Cost-effectiveness of nirsevimab and palivizumab for respiratory syncytial virus prophylaxis in preterm infants 29-34 6/7 weeks' gestation in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) hospitalizations have increased since the 2014 guideline update recommended against the use of palivizumab for preterm infants born ≥29 0/7 weeks' gestational age (GA) without additional risk factors. A novel drug candidate, nirsevimab, has been developed for this population. We analyzed the cost-effectiveness of palivizumab/nirsevimab vs. no prophylaxis in this population. METHODS: A hybrid-Markov model predicted the RSV clinical course in the first year of life and sequelae in the subsequent four years for preterm infants from the healthcare and societal perspectives. Model parameters were derived from the literature. We calculated costs and quality-adjusted life-years (QALYs) to produce an incremental cost-effectiveness ratio (ICER) evaluated at a willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses assessed model robustness. A threshold analysis examined nirsevimab pricing uncertainty. RESULTS: Compared to no prophylaxis, palivizumab costs $9572 and $9584 more from the healthcare and societal perspectives, respectively, with 0.0019 QALYs gained per patient over five years, resulting in ICERs >$5 million per QALY from each perspective. Results were robust to parameter uncertainties; probabilistic sensitivity analysis revealed that no prophylaxis had a 100% probability of being cost-effective. The threshold analysis suggested that nirsevimab is not cost-effective when compared to no prophylaxis if the price exceeds $1962 from a societal perspective. CONCLUSION: Palivizumab is dominated by no prophylaxis for preterm infants 29 0/7-34 6/7 weeks' GA with no additional risk factors. Relevant stakeholders should consider alternatives to palivizumab for this population that are both effective and economical.

Dental Protraction Versus Surgery for Cleft Lip and Palate: A Budget Impact Analysis.

Class III malocclusion for individuals with cleft lip and palate has historically been managed with surgery. Orthodontic protraction is a noninvasive alternative that may be associated with lower costs. This analysis investigated the budget impact of protraction versus surgery from an institutional perspective. Using a decision tree, analysis was conducted using costs derived from Medicaid reimbursement codes and using actual institutional reimbursement. Probabilities of success, failure, and complications were based on a clinical trial comparing the 2 treatment modalities. One-way and probabilistic sensitivity analyses tested the robustness of results to model parameters. Based on Medicaid fee schedules and failure rates requiring additional surgery, the total cost of protraction was $79,506 versus $172,807 for surgery, resulting in $93,302 cost-savings per patient. The cost and probability of surgery success, as well as the cost of surgery failure and repeat surgery, had the largest impact on these cost-savings. Probabilistic sensitivity analysis showed cost-savings of nearly $92,000 or higher in >50% of simulations. This study showed that protraction is associated with lower costs than surgery and may present a cost-effective alternative to surgery in eligible, appropriate patients.

Estimating the cost of inappropriate antibiotic prophylaxis prior to dental procedures.

Inappropriate dental antibiotic prescriptions to prevent infective endocarditis in the United States results in ∼$31 million in excess costs to the healthcare system and patients. This includes out-of-pocket costs ($20.5 million), drug costs ($2.69 million) and adverse event costs (eg, Clostridioides difficile and hypersensitivity) of $5.82 million (amoxicillin), $1.99 million (clindamycin), and $380,849 (cephalexin).

The financial burden experienced by families of preterm infants after NICU discharge.

BACKGROUND AND OBJECTIVES: Describe the financial burden and worry that families of preterm infants experience after discharge from the neonatal intensive care unit (NICU). METHODS: We surveyed 365 parents of preterm infants in a cross-sectional study regarding socio-demographics, supplemental security income (SSI), and financial worry. We completed a multivariable logistic regression model to examine the adjusted association of financial worry with modifiable factors. RESULTS: We found that 53% of participants worried about healthcare costs after NICU discharge. After adjusting for socio-demographic and infant characteristics, we identified that, aOR (95% CI), out-of-pocket costs from the NICU index hospitalization, 3.51 (1.7, 7.26) and durable medical equipment use, 2.41 (1.11, 5.23) was associated with increased financial worry while enrollment in SSI, 0.38 (0.19, 0.76) was associated with decreased financial worry. CONCLUSIONS: We identified factors that could contribute to financial burden after NICU discharge that may advise future work to target financial support systems.

Early transplantation maximizes survival in severe acute-on-chronic liver failure: Results of a Markov decision process model.

BACKGROUND & AIMS: Uncertainties exist surrounding the timing of liver transplantation (LT) among patients with acute-on-chronic liver failure grade 3 (ACLF-3), regarding whether to accept a marginal quality donor organ to allow for earlier LT or wait for either an optimal organ offer or improvement in the number of organ failures, in order to increase post-LT survival. METHODS: We created a Markov decision process model to determine the optimal timing of LT among patients with ACLF-3 within 7 days of listing, to maximize overall 1-year survival probability. RESULTS: We analyzed 6 groups of candidates with ACLF-3: patients age ≤60 or >60 years, patients with 3 organ failures alone or 4-6 organ failures, and hepatic or extrahepatic ACLF-3. Among all groups, LT yielded significantly greater overall survival probability vs. remaining on the waiting list for even 1 additional day (p <0.001), regardless of organ quality. Creation of 2-way sensitivity analyses, with variation in the probability of receiving an optimal organ and expected post-transplant mortality, indicated that overall survival is maximized by earlier LT, particularly among candidates >60 years old or with 4-6 organ failures. The probability of improvement from ACLF-3 to ACLF-2 does not influence these recommendations, as the likelihood of organ recovery was less than 10%. CONCLUSION: During the first week after listing for patients with ACLF-3, earlier LT in general is favored over waiting for an optimal quality donor organ or for recovery of organ failures, with the understanding that the analysis is limited to consideration of only these 3 variables. LAY SUMMARY: In the setting of grade 3 acute-on-chronic liver failure (ACLF-3), questions remain regarding the timing of transplantation in terms of whether to proceed with liver transplantation with a marginal donor organ or to wait for an optimal liver, and whether to transplant a patient with ACLF-3 or wait until improvement to ACLF-2. In this study, we used a Markov decision process model to demonstrate that earlier transplantation of patients listed with ACLF-3 maximizes overall survival, as opposed to waiting for an optimal donor organ or for improvement in the number of organ failures.

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.

The association of inborn status and resource utilization among neonates who received extracorporeal membrane oxygenation.

BACKGROUND: Many studies have established that extracorporeal membrane oxygenation (ECMO) can be a cost-effective treatment in some populations, but limited data exist on which factors are associated with length of stay (LOS) and total hospital costs. This study aimed to determine if inborn (i.e., cared for in their birth hospitals) neonates who receive ECMO have different resource utilization and outcomes compared to outborn (i.e., not cared for in their birth hospitals) neonates who receive ECMO. METHODS: A retrospective cohort study was conducted using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997-2012. Neonates (infants, <28 days) placed on ECMO were categorized as either inborn or outborn. Salient clinical characteristics were compared between groups. A multivariable analysis was performed to identify the factors associated with length of stay (LOS), total hospital costs, and mortality in these two patient populations. RESULTS: Of 5,152 neonates receiving ECMO, 800 were inborn and 4,352 were outborn. Inborn neonates were more frequently diagnosed with cardiac-related diagnoses (70.5% vs 62.1%, p < 0.001). After adjusting for demographics and hospital-level factors, inborn neonates had longer hospital LOS (13.2 days, 95% CI, 8.7-18.7; p < 0.001), higher total encounter costs ($62,000, 95% CI, 40,000-85,000; p < 0.001) and higher mortality (OR 2.4, 95% CI 1.9-2.9; p < 0.001) compared to outborn neonates. CONCLUSIONS: Inborn neonates placed on ECMO were more frequently diagnosed with cardiac-related diseases or congenital diaphragmatic hernia, had longer LOS, higher total encounter costs, and higher mortality rates relative to their outborn counterparts, and likely represent a higher risk population. These two populations of infants may be inherently different and their differences should be further explored to inform decision making about optimal site of delivery.

Cost-benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin.

OBJECTIVES: Area under the time-concentration curve (AUC) -guided dosing provides better estimates of exposure than vancomycin trough concentrations. Though clinical benefits have been reported, the costs of AUC-guided dosing are uncertain. The objective of this study was to quantify the costs of single-sample Bayesian or two-sample AUC strategies versus trough-guided dosing. METHODS: A cost-benefit analysis from the institutional perspective was conducted using a decision tree to model the probabilities and costs of acute kidney injury (AKI) associated with vancomycin administered over 48 hours up to 21+ days. Costs included vancomycin concentrations, Bayesian software and AKI hospitalization costs, and probabilities were obtained from primary literature. Robustness was assessed via both one-way and probabilistic sensitivity analyses. RESULTS: In the base-case model, two-sample AUC versus trough dosing saved an average of US$ 846 per patient encounter, and single-sample Bayesian AUC versus trough dosing saved an average of US$ 2065 per patient encounter. This translates into annual cost-savings of US$ 846 810 and US$ 2 065 720 for two-sample and single-sample Bayesian methods versus trough dosing, respectively, assuming 1000 vancomycin-treated patients per year. Assuming a budget of US$ 100 000 per year for Bayesian software, an institution would need to treat ≥41 patients with vancomycin for at least 48 hours to break even. CONCLUSIONS: There are significant institutional cost benefits using two-sample AUC or single-sample Bayesian methods over trough dosing, even after accounting for the annual costs of Bayesian programs. The potential to decrease rates of AKI, improve clinical outcomes and reduce costs to the institution strongly warrants consideration of improved dosing methods for vancomycin.

Lifetime Burden of Adult Congenital Heart Disease in the USA Using a Microsimulation Model.

Congenital heart defects (CHD) represent a growing burden of illness among adults. We estimated the lifetime health, education, labor, and social outcomes of adults with CHD in the USA using the Future Adult Model, a dynamic microsimulation model that has been used to study the lifetime impacts of a variety of chronic diseases. We simulated a cohort of adult heads of households > 25 years old derived from the Panel Survey of Income Dynamics who reported a childhood heart problem as a proxy for CHD and calculated life expectancy, disability-free and quality-adjusted life years, lifetime earnings, education attainment, employment, development of chronic disease, medical spending, and disability insurance claiming status. Total burden of disease was estimated by comparing to a healthy cohort with no childhood heart problem. Eighty-seven individuals reporting a childhood heart problem were identified from the PSID and were used to generate the synthetic cohort simulated in the model. Life expectancy, disability-free, quality-adjusted, and discounted quality-adjusted life years were an average 4.6, 6.7, 5.3, and 1.4 years lower than in healthy adults. Lung disease, cancer, and severe mental distress were more common compared to healthy individuals. The CHD cohort earned $237,800 less in lifetime earnings and incurred higher average total medical spend by $66,600 compared to healthy individuals. Compared to healthy adults, the total burden of CHD is over $500K per adult. Despite being among the healthiest adults with CHD, there are significant decrements in life expectancy, employment, and lifetime earnings, with concomitant increases in medical spend.

Impact of Confounding on Cost, Survival, and Length-of-Stay Outcomes for Neonates with Hypoplastic Left Heart Syndrome Undergoing Stage 1 Palliation Surgery.

The objective of this analysis was to update trends in LOS and costs by survivorship and ECMO use among neonates with hypoplastic left heart syndrome (HLHS) undergoing stage 1 palliation surgery using 2016 data from the Healthcare Cost and Utilization Project Kids' Inpatient Database. We identified neonates ≤ 28 days old with HLHS undergoing Stage 1 surgery, defined as a Norwood procedure with modified Blalock-Taussig (BT) shunt, Sano modification, or both. Multivariable regression with year random effects was used to compare LOS and costs by hospital region, case volume, survivorship, and ECMO vs. no ECMO. An E-value analysis, an approach for conducting sensitivity analysis for unmeasured confounding, was performed to determine if unmeasured confounding contributed to the observed effects. Significant differences in total costs, LOS, and mortality were noted by hospital region, ECMO use, and sub-analyses of case volume. However, other than ECMO use and mortality, the maximum E-value confidence interval bound was 1.71, suggesting that these differences would disappear with an unmeasured confounder 1.71 times more associated with both the outcome and exposure (e.g., socioeconomic factors, environment, etc.) Our findings confirm previous literature demonstrating significant resource utilization among Norwood patients, particularly those undergoing ECMO use. Based on our E-value analysis, differences by hospital region and case volume can be explained by moderate unobserved confounding, rather than a reflection of the quality of care provided. Future analyses on surgical quality must account for unobserved factors to provide meaningful information for quality improvement.

United States Valuation of EQ-5D-5L Health States Using an International Protocol.

OBJECTIVE: To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. METHODS: Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. RESULTS: Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from -0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). CONCLUSIONS: A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

Application of pharmacoeconomics to formulary management in a health system setting.

PURPOSE: A novel value-based approach to evaluate costly specialty drugs for formulary addition was developed. SUMMARY: In February 2016, Stanford Health Care launched the specialty drug subcommittee (SDSC), a subcommittee of the pharmacy and therapeutics committee, responsible for the formulary review of specialty pharmaceuticals. A process was developed for value-based review that includes not only consideration of clinical trial data and institutional acquisition costs but also internal patient outcomes and a cost-effectiveness model using internal financial data. A Markov model was developed to assess the value of trabectedin, which was approved for formulary addition in April 2016, relative to the addition of dacarbazine. The economic model and internal patient outcome analysis were presented to the prescribing oncologist and the SDSC for review. Internal data revealed that fewer patients than had been estimated received trabectedin, with outcomes significantly worse than those observed in the clinical trial leading to Food and Drug Administration approval. In the cost-effectiveness model, trabectedin had higher costs and poorer outcomes compared with dacarbazine. Based on the economic model, low utilization, and real-world outcomes, trabectedin was removed from formulary and a restrictive treatment pathway for nonformulary use, developed by the primary prescriber, was implemented. This process has since been applied to 11 more specialty drugs. CONCLUSION: Internal cost-effectiveness models in combination with real-world patient outcomes data can be effective formulary management tools. Engagement and collaboration with the requesting provider are key to developing thoughtful treatment pathways.

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.

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.