Clinical and economic outcomes of adding [18F]FES PET/CT in estrogen receptor status identification in metastatic and recurrent breast cancer in the US.

BACKGROUND AND OBJECTIVES: Correct identification of estrogen receptor (ER) status in breast cancer (BC) is crucial to optimize treatment; however, standard of care, involving biopsy and immunohistochemistry (IHC), and other diagnostic tools such as 2-deoxy-2-[18F]fluoro-D-glucose or 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), can yield inconclusive results. 16α-[18F]fluoro-17ß-fluoroestradiol ([18F]FES) can be a powerful tool, providing high diagnostic accuracy of ER-positive disease. The aim of this study was to estimate the budget impact and cost-effectiveness of adding [18F]FES PET/CT to biopsy/IHC in the determination of ER-positive status in metastatic (mBC) and recurrent breast cancer (rBC) in the United States (US). METHODS: An Excel-based decision tree, combined with a Markov model, was developed to estimate the economic consequences of adding [18F]FES PET/CT to biopsy/IHC for determining ER-positive status in mBC and rBC over 5 years. Scenario A, where the determination of ER-positive status is carried out solely through biopsy/IHC, was compared to scenario B, where [18F]FES PET/CT is used in addition to biopsy/IHC. RESULTS: The proportion of true positive and true negative test results increased by 0.2 to 8.0 percent points in scenario B compared to scenario A, while re-biopsies were reduced by 94% to 100%. Scenario B resulted in cost savings up to 142 million dollars. CONCLUSIONS: Adding [18F]FES PET/CT to biopsy/IHC may increase the diagnostic accuracy of the ER status, especially when a tumor sample cannot be obtained, or the risk of a biopsy-related complication is high. Therefore, adding [18F]FES PET/CT to biopsy/IHC would have a positive impact on US clinical and economic outcomes.

Pharmacokinetic parameter driven outcomes model predicts a reduction in bleeding events associated with BAY 81-8973 versus antihemophilic factor (recombinant) plasma/albumin-free method in a Chinese healthcare setting.

BACKGROUND: Long-term prophylactic therapy is considered the standard of care for hemophilia A patients. This study models the long-term clinical and cost outcomes of two factor VIII (FVIII) products using a pharmacokinetic (PK) simulation model in a Chinese population. METHODS: Head-to-head PK profile data of BAY 81-8973 (KOVALTRY®) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, ADVATE®) were applied to a two-state (alive and dead) Markov model to simulate blood FVIII concentrations at a steady state in prophylactically-treated patients with hemophilia A. Worsening of the Pettersson score was simulated and decline was associated with the probability of having orthopaedic surgery. The only difference between the compounds was FVIII concentration at a given time; each subject was treated with 25 IU/kg every 3 days. The model used a lifetime horizon, with cycle lengths of 1 year. RESULTS: Cumulative bleeding events, joint bleeding events, and major bleeding events were reduced by 19.3% for BAY 81-8973 compared to rAHF-PFM. Hospitalizations and hospitalization days were also reduced by 19.3% for BAY 81-8973 compared to rAHF-PFM. BAY 81-8973 resulted in both cost savings and a gain in quality adjusted life years (QALYs) compared to rAHF-PFM. CONCLUSION: Based on modeled head-to-head comparisons, differences in PK-properties between BAY 81-8973 and rAHF-PFM result in a reduced number of bleeding events, leading to reduced costs and increased quality of life for BAY 81-8973. These results should be used to inform clinical practice in China when caring for patients with severe hemophilia A.

A comprehensive analysis of clinical, quality of life, and cost-effectiveness outcomes of key treatment options for benign prostatic hyperplasia.

Treatment options for men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) have variable efficacy, safety, and retreatment profiles, contributing to variations in patient quality of life and healthcare costs. This study examined the long-term cost-effectiveness of generic combination therapy (CT), prostatic urethral lift (PUL), water vapor thermal therapy (WVTT), photoselective vaporization of the prostate (PVP), and transurethral resection of the prostate (TURP) for the treatment of BPH. A systematic literature review was performed to identify clinical trials of CT, PUL, WVTT, PVP, and TURP that reported change in International Prostate Symptom Score (IPSS) for men with BPH and a prostate volume ≤80 cm3. A random-effects network meta-analysis was used to account for the differences in patient baseline clinical characteristics between trials. An Excel-based Markov model was developed with a cohort of males with a mean age of 63 and an average IPSS of 22 to assess the cost-effectiveness of these treatment options at 1 and 5 years from a US Medicare perspective. Procedural and adverse event (AE)-related costs were based on 2021 Medicare reimbursement rates. Total Medicare costs at 5 years were highest for PUL ($9,580), followed by generic CT ($8,223), TURP ($6,328), PVP ($6,152), and WVTT ($2,655). The total cost of PUL was driven by procedural ($7,258) and retreatment ($1,168) costs. At 5 years, CT and PUL were associated with fewer quality-adjusted life years (QALYs) than WVTT, PVP, and TURP. Compared to WVTT, the incremental cost-effectiveness ratios (ICERs) for both TURP and PVP were above a willingness-to-pay threshold of $50,000/QALY (TURP: $64,409/QALY; PVP: $87,483/QALY). This study provides long-term cost-effectiveness evidence for several common treatment options for men with BPH. WVTT is an effective and economically viable treatment in resource-constrained environments.

Cost-Effectiveness and Budget Impact of Emerging Minimally Invasive Surgical Treatments for Benign Prostatic Hyperplasia.

Background: Benign prostatic hyperplasia (BPH) is one of the most prevalent and costly chronic conditions among middle-aged and elderly men. Prostatic urethral lift (PUL) and convective water vapor thermal therapy (WVTT) are emerging minimally invasive surgical treatments as an alternative to traditional treatment options for men with moderate-to-severe BPH. This study evaluated the cost-effectiveness and budget impact of PUL and WVTT for men with BPH using long-term clinical outcomes. Methods: The cost-effectiveness and budget impact models were developed from a US Medicare perspective over a 4-year time horizon. The models were populated with males with a mean age of 63 and an average International Prostate Symptom Score (IPSS) of 22. Clinical inputs were extracted from the LIFT and Rezum II randomized controlled trials at 4 years. Utility values were assigned using IPSS and BPH severity levels. Procedural, adverse event, retreatment, follow-up, and medication costs were based on 2019 Medicare payment rates and Medicare Part D drug spending. One-way and probabilistic sensitivity analyses (PSAs) were performed. Results: At 4 years, PUL was associated with greater retreatment rates (24.6% vs 10.9%), lower quality-adjusted life-years (QALYs) (3.490 vs 3.548) and higher total costs (US$7393 vs US$2233) compared with WVTT, making WVTT the more effective and less costly treatment strategy. The 70% total cost difference of PUL and WVTT was predominantly driven by higher PUL procedural (US$5617 vs US$1689) and retreatment (US$976 vs US$257) costs. The PSA demonstrated that relative to PUL, WVTT yielded higher QALYs and lower costs 99% and 100% of the time, respectively. Conclusions: Compared to PUL, WVTT was a cost-effective and cost-saving treatment of moderate-to-severe BPH. These findings provide evidence for clinicians, payers, and health policy makers to help further define the role of minimally invasive surgical treatments for BPH.

Cost-effectiveness of overactive bladder treatments: from the US payer perspective.

AIM: To assess the cost-effectiveness of onabotulinumtoxinA (onabotA), implantable sacral nerve stimulation devices, percutaneous tibial nerve stimulation, anticholinergic medications and mirabegron compared with best supportive care (BSC) for management of refractory overactive bladder (OAB). METHODS: A Markov model was developed to compare the cost-effectiveness of treatment options with BSC over a 10-year time horizon. Resource utilization, discontinuation rates and costs were derived from unpublished and published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. RESULTS: Treatment with onabotA 100U produced the largest gain in QALYs (7.179) and lowest estimated incremental cost-effectiveness ratio ($32,680/QALY) of all assessed treatments compared with BSC. CONCLUSION: Compared with BSC, onabotA 100U was the most cost-effective treatment option for patients with refractory OAB.

Effect of Diabetes Treatment-Related Attributes on Costs to Type 2 Diabetes Patients in a Real-World Population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) results in a substantial economic burden on patients, health care systems, and society. Most literature assessing the cost of T2DM focuses on the long-term complications of the disease, the association between glucose control and cost, and patient characteristics resulting in poor and costly outcomes. However, it is likely that attributes specific to diabetes therapy can affect the use of costly resources. OBJECTIVE: To estimate the effect of diabetes treatment-related attributes, such as improved efficacy, adherence, and reduced risk for hypoglycemia, on costs to T2DM patients. METHODS: An observational, retrospective study was conducted using the Optum Clinformatics Database, which links medical and pharmacy claims to laboratory results. Patients aged ≥ 18 years with T2DM who had ≥ 1 antidiabetic medication claim; ≥ 1 hemoglobin A1c (A1c) test result; continuous enrollment in the health plan from April 1, 2010, to March 31, 2011; and at least 1 follow-up day were included. Nondiabetes specific total, inpatient, outpatient, emergency room, and other costs (along with antidiabetes medication costs) were defined for each patient. Generalized linear models with logarithm link were used to predict the 1-year and cumulative 3-year costs. Demographic factors and comorbidities were included as covariates in addition to the diabetes treatment-related attributes. RESULTS: In the entire analysis cohort, the average 3-year cost per patient was $74,862. The percentage effect on cost of diabetes treatment-related variables ranged from -18% to 429%. Drug adherence was associated with lower inpatient, outpatient, and emergency room costs and higher drug costs. Hypoglycemia was associated with higher inpatient, outpatient, emergency room, and other direct costs (except antidiabetic drug costs). Compared with A1c values ≤ 7%, patients with higher levels were associated with higher total and drug costs. CONCLUSIONS: Study results demonstrate the association between diabetes treatment-related attributes and costs, including inpatient, outpatient, drug, and total costs. This association raises the question: what would the effect of a new diabetes therapy, with high efficacy, high adherence, and reduced risk of hypoglycemia have on economic outcomes? DISCLOSURES: Funding from Sanofi supported this study. Tong was an employee of ProUnlimited, under contract with Sanofi during the time of the study. Kitio-Dschassi was a Sanofi employee at time of the analysis. Meng, Casciano, Stern, and Gultyaev are employees of LASER Analytica, which received research funds from Sanofi to conduct this database analysis. Lee was an employee at LASER Analytica at the time of the analysis and has received grants from Sanofi. This manuscript was presented as a poster at the American Diabetes Association, 76th Scientific Sessions; New Orleans, Louisiana; June 10-14, 2016. Study concept and design were contributed by Meng, Casciano, Gultyaev, and Kitio-Dschassi. Meng and Stern collected the data, and data interpretation was performed by Casciano, Lee, Tong, and Kitio-Dschassi. The manuscript was written primarily by Lee, along with Meng and Stern, and revised by Stern, Meng, Tong, Kitio-Dschassi, and Lee.

OnabotulinumtoxinA in the treatment of overactive bladder: a cost-effectiveness analysis versus best supportive care in England and Wales.

The cost-effectiveness of onabotulinumtoxinA (BOTOX(®)) 100 U + best supportive care (BSC) was compared with BSC alone in the management of idiopathic overactive bladder in adult patients who are not adequately managed with anticholinergics. BSC included incontinence pads and, for a proportion of patients, anticholinergics and/or occasional clean intermittent catheterisation. A five-state Markov model was used to estimate total costs and outcomes over a 10-year period. The cohort was based on data from two placebo-controlled trials and a long-term extension study of onabotulinumtoxinA. After discontinuation of initial treatment, a proportion of patients progressed to downstream sacral nerve stimulation (SNS). Cost and resource use was estimated from a National Health Service perspective in England and Wales using relevant reference sources for 2012 or 2013. Results showed that onabotulinumtoxinA was associated with lower costs and greater health benefits than BSC in the base case, with probabilistic sensitivity analysis indicating an 89 % probability that the incremental cost-effectiveness ratio would fall below £20,000. OnabotulinumtoxinA remained dominant over BSC in all but two scenarios tested; it was also economically dominant when compared directly with SNS therapy. In conclusion, onabotulinumtoxinA appears to be a cost-effective treatment for overactive bladder compared with BSC alone.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

OBJECTIVES: In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. METHODS: A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. RESULTS: All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. CONCLUSION: The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line yield better survival outcomes than those starting with pemetrexed-based combinations, a result that is attributable to the possibility of one further line of treatment with first-line bevacizumab-based treatment sequences.

Cost-effectiveness analysis of onabotulinumtoxinA (BOTOX(®)) for the management of urinary incontinence in adults with neurogenic detrusor overactivity: a UK perspective.

OBJECTIVES: To evaluate the cost effectiveness of onabotulinumtoxinA (BOTOX(®), 200 units [200 U]) for the management of urinary incontinence (UI) in adults with neurogenic detrusor overactivity (NDO) due to subcervical spinal cord injury or multiple sclerosis that is not adequately managed with anticholinergic drugs (ACHDs). PERSPECTIVE: UK National Health Service (NHS) perspective. METHODS: A Markov state-transition model was developed, which compared onabotulinumtoxinA + best supportive care (BSC) with BSC alone (comprising behavioural therapy and pads, alone or in combination with clean intermittent catheterization and possibly with ACHDs). Non-responders were eligible for invasive procedures. Health states were defined according to the reduction in UI episodes. Efficacy data and estimates of resource utilization were pooled from 468 patients on onabotulinumtoxinA in two phase III clinical trials. Drug costs (2013) and administration costs (NHS Reference Costs 2011-2012) were obtained from published sources. The time horizon of the model was 5 years, and costs and benefits were discounted at 3.5%. Scenario, one-way and probabilistic sensitivity analyses (PSAs) were conducted to explore uncertainties around the assumptions. RESULTS: In the base case, treatment with onabotulinumtoxinA + BSC over 5 years was associated with an increase in costs of £1,689 and an increase in quality-adjusted life-years (QALYs) of 0.4, compared with BSC alone, resulting in an incremental cost-effectiveness ratio of £3,850 per QALY gained. Sensitivity analyses showed that utility values had the greatest influence on model results. PSA suggests that onabotulinumtoxinA + BSC had a 100 % probability of being cost effective at a willingness to pay of <£20,000. CONCLUSION: For adult patients with NDO who are not adequately managed with ACHDs, onabotulinumtoxinA + BSC appears to be a cost-effective use of resources in the UK NHS.

Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain.

BACKGROUND: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain. METHODS: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses. RESULTS: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working fulltime and the proportion of patients who were able to return to work. CONCLUSION: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.

Development and validation of the Economic Assessment of Glycemic Control and Long-Term Effects of diabetes (EAGLE) model.

BACKGROUND: The Economic Assessment of Glycemic control and Long-term Effects of diabetes (EAGLE) model was developed to provide a flexible and comprehensive tool for the simulation of the long-term effects of diabetes treatment and related costs in type 1 and type 2 diabetes. METHODS: EAGLE simulations are based on risk equations, which were developed using published data from several large studies including the Diabetes Control and Complications Trial, the United Kingdom Prospective Diabetes Study, and the Wisconsin Epidemiological Study of Diabetic Retinopathy. Risk equations for the probability of complications (including hypoglycemia, retinopathy, macular edema, end-stage renal disease, neuropathy, diabetic foot syndrome, myocardial infarction, and stroke) were based on regression analyses, using linear, exponential, and quadratic regression formulae. Subsequent cost calculations are made from the simulated event rates. Internal validation of the EAGLE model was completed by comparing simulated event rates with the published event rates used as the basis for the model. RESULTS: EAGLE provides microsimulations of virtual patient cohorts for type 1 and type 2 diabetes over n years in 1-year cycles. Complications include microvascular and macrovascular events and death, which are calculated over time as cumulative incidences. Glycosylated hemoglobin levels over time are simulated in relation to treatment regimen. Internal validation demonstrated that each mean event rate simulated by EAGLE overlapped with the published mean event (within a range of +/-10%). CONCLUSIONS: The EAGLE model is an evidence-based, internally valid tool for the assessment of the long-term effects of diabetes treatment and related costs.