Cost Effectiveness of Early Endovenous Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis in the United Kingdom.

OBJECTIVE: Early clot removal using endovascular intervention aims to reduce post-thrombotic syndrome (PTS) following iliofemoral deep venous thrombosis (DVT). This may reduce long term morbidity but incurs a higher initial cost. This study examined the cost effectiveness of catheter directed thrombolysis (CDT) and pharmacochemical thrombectomy (PMT) compared with oral anticoagulation (OAC) alone for treatment of acute iliofemoral DVT in the United Kingdom. METHODS: A combined decision tree (acute DVT complications) and Markov model (long term complications [PTS]) was used for decision analytic modelling with five states: no PTS, mild PTS, moderate PTS, severe PTS, and dead. All patients started with acute DVT. Patients who survived acute complications transitioned into the Markov model. Cycle time was six months. A healthcare payer perspective and lifetime horizon was used, adjusting for excess mortality due to history of thrombosis. Data for probabilities, transition probabilities, mortality, and utilities were obtained from the published literature. Cost data were obtained from UK NHS tariffs and published literature. Outcomes were mean lifetime cost, quality adjusted life years (QALYs), and cost effectiveness. RESULTS: Over a patient's lifetime, OAC was more costly (£37 206) than CDT (£32 043) and PMT (£36 288). Mean lifetime QALYs for OAC (12.9) were lower than CDT (13.5) and PMT (13.3). Therefore, in the incremental cost effectiveness analysis, both CDT and PMT were dominant: CDT was less costly (-£5 163) and more effective (+0.6 QALYs) than OAC, and PMT was also less costly (-£917) and more effective (+0.3 QALYs) than OAC. Results were robust to univariable sensitivity analyses, but probabilistic sensitivity analyses suggested considerable parameter uncertainty. CONCLUSION: Early interventional treatment of iliofemoral DVT is cost effective in the UK. Future clinical and epidemiological studies are needed to characterise parameter uncertainty. Further analysis of modern practice, alternative treatments, and optimised care models is warranted.

Cost-Effectiveness Analysis of Pertuzumab With Trastuzumab and Chemotherapy Compared to Trastuzumab and Chemotherapy in the Adjuvant Treatment of HER2-Positive Breast Cancer in the United States.

OBJECTIVE: The APHINITY trial assessed the effectiveness and the safety of adding pertuzumab to trastuzumab and chemotherapy (THP) compared to trastuzumab and chemotherapy (TH) in the adjuvant management of human epidermal growth factor 2-positive (HER2+) breast cancer. We performed a study to project the potential cost-effectiveness of THP vs. TH. STUDY DESIGN: Trial-based cost-utility modeling analysis. METHODS: We performed an economic evaluation from a payer perspective using a Markov model with six health states: invasive disease-free survival, non-metastatic recurrence, remission, first-line metastatic, subsequent line metastatic, and death. We parameterized the model using data from both arms in APHINITY extrapolated to a patient's lifetime horizon. Estimates of health state utilities were based on EQ-5D trial data and the literature, and costs were estimated from government sources and the published literature. The primary outcomes of the model were life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed via univariate and probabilistic sensitivity analyses. RESULTS: For the intention-to-treat population, the model projected improved outcomes (by 0.50 LYs and 0.45 QALYs) and increased costs (by $74 420) for ICERs of $147 774/LY gained and $167 185/QALY gained for PHT vs. HT patients. In the node-positive patient population, the model projected improved outcomes (by 0.86 LYs and 0.76 QALYs) and increased costs (by $66 647) for ICERs of $77 684/LY gained and $87 929/QALY gained. For the hormone-receptor-negative patient population, the model projected health gains, increased costs, and ICERs of $147 022/LY gained and $166 518/QALY gained. The results were sensitive to changes in the model time horizon. CONCLUSION: The addition of pertuzumab to the available regimens for HER2+ early breast cancer is likely to be cost-effective for patients in the U.S. at high risk of recurrence.

Cost Utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease.

OBJECTIVE: The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration-approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC). STUDY DESIGN: A 2-state Markov model, alive and dead, with a lifetime horizon. METHODS: Visual acuity (VA) and visual field (VF) were tracked to model quality-adjusted life-years (QALYs). VN led to an improvement in VA and VF that we assumed was maintained for 10 years followed by a 10-year waning period. The cost of VN was $850 000, and other direct medical costs for depression and trauma were included for a US healthcare system perspective. A modified societal perspective also included direct nonmedical costs and indirect costs. RESULTS: VN provided an additional 1.3 QALYs over the remaining lifetime of an individual. The average total lifetime direct medical cost for individuals treated with VN was $1 039 000 compared with $213 400 for SoC, leading to an incremental cost-effectiveness ratio (ICER) of $643 800/QALY from the US healthcare system perspective. Direct nonmedical costs totalled $1 070 900 for VN and $1 203 300 for SoC, and indirect costs totalled $405 400 for VN and $482 900 for SoC, leading to an ICER of $480 100/QALY from the modified societal perspective. CONCLUSIONS: At the current price, VN was unlikely to reach traditional cost-effectiveness standards compared with SoC. VN has important implications for both development and pricing of future gene therapies; therefore clinical and economic analyses must be carefully considered.

Study protocol: using a mobile phone-based application to increase awareness and uptake of sexual and reproductive health services among the youth in Uganda. A randomized controlled trial.

BACKGROUND: Several cost-effective programs are being implemented around the world that use mobile technology to improve Sexual and Reproductive Health (SRH) uptake and awareness among youth. Mobile phone applications are a viable and effective means of increasing access to SRH services and tools in low and middle-income countries. This paper presents a protocol for a pilot study of a novel program, a mobile phone-based sexual and reproductive health services awareness and delivery application with the objective of increasing the demand for SRH services amongst the youth in Uganda. METHODS: The study employs rigorous evaluation methods to ascertain the impact of the mobile application. We propose a randomized control trial study to determine the causal effect of the mobile phone app in creating awareness and increasing uptake of sexual and reproductive health services in Uganda. The main outcome of the impact evaluation is the percentage change in the SRH services and tools uptake, SRH knowledge and sexual behavior. We will also conduct a model-based incremental cost-effectiveness analysis (CEA) and budget impact analysis (BIA). The main outcomes of the economic evaluation will be the average cost per app user, cost per app service and tool provided. We will also test the in-app advertising model as a way to generate revenue to sustain the program subsidies and related costs. DISCUSSION: The study seeks to establish the proof of concept of using a mobile application to increase create awareness and increase uptake of SRH tools and services among youth in Uganda. The study results will lead to the development of a demand-driven, culturally-relevant, and easy-to-use mobile app to enhance the uptake of SRH services among the youth in Uganda and globally. TRIAL REGISTRATION: MUREC1/7 No. 07/05-18 . Registered 29th June 2018.

Impact of pharmacy worker training and deployment on access to essential medicines for children under five in Malawi: a cluster quasi-experimental evaluation.

BACKGROUND: Poor access to essential medicines is common in many low- and middle-income countries, partly due to an insufficient and inadequately trained workforce to manage the medicines supply chain. We conducted a prospective impact evaluation of the training and deployment of pharmacy assistants (PAs) to rural health centers in Malawi. METHODS: A quasi-experimental design was used to compare access to medicines in two districts where newly trained PAs were deployed to health centers (intervention) and two districts with no trained PAs at health centers (comparison). A baseline household survey and two annual post-intervention household surveys were conducted. We studied children under five years with a history of fever, cough and difficulty in breathing, and diarrhea in the previous two weeks. We collected data on access to antimalarials, antibiotics and oral rehydration salts (ORS) during the childrens' symptomatic periods. We used difference-in-differences regression models to estimate the impact of PA training and deployment on access to medicines. RESULTS: We included 3974 children across the three rounds of annual surveys: 1840 (46%) in the districts with PAs deployed at health centers and 2096 (53%) in districts with no PAs deployed at health centers. Approximately 80% of children had a fever, nearly 30% had a cough, and 43% had diarrhea in the previous two weeks. In the first year of the program, the presence of a PA led to a significant 74% increase in the odds of access to any antimalarial, and a significant 49% increase in the odds of access to artemisinin combination therapies. This effect was restricted to the first year post-intervention. There was no effect of presence of a PA on access to antibiotics or ORS. CONCLUSION: The training and deployment of pharmacy assistants to rural health centers in Malawi increased access to antimalarial medications over the first year, but the effect was attenuated over the second year. Pharmacy assistants training and deployment demonstrated no impact on access to antibiotics for pneumonia or oral rehydration salts for diarrhea.

Study protocol: incentives for increased access to comprehensive family planning for urban youth using a benefits card in Uganda. A quasi-experimental study.

BACKGROUND: The use of contraception is one of the most cost-effective public health interventions and has the potential to prevent about 30% of maternal and 10% of child deaths in developing countries. Voucher-based initiatives for family planning are an effective and viable means of increasing contraceptive use. In this paper, we present a protocol for a pilot study of a novel incentive, a family planning benefits card (FPBC) program to increase uptake of family planning services among urban poor youth in Uganda while leveraging private sector funding. METHODS: The study employs both impact and health economic evaluation methods to assess the effect of the FPBC program. We propose a quasi-experimental study design with two separate pre- and post-samples to measure program effectiveness. The main outcome of the impact evaluation is the percentage change in the prevalence of modern contraceptive use and unmet need for contraception. We will also conduct model-based incremental cost-effectiveness and budget impact analyses. The main outcomes of the economic evaluation are the cost per enrolled youth and cost per pregnancy averted, and cost per disability-adjusted life-year (DALY) averted. We will also pilot a corporate social responsibility model of sponsorship for the FPBC program in partnership with local corporations. Budget impact analysis will examine the potential affordability of scaling up the FPBC program and the fiscal implications of this scale up to the corporate social responsibility (CSR) budgets of partner corporations, the government, and the individual taxpayer. DISCUSSION: In this study, we propose an impact and economic evaluation to establish the proof concept of using a FPBC program to increase uptake of family planning services among urban poor youth in Uganda. The results of this study will present stakeholders in Uganda and internationally with a potentially viable option for corporate-sponsored access to family planning in urban poor communities. TRIAL REGISTRATION: MUREC1/7 No. 10/05-17. Registered 19th July 2017.

Budget impact of dostarlimab plus carboplatin-paclitaxel for primary advanced or recurrent endometrial cancer from a third-party US payer perspective.

AIM: Dostarlimab plus carboplatin-paclitaxel (CP) significantly increased progression-free survival in patients with primary advanced or recurrent endometrial cancer (pA/rEC) vs CP alone in the RUBY trial (NCT03981796). This analysis estimated the per-member-per-month (PMPM) costs of introducing dostarlimab + CP as a treatment alternative from a third-party US payer perspective. MATERIALS AND METHODS: A budget impact model was developed to estimate the costs of introducing dostarlimab + CP into commercial and Medicare health plans over a 3-year time horizon (2023-2025). Costs were sourced from relevant literature and US-specific databases and were calculated using epidemiology data, clinical inputs, treatment costs, and market share estimates. Clinical inputs were sourced from primary clinical trials for each respective treatment (ie, dostarlimab + CP, CP, pembrolizumab, pembrolizumab plus lenvatinib, bevacizumab + CP, and pembrolizumab + CP). Current and future market shares assumed dostarlimab + CP reduced the market share of CP only. Analyses were performed in mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations using a US 2023 cost year. RESULTS: For a commercial plan, the model estimated (dMMR/MSI-H and overall populations) that 7 and 26 patients would be treated with dostarlimab + CP, respectively; average annual budget impacts per patient treated were $118,257 and $116,094; average budget impacts per patient treated per month (PPPM) were $9,855 and $9,675; average budget impacts PMPM were $0.02 and $0.06. For a Medicare plan, the model estimated that 28 and 93 patients, respectively, would be treated with dostarlimab + CP. Average annual budget impacts per patient treated and PPPM were the same as those for the commercial plan in both populations; average budget impacts PMPM were $0.07 and $0.22, respectively. CONCLUSIONS: Introducing dostarlimab + CP as a first-line treatment for patients with pA/rEC results in minimal budget impact PMPM from a US third-party payers' perspective. Together with the efficacy and safety results from RUBY, these results support the use of dostarlimab + CP as a treatment option.

Dostarlimab with carboplatin-paclitaxel is a recently approved treatment for newly diagnosed advanced or recurrent endometrial cancer. This analysis was done to estimate the added costs that US commercial and Medicare health plans would have over 3 years if this treatment was covered. This analysis found that the budget increase for covering dostarlimab with carboplatin-paclitaxel was small ($0.02-$0.06 per commercial plan member per month; $0.07-$0.22 per Medicare plan member per month).

Health-related quality of life and social support among women treated for abortion complications in western Uganda.

BACKGROUND: While the impact of abortion complications on clinical outcomes and healthcare costs has been reported, we found no reports of their impact on Health-Related Quality of Life (HRQoL), nor the role of social support in moderating such outcomes. In this study, we performed an assessment of the relationship between abortion complications, HRQoL and social support among women in Uganda. METHODS: We interviewed women who were discharged after treatment for abortion complications and, as a comparison, women visiting a regional referral hospital for routine obstetric care. We administered the EuroQol instrument and the Social Support Questionnaire Short-Form, and collected demographic and socioeconomic data. We performed descriptive analyses using t-tests, Wilcoxon rank-sum tests and chi-square tests, and multivariable linear regressions with interaction effects to examine the associations between abortion complications, EQ-5D utility scores and social support. RESULTS: Our study included 139 women (70 with abortion complications, and 69 receiving routine obstetric care). In four out of the 5 dimensions of the EQ-5D, a larger proportion of women with abortion complications reported "some or severe" problems than women receiving routine obstetric care (self-care: 42% v 24%, p=0.033; usual activities: 49% v 16%, p<0.001; pain/discomfort: 68% v 25%, p<0.001; and anxiety/depression: 60% v 22%, p<0.001). After adjusting for age, social support, wealth tertile, employment status, marital status, and HIV status, women with abortion complications had a 0.12 (95% CI: 0.07, 0.18, p < 0.001) lower mean EQ-5D utility score than those receiving routine obstetric care. An analysis of the modifying effect of social support showed that a one-unit higher average number of people providing social support was associated with larger mean difference in EQ-5D utility score when comparing the two groups, while a one unit higher average satisfaction score with social support was associated with smaller mean differences in EQ-5D utility score. CONCLUSIONS: Our study suggests that abortion complications are associated with diminished HRQoL and the magnitude of the association depends on social support. However, the mediating role of social support in a setting of social and legal proscriptions to induced abortion is complex.

Adverse event costs associated with first-line therapy for advanced non-small cell lung cancer in the United States: An analysis of clinical trials of immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors, such as pembrolizumab, nivolumab, and atezolizumab, have demonstrated substantial survival benefits in patients with advanced non-small cell lung cancer (NSCLC). However, there is limited evidence on their relative safety profiles and adverse event (AE)-related cost burden. OBJECTIVE: To compare the AE management costs of nivolumab plus ipilimumab with and without limited chemotherapy with those of chemotherapy, pembrolizumab plus chemotherapy, and atezolizumab plus chemotherapy in a first-line setting among patients with advanced NSCLC. METHODS: The mean per-patient AE costs were estimated using the incidence of all-cause grade 3/4 AEs with any-grade incidence greater than or equal to 15% and the corresponding costs of AE management in the inpatient setting. AE rates were obtained from individual patient data from the CheckMate 227 and CheckMate 9LA trials for nivolumab plus ipilimumab with/without limited chemotherapy and aggregated data from the KEYNOTE-189 and KEYNOTE-407 trials for pembrolizumab plus chemotherapy and the IMpower130 trial for atezolizumab plus chemotherapy. AE management costs from the third-party payer perspective were estimated based on inpatient medical costs from the 2016 United States Healthcare Cost and Utilization Project National Inpatient Sample. All costs were inflated to 2020 US dollars. RESULTS: Nivolumab plus ipilimumab and nivolumab plus ipilimumab plus limited chemotherapy were associated with lower per-patient grade 3/4 AE costs compared with chemotherapy ($1,708 and $624 lower over the treatment course, respectively). Compared with pembrolizumab plus chemotherapy, nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs in patients with nonsquamous histology (difference: -$4,866) and squamous histology (difference: -$3,795), and nivolumab plus ipilimumab with limited chemotherapy also had lower AE costs for both nonsquamous (difference: -$2,800) and squamous (difference: -$2,753) disease. Similarly, nivolumab plus ipilimumab and nivolumab plus ipilimumab plus limited chemotherapy were also associated with lower AE costs ($11,400 and $8,809 lower, respectively) compared with atezolizumab plus chemotherapy among patients with nonsquamous disease. In particular, nivolumab plus ipilimumab without or with limited chemotherapy were associated with much lower AE costs of hematological AEs compared with chemotherapy and other immune checkpoint inhibitor-based treatments in combination with a full course of chemotherapy. CONCLUSIONS: Nivolumab plus ipilimumab with/without limited chemotherapy was associated with lower AE management costs compared with chemotherapy, pembrolizumab plus chemotherapy, and atezolizumab plus chemotherapy as first-line treatment for advanced NSCLC. The AE cost benefits were largely driven by the lower cost burden for hematological AEs for nivolumab plus ipilimumab with/without limited chemotherapy. DISCLOSURES This study was supported by Bristol-Myers Squibb. The sponsor was involved in all aspects of the work and in the decision to submit the manuscript for publication. Dr Stenehjem has received consulting fees from Bristol-Myers Squibb. Dr Lubinga was an employee of Bristol-Myers Squibb at the time of the study's conduct and holds stock/options. Drs Betts and Wu are employees of Analysis Group, Inc., a consulting company that has received funding from Bristol-Myers Squibb for this research.

Better together? costs of first-line chemoimmunotherapy for advanced non-small cell lung cancer.

OBJECTIVES: Recent advances have created options for first-line (1L) treatment of advanced/metastatic non-small cell lung cancer (aNSCLC). The study objectives were to describe the utilization of 3 classes of 1L treatment-chemotherapy (CT), immunotherapy (IO), and chemoimmunotherapy (IO+CT)-and the total, third-party payer, direct health care costs. STUDY DESIGN: Retrospective, administrative claims database analysis of patients with aNSCLC who initiated 1L treatment between January 1, 2017, and May 31, 2019, with IO, CT, or IO+CT. METHODS: Microcosting enumerated health care resource utilization, including antineoplastic drug costs, using standardized costs. Generalized linear models estimated per-patient per-month (PPPM) costs during 1L treatment, and adjusted cost differences in 1L among treatment cohorts were calculated using recycled predictions. RESULTS: A total of 1317 IO-, 5315 CT-, and 1522 IO+CT-treated patients were identified. Utilization of CT declined from 72.3% to 47.6% between 2017 and 2019, replaced by use of IO+CT, which increased from 1.8% to 29.8%. Total PPPM costs in 1L were highest with IO+CT at $32,436, compared with $19,000 and $17,763 in the CT and IO cohorts, respectively. Adjusted analyses showed that PPPM costs were $13,933 (95% CI, $11,760-$16,105) higher in the IO+CT vs IO cohort (P < .001) and IO costs were $1024 (95% CI, $67-$1980) lower than CT (P = .04). CONCLUSIONS: IO+CT accounts for almost one-third of 1L aNSCLC treatment modalities, coinciding with a reduction in treatment with CT. Costs for patients treated with IO were lower than those for patients treated with both IO+CT and CT alone, driven primarily by antineoplastic drug and associated medical costs.

Cost-effectiveness analysis of nivolumab plus ipilimumab versus platinum-doublet chemotherapy for first-line treatment of stage IV or recurrent non-small cell lung cancer in the United States.

AIM: We evaluated the cost-effectiveness of nivolumab in combination with ipilimumab (NIVO + IPI) versus platinum-doublet chemotherapy (PDC) for the first-line treatment of stage IV or recurrent non-small cell lung cancer (NSCLC) from a third-party payer perspective in the United States (US). METHODS: A partitioned survival model was developed using efficacy, safety, and utility inputs derived from Part 1 of the phase 3 CheckMate 227 trial (NCT02477826) with 37.7-month minimum follow-up for overall survival (OS). OS and progression-free (PF) survival were extrapolated over a 20-year time-horizon using parametric spline-based models selected based on goodness of fit and validated with data from external sources. Duration of treatment Kaplan-Meier curves were used for treatment cost calculations. US-specific costs (2021 dollars) for drug acquisition, administration, and monitoring; disease management (PF and progressed disease health states); end-of-life care; adverse events; and subsequent treatments were derived from publicly available sources. Time-to-death utilities were applied in the base case, whereas treatment-specific progression-based utilities were tested in a scenario analysis. Main outcomes included incremental cost per life-year gained (LYG) and quality-adjusted life-year (QALY). Model uncertainty was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: NIVO + IPI resulted in 1.53 additional life-years, 1.33 additional QALYs, and $142 088 in additional costs compared with PDC. The incremental cost per LYG was $92 651, whereas incremental cost per QALY gained was $106 553. The application of treatment-specific progression-based utilities yielded an incremental cost per QALY gained of $117 076. Probabilistic sensitivity analysis revealed a 98% probability that NIVO + IPI was cost-effective versus PDC at a willingness-to-pay threshold of $150 000 per QALY. CONCLUSIONS: NIVO + IPI was estimated to be cost-effective as a first-line treatment for stage IV or recurrent NSCLC in the US, with increased survival and higher cost compared with PDC.

Cost-effectiveness analysis of nivolumab plus ipilimumab plus two cycles of platinum-doublet chemotherapy versus platinum-doublet chemotherapy alone for first-line treatment of stage IV or recurrent non-small cell lung cancer in the United States.

AIM: This economic analysis evaluated the cost-effectiveness of nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of platinum-doublet chemotherapy (PDC) compared with four cycles of PDC as first-line treatment for patients with advanced NSCLC in the United States (US). METHODS: A partitioned survival model was constructed with three mutually exclusive health states: progression free, progressed disease, and death. The analysis was conducted from a US healthcare payer perspective, using a time horizon of 25 years. Costs and outcomes were discounted at 3% annually. Survival outcomes from CheckMate 9LA were extrapolated with longer follow-up data from CheckMate 227 Part 1 (NIVO + IPI) and validated against data from other relevant clinical trials and real-world registries. Health-related quality of life utility values were derived from EQ-5D-3L data collected in CheckMate 9LA. US-specific costs (2020 dollars) were used for disease management; drug acquisition, administration, and monitoring; end-of-life care; adverse events; and subsequent treatments. Model outcomes included life years (LYs) gained, quality-adjusted LYs (QALYs) gained, and incremental cost-effectiveness ratio (ICER) for NIVO + IPI + PDC versus PDC. Sensitivity and scenario analyses were conducted. RESULTS: NIVO + IPI + PDC was associated with higher projected health benefits than PDC, including gains in LYs (3.71 vs 1.89) and QALYs (2.86 vs 1.37), and higher costs ($317,581 vs $119,909). The ICER was $132,960/QALY gained. NIVO + IPI + PDC had a 78-100% probability of being cost-effective at a willingness-to-pay threshold of $150,000-$250,000/QALY. Sensitivity and scenario analyses indicated that the results were robust to changes in key parameters. LIMITATIONS: The inherent limitation in extrapolating clinical trial data was mitigated using data from the more mature CheckMate 227 Part 1 trial and validating the outcomes against data from other relevant trials and real-world registries. CONCLUSION: NIVO + IPI + PDC (two cycles) provides a new first-line treatment option for patients with advanced NSCLC that is cost-effective within a range considered acceptable in the US.

Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study.

BACKGROUND: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10. RESULTS: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK (p = 0.01), EGFR (p < 0.01), and TP53 (p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21-0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21-0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. CONCLUSIONS: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.

Cost-effectiveness of nivolumab in patients with NSCLC in the United States.

OBJECTIVES: To determine the lifetime cost-effectiveness of nivolumab vs docetaxel in advanced squamous and nonsquamous non-small cell lung cancer (NSCLC) following platinum-based chemotherapy from a US payer perspective. STUDY DESIGN: Trial- and cohort-based cost-effectiveness analyses. METHODS: The analyses used partitioned survival models with 3 mutually exclusive health states: progression free, progressed disease, and death. The mean starting age was 61 years. Clinical parameters were derived from the 2 registrational, randomized, phase 3 trials with a minimum follow-up of 5 years. Costs were derived from published literature. The primary outcomes were quality-adjusted life-years (QALYs), life-years gained (LYG), and incremental cost-effectiveness ratios (ICERs). Costs and outcomes were discounted at 3% per annum. Uncertainty was examined using univariate and probabilistic sensitivity analyses. RESULTS: In patients with squamous NSCLC, the use of nivolumab improved life-years (LYs) and QALYs by 1.23 and 0.99, respectively, compared with docetaxel. Costs were increased by $99,677, resulting in ICERs of $100,776 per QALY and $81,294 per LYG. In patients with nonsquamous NSCLC, nivolumab increased LYs and QALYs by 0.99 and 0.80, respectively. Costs were increased by $94,174, resulting in ICERs of $117,739 per QALY and $94,849 per LYG. ICERs were most sensitive to the discount rates applied to costs and outcomes. At a willingness-to-pay threshold of $150,000, nivolumab had probabilities of 91% and 99% of being cost-effective in patients with squamous and nonsquamous NSCLC, respectively. CONCLUSIONS: Nivolumab is likely to be cost-effective for the treatment of patients with advanced NSCLC following platinum-based chemotherapy in the United States.

Real-World Effectiveness of Nivolumab Monotherapy After Prior Systemic Therapy in Advanced Non-Small-Cell Lung Cancer in the United States.

BACKGROUND: In phase 3 clinical trials, nivolumab prolonged overall survival (OS) compared to chemotherapy in patients with previously treated advanced non-small-cell lung cancer (NSCLC). This retrospective real-world study evaluated OS in patients receiving nivolumab for previously treated advanced NSCLC primarily in US community hospitals. PATIENTS AND METHODS: Patient data were taken from electronic health records in the Flatiron Health oncology database. OS was evaluated in patients receiving nivolumab monotherapy for nonsquamous or squamous advanced NSCLC after prior chemotherapy; subgroup analyses were performed by Eastern Cooperative Oncology Group performance status (ECOG PS), age, and other baseline characteristics. Cox analysis was used to determine OS predictors. RESULTS: Of 3019 included patients, 1968 (65%) had nonsquamous and 1051 (35%) had squamous histology. In both cohorts, approximately 20% of patients had a verified ECOG PS ≥ 2, and > 25% were aged ≥ 75 years. For all patients, median OS in the nonsquamous and squamous cohorts was 8.6 months (95% confidence interval [CI], 8.0-9.3) and 7.4 months (95% CI, 6.8-8.5), respectively; for those with ECOG PS 0-1, median OS was 10.8 months (95% CI, 9.8-11.8) and 8.7 months (95% CI, 7.6-9.7), respectively. In both cohorts, programmed death ligand 1 expression ≥ 1% and ECOG PS 0-1 were associated with longer OS (P < .05); the number of prior lines of therapy and age ≥ 75 years had no significant association with OS. CONCLUSIONS: This study confirmed the effectiveness of nivolumab monotherapy for previously treated advanced NSCLC in real-world clinical practice. Poor ECOG PS, but not advanced age, was associated with shorter OS.

Cost-utility and budget impact of methylene blue-treated plasma compared to quarantine plasma.

BACKGROUND: Methylene blue and visible light treatment and quarantine are two methods used to reduce adverse events, mostly infections, associated with the transfusion of fresh-frozen plasma. The objective of this study was to estimate and compare the budget impact and cost-utility of these two methods from a payer's perspective. MATERIALS AND METHODS: A budget impact and cost-utility model simulating the risks of hepatitis B virus, hepatitis C virus, cytomegalovirus, a West Nile virus-like infection, allergic reactions and febrile non-haemolytic transfusion reactions achieved using plasma treated with methylene blue and visible light (MBP) and quarantine plasma (QP) was constructed for Spain. QP costs were estimated using data from one blood centre in Spain and published literature. The costs of producing fresh-frozen plasma from whole blood, apheresis plasma, and multicomponent apheresis, and separately for passive and active methods of donor recall for QP were included. Costs and outcomes over a 5-year and lifetime time horizon were estimated. RESULTS: Compared to passive QP, MBP led to a net increase of € 850,352, and compared to active QP, MBP led to a net saving of € 5,890,425 over a 5-year period. Compared to passive QP, MBP increased the cost of fresh-frozen plasma per patient by € 7.21 and had an incremental cost-utility ratio of € 705,126 per quality-adjusted life-year. Compared to active QP, MBP reduced cost by € 50.46 per patient and was more effective. DISCUSSION: Plasma collection method and quarantine approach had the strongest influence on the budget impact and cost-utility of MBP. If QP relies on plasma from whole blood collection and passive quarantine, it is less costly than MBP. However, MPB was estimated to be more effective than QP in all analyses.

Acceptability of cervical cancer screening using visual inspection among women attending a childhood immunization clinic in Uganda.

OBJECTIVE: To evaluate the acceptability and performance of cervical cancer (CC) screening using visual inspection with acetic acid (VIA) integrated into a rural immunization clinic in Uganda. METHODS/MATERIALS: We conducted a cross-sectional pilot study in rural Uganda. We explored associations between women's characteristics and acceptance of VIA testing. We collected samples for Papanicolaou (Pap) smear testing in a random subset of women and used results from this test as a comparator for assessing VIA performance. RESULTS: We enrolled 625 women of whom 571 (91.4%) accepted and 54 (8.6%) refused CC screening. In the univariate model, age (Odds Ratio (OR)=1.10; p-value<0.001) and employment status (OR 2.00; p-value=0.019) were significantly associated with acceptance of VIA screening. In the multivariate model, no characteristic was independently associated with acceptance of VIA screening after adjusting for other factors. Compared to reference Pap smear, CC screening with VIA had a sensitivity of 50% and a specificity of 97.7%. CONCLUSIONS: CC screening with VIA is highly acceptable in the setting of rural immunization clinics in Uganda. Studies to assess which screening method would be the most effective and cost-effective are needed before stakeholders can consider adopting screening programs at scale.

A Cost-Effectiveness Tool to Guide the Prioritization of Interventions for Rheumatic Fever and Rheumatic Heart Disease Control in African Nations.

BACKGROUND: Rheumatic heart disease (RHD) prevalence and mortality rates remain especially high in many parts of Africa. While effective prevention and treatment exist, coverage rates of the various interventions are low. Little is known about the comparative cost-effectiveness of different RHD interventions in limited resource settings. We developed an economic evaluation tool to assist ministries of health in allocating resources and planning RHD control programs. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a Markov model of the natural history of acute rheumatic fever (ARF) and RHD, taking transition probabilities and intervention effectiveness data from previously published studies and expert opinion. Our model estimates the incremental cost-effectiveness of scaling up coverage of primary prevention (PP), secondary prevention (SP) and heart valve surgery (VS) interventions for RHD. We take a healthcare system perspective on costs and measure outcomes as disability-adjusted life-years (DALYs), discounting both at 3%. Univariate and probabilistic sensitivity analyses are also built into the modeling tool. We illustrate the use of this model in a hypothetical low-income African country, drawing on available disease burden and cost data. We found that, in our hypothetical country, PP would be cost saving and SP would be very cost-effective. International referral for VS (e.g., to a country like India that has existing surgical capacity) would be cost-effective, but building in-country VS services would not be cost-effective at typical low-income country thresholds. CONCLUSIONS/SIGNIFICANCE: Our cost-effectiveness analysis tool is designed to inform priorities for ARF/RHD control programs in Africa at the national or subnational level. In contrast to previous literature, our preliminary findings suggest PP could be the most efficient and cheapest approach in poor countries. We provide our model for public use in the form of a Supplementary File. Our research has immediate policy relevance and calls for renewed efforts to scale up RHD prevention.