Cost-Effectiveness of Lisocabtagene Maraleucel Versus Axicabtagene Ciloleucel and Tisagenlecleucel in the Third-Line or Later Treatment Setting for Relapsed or Refractory Large B-cell Lymphoma in the United States.

INTRODUCTION: The objective of this study was to evaluate the cost-effectiveness of lisocabtagene maraleucel (liso-cel) versus other available chimeric antigen receptor T-cell therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), in patients who had received at least two prior therapies from a United States (US) commercial third-party payer perspective. METHODS: To capture this heterogeneity in survival outcomes, we used mixture cure models to extrapolate progression-free survival (PFS) and overall survival (OS). Patient-level data from TRANSCEND NHL 001 for liso-cel and reconstructed patient-level data from ZUMA-1 for axi-cel, JULIET for tisa-cel, and SCHOLAR-1 for salvage chemotherapy, derived using the Guyot method, were used for OS and PFS. The model included adverse events associated with liso-cel, axi-cel, and tisa-cel. RESULTS: Liso-cel was less costly (incremental cost of - $74,980) and marginally more effective (0.002 incremental quality-adjusted life-years [QALY]) than axi-cel and had an incremental cost of $67,925 and 2.02 incremental QALYs over tisa-cel in the base case. Results remained consistent in sensitivity analyses, with the liso-cel OS cure fraction being the main driver of cost-effectiveness compared with both axi-cel and tisa-cel. CONCLUSION: This analysis estimated that liso-cel is cost-effective compared with tisa-cel and axi-cel from a commercial US payer perspective.

Modeling long-term health and economic implications of new treatment strategies for Parkinson's disease: an individual patient simulation study.

Background: Simulation modeling facilitates the estimation of long-term health and economic outcomes to inform healthcare decision-making. Objective: To develop a framework to simulate progression of Parkinson's disease (PD), capturing motor and non-motor symptoms, clinical outcomes, and associated costs over a lifetime. Methods: A patient-level simulation was implemented accounting for individual variability and interrelated changes in common disease progression scales. Predictive equations were developed to model progression for newly diagnosed patients and were combined with additional sources to inform long-term progression. Analyses compared a hypothetical disease-modifying therapy (DMT) with a standard of care to explore the drivers of cost-effectiveness. Results: The equations captured the dependence between the various measures, leveraging prior values and rates of change to obtain realistic predictions. The simulation was built upon several interrelated equations, validated by comparison with observed values for the Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) and UPDRS subscales over time. In a case study, disease progression rates, patient utilities, and direct non-medical costs were drivers of cost-effectiveness. Conclusions: The developed equations supported the simulation of early PD. This model can support conducting simulations to inform internal decision-making, trial design, and strategic planning early in the development of new DMTs entering clinical trials.

Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

OBJECTIVE: This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. METHODS: A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. RESULTS: Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. CONCLUSION: Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.

Simulation and matching-based approaches for indirect comparison of treatments.

Estimates of the relative effects of competing treatments are rarely available from head-to-head trials. These effects must therefore be derived from indirect comparisons of results from different studies. The feasibility of comparisons relies on the network linking treatments through common comparators; the reliability of these may also be impacted when the studies are heterogeneous or when multiple intermediate comparisons are needed to link two specific treatments of interest. Simulated treatment comparison and matching-adjusted indirect comparison have been developed to address these challenges. These focus on comparisons of outcomes for two specific treatments of interest by using patient-level data for one treatment (the index) and published results for the other treatment (the comparator) from compatible studies, taking into account possible confounding due to population differences. This paper provides an overview of how and when these approaches can be used as an alternative or to complement standard MTC approaches.

Methods for adjusting for bias due to crossover in oncology trials.

Trials of new oncology treatments often involve a crossover element in their design that allows patients receiving the control treatment to crossover to receive the experimental treatment at disease progression or when sufficient evidence about the efficacy of the new treatment is achieved. Crossover leads to contamination of the initial randomized groups due to a mixing of the effects of the control and experimental treatments in the reference group. This is further complicated by the fact that crossover is often a very selective process whereby patients who switch treatment have a different prognosis than those who do not. Standard statistical techniques, including those that attempt to account for the treatment switch, cannot fully adjust for the bias introduced by crossover. Specialized methods such as rank-preserving structural failure time (RPSFT) models and inverse probability of censoring weighted (IPCW) analyses are designed to deal with selective treatment switching and have been increasingly applied to adjust for crossover. We provide an overview of the crossover problem and highlight circumstances under which it is likely to cause bias. We then describe the RPSFT and IPCW methods and explain how these methods adjust for the bias, highlighting the assumptions invoked in the process. Our aim is to facilitate understanding of these complex methods using a case study to support explanations. We also discuss the implications of crossover adjustment on cost-effectiveness results.

Lifetime economic burden of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the most common cancer affecting men in the United States. The initial treatment and subsequent monitoring of PCa patients places a large burden on U.S. health care systems. The objectives of this study were to estimate the total and disease-related per-patient lifetime costs using a phase-based model of cancer care for PCa patients enrolled in Medicare. METHODS: A model was developed to estimate life-time costs for patients diagnosed with PCa. Patients ≥ 65 years old and diagnosed with PCa between calendar years 1991-2002 were selected from the SEER database. Using SEER, we estimated survival times for PCa patients from diagnosis until death. The period of time patients contributed to treatment phases was determined using an algorithm designed to model the natural history of PCa. Costs were obtained from the US SEER-Medicare database and estimated during specific phases of care. Cost estimates were then combined with survival data to yield total and PCa-related life-time costs. RESULTS: Overall, the model estimated life-time costs of $110,520 (95% CI 110,324-110,739) per patient. PCa-related costs made up approximately 31% of total costs ($34,432). CONCLUSIONS: Prostate cancer places a significant burden on U.S. health-care systems with average life-time PCa-related costs in excess of $30,000.

Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS).

OBJECTIVE: To evaluate and compare healthcare resource use and related costs in chronic migraine and episodic migraine in the USA and Canada. BACKGROUND: Migraine is a common neurological disorder that produces substantial disability for sufferers around the world. Several studies have quantified overall costs associated with migraine in general, with recent estimates ranging from $581 to $7089 per year. Although prior studies have characterized the clinical and humanistic burden of chronic migraine relative to episodic migraine, to the best of our knowledge only 1 previous study has compared chronic migraine and episodic migraine healthcare costs. The purpose of this study was to quantify and compare the direct medical costs of chronic migraine and episodic migraine using medical resource use data collected as part of the International Burden of Migraine Study. METHODS: Cross-sectional data were collected from respondents in 10 countries via a Web-based survey. Respondents were classified as chronic migraine (≥15 headache days/month) or episodic migraine (<15 headache days/month). Data collection included socio-demographic and clinical characteristics and medical resource use for headache (clinician and emergency department visits and hospitalizations over the preceding 3 months and medications over the preceding 4 weeks). Unit cost data were collected outside of the Web-based survey using publicly available sources and then applied to resource use profiles. Cost estimates are presented in 2010 US and Canadian dollars. RESULTS: In this manuscript, the analysis included data from respondents with migraine in the USA (N=1204) and Canada (N=681). The most common medical services utilized by all respondents included headache-specific medication, healthcare provider visits, emergency department visits, and diagnostic testing. In the USA, approximately one-quarter (26.2%) of chronic migraine participants vs 13.9% of episodic migraine participants reported visiting a primary care physician in the preceding 3 months (P<.001). In Canada, one-half (48.2%) of chronic migraine participants had a primary care physician visit, compared with 12.3% of episodic migraine subjects (P< .0001). Total mean headache-related costs for participants with chronic migraine in the USA were $1036 (±$1334) over 3 months compared to $383 (±807, P< .001) for persons with episodic migraine. In Canada, total mean headache-related costs among chronic migraine subjects were $471 (±1022) compared to $172 (±920, P< .001) for episodic migraine subjects. CONCLUSIONS: Chronic migraine was associated with higher medical resource use and total costs compared to episodic migraine. Therapies that reduce headache frequency could become important approaches for containing or reducing headache-related medical costs.

Evaluation of the consequences associated with diffuse vascular disease history in patients diagnosed with peripheral arterial disease: estimates from Saskatchewan health data.

BACKGROUND: Peripheral arterial disease (PAD) is caused by narrowing of the arteries in the lower extremities. Limited data exist concerning the impact of diffuse vascular disease (DVD) on prognosis and costs. Thus, the objective of this study is to estimate the impact of DVD on morbidity, mortality and costs. METHODS: PAD was identified between 1985 and 1995 and classified by extent of DVD at diagnosis: none (PAD only, reference group), prior myocardial infarction (MI), prior stroke, prior MI and stroke (MI + stroke), prior transient ischemic attack (TIA). Deaths and hospitalizations were identified through December 2000. Hospitalization costs were estimated from the Ontario Case Cost Project, reported in 2002 $CAD. Proportional hazards analyses measured the impact of vascular involvement on mortality while controlling for risk factors (e.g., age, cardiovascular history). RESULTS: Overall, 16,439 patients with PAD were included; 14.8% had a prior MI, 10.2% a prior stroke, 2.6% prior MI + stroke, 6.4% prior TIA, two-thirds had PAD only. Median survival was shorter for patients with prior MI (9.3 yrs), TIA (6.3), stroke (4.7), and MI+stroke (4.1) versus the reference group (9.9, p < 0.05, all comparisons). Analyses revealed that the death risk was 60% higher in patients with prior stroke and 84% higher for MI + stroke. Atherothrombotic and bleeding event-related costs were $712, $337, $268, and $170 higher per patient/year of follow-up in patients with a history of MI+stroke, MI, stroke, and TIA, respectively. CONCLUSION: Patients diagnosed with PAD with DVD have higher risk of poor outcomes and increased costs.

Cost-effectiveness of prasugrel versus clopidogrel in patients with acute coronary syndromes and planned percutaneous coronary intervention: results from the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-Thrombolysis in Myocardial Infarction TRITON-TIMI 38.

BACKGROUND: In patients with acute coronary syndromes and planned percutaneous coronary intervention, the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) demonstrated that treatment with prasugrel versus clopidogrel was associated with reduced rates of cardiovascular death, MI, or stroke and an increased risk of major bleeding. We evaluated the cost-effectiveness of prasugrel versus clopidogrel from the perspective of the US healthcare system by using data from TRITON-TIMI 38. METHODS AND RESULTS: Detailed resource use data were prospectively collected for all patients recruited from 8 countries (United States, Australia, Canada, Germany, Italy, Spain, United Kingdom, and France; n=3373 prasugrel, n=3332 clopidogrel). Hospitalization costs were estimated on the basis of diagnosis-related group and in-hospital complications. Cardiovascular medication costs were estimated by using net wholesale prices (clopidogrel=$4.62/d; prasugrel=$5.45/d). Life expectancy was estimated from in-trial cardiovascular and bleeding events with the use of statistical models of long-term survival from a similar population from the Saskatchewan Health Database. Over a median follow-up of 14.7 months, average total costs (including study drug) were $221 per patient lower with prasugrel (95% confidence interval, -759 to 299), largely because of a lower rate of rehospitalization involving percutaneous coronary intervention. Prasugrel was associated with life expectancy gains of 0.102 years (95% confidence interval, 0.030 to 0.180), primarily because of the decreased rate of nonfatal MI. Thus, compared with clopidogrel, prasugrel was an economically dominant treatment strategy. If a hypothetical generic cost for clopidogrel of $1/d is used, the incremental net cost with prasugrel was $996 per patient, yielding an incremental cost-effectiveness ratio of $9727 per life-year gained. CONCLUSIONS: Among acute coronary syndrome patients with planned percutaneous coronary intervention, treatment with prasugrel versus clopidogrel for up to 15 months is an economically attractive treatment strategy. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov. Unique identifier: NCT00097591.

Economic evaluation of atorvastatin for prevention of recurrent stroke based on the SPARCL trial.

OBJECTIVES: This study evaluated the economic implications of results obtained by the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. METHODS: To enable long-term projection of the trial results, a discrete event simulation of the course of clinical care after a recent stroke or transient ischemic attack (TIA) was developed. It generates pairs of identical patients; both receive usual care, one receives atorvastatin in addition. Their clinical course is simulated based on their risk of stroke, cardiovascular events, and case fatality rates taken from SPARCL, life expectancy from Saskatchewan Health data, and utility weights from literature. Costs, from a US health-care payer perspective in 2005 US dollars, were estimated for a within-trial 5-year period; survival and quality-adjusted life-years (QALYs) were extrapolated over a patient's lifetime; all discounted at 3%/year. RESULTS: The prevention of stroke, coronary, and other cardiovascular events expected with atorvastatin translates to mean gains of 0.155 life-years gained and 0.172 QALYs per patient over their lifetime. Reducing associated medical costs ($8405 vs. $11,237) but increasing drug costs ($13,984 vs. $8752) results in net $2400/patient, or $13,916/QALY gained. Probabilistic sensitivity analysis indicates no simulations yield ratios above $50,000/QALY. CONCLUSION: Prescribing atorvastatin for patients with prior stroke or TIA is expected to provide health benefits at an acceptable cost in the United States.

Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

INTRODUCTION: This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. METHODS: A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. RESULTS: Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. CONCLUSION: Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

Clinical and economic burden of infused iron chelation therapy in the United States.

BACKGROUND: Patients requiring chronic blood transfusions are at risk for iron overload, which, if not treated by iron chelation therapy (ICT), can create serious organ damage and reduce life expectancy. Current ICT requires burdensome 8- to 12-hour infusions five to seven times per week. STUDY DESIGN AND METHODS: A naturalistic study of the burden of infused ICT was conducted in four US centers. Data from the initial and most recent years of ICT were collected from medical charts of consenting thalassemia (n = 40) and sickle cell disease (n = 9) patients. Quality of life (QoL), treatment satisfaction, and ICT-related resource utilization data were also collected from a patient interview. RESULTS: Mean serum ferritin levels during the initial (2519 +/- 1382 ng/mL) and most recent (2741 +/- 2532 ng/mL) years remained unacceptably high and increased over time (306 +/- 2200 ng/mL; mean of 20+/- years of therapy). Within 30 days before interview, 55 percent of patients suffered at least one ICT-related adverse event; 76 percent missed at least one dose. QoL, measured by the SF-36, and treatment satisfaction appear compromised in this cohort. Although total annual costs of ICT were estimated at USD $30,000 to $35,000, drug accounted for only 50 to 60 percent of this amount. CONCLUSIONS: Infused ICT may not provide adequate effectiveness in the real world. High ferritin levels seem to be associated with ICT noncompliance, likely in relation to the bothersome mode of administration and side effects. The total cost of ICT appears to well exceed that of drug alone.

The time course of subsequent hospitalizations and associated costs in survivors of an ischemic stroke in Canada.

BACKGROUND: Documentation of the hospitalizations rates following a stroke provides the inputs required for planning health services and to evaluate the economic efficiency of any new therapies. METHODS: Hospitalization rates by cause were examined using administrative data on 18,695 patients diagnosed with ischemic stroke (first or subsequent, excluding transient ischemic attack) in Saskatchewan, Canada between 1990 and 1995. Medical history was available retrospectively to January 1980 and follow-up was complete to March 2000. Analyses evaluated the rate and timing of all-cause and cardiovascular hospitalizations within discrete periods in the five years following the index stroke. Cardiovascular hospitalizations included patients with a primary diagnosis of ischemic stroke, transient ischemic attack, myocardial infarction, stable or unstable angina, heart failure or peripheral arterial disease. RESULTS: One-third (36%) of patients were identified by a hospitalized stroke. Mean age was 70.5 years, 48.0% were male, half had a history of stroke or a transient ischemic attack at the time of their index stroke. Three-quarters of the patients (72.7%) were hospitalized at least once during a mean follow-up of 4.6 years, accruing CAD $24 million in the first year alone. Of all hospitalizations, 20.4% were related to cardiovascular disease and 1.6% to bleeds. In the month following index stroke, 12.5% were admitted, an average of 1.04 times per patient hospitalized. Strokes accounted for 33% of all hospitalizations in the first month. The rate diminished steadily throughout the year and stabilized in the second year when approximately one-third of patients required hospitalization, at a rate of about one hospitalization for every two patient-years. Mean lengths of stay ranged from nine days to nearly 40 days. Close-fitting Weibull functions allow highly specific probability estimates. Other cardiovascular risk factors significantly increased hospitalization rates. CONCLUSION: After stroke, there are frequent hospitalizations accounting for substantial additional costs. Though these rates drop after one year, they remain high over time. The number of other cardiovascular causes of hospitalization confirms that stroke is a manifestation of disseminated atherothrombotic disease.