BackgroundMucormycosis is a rare and potentially fatal fungal infection occurring primarily in severely immunosuppressed patients. Because it is so rare, reports in the literature are mainly limited to case reports or small case series. The aim of this study was to evaluate inpatient mortality, length of stay (LOS), and costs among a matched sample of high-risk patients with and without mucormycosis in a large nationally representative database.MethodsWe conducted a retrospective analysis using the 2003–2010 Healthcare Cost and Utilization Project – Nationwide Inpatient Sample (HCUP-NIS). The NIS is a nationally representative 20% sample of hospitalizations from acute care United States (US) hospitals, with survey weights available to compute national estimates. We classified hospitalizations into four mutually exclusive risk categories for mucormycosis: A- severely immunocompromised, B- critically ill, C- mildly/moderately immunocompromised, D- major surgery or pneumonia. Mucormycosis hospitalizations (“cases”) were identified by ICD-9-CM code 117.7. Non-mucormycosis hospitalizations (“non-cases”) were propensity-score matched to cases 3:1. We examined demographics, clinical characteristics, and hospital outcomes (mortality, LOS, costs). Weighted results were reported.ResultsFrom 319,366,817 total hospitalizations, 5,346 cases were matched to 15,999 non-cases. Cases and non-cases did not differ significantly in age (49.6 vs. 49.7 years), female sex (40.5% vs. 41.0%), White race (53.3% vs. 55.9%) or high-risk group (A-49.1% vs. 49.0%, B-20.0% vs. 21.8%, C-25.5% vs. 23.8%, D-5.5% vs. 5.4%). Cases experienced significantly higher mortality (22.1% vs. 4.4%, P < 0.001), with mean LOS and total costs more than 3-fold higher (24.5 vs. 8.0 days and $90,272 vs. $25,746; both P < 0.001).ConclusionsIn a national hospital database, hospitalizations with mucormycosis had significantly higher inpatient mortality, LOS, and hospital costs than matched hospitalizations without mucormycosis. Findings suggest that interventions to prevent or more effectively treat mucormycosis are needed.

In identifying issues associated with emerging IPF treatments, we demonstrate the value of qualitative research in understanding the views of diverse stakeholders and in providing a basis for future survey research. As such, qualitative methods should play an important role in understanding the benefits and risks of emerging therapies and in promoting patient-centered drug development.

Aims: Heart failure with reduced ejection fraction (HFrEF) has a substantial impact on costs and patients' quality-of-life. This study aimed to estimate the cost-effectiveness of implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy pacemakers (CRT-P), cardiac resynchronization therapy defibrillators (CRT-D), and optimal pharmacologic therapy (OPT) in patients with HFrEF, from a US payer perspective. Materials and methods: The analyses were conducted by adapting the UK-based cost-effectiveness analyses (CEA) to the US payer perspective by incorporating real world evidence (RWE) on baseline hospitalization risk and Medicare-specific costs. The CEA was based on regression equations estimated from data from 13 randomized clinical trials (n ¼ 12,638). Risk equations were used to predict all-cause mortality, hospitalization rates, health-related quality-of-life, and device-specific treatment effects (vs. OPT). These equations included the following prognostic characteristics: age, QRS duration, New York Heart Association (NYHA) class, ischemic etiology, and left bundle branch block (LBBB). Baseline hospitalization rates were calibrated based on RWE from Truven Health Analytics MarketScan data (2009)(2010)(2011)(2012)(2013)(2014). A US payer perspective, lifetime time horizon, and 3% discount rates for costs and outcomes were used. Benefits were expressed as quality-adjusted life-years (QALYs). Incremental costeffectiveness analysis was conducted for 24 sub-groups based on LBBB status, QRS duration, and NYHA class. Results: Results of the analyses show that CRT-D was the most cost-effective treatment at a $100,000/ QALY threshold in 14 of the 16 sub-groups for which it is indicated. Results were most sensitive to changes in estimates of hospitalization costs. Limitations: Study limitations include small sample sizes for NYHA I and IV sub-groups and lack of data availability for duration of treatment effect. Conclusions: CRT-D has higher greater cost-effectiveness across more sub-groups in the indicated patient populations against as compared to OPT, ICD, and CRT-P, from a US payer perspective.

Background Survival heterogeneity and limited trial follow-up present challenges for estimating lifetime benefits of oncology therapies. This study used CheckMate 067 (NCT01844505) extended follow-up data to assess the predictive accuracy of standard parametric and flexible models in estimating the long-term overall survival benefit of nivolumab plus ipilimumab (an immune checkpoint inhibitor combination) in advanced melanoma. Methods Six sets of survival models (standard parametric, piecewise, cubic spline, mixture cure, parametric mixture, and landmark response models) were independently fitted to overall survival data for treatments in CheckMate 067 (nivolumab plus ipilimumab, nivolumab, and ipilimumab) using successive data cuts (28, 40, 52, and 60 mo). Standard parametric models allow survival extrapolation in the absence of a complex hazard. Piecewise and cubic spline models allow additional flexibility in fitting the hazard function. Mixture cure, parametric mixture, and landmark response models provide flexibility by explicitly incorporating survival heterogeneity. Sixty-month follow-up data, external ipilimumab data, and clinical expert opinion were used to evaluate model estimation accuracy. Lifetime survival projections were compared using a 5% discount rate. Results Standard parametric, piecewise, and cubic spline models underestimated overall survival at 60 mo for the 28-mo data cut. Compared with other models, mixture cure, parametric mixture, and landmark response models provided more accurate long-term overall survival estimates versus external data, higher mean survival benefit over 20 y for the 28-mo data cut, and more consistent 20-y mean overall survival estimates across data cuts. Conclusion This case study demonstrates that survival models explicitly incorporating survival heterogeneity showed greater accuracy for early data cuts than standard parametric models did, consistent with similar immune checkpoint inhibitor survival validation studies in advanced melanoma. Research is required to assess generalizability to other tumors and disease stages. Highlights Given that short clinical trial follow-up periods and survival heterogeneity introduce uncertainty in the health technology assessment of oncology therapies, this study evaluated the suitability of conventional parametric survival modeling approaches as compared with more flexible models in the context of immune checkpoint inhibitors that have the potential to provide lasting survival benefits. This study used extended follow-up data from the phase III CheckMate 067 trial (NCT01844505) to assess the predictive accuracy of standard parametric models in comparison with more flexible methods for estimating the long-term survival benefit of the immune checkpoint inhibitor combination of nivolumab plus ipilimumab in advanced melanoma. Mixture cure, parametric mixture, and landmark response models provided more accurate estimates of long-term overall survival versus external data than other models tested. In this case study with immune checkpoint inhibitor therapies in advanced melanoma, extrapolation models that explicitly incorporate differences in cancer survival between observed or latent subgroups showed greater accuracy with both early and later data cuts than other approaches did.

Aims: The objective of this study was to evaluate the cost-effectiveness of nivolumab in combination with ipilimumab (nivo þ ipi) compared to current therapeutic alternatives in first-line treatment of patients with advanced melanoma from the Japanese national healthcare payer perspective using 48month survival data from the CheckMate 067 Phase III trial. Materials and methods: A three-state partitioned survival model was developed from projections of overall survival (OS) and progression-free survival (PFS) to estimate accrued quality-adjusted survival and costs over a 30-year time horizon. The analysis included nivo þ ipi, nivolumab, and ipilimumab monotherapies (the three treatments included in CheckMate 067). Drug acquisition, administration, disease management, subsequent therapy, and adverse event (AE) costs were obtained via published sources and expert input (solicited via Delphi panel). AE frequencies were collected from the Checkmate 067 trial. Utility weights were estimated from the Checkmate 067 trial, based on Japanese tariffs. Results were presented as incremental cost-utility ratios (ICURs, cost per quality-adjusted life-year (QALY)). Results: Nivo þ ipi had the greatest estimated survival among the three competing treatments, followed by nivolumab monotherapy accruing the second greatest survival. The incremental cost-effectiveness of nivo þ ipi was ¥778,000 per QALY vs. nivolumab and ¥1,584,000 per QALY vs. ipilimumab. The results indicate that nivo þ ipi is cost-effective in Japan when compared to a threshold of ¥7,500,000 per QALY. This finding was found to be generally robust to sensitivity and scenario analyses. Limitations: Limitations include uncertainty in long-term survival extrapolations and lack of Japan-specific clinical data. Conclusions: This analysis indicates that adding ipilimumab to nivolumab therapy represents a costeffective new treatment option for patients with unresectable malignant melanoma in Japan.