Quantifying the Value of Reduced Health Disparities: Low-Dose Computed Tomography Lung Cancer Screening of High-Risk Individuals Within the United States.

OBJECTIVE: This study aimed to measure the value of increasing lung cancer screening rates for high-risk individuals and its impact on health disparities. METHODS: The model estimated changes in health economic outcomes if low-dose computed tomography screening increased from current to 100% compliance, following clinical guidelines. Current low-dose computed tomography screening rates were estimated by income, education, and race, using 2017-2019 Behavioral Risk Factor Surveillance System data. The model contained a decision tree module to segment the population by screening outcomes and a Markov chain module to estimate cancer progression over time. Model parameters included information on survival, quality of life, and costs related to cancer diagnosis, treatment, and adverse events. Distributional cost-effectiveness analysis estimated the net monetary value from reduced health disparities-measured using quality-adjusted life expectancy-across income, education, and race groups. Outcomes were assessed over 30 years. RESULTS: Lung cancer screening eligibility using US Preventive Services Task Force guidelines was higher for individuals with income <$15 000 (47.2%) and without a high-school education (46.1%) than individuals with income >$50 000 (16.6%) and with a college degree (13.5%), respectively. Increasing lung cancer screening to 100% compliance was cost-effective ($64 654 per quality-adjusted life-year) and produced economic value by up to $560 per person ($182.1 billion for United States overall). Up to 32.2% of the value was due to reductions in health disparities. CONCLUSIONS: Significant value in increasing lung cancer screening rates derived from reducing health disparities. Policy makers and clinicians may not be appropriately prioritizing cancer screening if value from reducing health disparities is unconsidered.

A Decade of Health Innovation: The Impact of New Medicines on Patient Health and the Implications for NICE's Size of Benefit Multiplier.

OBJECTIVES: This study aimed to estimate the incremental health benefits of pharmaceutical innovations approved between 2011 and 2021 and the share that would surpass the National Institute for Health and Care Excellence (NICE) "size of benefit" decision weight thresholds. METHODS: We identified all US-approved drugs between 2011 and 2021. Health benefits, in terms of quality-adjusted life-years (QALYs) for each treatment, were extracted from published cost-effectiveness analyses. Summary statistics by therapeutic area and cell/gene therapy status identified the treatments with the largest QALY gains. RESULTS: The Food and Drug Administration approved 483 new therapies between 2011 and 2021 and of these 252 had a published cost-effectiveness analysis meeting our inclusion criteria. The average incremental health benefits produced by these treatments were 1.04 QALYs (SD = 2.00) relative to standard of care, with wide variation by therapeutic area. Pulmonary and ophthalmologic therapies produced the highest health benefits with 1.47 (SD = 2.17, n = 13) and 1.41 QALYs gained (SD = 3.53, n = 7), respectively; anesthesiology and urology had the lowest gains (< 0.1 QALYs). Cell and gene therapies produced an average health benefit that was 4 times greater than noncell and gene therapies (4.13 vs 0.96). Among the top treatments in terms of incremental QALYs gained, half (10 of 20) were oncology therapies. Three of 252 treatments (1.2%) met NICE's threshold for a "size of benefit" multiplier. CONCLUSIONS: Treatments for rare disease, oncology, and cell and gene therapies produced some of the highest level of health innovation relative to previous standard of care, but few therapies would have qualified for NICE's "size of benefit" multiplier as currently constructed.

Measuring the Value Healthy Individuals Place on Generous Insurance Coverage of Severe Diseases: A Stated Preference Survey of Adults Diagnosed With and Without Lung Cancer.

OBJECTIVES: To compare the ex ante willingness to pay (WTP) of healthy individuals for generous insurance coverage of novel lung cancer treatments to the WTP for coverage of such treatment among individuals with lung cancer. METHODS: A survey was administered to 2 cohorts of US adults: (1) healthy individuals without cancer and (2) individuals diagnosed with lung cancer. A multiple random staircase survey design was used to elicit respondent WTP for coverage of novel lung cancer therapy associated with survival gains. RESULTS: Of the 84 937 healthy individuals invited, 300 completed the survey. Of the 36 249 in the lung cancer cohort invited, 250 completed the survey. Mean age by cohort was 50.0 (SD 14.6) and 48.4 (SD 16.8) years, and 55.2% and 47.2% were female, respectively. Respondents in the healthy and lung cancer cohorts were willing to pay $97.52 (95% confidence interval (CI) $89.89-$105.15) and $22 304 (95% CI $20 194-$24 414) per month, respectively, for coverage of a novel therapy providing 5-year survival of 15% versus standard-of-care therapy with a 5-year survival of 4%. After accounting for the likelihood that healthy individuals are diagnosed with lung cancer in the future, we estimated that 89.8% of the total value of new lung cancer treatments comes from the WTP healthy individuals place on generous insurance coverage. CONCLUSIONS: Total societal willingness to pay for lung cancer is much higher than conventionally thought, as most healthy individuals are risk-averse and highly value having lung cancer treatments available to them in the future.

Adoption of Digital Health Technologies in the Practice of Behavioral Health: Qualitative Case Study of Glucose Monitoring Technology.

BACKGROUND: Evaluation of patients with serious mental illness (SMI) relies largely on patient or caregiver self-reported symptoms. New digital technologies are being developed to better quantify the longitudinal symptomology of patients with SMI and facilitate disease management. However, as these new technologies become more widely available, psychiatrists may be uncertain about how to integrate them into daily practice. To better understand how digital tools might be integrated into the treatment of patients with SMI, this study examines a case study of a successful technology adoption by physicians: endocrinologists' adoption of digital glucometers. OBJECTIVE: This study aims to understand the key facilitators of and barriers to clinician and patient adoption of digital glucose monitoring technologies to identify lessons that may be applicable across other chronic diseases, including SMIs. METHODS: We conducted focus groups with practicing endocrinologists from 2 large metropolitan areas using a semistructured discussion guide designed to elicit perspectives of and experiences with technology adoption. The thematic analysis identified barriers to and facilitators of integrating digital glucometers into clinical practice. Participants also provided recommendations for integrating digital health technologies into clinical practice more broadly. RESULTS: A total of 10 endocrinologists were enrolled: 60% (6/10) male; a mean of 18.4 years in practice (SD 5.6); and 80% (8/10) working in a group practice setting. Participants stated that digital glucometers represented a significant change in the treatment paradigm for diabetes care and facilitated more effective care delivery and patient engagement. Barriers to the adoption of digital glucometers included lack of coverage, provider reimbursement, and data management support, as well as patient heterogeneity. Participant recommendations to increase the use of digital health technologies included expanding reimbursement for clinician time, streamlining data management processes, and customizing the technologies to patient needs. CONCLUSIONS: Digital glucose monitoring technologies have facilitated more effective, individualized care delivery and have improved patient engagement and health outcomes. However, key challenges faced by the endocrinologists included lack of reimbursement for clinician time and nonstandardized data management across devices. Key recommendations that may be relevant for other diseases include improved data analytics to quickly and accurately synthesize data for patient care management, streamlined software, and standardized metrics.

Using Information on Patient Adherence to Antipsychotic Medication to Understand Their Adherence to Other Medications.

PURPOSE: To assess how patient adherence to atypical antipsychotic medications is associated with adherence to concurrently used medications that treat other serious mental illnesses (SMIs), type-2 diabetes, or hypertension. METHODS: Among patients who had been diagnosed with an SMI (i.e., bipolar disorder, major depressive disorder, or schizophrenia) in the previous year, we used health-insurance claims data to measure adherence based on medication fills. Patients diagnosed with an SMI were required to have 1) a prescription for an atypical oral antipsychotic, and 2) another SMI therapy or oral anti-diabetic or antihypertensive agent in the same year. The patient's concurrent adherence to an antipsychotic and one of 23 other medications was measured by the proportion of days covered (PDC) over a one-year period. Patients were considered adherent when the PDC was ≥ 80%. The strength of the association between their atypical antipsychotic adherence and their concurrent medication adherence was evaluated using the following metrics: accuracy, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The average (standard deviation) age of patients (N = 129,614) was 44.8 (14.8) years and 62.2% of patients were female. The median accuracy based on atypical antipsychotic adherence to the other 23 medications was 67% (range, 55-71%; statistically different from 50% accuracy in all cases, P < 0.001). Accuracy was higher than physician predictions of adherence from previous studies (53%). The negative predictive value of antipsychotic adherence (75%; range, 62-88%) was generally higher than the PPV (62%; range, 43-67%; all, P < 0.001). CONCLUSION: Information on patient adherence to antipsychotics provides significant insight into adherence to other medications often used by patients with SMI. Because NPV is higher than PPV, adherence to antipsychotics is likely to be a necessary but not sufficient condition for patients with SMI regarding adherence to non-SMI medications.

Long-Term Health and Economic Value of Improved Mobility among Older Adults in the United States.

BACKGROUND: Mobility impairments have substantial physical and mental health consequences, resulting in diminished quality of life. Most studies on the health economic consequences of mobility limitations focus on short-term implications. OBJECTIVES: To examine the long-term value of improving mobility in older adults. METHODS: Our six-step approach used clinical trial data to calibrate mobility improvements and estimate health economic outcomes using a microsimulation model. First, we measured improvement in steps per day calibrated with clinical trial data examining hylan G-F 20 viscosupplementation treatment. Second, we created a cohort of patients 51 years and older with osteoarthritis. In the third step, we estimated their baseline quality of life. Fourth, we translated steps-per-day improvements to changes in quality of life using estimates from the literature. Fifth, we calibrated quality of life in this cohort to match those in the trial. Last, we incorporated these data and parameters into The Health Economic Medical Innovation Simulation model to estimate how mobility improvements affect functional status limitations, medical expenditures, nursing home utilization, employment, and earnings between 2012 and 2030. RESULTS: In our sample of 12.6 million patients, 66.7% were female and 70% had a body mass index of more than 25 kg/m2. Our model predicted that a 554-step-per-day increase in mobility would reduce functional status limitations by 5.9%, total medical expenditures by 0.9%, and nursing home utilization by 2.8%, and increase employment by 2.9%, earnings by 10.3%, and monetized quality of life by 3.2% over this 18-year period. CONCLUSIONS: Interventions that improve mobility are likely to reduce long-run medical expenditures and nursing home utilization and increase employment.

Patient Versus Physician Valuation of Durable Survival Gains: Implications for Value Framework Assessments.

BACKGROUND: Previous research indicates that patients value therapies that provide durable or tail-of-the-curve survival gains, but it is unclear whether physicians share these preferences. OBJECTIVE: To compare patient and physician preferences for treatments with a positive probability of durable survival gains relative to those with fixed survival gains. METHODS: Patients with advanced stage melanoma or lung cancer and the oncologists who treated these patients were surveyed. The primary end point was the share of respondents who selected a therapy with a variable survival profile, with some patients experiencing long-term durable survival and others experiencing much shorter survival, compared to a therapy with a fixed survival duration. Parameter estimation by sequential testing was applied to calculate the length of nonvarying survival that would make respondents indifferent between that survival and therapy with durable survival. RESULTS: The sample comprised 165 patients (lung = 84, melanoma = 81) and 98 physicians. For lung cancer, 65.5% of patients preferred the therapy with a variable survival profile, compared with 40.8% of physicians (Δ = 24.7%; P < 0.001). For melanoma, these figures were 63.0% for patients and 29.7% for physicians (Δ = 33.3%; P < 0.001). Patients' indifference point implied that therapies with a variable survival profile are preferred unless the treatment with fixed survival had 13.6 months (melanoma) or 11.6 months (lung) longer mean survival; physicians would prescribe treatments with a fixed survival if the treatment had 7.5 months (melanoma) or 1.0 month (lung) shorter survival than the variable survival profile. CONCLUSIONS: Patients place a high value on therapies that provide a chance of durable or "tail-of-the-curve" survival, whereas physicians do not. Value frameworks should incorporate measures of tail-of-the-curve survival gains into their methodologies.

Value-Based Payments and Incentives to Improve Care: A Case Study of Patients with Type 2 Diabetes in Medicare Advantage.

OBJECTIVES: To estimate the impact of increased glycated hemoglobin (A1C) monitoring and treatment intensification for patients with type 2 diabetes (T2D) on quality measures and reimbursement within the Medicare Advantage Star (MA Star) program. METHODS: The primary endpoint was the share of patients with T2D with adequate A1C control (A1C ≤ 9%). We conducted a simulation of how increased A1C monitoring and treatment intensification affected this end point using data from the National Health and Nutrition Examination Survey and clinical trials. Using the estimated changes in measured A1C levels, we calculated corresponding changes in the plan-level A1C quality measure, overall star rating, and reimbursement. RESULTS: At baseline, 24.4% of patients with T2D in the average plan had poor A1C control. The share of plans receiving the highest A1C rating increased from 27% at baseline to 49.5% (increased monitoring), 36.2% (intensification), and 57.1% (joint implementation of both interventions). However, overall star ratings increased for only 3.6%, 1.3%, and 4.8% of plans, respectively, by intervention. Projected per-member per-year rebate increases under the MA Star program were $7.71 (monitoring), $2.66 (intensification), and $10.55 (joint implementation). CONCLUSIONS: The simulation showed that increased monitoring and treatment intensification would improve A1C levels; however, the resulting average increases in reimbursement would be small.

Predicting Real-World Effectiveness of Cancer Therapies Using Overall Survival and Progression-Free Survival from Clinical Trials: Empirical Evidence for the ASCO Value Framework.

OBJECTIVES: To measure the relationship between randomized controlled trial (RCT) efficacy and real-world effectiveness for oncology treatments as well as how this relationship varies depending on an RCT's use of surrogate versus overall survival (OS) endpoints. METHODS: We abstracted treatment efficacy measures from 21 phase III RCTs reporting OS and either progression-free survival or time to progression endpoints in breast, colorectal, lung, ovarian, and pancreatic cancers. For these treatments, we estimated real-world OS as the mortality hazard ratio (RW MHR) among patients meeting RCT inclusion criteria in Surveillance and Epidemiology End Results-Medicare data. The primary outcome variable was real-world OS observed in the Surveillance and Epidemiology End Results-Medicare data. We used a Cox proportional hazard regression model to calibrate the differences between RW MHR and the hazard ratios on the basis of RCTs using either OS (RCT MHR) or progression-free survival/time to progression surrogate (RCT surrogate hazard ratio [SHR]) endpoints. RESULTS: Treatment arm therapies reduced mortality in RCTs relative to controls (average RCT MHR = 0.85; range 0.56-1.10) and lowered progression (average RCT SHR = 0.73; range 0.43-1.03). Among real-world patients who used either the treatment or the control arm regimens evaluated in the relevant RCT, RW MHRs were 0.6% (95% confidence interval -3.5% to 4.8%) higher than RCT MHRs, and RW MHRs were 15.7% (95% confidence interval 11.0% to 20.5%) higher than RCT SHRs. CONCLUSIONS: Real-world OS treatment benefits were similar to those observed in RCTs based on OS endpoints, but were 16% less than RCT efficacy estimates based on surrogate endpoints. These results, however, varied by tumor and line of therapy.

Evaluating Matching-Adjusted Indirect Comparisons in Practice: A Case Study of Patients with Attention-Deficit/Hyperactivity Disorder.

Differences in patient characteristics across trials may bias efficacy estimates from indirect treatment comparisons. To address this issue, matching-adjusted indirect comparison (MAIC) measures treatment efficacy after weighting individual patient data to match patient characteristics across trials. To date, however, there is no consensus on how best to implement MAIC. To address this issue, we applied MAIC to measure how two attention-deficit/hyperactivity disorder (ADHD) treatments (guanfacine extended release and atomoxetine hydrochloride) affect patients' ADHD symptoms, as measured by the ADHD Rating Scale IV score. We tested MAIC sensitivity to: matched patient characteristics, matched statistical moments, weighting matrix, and placebo-arm matching (i.e., matching on outcomes in the placebo arm). After applying MAIC, guanfacine and atomoxetine had similar reductions in ADHD symptoms (Δ: 0.4, p < 0.737). The results were similar for three of four sensitivity analyses. When we applied MAIC with placebo-arm matching, however, guanfacine reduced symptoms more than atomoxetine (Δ: -3.9, p < 0.004). We discuss the implication of this finding and advise MAIC practitioners to carefully consider the use of placebo-arm matching, depending on the presence of residual confounding across trials. Copyright © 2016 John Wiley & Sons, Ltd.

Physician and Patient Preferences for Nonvalvular Atrial Fibrillation Therapies.

OBJECTIVES: The objective of this study was to compare patient and physician preferences for different antithrombotic therapies used to treat nonvalvular atrial fibrillation (NVAF). METHODS: Patients diagnosed with NVAF and physicians treating such patients completed 12 discrete choice questions comparing NVAF therapies that varied across five attributes: stroke risk, major bleeding risk, convenience (no regular blood testing/dietary restrictions), dosing frequency, and patients' out-of-pocket cost. We used a logistic regression to estimate the willingness-to-pay (WTP) value for each attribute. RESULTS: The 200 physicians surveyed were willing to trade off $38 (95% confidence interval [CI] $22 to $54] in monthly out-of-pocket cost for a 1% (absolute) decrease in stroke risk, $14 (95% CI $8 to $21) for a 1% decrease in major bleeding risk, and $34 (95% CI $9 to $60) for more convenience. The WTP value among 201 patients surveyed was $30 (95% CI $18 to $42) for reduced stroke risk, $16 (95% CI $9 to $24) for reduced bleeding risk, and -$52 (95% CI -$96 to -6) for convenience. The WTP value for convenience among patients using warfarin was $9 (95% CI $1 to $18) for more convenience, whereas patients not currently on warfarin had a WTP value of -$90 (95% CI -$290 to -$79). Both physicians' and patients' WTP value for once-daily dosing was not significantly different from zero. On the basis of survey results, 85.0% of the physicians preferred novel oral anticoagulants (NOACs) to warfarin. NOACs (73.0%) were preferred among patients using warfarin, but warfarin (78.2%) was preferred among patients not currently using warfarin. Among NOACs, both patients and physicians preferred apixaban. CONCLUSIONS: Both physicians and patients currently using warfarin preferred NOACs to warfarin. Patients not currently using warfarin preferred warfarin over NOACs because of an apparent preference for regular blood testing/dietary restrictions.

Cost-effectiveness of sotagliflozin for the treatment of patients with diabetes and recent worsening heart failure.

Aim: To assesses the cost-effectiveness of sotagliflozin for the treatment of patients hospitalized with heart failure and comorbid diabetes. Materials & methods: A de novo cost-effectiveness model with a Markov structure was created for patients hospitalized for heart failure with comorbid diabetes. Outcomes of interest included hospital readmissions, emergency department visits and all-cause mortality measured over a 30-year time horizon. Baseline event frequencies were derived from published real-world data studies; sotagliflozin's efficacy was estimated from SOLOIST-WHF. Health benefits were calculated quality-adjusted life years (QALYs). Costs included pharmaceutical costs, rehospitalization, emergency room visits and adverse events. Economic value was measured using the incremental cost-effectiveness ratio (ICER). Results: Sotagliflozin use decreased annualized rehospitalization rates by 34.5% (0.228 vs 0.348, difference: -0.120), annualized emergency department visits by 40.0% (0.091 vs 0.153, difference: -0.061) and annualized mortality by 18.0% (0.298 vs 0.363, difference: -0.065) relative to standard of care, resulting in a net gain in QAYs of 0.425 for sotagliflozin versus standard of care. Incremental costs using sotagliflozin increased by $19,374 over a 30-year time horizon of the patient, driven largely by increased pharmaceutical cost. Estimated ICER for sotagliflozin relative to standard of care was $45,596 per QALY. Conclusion: Sotagliflozin is a cost-effective addition to standard of care for patients hospitalized with heart failure and comorbid diabetes.

How adoption of new pharmaceuticals can impact US health system reimbursement under alternative payment models: An economic model measuring the impact of sotagliflozin among patients with heart failure and diabetes.

BACKGROUND: Heart failure (HF) is among the leading causes of death in the United States. Further, patients hospitalized because of HF with comorbid diabetes mellitus (DM) are at a significantly increased risk of death and rehospitalization. Results from the SOLOIST-WHF trial show that sotagliflozin lowered rates of readmission among hospitalized patients with HF and comorbid DM. However, it is unclear what the economic impact of the use of sotagliflozin would be on hospitals and health systems, particularly in an age where provider reimbursement is increasingly tied to value. OBJECTIVE: To quantify the 1-year financial impact on US provider health systems of adopting sotagliflozin relative to standard of care (SoC) across different alternative payment models. METHODS: This study created a 3-part decision tree model to quantify the financial impact of using sotagliflozin to treat patients hospitalized with HF in a US hospital setting. The model first estimated the clinical and economic outcomes of health systems with current SoC (no sotagliflozin) to treat US patients hospitalized for HF with comorbid DM. Then, using the results from the SOLOIST trial, the changes in clinical and economic outcomes with sotagliflozin adoption were modeled. Finally, the differences in health care utilization between sotagliflozin and SoC arms were translated to differences in health system reimbursement in the context of 3 common alternative payment models (APMs) in addition to the baseline fee-for-service (FFS) model: FFS with the Hospital Readmissions Reduction Program, the Bundled Payments for Care Improvement-Advanced program, and Accountable Care Organizations. RESULTS: A typical community hospital would have 83.4 patients per year on average with an index HF hospitalization with comorbid DM. The model predicted that sotagliflozin would reduce the probability of hospitalization, emergency department visits, and deaths by 29.3%, 38.5%, and 17.8%, respectively, compared with SoC. For hospitals not participating in APM programs, sotagliflozin resulted in a net loss of $92.94 per person ($7,754 per health system). Conversely, when accounting for provider health system participation in APMs, sotagliflozin adoption increased financial returns by $4,720 per person ($305,604 per health system) under the Hospital Readmissions Reduction Program, $1,200 per person ($100,106 per health system) for the Bundled Payments for Care Improvement-Advanced program, and $1,078 per person ($31,029 per health system) for Accountable Care Organizations. Based on the national average composition of APM reimbursement, sotagliflozin adoption resulted in a $1,576 increase in margin per patient with HF ($105,454 per health system). CONCLUSIONS: Although sotagliflozin adoption reduced health system revenue in an FFS payment model, it led to a net positive financial impact after accounting for APM bonus payments.

Quantifying the insurance value for rare diseases: Duchenne muscular dystrophy.

OBJECTIVES: To quantify the magnitude of an ISPOR novel value element, insurance value, as applied to new treatments for a rare, severe disease with pediatric onset: Duchenne muscular dystrophy (DMD). STUDY DESIGN: Prospective survey of individuals planning to have children in the future. METHODS: A survey was administered to US adults (aged ≥ 21 years) planning to have a child in the future to elicit willingness to pay (WTP) for insurance coverage for a new hypothetical DMD treatment that improved mortality and morbidity relative to the current standard of care. To identify an indifference point between status quo insurance and insurance with additional cost that would cover the treatment if respondents had a child with DMD, a multiple random staircase design was used. Insurance value-the value individuals receive from a reduction in future health risks-was calculated as the difference between respondent's WTP and what a risk-neutral individual would pay. The risk-neutral value was the product of the (1) probability of having a child with DMD (decision weighted), (2) quality-adjusted life-years (QALYs) gained from the new treatment, and (3) WTP per QALY. RESULTS: Among 207 respondents, 80.2% (n = 166) were aged 25 to 44 years, and 59.9% (n = 124) were women. WTP for insurance coverage of the hypothetical treatment was $973 annually, whereas the decision-weighted risk-neutral value was $452 per year. Thus, insurance value constituted 53.5% ($520) of value for new DMD treatments. CONCLUSIONS: Individuals planning to have children in the future are willing to pay more for insurance coverage of novel DMD treatments than is assumed under risk-neutral, QALY-based frameworks.

Treatment Patterns and Healthcare Resource Utilization of Patients With Paroxysmal Nocturnal Hemoglobinuria: A Retrospective Claims Data Analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder commonly treated with complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan. This study aims to describe treatment patterns, healthcare resource utilization, and cost for newly diagnosed PNH patients in 2 large, health insurance claims databases: MarketScan and Optum. Among the 271 patients meeting the inclusion criteria in MarketScan, 57.9% were female, and the average age was 46.6 years. Among these newly diagnosed patients, 25.1% (n = 68) of patients received a PNH-specific pharmacologic treatment, and the average time from diagnosis to treatment was 4.7 months. The medication possession ratio was 97.0%, but discontinuation was common (58.8%). The average per-patient-per-month costs were $18,978, driven by pharmacy and infusion ($11,182), outpatient ($4086), and inpatient ($3318) costs. Despite the availability of multiple treatments, 39.9% of patients had an inpatient stay, and 50.9% had an emergency department visit. Better care management and the introduction of new treatment options are needed to address delays between diagnosis and treatment, and high rates of hospitalization and emergency department use among patients with PNH.

Use of Conditionally Essential Amino Acids and the Economic Burden of Postoperative Complications After Fracture Fixation: Results from a Cost Utility Analysis.

Objective: To measure the economic impact of conditionally essential amino acids (CEAA) among patients with operative treatment for fractures. Methods: A decision tree model was created to estimate changes in annual health care costs and quality of life impact due to complications after patients underwent operative treatment to address a traumatic fracture. The intervention of interest was the use of CEAA alongside standard of care as compared to standard of care alone. Patients were required to be aged ≥18 and receive the surgery in a US Level 1 trauma center. The primary outcomes were rates of post-surgical complications, changes in patient quality adjusted life years (QALYs), and changes in cost. Cost savings were modeled as the incremental costs (in 2022 USD) of treating complications due to changes in complication rates. Results: The per-patient cost of complications under CEAA use was $12,215 compared to $17,118 under standard of care without CEAA. The net incremental cost savings per patient with CEAA use was $4902, accounting for a two-week supply cost of CEAA. The differences in quality-adjusted life years (QALYs) under CEAA use and no CEAA use was 0.013 per person (0.739 vs 0.726). Modeled to the US population of patients requiring fracture fixations in trauma centers, the total value of CEAA use compared to no CEAA use was $316 million with an increase of 813 QALYs per year. With a gain of 0.013 QALYs per person, valued at $150,000, and the incremental cost savings of $4902 resulted in net monetary benefit of $6852 per patient. The incremental cost-effectiveness ratio showed that the use of CEAA dominated standard of care. Conclusion: CEAA use after fracture fixation surgery is cost saving. Level of Evidence: Level 1 Economic Study.

White Paper on the Value of Time Savings for Patients and Healthcare Providers of Breast Cancer Therapy: The Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection as an Example.

Health technology assessments and value frameworks are becoming increasingly important for clinical decision-making. Most of these frameworks, however, focus on value to payers rather than patients and healthcare providers and may ignore other sources of economic value such as patient and physician time cost, impact on productivity, and direct health system costs. This article focusses on fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in the treatment of HER2-positive breast cancer. We review relevant clinical evidence, examine data on time and resource use of the subcutaneous administration of trastuzumab compared with intravenous treatment and how it can be extrapolated to PH FDC SC, and discuss the value PH FDC SC can bring to patients and healthcare providers. We will also provide our own experiences of PH FDC SC from the healthcare (oncologist, healthcare economist, pharmacist) and patient point of view. The data, combined with our personal experiences, suggest that switching from intravenous pertuzumab and trastuzumab to PH FDC SC could reduce non-drug costs for healthcare providers treating patients with HER2-positive breast cancer through time savings and other economic benefits. Furthermore, PH FDC SC could also save patient time given its shorter administration and post-injection observation time versus intravenous infusions, potentially resulting in reduced productivity loss. These benefits could be applied to other subcutaneous formulations, either currently available or in development.

New therapies are increasingly assessed by looking at their value to those who pay for them rather than their value to patients and healthcare providers. Value assessments conducted from the payers' perspective often ignore such things as patient and healthcare system time and costs. The fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (also known as pertuzumab, trastuzumab, and hyaluronidase-zzxf, abbreviated to PH FDC SC), is injected under the skin to treat a subtype of breast cancer called HER2-positive breast cancer. PH FDC SC is as effective as pertuzumab and trastuzumab, which are infused separately into a vein, but takes a lot less time to administer to patients. This transition is similar to what was seen when a subcutaneous version of trastuzumab was developed and compared to the intravenous original. Also, subcutaneous trastuzumab reduced costs associated with treating patients compared with intravenous infusions. The same benefits of PH FDC SC to patients and healthcare providers can be expected, and our personal experiences as an oncologist, healthcare economist, patient, and pharmacist agree. PH FDC SC could save patient and healthcare provider time given its shorter injection and observation times versus intravenous infusions, potentially resulting in better productivity for these people and a smaller cost to healthcare providers. These benefits could be applied to other subcutaneous formulations, either currently available or in development.

Estimating the impact of biosimilar entry on prices and expenditures in rheumatoid arthritis: a case study of targeted immune modulators.

OBJECTIVE: To model changes in prices, utilization, and expenditures of targeted immune modulators (TIMs) for rheumatoid arthritis, accounting for biosimilar entry. METHODS: Using IQVIA National Sales Perspective data between 2013 and 2019, we examined sales and expenditures of biologics and non-biological complex molecules, 20 quarters before and after patent exclusivity milestones. We estimated the impact of a molecule's exclusivity milestones and biosimilar entry on prices, using a regression discontinuity design (RDD). We then combined the RDD estimate with historical trends to assess the impact of adalimumab's exclusivity milestones on future TIM expenditures. RESULTS: Changes in average molecule prices were associated largely with biosimilar uptake. For molecules with relatively high biosimilar uptake (>60%), prices fell considerably (-21.2% to -59.3%) one year after exclusivity milestones, whereas molecules with lower biosimilar uptake (<10%) experienced smaller price decreases (-2.4% to -8.4%). Average price reduction at the molecule level after biosimilar entry was not significant (-18.6%; p = .657). When applying the RDD results after adalimumab's exclusivity milestones, its projected share of total TIM market expenditures decreased from 48.0% in 2019 to 26.0% in 2025, whereas expenditures on Janus kinase inhibitors increased from 4.0% to 34.0%. CONCLUSIONS: Biologics facing biosimilar competition may experience price decreases, potentially offering substantial savings to payers, patients, and society, although the magnitude of these estimates depends on biosimilar uptake. Formulary placement, along with manufacturer-payer dynamics, may also play a role in determining the impact on price and market uptake of biosimilars.

Are caregivers ready for digital? Caregiver preferences for health technology tools to monitor medication adherence among patients with serious mental illness.

Background: Adherence to antipsychotic medication is critical for bipolar disorder (BPD), major depression (MDD) and schizophrenia (SCZ) patients. Digital tools have emerged to monitor medication adherence along with tracking general health. Evidence on physician or patient preferences for such tools exists but is limited among caregivers. The study objective was to assess preferences and willingness-to-pay (WTP) for medication adherence monitoring tools among caregivers of SMI patients. Methods: A web-based survey was administered to caregivers of adult SMI patients. Twelve discrete choice questions comparing adherence monitoring tools that varied across two attribute bundles: (1) tool attributes including source of medication adherence information, frequency of information updates, access to adherence information, and physical activity, mood, and rest tracking, and (2) caregiver monthly out-of-pocket cost attribute were administered to caregiver respondents. Attributes were parameterized for both digital and non-digital tools. Random utility models were used to estimate caregivers' preferences and WTP. Results: Among 184 study-eligible caregivers, 57, 61 and 66 participants cared for BPD, MDD, and SCZ patients, respectively. Caregivers highly preferred (odds ratio (OR): 7.34, 95% confidence interval (CI): 5.00-10.79) a tool that tracked medication ingestion using a pill embedded with an ingestible event market (IEM) sensor and tracked patients' physical activity, mood, and rest than a non-digital pill organizer. Additionally, caregivers were willing to pay $255 per month (95% CI: $123-$387) more for this tool compared to a pill organizer. Conclusion: Caregivers of SMI patients highly preferred and were willing to pay more for digital tools that not only measures medication ingestion but also tracks general health.

Economic burden of antibiotic-not-susceptible isolates in uncomplicated urinary tract infection: Analysis of a US integrated delivery network database.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs) are one of the most common bacterial infections in the United States (US). Contemporary data are important for understanding the health economic impact of antimicrobial-resistant uUTIs. We compared the economic burden among patients with uUTI isolates susceptible or not-susceptible to the initial antibiotic prescription. METHODS: This retrospective cohort study utilized electronic health record data (1 July 2016-31 March 2020) from a large Mid-Atlantic US integrated delivery network database. Patients were females aged ≥ 12 years with a uUTI, who received oral antibiotic treatment and had ≥ 1 urine culture within ± 5 days of diagnosis. The primary outcome was the difference in healthcare resource use and costs (all-cause, urinary tract infection [UTI]-related) among patients with susceptible versus not-susceptible isolates during the 6 months after the index uUTI diagnosis. Secondary outcomes included: pharmacy costs, hospital admissions and emergency department visits, as well as the probability of uUTI progressing to complicated UTI (cUTI) between patients with susceptible and not-susceptible isolates. Patient outcomes were compared using 1:1 propensity score matching. Winsorized costs were adjusted to 2020 quarter 1 US dollars ($). RESULTS: A total of 2565 patients were eligible for analysis. The propensity score-matched sample comprised 2018 patients, with an average age of 44.0 and 41.0 years for the susceptible and not-susceptible populations, respectively. In the 6 months post-index uUTI event, patients with not-susceptible isolates had significantly more all-cause prescriptions orders (+ 1.41 [P = 0.001]), UTI-related prescriptions orders (+ 0.26 [P < 0.001]) and a higher probability of all-cause inpatient (+ 1.4% [P = 0.009]), outpatient (+ 6.1% [P = 0.006]), or UTI-related outpatient (+ 3.7% [P = 0.039]) encounters. Patients with a uUTI and an antibiotic-not-susceptible isolate were significantly more likely to progress to cUTI than those with susceptible isolates (odds ratio: 2.35 [confidence interval: 1.66-3.33; P < 0.001]). Over 6 months, patients with not-susceptible versus susceptible isolates had significantly higher all-cause costs (+ $426 [P = 0.031]) and UTI-related costs (+ $157 [P = 0.034]). CONCLUSIONS: Patients with a uUTI caused by antibiotic-not-susceptible isolates had higher healthcare resource usage, costs, and increased likelihood of progressing to cUTI than those with antibiotic-susceptible isolates.