in the better-seeing eye was developed. Clinical efficacy was taken from the clinical trials. Costs of treatment, comorbidities (eg, depression, fractures, need for assisted living), vision rehabilitation, visual aids, and adverse events were considered. Costs, utilities, and mortality were estimated from data from the available published literature. Costs were reported in 2004 Canadian dollars, and costs and outcomes were discounted at 3% per annum. Lifetime costs, quality-adjusted life-years (QALYs), and vision years gained (VYGs) were estimated. Sensitivity analyses were performed to determine model robustness. Results: Patients who received pegaptanib experienced more QALYs gained (4.17) and VYGs (3.83) compared with patients who received PDT (3.87 and 3.01, respectively) or standard care (3.96 and 3.26). Mean total costs per patient were greater in patients who received pegaptanib compared to those who received PDT or standard care ($20,016 vs $15,345 or $7669, respectively). The incremental cost per QALY in patients receiving pegaptanib compared to those receiving PDT was $49,052 and $59,039 for patients receiving pegaptanib versus standard care. The incremental cost per VYG was $20,401 and $21,559 with pegaptanib versus PDT and standard care, respectively. Sensitivity analyses found that the model was relatively robust to changes in various model parameters. Conclusion: The results of this analysis suggest that in Canada, pegaptanib is a cost-effective treatment for subfoveal wet AMD in elderly patients, regardless of lesion subtype, compared to PDT with verteporfin and to standard care.

Effects of ICD implantation on quality-adjusted life years in patients with congestive heart failure

Background Effects of prophylactic implantable cardioverter–defibrillator (ICD) on quality-adjusted life years (QALYs) in patients with congestive heart failure are uncertain. Methods We developed a decision model for patients at risk of sudden death due to reduced ejection fraction and who had no history of life-threatening ventricular arrhythmias. It estimated the QALYs for ICD strategy as a primary prevention for sudden cardiac death and conventional strategy without antiarrhythmic therapies. Results In a 3-year time period, the QALYs for patients with conventional strategy were higher than that of ICD strategy (2.19 years vs. 2.14 years). When the mortality rate of conventional strategy exceeded 8.6%/year and the hazard ratio of death for the ICD strategy was lower than 0.70, the ICD strategy was the superior treatment option. Conclusions The QALYs of patients with ICD could be lower than that of conventional strategy. Incorporating quality of life could affect decision making of ICD implantation.

Feasibility and cost‐effectiveness of using magnification chromoendoscopy and pepsinogen serum levels for the follow‐up of patients with atrophic chronic gastritis and intestinal metaplasia

The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia may lead to early diagnosis of gastric cancer. However, to-date no cost-effective model has been proposed. Improved endoscopic examination using magnification chromoendoscopy together with non-invasive functional assessment with pepsinogen serum levels are accurate in the diagnosis of intestinal metaplasia (extension) and minute dysplastic lesions. The aim of this study was to assess the feasibility and cost-effectiveness of a follow-up model for patients with atrophic chronic gastritis and intestinal metaplasia based on gastric mucosal status using magnification chromoendoscopy and pepsinogen. A cohort of patients with lesions as severe as atrophic chronic gastritis were followed-up according to a standardized protocol using magnification chromoendoscopy with methylene blue and measurement of serum pepsinogen I and II levels. A single node decision tree and Markov chain modeling were used to define cost-effectiveness of this follow-up model versus its absence. Transition rates were considered time-independent and calculated using primary data following cohort data analysis. Costs, quality of life and survival were estimated based on published data and extensive sensitivity analysis was performed. A total of 100 patients were successfully followed-up over 3 years. Seven cases of dysplasia were diagnosed during follow-up, all among patients with incomplete intestinal metaplasia at baseline, six of whom had extensive (pepsinogen I to II ratio <3) incomplete intestinal metaplasia. For those individuals with atrophic chronic gastritis or complete intestinal metaplasia, a yearly measurement of pepsinogen levels or an endoscopic examination on a 3-yearly basis would cost 455 euros per quality-adjusted life year (QALY) gain. Endoscopic examination and pepsinogen serum level measurement on a yearly basis would cost 1868 euros per QALY for patients with extensive intestinal metaplasia. The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia is both feasible and cost-effective if improved accurate endoscopic examination of gastric mucosa together with non-invasive assessment of gastric mucosal status are used to identify individuals at high-risk for development of gastric cancer.