Fexapotide triflutate vs oral pharmacotherapy as initial therapy for moderate-to-severe benign prostate hyperplasia patients: a cost-effectiveness analysis.

BACKGROUND: To assess the price range in which fexapotide triflutate (FT), a novel injectable, is cost-effective relative to current oral pharmacotherapy (5 α-reductase inhibitor, α-blocker, 5 α-reductase inhibitor and α-blocker combination therapy) as initial therapy followed by surgery for moderate-to-severe benign prostate hyperplasia patients with lower urinary tract symptoms (BPH-LUTS). METHODS: We developed a microsimulation decision-analytic model to track the progression of BPH-LUTS and associated costs and quality-adjusted life years in the target population. The cost-effectiveness analysis was performed from Medicare's perspective with a time horizon of 4 years using 2019 US dollars for all costs. The microsimulation model considered treatment patterns associated with nonadherence to oral medication and progression to surgery. Model parameters were estimated from large randomized controlled trials, literature and expert opinion. For each initial treatment option, simulations were performed with 1000 iterations, with 1000 patients per iteration. RESULTS: Three upfront oral pharmacotherapy options are close in cost-effectiveness, with combination therapy being the most cost-effective option. Relative to upfront oral pharmacotherapy options, FT slightly increases quality-adjusted life years (QALY) per patient (1.870 (95% CI, 1.868 to 1.872) vs. 1.957 (95% CI, 1.955 to 1.959) QALYs). Under the willingness-to-pay (WTP) threshold of $150,000 per QALY, at price per injection of $14,000, FT is about as cost-effective as upfront oral pharmacotherapy options with net monetary benefit (NMB) $279,168.54. Under the WTP threshold of $50,000 per QALY, at price per injection of $5,000, FT is about as cost-effective as upfront oral pharmacotherapy options with NMB $92,135.18. In an alternative 10-year time horizon scenario, FT price per injection at $11,000 and $4,500 makes FT as cost-effective as oral pharmacotherapies. One-way sensitivity analysis showed this result is most sensitive to upfront therapy prices, FT efficacy and initial IPSS. At price per injections of $5,000, $10,000 and $15,000, the probability that FT is either cost-effective or dominant compared to upfront oral pharmacotherapy options using a WTP threshold of $150,000 per QALY is 100%, 93% and 40%, respectively. CONCLUSIONS: Compared to upfront oral pharmacotherapy options, FT would be cost-effective at a price per injection below $14,000, assuming a WTP threshold of $150,000 per QALY.

Cost-effectiveness analysis of extended extracorporeal membrane oxygenation duration in newborns with congenital diaphragmatic hernia in the United States.

BACKGROUND: The duration of extracorporeal membrane oxygenation (ECMO) has been historically confined in many centers to two weeks. We evaluated the cost-effectiveness of additional weeks on ECMO beyond two weeks for newborns with congenital diaphragmatic hernia (CDH) who may require longer stays to maximize survival potential. METHODS: We modeled lifetime outcomes using a decision tree from the US societal perspective. Survival at discharge, probability of long-term sequelae, direct medical costs, indirect costs, and quality-adjusted life years (QALY) for long-term disability were considered. Considering the nature of severity of CDH, we used $200,000 per QALY as the willingness-to-pay threshold in the base case. RESULTS: The lifetime costs per CDH infant generated from staying on ECMO for ≤2 weeks, 2-3 weeks, and >3 weeks are $473,334, $654,771, $1,007,476, respectively (2018 USD), and the total QALYs gained from each treatment arm are 1.83, 3.6, and 5.05. In the base case, the net monetary benefits are -$108,034 for ECMO ≤2 weeks, $64,258 for 2-3 weeks, and $2955 for >3 weeks. In probabilistic simulations, a duration of ≤2 weeks is dominated by a duration of 2-3 weeks in 65.3% of cases and dominated by > 3 weeks in 60.2% of cases. A duration of 2-3 weeks is more cost-effective than >3 weeks in 68.6% of simulations. CONCLUSION: Our findings suggest that 2-3 weeks of ECMO may be the most cost-effective for CDH infants that are unable to wean off at 2 weeks from the US societal perspective. Regardless of ECMO duration, ECMO use generates positive incremental NMB at WTP of $200,000 if the survival probability is greater than 0.3. Future research must be conducted to evaluate the long-term outcomes and sequelae of CDH patients post-discharge to better inform the clinical decision-making in neonatal intensive care unit.

Where Do We Go From Here? A Framework for Using Susceptible-Infectious-Recovered Models for Policy Making in Emerging Infectious Diseases.

OBJECTIVES: Throughout the coronavirus disease 2019 pandemic, susceptible-infectious-recovered (SIR) modeling has been the preeminent modeling method to inform policy making worldwide. Nevertheless, the usefulness of such models has been subject to controversy. An evolution in the epidemiological modeling field is urgently needed, beginning with an agreed-upon set of modeling standards for policy recommendations. The objective of this article is to propose a set of modeling standards to support policy decision making. METHODS: We identify and describe 5 broad standards: transparency, heterogeneity, calibration and validation, cost-benefit analysis, and model obsolescence and recalibration. We give methodological recommendations and provide examples in the literature that employ these standards well. We also develop and demonstrate a modeling practices checklist using existing coronavirus disease 2019 literature that can be employed by readers, authors, and reviewers to evaluate and compare policy modeling literature along our formulated standards. RESULTS: We graded 16 articles using our checklist. On average, the articles met 6.81 of our 19 categories (36.7%). No articles contained any cost-benefit analyses and few were adequately transparent. CONCLUSIONS: There is significant room for improvement in modeling pandemic policy. Issues often arise from a lack of transparency, poor modeling assumptions, lack of a system-wide perspective in modeling, and lack of flexibility in the academic system to rapidly iterate modeling as new information becomes available. In anticipation of future challenges, we encourage the modeling community at large to contribute toward the refinement and consensus of a shared set of standards for infectious disease policy modeling.

Diagnosing newborns with suspected mitochondrial disorders: an economic evaluation comparing early exome sequencing to current typical care.

PURPOSE: To determine the value of early exome sequencing (eES) relative to the current typical care (TC) in the diagnosis of newborns with suspected severe mitochondrial disorders (MitD). METHODS: We used a decision tree-Markov hybrid to model neonatal intensive care unit (NICU)-related outcomes and costs, lifetime costs and quality-adjusted life-years among patients with MitD. Probabilities, costs, and utilities were populated using published literature, expert opinion, and the Pediatric Health Information System database. Incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB) were calculated from lifetime costs and quality-adjusted life-years for singleton and trio eES, and TC. Robustness was assessed using univariate and probabilistic sensitivity analyses (PSA). Scenario analyses were also conducted. RESULTS: Findings indicate trio eES is a cost-minimizing and cost-effective alternative to current TC. Diagnostic probabilities and NICU length-of-stay were the most sensitive model parameters. Base case analysis demonstrates trio eES has the highest incremental NMB, and PSA demonstrates trio eES had the highest likelihood of being cost-effective at a willingness-to-pay (WTP) of $200,000 relative to TC, singleton eES, and no ES. CONCLUSION: Trio and singleton eES are cost-effective and cost-minimizing alternatives to current TC in diagnosing newborns suspected of having a severe MitD.

Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

OBJECTIVES: Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin. METHODS: A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective. RESULTS: For overall CDI treatment, oral vancomycin had a cost of $39 178 and was associated with a gain of 11.64 quality-adjusted life-years (QALYs). Extended-pulsed fidaxomicin had a higher QALY gain of 11.65 at a lower cost of $37 613, and therefore was dominant over vancomycin. Standard fidaxomicin had a QALY gain of 11.94 versus vancomycin at an incremental cost of $495 per QALY. Bezlotoxumab plus vancomycin led to a QALY gain of 11.77 at an incremental cost of $17 746 per QALY. At the willingness-to-pay (WTP) threshold of $150 000 per QALY, extended-pulsed fidaxomicin, bezlotoxumab plus vancomycin and standard fidaxomicin were more cost-effective compared with vancomycin alone, yielding incremental net monetary benefits of $3248, $17 011 and $44 308, respectively. One-way sensitivity analysis suggested that the probabilities of sustained cure from the initial episode were the most sensitive inputs, and results were overall not particularly sensitive to any drug costs. CONCLUSIONS: Based on a WTP threshold of $150 000, standard fidaxomicin was estimated to be the most cost-effective treatment. Standard-of-care vancomycin was dominated by extended-pulsed fidaxomicin for treating an episode of CDI and preventing further recurrence, and the addition of bezlotoxumab to vancomycin was dominated by standard fidaxomicin.

Reconstruction After Salvage Total Laryngectomy: A Cost-effectiveness Analysis.

OBJECTIVE: To determine the most cost-effective reconstruction method after salvage total laryngectomy. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Tertiary care hospitals with head and neck oncologic and reconstructive surgeons. SUBJECTS AND METHODS: We constructed a Markov-based decision model to compare reconstruction by primary closure to pectoralis flap and free flap after salvage total laryngectomy. The model simulated disease with transition probabilities and health utilities found in primary literature and estimated the average overall cost of each reconstructive method using Medicare billing codes. Effectiveness was compared using quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were performed to scrutinize the conclusions of our model. Reconstruction methods were compared using incremental cost-effectiveness ratios (ICERs). In the United States, less than $150,000 per QALY gained is considered cost-effective (2019 US dollars). RESULTS: Our base case analysis revealed that primary closure was less expensive ($44,370) and yielded more QALYs (0.91) than both pectoralis ($45,163, 0.81 QALYs) and free flap ($46,244, 0.85 QALYs), making it the most cost-effective option. Between flaps, free flap was cost-effective over pectoralis flap (ICER = $27,025/QALY gained). Sensitivity analyses showed primary closure as cost-effective 69% of the time over either flap. These conclusions were sensitive to the health utilities (quality of life) of each method of reconstruction. CONCLUSION: Tissue flaps to augment closure after salvage total laryngectomy are not always the most cost-effective reconstructive option. The long-term morbidity of flap surgery oftentimes outweighs the benefit of lowering fistula rates after surgery. Careful consideration must be taken when advising patients of their reconstructive options.

Characterizing the Validity and Real-World Utility of Health Technology Assessments in Healthcare: Future Directions Comment on "Problems and Promises of Health Technologies: The Role of Early Health Economic Modelling".

With their article, Grutters et al raise an important question: What do successful health technology assessments (HTAs) look like, and what is their real-world utility in decision-making? While many HTAs are published in peer-reviewed journals, many are considered proprietary and their attributes remain confidential, limiting researchers' ability to answer these questions. Models for economic evaluations like cost-effectiveness analyses (CEAs) synthesize a wide range of evidence, are often statistically and mathematically sophisticated, and require untestable assumptions. As such, there is nearly universal agreement among researchers that enhancing transparency is an important issue in health economic modeling. However, the definition of transparency and guidelines for its implementation vary. Model registration combined with a linked database of model-based economic evaluations has been proposed as a solution, whereby registered models and their accompanying technical and nontechnical documentation are sourced into a single publicly-available repository, ideally in a standardized format to ensure consistent and complete representation of features, code, data sources, results, validation exercises, and policy recommendations. When such a repository is ultimately created, modelers will not have to reinvent the wheel for every new drug launched or new treatment pathway. These more open and transparent approaches will have substantial implications for model accuracy, reliability, and validity, improving trust and acceptance by healthcare decision-makers.

Outcomes and Utilization of Adjuvant Chemotherapy for Stage II Colon Cancer in the Oxaliplatin Period: A SEER-Medicare Analysis.

PURPOSE: Previous SEER (Surveillance, Epidemiology, and End Results)-Medicare analyses have shown no definitive survival benefit for adjuvant chemotherapy (AC) with fluoropyrimidines. Impact of oxaliplatin-containing regimens for elderly stage II patients in real-world setting is unknown. We explored the utilization and outcome of AC after the Food and Drug Administration (FDA) approval of oxaliplatin. PATIENTS AND METHODS: Patients with stage II colon cancer (2004-2011) who underwent resection were selected for this analysis. Medicare claims data were used to ascertain the administration of AC within 120 days after surgery. The primary endpoint of the analysis was overall survival. We used the Cox proportional hazards model to estimate the effect of AC while adjusting for clinical and sociodemographic variables available in SEER. To adjust for referral pattern, a source of selection bias, we conducted an instrumental variable analysis using the surgeon of record and health service area. RESULTS: A total of 16,468 patients were identified and 12.1% received AC. AC recipients were significantly younger, more likely to be male, nonwhite, married, and had lower comorbidity index. Their tumors had a more advanced stage, more likely to be left sided, and were less differentiated. The hazard ratio (HR) from the Cox model showed a statistically significant survival advantage for AC (HR=0.847, 95% confidence interval: 0.782-0.916). However, results from the instrumental variable analysis indicated that there was no definitive benefit of survival in AC recipients (HR=1.779, 95% confidence interval: 0.927-3.415). AC use decreased over time. CONCLUSIONS: After controlling for referral patterns, administration of AC provided no definitive survival benefit. Future studies may elucidate the elderly population who may benefit from AC.

Cost-Effectiveness Analysis of Four Common Diagnostic Methods for Clostridioides difficile Infection.

BACKGROUND: No studies have evaluated the cost-effectiveness of single and two-step different diagnostic test strategies for Clostridioides difficile infection (CDI), including direct and indirect costs. OBJECTIVE: To evaluate the cost-effectiveness of commonly available diagnostic tests for CDI including nucleic acid amplification testing (NAAT) alone, glutamate dehydrogenase followed by enzyme immunoassay for toxin (GDH/EIA), GDH then NAAT (GDH/NAAT), and NAAT then EIA (NAAT/EIA). DESIGN: Decision tree model from the US societal perspective with inputs derived from the literature. Willingness-to-pay threshold was set at $150,000 per quality-adjusted life year (QALY) gained. To assess the impact of uncertainty in model inputs on the findings, we performed one-way and probabilistic sensitivity analyses. PARTICIPANTS: We conducted the analysis to represent a population aged 65 years old with diarrhea who received a CDI diagnostic test. MAIN MEASURES: Incremental cost-effectiveness ratios (ICER) and incremental net monetary benefits (INMB). KEY RESULTS: NAAT alone was the most cost-effective approach overall; GDH/NAAT was the most cost-effective two-step option. NAAT alone led to the highest QALYs gained, at an incremental cost of $54,547 (vs. GDH/NAAT), $55,410 (vs. GDH/EIA), and $50,231 (vs. NAAT/EIA) per QALY gained. NAAT/EIA was not cost-effective compared to any other strategy. GDH/NAAT resulted in a higher QALY compared to GDH/EIA, at an incremental cost of $96,841 per QALY gained. Variability in the likelihood of comorbidities, CDI probability, and age at disease onset did not substantially change the results. One-way sensitivity analyses showed that results were most sensitive to likelihood of recurrence, followed by CDI mortality rate and probability of severe CDI. Probabilistic sensitivity analyses explored known uncertainties in the base case and confirmed the robustness of the results. CONCLUSIONS: NAAT alone and GDH/NAAT (among the two-step options) were the most cost-effective diagnostic test approaches for CDI.

Now Is the Time for Transparency in Value-Based Healthcare Decision Modeling.

In contrast to many other countries, during the 20 years since the founding of Value in Health, the United States has moved further away from using value-based healthcare decision modeling (VHDM) for drugs and other medical care choices. US public and private health plans can be typically characterized as using "budget impact" decision making rather than VHDM, with drugs having low per-member per-month spending likely to be covered and reimbursed regardless of value. Orphan drugs and specialty drugs with relatively few patients (eg, end-stage cancer drugs) are often covered, whether cost-effective or not, because health plans want to avoid negative publicity. Although there are many explanations for the poor US uptake of VHDM, a key reason is that VHDM models and data often lack transparency and are not generally made available to researchers for independent verification and reproducibility. This violates the scientific method, and is counter to the stated position of the National Academy of Sciences and the top journals in the sciences and social sciences. Value in Health and related peer-reviewed journals could make a key contribution to improving scientific rigor and real-world healthcare decision-maker acceptability by requiring that VHDM models, source code, and data used in published articles be made freely available to interested readers.

Early onset sepsis calculator-based management of newborns exposed to maternal intrapartum fever: a cost benefit analysis.

OBJECTIVE: To determine potential net monetary benefit of an early onset sepsis calculator-based approach for management of neonates exposed to maternal intrapartum fever, compared to existing guidelines. STUDY DESIGN: We performed a cost-benefit analysis comparing two management approaches for newborns >34 weeks gestational age exposed to maternal intrapartum fever. Probabilities of sepsis and meningitis, consequences of infection and antibiotic use, direct medical costs, and indirect costs for long-term disability and mortality were considered. RESULTS: A calculator-based approach resulted in a net monetary benefit of $3998 per infant with a 60% likelihood of net benefit in probabilistic sensitivity analysis. Our model predicted a 67% decrease in antibiotic use in the calculator arm. The absolute difference for all adverse clinical outcomes between approaches was ≤0.6%. CONCLUSIONS: Compared to existing guidelines, a calculator-based approach for newborns exposed to maternal intrapartum fever yields a robust net monetary benefit, largely by preventing unnecessary antibiotic treatment.

Cost-effectiveness of rivaroxaban versus warfarin for treatment of nonvalvular atrial fibrillation in patients with worsening renal function.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) is highly prevalent and increases the risks of cardiovascular events. In a recent subgroup analysis, treatment response was shown to vary for patients exhibiting worsening renal function (WRF) on-treatment. It is important to understand the cost-effectiveness of novel oral anticoagulant (NOAC) use in this population. METHODS: A cost-effectiveness analysis (CEA) was conducted using a Markov model to determine whether NOAC rivaroxaban treatment is cost-effective relative to warfarin in NVAF patients with on-treatment WRF. Input parameters were sourced from clinical literature including a multicenter clinical trial and subgroup analysis. We studied elderly US male patients at increased risk for stroke (CHADS2 score ≥ 2) undergoing treatment for NVAF and exhibiting WRF. Main outcome measures included total healthcare costs in 2017 US dollars (societal perspective), total quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net monetary benefits (INMB) per-patient. RESULTS: The remaining lifetime use of rivaroxaban is associated with 5.69 QALYs at a cost of $66,075 per patient, while warfarin produced 5.22 QALYs with costs of $78,504 per patient. At a willingness-to-pay (WTP) of $150,000 per QALY, incremental net monetary benefits (INMB) per patient are $83,590. In our population, treatment with warfarin was dominated by rivaroxaban in 99.4% of 10,000 simulations. CONCLUSIONS: Rivaroxaban is likely a dominant treatment over warfarin in elderly US male NVAF patients exhibiting WRF, providing increased QALYs at a decreased overall cost. Application of these findings may require healthcare providers to predict which patients are likely to exhibit WRF.

Behavioral Economics Interventions to Improve Outpatient Antibiotic Prescribing for Acute Respiratory Infections: a Cost-Effectiveness Analysis.

BACKGROUND: Behavioral economics interventions have been shown to effectively reduce the rates of inappropriate antibiotic prescriptions for acute respiratory infections (ARIs). OBJECTIVE: To determine the cost-effectiveness of three behavioral economic interventions designed to reduce inappropriate antibiotic prescriptions for ARIs. DESIGN: Thirty-year Markov model from the US societal perspective with inputs derived from the literature and CDC surveillance data. SUBJECTS: Forty-five-year-old adults with signs and symptoms of ARI presenting to a healthcare provider. INTERVENTIONS: (1) Provider education on guidelines for the appropriate treatment of ARIs; (2) Suggested Alternatives, which utilizes computerized clinical decision support to suggest non-antibiotic treatment choices in lieu of antibiotics; (3) Accountable Justification, which mandates free-text justification into the patient's electronic health record when antibiotics are prescribed; and (4) Peer Comparison, which sends a periodic email to prescribers about his/her rate of inappropriate antibiotic prescribing relative to clinician colleagues. MAIN MEASURES: Discounted costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. KEY RESULTS: Each intervention has lower costs but higher QALYs compared to provider education. Total costs for each intervention were $178.21, $173.22, $172.82, and $172.52, and total QALYs were 14.68, 14.73, 14.74, and 14.74 for the control, Suggested Alternatives, Accountable Justification, and Peer Comparison groups, respectively. Results were most sensitive to the quality-of-life of the uninfected state, and the likelihood and costs for antibiotic-associated adverse events. CONCLUSIONS: Behavioral economics interventions can be cost-effective strategies for reducing inappropriate antibiotic prescriptions by reducing healthcare resource utilization.

A cost-effectiveness analysis of reslizumab in the treatment of poorly controlled eosinophilic asthma.

Introduction: Poorly controlled severe eosinophilic asthma is difficult and costly to manage. Reslizumab, an add-on treatment for adults with severe eosinophilic asthma, reduces the number of exacerbations and improves the quality of life (QoL). The objective of this study was to evaluate the cost-effectiveness of reslizumab. Methods: A Markov model was used to compare the cost-effectiveness of add-on reslizumab with the standard-of-care (SOC) from the US societal perspective over a five-year time horizon. Efficacy and safety inputs for the model were based on data from two clinical trials (NCT01287039 and NCT01285323). Other model inputs, including mortality rates, costs, and utility, were estimated from literature, the Centers for Disease Control and Prevention (CDC), the US Department of Veterans Affairs (VA) and the Centers for Medicare and Medicaid Services (CMS). One-way, threshold, and probabilistic sensitivity analyses (PSA) were performed. Adherence, treatment response, and the placebo effect were evaluated in separate scenario analyses. Results: The base case incremental cost-effectiveness ratio (ICER) was $697 403 (2017 USD) per quality-adjusted life-years (QALYs). In the PSA, reslizumab becomes cost-effective in 50% of the iterations at a willingness-to-pay (WTP) threshold of $689 000. The model is most sensitive to the QoL improvement with reslizumab treatment in the one-way and threshold analyses. The response and adherence models had lower ICERs than the base model but still above $500 000. The ICER of the placebo effect model was $29 820. Conclusions: The improvement in QoL and exacerbation rates with reslizumab are associated with high costs, making reslizumab unlikely to be cost-effective at the $200 000 WTP threshold.

Cost-effectiveness Analysis of Sequential Treatment of Abaloparatide Followed by Alendronate Versus Teriparatide Followed by Alendronate in Postmenopausal Women With Osteoporosis in the United States.

BACKGROUND: The US Food and Drug Administration has recently approved abaloparatide (ABL) for treatment of women with postmenopausal osteoporosis (PMO) at high risk of fracture. With increasing health care spending and drug prices, it is important to quantify the value of newly available treatment options for PMO. OBJECTIVE: To determine cost-effectiveness of ABL compared with teriparatide (TPTD) for treatment of women with PMO in the United States. METHODS: A discrete-event simulation (DES) model was developed to assess cost-effectiveness of ABL from the US health care perspective. The model included three 18-month treatment strategies with either placebo (PBO), TPTD, or ABL, all followed by additional 5-year treatment with alendronate (ALN). High-risk patients were defined as women with PMO ⩾65 years old with a prior vertebral fracture. Baseline clinical event rates, risk reductions, and patient characteristics were based on the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. RESULTS: Over a 10-year period, the DES model yielded average total discounted per-patient costs of $10 212, $46 783, and $26 837 and quality-adjusted life-years (QALYs) of 6.742, 6.781, and 6.792 for PBO/ALN, TPTD/ALN, and ABL/ALN, respectively. Compared with TPTD/ALN, ABL/ALN accrued higher QALYs at lower cost and produced an incremental cost-effectiveness ratio (ICER) of $333 266/QALY relative to PBO/ALN. In high-risk women, ABL/ALN also had more QALYs and less cost over TPTD/ALN and yielded an ICER of $188 891/QALY relative to PBO/ALN. Conclusion and Relevance: ABL is a dominant treatment strategy over TPTD. In women with PMO at high risk of fracture, ABL is an alternative cost-effective treatment.

Cost-Effectiveness Comparison of Ustekinumab, Infliximab, or Adalimumab for the Treatment of Moderate-Severe Crohn's Disease in Biologic-Naïve Patients.

STUDY OBJECTIVE: Ustekinumab was recently approved by the United States U.S. Food and Drug Administration for the treatment of Crohn's disease. In this analysis, we aimed to compare the cost-effectiveness of ustekinumab, infliximab, or adalimumab for the treatment of moderate-severe Crohn's disease in patients who failed conventional therapy (i.e., corticosteroids and immunomodulators) but were naïve to tumor necrosis factor antagonists (i.e., biologic drugs). DESIGN: Cost-effectiveness analysis using a hybrid model structure (decision tree and Markov model). MEASUREMENTS AND MAIN RESULTS: A decision tree simulated biologic induction, and a Markov model simulated biologic and conventional therapy maintenance. Cycle length was 2 weeks with a discounted 5-year time horizon and a limited U.S. societal perspective in the base case; results from a payer perspective are also reported. Transition probabilities, direct costs, indirect costs, and utilities were obtained from the literature. To measure relative treatment value (i.e., order of treatment cost-effectiveness), net monetary benefits were reported for a $150,000 willingness-to-pay threshold per quality-adjusted life-year in the base case. Infliximab dominated both adalimumab and ustekinumab, with a net monetary benefit (NMB) of $9943 and $29,798, respectively, in the base case. Adalimumab dominated ustekinumab, with an NMB of $19,855. All biologics yielded similar quality-adjusted life-years (~3.5), whereas costs varied substantially ($50,510, $54,985, and $72,921 for infliximab, adalimumab, and ustekinumab, respectively). The payer perspective, alternate time horizons, and scenario analyses consistently showed infliximab dominance. One-way, threshold, and probabilistic sensitivity analyses confirmed the robustness of these results with respect to all parameters. Although biosimilars were not explicitly modeled as comparators, one-way sensitivity analysis showed that drug acquisition costs could alter relative treatment value but would have to be varied by at least 50%. CONCLUSION: For moderate-severe Crohn's disease, infliximab yields significantly more NMBs compared with both adalimumab and ustekinumab. Additional clinical (e.g., empiric dosing, biologic cycling) and quality-of-life (e.g., lost productivity, disutility of home injections) research is needed to allow for model frameworks and parameters that more accurately reflect the nuances of Crohn's disease treatment.

Impact of drug substitution on cost of care: an example of economic analysis of cetuximab versus panitumumab.

BACKGROUND: The alarming increase in the cost of cancer care is forcing all stakeholders to re-evaluate their approach to treatment. Drugs are the main contributor to the cost. To evaluate the significance of drug substitution on the cost of care we assessed the economic value of panitumumab vs. cetuximab in chemo-refractory metastatic CRC (mCRC) with wild-type KRAS from a US societal perspective. METHODS: We developed a Markov model with three health states: progression-free, progressive, and death. We calculated the transition probabilities between states using the ASPECCT trial report and US life tables. Costs of drug and administration were based on the Medicare reimbursement rates. Published data were used for cost of toxicities and utilities. All costs were converted to 2017 US dollars. The model used quality-adjusted life-years (QALYs) to measure health outcomes for each treatment option. RESULTS: Panitumumab and cetuximab produced 0.45 QALYs at a per patient cost of $66,006 and $71,956, respectively. The incremental net monetary benefit of panitumumab compared to cetuximab is $5237 under a societal willingness-to-pay threshold of $150,000. The model showed robustness to one-way sensitivity analyses and various alternative scenarios and was found to be most sensitive to the cost of cetuximab. CONCLUSIONS: Panitumumab can lower the cost of care without impacting outcomes in chemo-refractory mCRC settings. This finding provides a strong argument to consider panitumumab in lieu of cetuximab in these patients.

Cost-effectiveness Analysis of Regorafenib and TAS-102 in Refractory Metastatic Colorectal Cancer in the United States.

BACKGROUND: Regorafenib and TAS-102 are standard treatment options in refractory metastatic colorectal cancer based on improvement in overall survival by 6 and 8 weeks, respectively, when compared with best supportive care alone (BSC). Given the small incremental clinical benefit, we evaluated their cost-effectiveness from a United States payer's perspective. MATERIALS AND METHODS: A Markov model was constructed to compare costs and effectiveness of regorafenib, TAS-102, and BSC. Model inputs for clinical efficacy and adverse events were from the CORRECT trial (Regorafenib monotherapy for previously treated metastatic colorectal cancer: an international, multicentre, randomised, placebo-controlled, phase 3 trial) for regorafenib and the RECOURSE trial (Randomized, Double Blind, Phase 3 Study of TAS-102 plus Best Supportive Care [BSC] versus Placebo plus BSC in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) for TAS-102. The incremental cost-effectiveness ratios (ICERs) were reported to compare treatments. Model robustness was checked with univariate and probabilistic sensitivity analyses as well as a scenario analysis using the CONCUR trial data for regorafenib. RESULTS: In our base case, regorafenib and TAS-102 had the ICERs of $395,223 per quality-adjusted life year (QALY) and $399,740 per QALY versus BSC, respectively. Compared with regorafenib, TAS-102 provided an additional 0.041 QALY at the cost of $16,608 or $406,104 per QALY, but the differences were not robust in sensitivity analyses. The most influential parameters on the ICERs were efficacy and health state utility parameters as well as the cost of treating neutropenia. In probabilistic sensitivity analysis using cost-effectiveness acceptability curves, BSC was more cost-effective than both regorafenib and TAS-102 in 50% of repetitions at the willingness-to-pay threshold of $330,000 per QALY. CONCLUSION: Neither TAS-102 nor regorafenib are cost-effective at standard willingness-to-pay thresholds (ie, $150,000 per QALY) relative to BSC. There is no clear evidence that either treatment has better relative value.

First-line pembrolizumab in PD-L1 positive non-small-cell lung cancer: A cost-effectiveness analysis from the UK health care perspective.

BACKGROUND: Pembrolizumab has shown significant survival benefits in treating chemotherapy-naïve non-small-cell lung cancer patients (NSCLC) with increased level of PD-L1 expression. This analysis aimed to evaluate the cost-effectiveness of pembrolizumab as a first-line treatment for patients with PD-L1 positive NSCLC from the UK health care perspective. METHODS: A Markov model with progression-free, progressive disease and death states was developed. Clinical parameters were informed by the KEYNOTE-024 trial. Utility values were sourced from published literature. Cost data including drug acquisition costs, disease management costs, and adverse event costs were derived from British National Formulary and published literature. The model was run until 99% patients died. Both health outcomes and costs were discounted at an annual rate of 3.5%. Deterministic and probabilistic sensitivity analyses were performed to address the uncertainties around model parameters. RESULTS: In the base case, pembrolizumab is projected to increase patient's life expectancy by 1.32 life-years over chemotherapy (2.45 vs. 1.13) and 0.83 QALYs (1.55 vs. 0.71) at an additional cost of £72,465, yielding an incremental cost-effectiveness ratio of £86,913/QALY. When parameters were varied in the deterministic sensitivity analyses, results are most sensitive to duration of median overall survival in both groups. Probability sensitivity analyses showed that using a willingness-to-pay threshold of £50,000 per QALY, the probability of pembrolizumab being cost-effective is 29.4%. CONCLUSION: Using a willingness-to-pay threshold of £50,000, pembrolizumab is not cost-effective at its current list price and a discount of 50% or more is required for it to be cost-effective comparing to commonly prescribed chemotherapy. Risk-sharing contracts may be helpful in resolving some of the underlying uncertainty associated with the long-term survival and varying extent of patient response.