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

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

A Simulation Model to Evaluate the Potential Impact of Disease-Modifying Treatments on Burden of Illness in Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease that places a substantial burden on patients, caregivers, and society. The advent of disease-modifying treatments (DMTs) would represent a major advancement in the management of AD, particularly in early AD. It is important to understand the potential value of these therapies to individuals and society. METHODS: A modeling framework was developed to estimate the potential clinical and economic burden of AD in the USA by simulating the impact, relative to that of usual care, of a DMT with hypothesized availability beginning from 2022. The model assessed AD epidemiology, disease progression, and burden of illness from 2020 to 2050. Model outcomes included the total number of Americans with mild cognitive impairment (MCI) due to AD and mild, moderate, or severe AD dementia in community or residential care settings and their associated care costs, including direct medical and non-medical costs for healthcare resource use and indirect costs for caregiving. RESULTS: A hypothetical DMT was compared to the usual care under different effect scenarios based on delay in onset of AD (1, 3, and 5 years) and DMT uptake (25%, 50%, and 100%). A delay in the onset of AD by 5 years would reduce the prevalence of AD in 2050 by 6%, 12%, and 25%, resulting in savings of $0.783, $1.566, and $3.132 trillion from 2022 to 2050 for the 25%, 50%, and 100% uptake scenarios, respectively. CONCLUSION: This analysis demonstrated that DMTs that provide even small delays in the onset of AD can lead to an increase in disease-free years and sizable savings in the cost of care, providing significant benefits to patients, caregivers, and society.

Public health impact of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) in the first year of rollout in the United States.

BACKGROUND: As the body of evidence on COVID-19 and post-vaccination outcomes continues to expand, this analysis sought to evaluate the public health impact of the Pfizer-BioNTech COVID-19 Vaccine, BNT162b2, during the first year of its rollout in the US. METHODS: A combined Markov decision tree model compared clinical and economic outcomes of the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) versus no vaccination in individuals aged ≥12 years. Age-stratified epidemiological, clinical, economic, and humanistic parameters were derived from existing data and published literature. Scenario analysis explored the impact of using lower and upper bounds of parameters on the results. The health benefits were estimated as the number of COVID-19 symptomatic cases, hospitalizations and deaths averted, and Quality Adjusted Life Years (QALYs) saved. The economic benefits were estimated as the amount of healthcare and societal cost savings associated with the vaccine-preventable health outcomes. RESULTS: It was estimated that, in 2021, the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to averting almost 9 million symptomatic cases, close to 700,000 hospitalizations, and over 110,000 deaths, resulting in an estimated $30.4 billion direct healthcare cost savings, $43.7 billion indirect cost savings related to productivity loss, as well as discounted gains of 1.1 million QALYs. Scenario analyses showed that these results were robust; the use of alternative plausible ranges of parameters did not change the interpretation of the findings. CONCLUSIONS: The Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to generate substantial public health impact and vaccine-preventable cost savings in the first year of its rollout in the US. The vaccine was estimated to prevent millions of COVID-19 symptomatic cases and thousands of hospitalizations and deaths, and these averted outcomes translated into cost-savings in the billions of US dollars and thousands of QALYs saved. As only direct impacts of vaccination were considered, these estimates may be conservative.

Qualitative Thematic Analysis of Social Media Data to Assess Perceptions of Route of Administration for Antiretroviral Treatment among People Living with HIV.

BACKGROUND: HIV is a condition that requires lifelong treatment. Treatment options currently consist of oral antiretroviral therapies (ART) taken once or twice daily. Long-acting injectable HIV treatments are currently in development to be administered monthly or every other month. Preferences for route of administration could influence treatment adherence, which could affect treatment outcomes. The purpose of this study was to examine patient perceptions of oral and injectable routes of administration for ART. METHODS: Qualitative thematic analysis was conducted to examine 5122 online discussion threads by people living with HIV (PLHIV) in the POZ Community Forums from January 2013 to June 2018. Analysis focused on identifying perceptions of oral or injectable routes of administration for ART. Relevant threads were extracted and imported into the qualitative data analysis software package ATLAS.ti.8 so that text could be reviewed and coded. RESULTS: Analyses identified 684 relevant discussion threads including 2626 coded quotations from online posts by 568 PLHIV. The oral route of administration was discussed more frequently than injectable (2516 quotations for oral; 110 injectable). Positive statements on the oral route of administration commonly mentioned the small number of pills (276 quotations), dose frequency (245), ease of scheduling (153), and ease of use (146). PLHIV also noted disadvantages of the oral route of administration including negative emotional impact (166), difficulty with medication access (106), scheduling (131), and treatment adherence (121). Among the smaller number of PLHIV discussing injectable ART, common positive comments focused on dose frequency (34), emotional benefits of not taking a daily pill (7), potential benefits for adherence (6), overall convenience (6), and benefits for traveling (6). Some comments from PLHIV perceived the frequency of injections negatively (10), and others had negative perceptions of needles (8) or appointments required to receive injections (7). CONCLUSIONS: Qualitative analysis revealed that route of administration was frequently discussed among PLHIV on this online forum. While many expressed positive views about their daily oral medication regimen, others perceived inconveniences and challenges. Among PLHIV who were aware of a possible monthly injectable treatment, many viewed this new route of administration as a convenient alternative with potential to improve adherence.

Outcomes and costs of remote patient monitoring among patients with implanted cardiac defibrillators: An economic model based on the PREDICT RM database.

BACKGROUND: Remote monitoring of implantable cardioverter-defibrillators has been associated with reduced rates of all-cause rehospitalizations and mortality among device recipients, but long-term economic benefits have not been studied. METHODS AND RESULTS: An economic model was developed using the PREDICT RM database comparing outcomes with and without remote monitoring. The database included patients ages 65 to 89 who received a Boston Scientific device from 2006 to 2010. Parametric survival equations were derived for rehospitalization and mortality to predict outcomes over a maximum time horizon of 25 years. The analysis assessed rehospitalization, mortality, and the cost-effectiveness (expressed as the incremental cost per quality-adjusted life year) of remote monitoring versus no remote monitoring. Remote monitoring was associated with reduced mortality; average life expectancy and average quality-adjusted life years increased by 0.77 years and 0.64, respectively (6.85 life years and 5.65 quality-adjusted life years). When expressed per patient-year, remote monitoring patients had fewer subsequent rehospitalizations (by 0.08 per patient-year) and lower hospitalization costs (by $554 per patient year). With longer life expectancies, remote monitoring patients experienced an average of 0.64 additional subsequent rehospitalizations with increased average lifetime hospitalization costs of $2784. Total costs of outpatient and physician claims were higher with remote monitoring ($47 515 vs $42 792), but average per patient-year costs were lower ($6232 vs $6244). The base-case incremental cost-effectiveness ratio was $10 752 per quality-adjusted life year, making remote monitoring high-value care. CONCLUSION: Remote monitoring is a cost-effective approach for the lifetime management of patients with implantable cardioverter-defibrillators.

Health state utilities associated with attributes of migraine preventive treatments based on patient and general population preferences.

PURPOSE: While previous studies have estimated health state utilities associated with migraine severity and frequency, migraine treatments vary in other ways that may have an impact on patients' quality of life, preference, and utility. The purpose of this study was to estimate utilities associated with migraine treatment attributes including route of administration and treatment-related adverse events (AEs). METHODS: In time trade-off interviews, migraine patients and general population participants in the UK valued health state vignettes drafted based on literature, medication labels, and clinician interviews. All respondents valued migraine health states varying in route of administration. Each participant also valued eight health states (randomly selected from a total of 15) that added the description of an AE to a migraine health state. RESULTS: A total of 400 participants completed interviews (200 general population [49.0% female; mean age = 43.6 years]; 200 migraine patients [74.5% female; mean age = 45.8 years]). In the general population sample, mean utilities of health states without aura were 0.79 with daily oral medication, 0.78 with one injection per month, and 0.72 with 31-39 injections once every 3 months. The greatest disutilities (i.e., decreases in utility) were for AEs associated with oral medications (e.g., - 0.060 [fatigue] and - 0.098 [brain fog]). Differences among health states followed the same pattern in the patient sample as in the general population sample. CONCLUSIONS: Utilities estimated from the general population sample may be used to represent route of administration and AEs in cost-utility models. Results from the patient sample indicate that these treatment characteristics have an impact on patient preference.

Health state utilities associated with treatment options for acute myeloid leukemia (AML).

Aims: Acute myeloid leukemia (AML) treatment typically involves remission induction chemotherapy followed by consolidation chemotherapy. New treatments for AML have recently been introduced, including a chemotherapy formulation called CPX-351, which is administered via less time-intensive IV infusion than the standard "7 + 3" continuous infusion regimen of cytarabine plus an anthracycline. The purpose of this study was to estimate utilities that could be used in economic modeling of AML treatment. Materials and methods: In time trade-off interviews, participants from the UK general population valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML. The decrease in utility when adding these chemotherapy regimens represents the disutility of each regimen. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: Two hundred participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. Adding any chemotherapy significantly decreased utility (p < 0.0001). Induction had a mean disutility of -0.11 with CPX-351 and -0.15 with 7 + 3. Mean disutility for consolidation ranged from -0.03 with outpatient CPX-351 to -0.11 with inpatient 5 + 2. Utilities are also reported for other AML treatments (e.g. transplant, low-intensity chemotherapy). Limitations: One limitation is that the differences in adverse event profiles between the treatment regimens were based on clinician opinion. Future use of CPX-351 in clinical trials or clinical settings will provide additional information on its adverse event profile. Conclusions: While all chemotherapy regimens were associated with disutility, regimens with shorter hospitalization and less time-intensive infusion were generally perceived as preferable. These utilities may be useful in cost-utility models comparing the value of AML treatments.

Cost-effectiveness analysis of dabigatran versus rivaroxaban for stroke prevention in patients with non-valvular atrial fibrillation using real-world evidence in elderly US Medicare beneficiaries.

OBJECTIVE: Dabigatran and rivaroxaban have been approved by the US FDA to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients. Newly published real-world evidence based on the US population found that elderly Medicare patients with NVAF treated with rivaroxaban experienced statistically significant increases in intracranial hemorrhage (ICH) and major extracranial bleeding, and statistically nonsignificant decreases in thromboembolic stroke and acute myocardial infarction (AMI) compared with dabigatran. This study assessed the cost-effectiveness of dabigatran vs. rivaroxaban for the treatment of US Medicare NVAF patients. METHODS: A previously published Markov model was adapted to compare dabigatran and rivaroxaban. The model considered thromboembolic stroke, bleeding events, and AMI based on the published real-world event risks. Model outputs included clinical event rates, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Dabigatran patients experienced fewer ICH and major extracranial bleeding events than rivaroxaban patients, but more stroke and AMI events. Dabigatran was found to yield lower costs and higher QALYs than rivaroxaban, with incremental costs of -$3534 and incremental QALYs of 0.004. Results remained consistent in sensitivity analyses, with a positive net monetary benefit (willingness-to-pay thresholds of $50,000 and $100,000 per QALY) for dabigatran over rivaroxaban for all model inputs tested. CONCLUSIONS: In this study using US Medicare real-world data, dabigatran was found to dominate rivaroxaban. The analyses were limited by the short follow-up period of the real-world data and results may not be generalizable to other patient populations.

Modeling the trade-off between transmissibility and contact in infectious disease dynamics.

Symptom severity affects disease transmission both by impacting contact rates, as well as by influencing the probability of transmission given contact. This involves a trade-off between these two factors, as increased symptom severity will tend to decrease contact rates, but increase the probability of transmission given contact (as pathogen shedding rates increase with symptom severity). This paper explores this trade-off between contact and transmission given contact, using a simple compartmental susceptible-infected-recovered type model. Under mild assumptions on how contact and transmission probability vary with symptom severity, we give sufficient, biologically intuitive criteria for when the basic reproduction number varies non-monotonically with symptom severity. Multiple critical points are possible. We give a complete characterization of the region in parameter space where multiple critical points are located in the special case where contact rate decreases exponentially with symptom severity. We consider a multi-strain version of the model with complete cross-immunity and no super-infection. In this model, we prove that the strain with highest basic reproduction number drives the other strains to extinction. This has both evolutionary and epidemiological implications, including the possibility of an intervention paradoxically resulting in increased infection prevalence.