A cost-effectiveness analysis of reduced viral transmission with baloxavir marboxil versus oseltamivir or no treatment for seasonal and pandemic influenza management in the United Kingdom.

BACKGROUND: Baloxavir marboxil is an oral, single-dose, cap-dependent endonuclease inhibitor that reduces the duration of influenza symptoms and rapidly stops viral shedding. We developed a susceptible, exposed, infected, recovered (SEIR) model to inform a cost-effectiveness model (CEM) of baloxavir versus oseltamivir or no antiviral treatment in the UK. RESEARCH DESIGN AND METHODS: The SEIR model estimated the attack rates among otherwise healthy and high-risk individuals in seasonal and pandemic settings. The CEM assumed that a proportion of infected patients would receive antiviral treatment. Results were reported at the population level (per 10,000 at risk of infection). RESULTS: The SEIR model estimated greater reductions in infections with baloxavir. In a seasonal setting, baloxavir provided incremental cost-effectiveness ratios (ICERs) of £1884 per quality-adjusted life-year (QALY) gained versus oseltamivir and a dominant cost-effectiveness position versus no antiviral treatment in the total population; ICERs of £2574/QALY versus oseltamivir and £128/QALY versus no antiviral treatment were seen in the high-risk population. Baloxavir was also cost-effective versus oseltamivir or no antiviral treatment and reduced population-level health system occupancy concerns during a pandemic. CONCLUSION: Baloxavir treatment resulted in the fewest influenza cases and was cost-effective versus oseltamivir or no antiviral treatment from a UK National Health Service perspective.

Baloxavir marboxil ('baloxavir') is a prescription medicine for people who become ill with influenza (or 'the flu') that can reduce how long flu symptoms last and the likelihood of complications from the flu that may require going to the hospital. Baloxavir can also reduce the amount and duration of virus shed by infected individuals thus potentially slow or stop the flu from spreading to healthy people. We studied differences in reducing predicted flu infections between baloxavir and another flu treatment, known as oseltamivir, or no flu treatment at all. Treatment with baloxavir resulted in fewer flu infections in the UK population than oseltamivir or no treatment. We then studied how these differences might affect costs between baloxavir and oseltamivir or no treatment at a population level in the UK. Overall, in the majority of scenarios explored in the model, baloxavir was cost-effective as an antiviral treatment for people with the flu in the UK.

Atezolizumab in Combination with Bevacizumab for the Management of Patients with Hepatocellular Carcinoma in the First-Line Setting: Systematic Literature Review and Meta-Analysis.

Background: In 2020, atezolizumab-bevacizumab became the new standard of care (SOC) for first-line unresectable hepatocellular carcinoma (HCC) patients, following a decade where sorafenib was the preferred first-line treatment. In the last few years, a number of novel systemic treatments with non-inferiority and superiority to sorafenib have been approved as first-line treatments. Objectives: The objective of this systematic literature review (SLR) and network meta-analysis (NMA) was to compare randomised controlled trial evidence for atezolizumab-bevacizumab with globally relevant pharmacological comparators for first-line treatment of patients with unresectable HCC. Methods: Randomised controlled trials investigating first-line treatment of HCC in adults with no prior systemic treatment were eligible for inclusion into the SLR and were retrieved from Embase, MEDLINE, and Evidence-Based Medicine (EBM) Reviews. Interventions of interest for the NMA included atezolizumab-bevacizumab, sorafenib, lenvatinib, durvalumab (including in combination with tremelimumab), cabozantinib (including in combination with atezolizumab), camrelizumab (including in combination with rivoceranib), pembrolizumab (including in combination with lenvatinib), and tislelizumab. Random effects NMA was conducted for survival endpoints within a Bayesian framework with an informative prior distribution for between-study heterogeneity. The hazard ratios for relative treatment effect were estimated with 95% credible intervals (CrIs). Results: The SLR identified 49 studies, of which eight formed a connected evidence network permitting the indirect treatment comparison of atezolizumab-bevacizumab with comparators of interest. The indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus most comparators. All indirect treatment comparison results for atezolizumab-bevacizumab included the null value within the 95% CrI (n = 1) for OS and progression-free survival (PFS). Conclusions: The results of the NMA indicate atezolizumab-bevacizumab is associated with superior or comparable OS and PFS together with a manageable safety profile compared with globally relevant comparators in the unresected HCC indication. The findings support that atezolizumab-bevacizumab remains SOC for the management of first-line unresectable HCC patients.

Multiple Real-World Data Sources in a Bayesian Framework to Inform Long-Term Survival Estimates of Mosunetuzumab in Patients with Follicular Lymphoma.

INTRODUCTION: Patients with follicular lymphoma (FL) receiving third-line or later (3L +) therapy have long survival, which can make estimating long-term overall survival (OS) from trial data challenging. The objective of this study was to estimate long-term OS for mosunetuzumab from the GO29781 trial (NCT02500407) using multiple real-world databases (RWDs) in a Bayesian framework. METHODS: Seven RWD sources for patients with FL receiving 3L + therapy and the expansion cohort in the GO29781 trial for mosunetuzumab were used. Hazard trends from the RWD sources were analyzed, and disease-wide pointwise OS and its corresponding uncertainty were estimated using Bayesian random-effects meta-analysis from the RWD sources. Pointwise OS obtained was used as an informative prior in Bayesian survival extrapolations to data from patients receiving mosunetuzumab. Results after adjusting for background mortality were compared to equivalent frequentist extrapolations using trial data only. RESULTS: Hazard patterns from RWD sources supported a constant or linearly decreasing hazard. Mean pointwise OS for patients with FL receiving 3L + therapy was estimated at 0.52 (95% credible interval, 0.29-0.85) at 8 years. Bayesian extrapolations for mosunetuzumab produced median survival estimates of 11.6 (6.7-20.7) years to 17.0 (6.4-22.7) years depending on the distribution used, reducing uncertainty by 20% to 46% relative to the frequentist estimation. CONCLUSION: Multiple RWD sources can be synthesized to augment the credibility of data with short follow-up, long patient survival, and few events to effectively estimate long-term survival and reduce estimated uncertainty. This method can be applied to other indications with similar characteristics. CLINICAL TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT02500407, July 16, 2015.

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy.

A comparison of clinical outcomes in the third or subsequent line (3 L+) of systemic therapy between a real-world data (RWD) external control cohort and a mosunetuzumab single-arm clinical trial cohort is presented. Data for 3 L + patients with relapsed/refractory follicular lymphoma (FL) were obtained from the mosunetuzumab single-arm trial (n = 90) and a US electronic health records database (n = 158), with patients meeting key eligibility criteria from the trial, balanced on pre-specified prognostic factors. Overall response and complete response rates were 80% and 60% in the mosunetuzumab cohort and 75% and 33% in the RWD cohort, odds ratios of 1.23 (95% CI, 0.52-2.93) and 3.18 (95% CI, 1.41-7.17), respectively. Hazard ratios for progression-free survival and overall survival were 0.82 (95% CI, 0.53-1.27) and 0.43 (95% CI, 0.19-0.94). These findings support a clinically meaningful benefit of mosunetuzumab monotherapy as a chemotherapy-free option for the 3 L + FL population.

Impact of Influenza and Influenza-Like Illness on Work Productivity Outcomes: A Systematic Literature Review.

BACKGROUND: Influenza is a persistent public health problem with a significant burden on patients, employers, and society. A systematic review by Keech and Beardsworth (2008) characterized the burden of influenza/influenza-like illness (ILI) on absenteeism. We conducted a systematic literature review evaluating the impact of influenza/ILI on work productivity among adults as an update to the work of Keech and Beardsworth. METHODS: This systematic review identified studies evaluating the impact of influenza/ILI on absenteeism, presenteeism, or related work productivity measures for employees and employed caregivers based on laboratory confirmation, physician diagnosis, and/or self-reported illness. Eligible studies were in English, French, or German published from 7 March 2007 through 15 February 2022, in PubMed, Embase, or BIOSIS. Two reviewers completed screening and full-text review, with conflicts resolved by a third advisor. Summary data were extracted by two analysts; all records were quality checked by one analyst. Work productivity outcomes were summarized qualitatively, and risk of bias was not evaluated. RESULTS: A total of 14,387 records were retrieved; 12,245 titles/abstracts were screened and 145 full-text publications were reviewed, of which 63 were included in the qualitative assessment. Studies of self-reported ILI were most frequent (49%), followed by laboratory-confirmed cases (37%) and physician diagnoses (11%). Overall, approximately 20-75% of employees missed work due to illness across study settings and populations. Mean time out of work among ill employees varied widely across study designs and populations, ranging from < 1 to > 10 days, and was often reported to be approximately 2-3 days. Considerable heterogeneity was observed across study designs, populations, and outcomes. Most employees (≈ 60-80%) reported working while experiencing influenza/ILI symptoms. Reporting of costs was sparse and heterogeneous; one study reported annual costs of influenza-related absences equating to $42,851 per 100,000 employee health plan members. Results were partitioned based on the following categories. Among otherwise healthy adults, 1-74% of workers missed ≥1 workday due to influenza/ILI, for a mean [standard deviation (SD)] of 0.5 (1.44) to 5.3 (4.50) days, and 42-89% reported working while ill, for a mean (SD) of 0.3 (0.63) to 4.4 (3.73) days. Among working caregivers, 50-75% missed work to care for children/household members with influenza/ILI, for 1-2 days on average. Similarly, the mean absenteeism among healthcare workers ranged from 0.5 to 3.2 days. Across studies evaluating vaccination status, generally smaller proportions of vaccinated employees missed time from work due to influenza/ILI. CONCLUSIONS: This systematic review summarized the productivity burden of influenza/ILI on the worldwide working-age population. Despite notable heterogeneity in study designs, influenza/ILI case definitions, and productivity outcome measures, this review highlighted the substantial productivity burden that influenza/ILI may have on employees, employers, and society, consistent with the findings of Keech and Beardsworth (2008).

The flu ('influenza') has an effect on patients, their families, employers, and society. A review of medical studies from 1995 to 2007 reported how having the flu or a flu-like illness causes people to miss work. We updated that paper using the same approach, and found 63 new studies from 2007 to February 2022. Overall, up to 75% of employees missed work when they had the flu or a flu-like illness. Their average time out of work was usually 2­3 days each time they were sick. Most employees who had the flu or flu-like illness also said that they continued to work while they were sick (60­80%). Most employed adults who were caregivers for someone else with the flu said that they missed work to care for someone else for an average of 1­2 days. Overall, people who were vaccinated against the flu missed less time from work compared with their peers who were not vaccinated. This review of published medical studies showed that the flu and flu-like illness has a meaningful impact on people's ability to work, which also impacts their employers and society.

Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis.

BACKGROUND: Most phase 3 clinical trials of systemic therapy for first-line unresectable hepatocellular carcinoma (HCC) have failed, with the exception of SHARP, REFLECT, and IMbrave150. We conducted indirect comparisons of therapies evaluated for first-line HCC treatment. SUMMARY: We conducted a systematic review and meta-analysis of treatments for adults with locally advanced or metastatic unresectable HCC and no prior systemic treatment, including atezolizu-mab plus bevacizumab, sorafenib, lenvatinib, nivolumab, selective internal radiotherapy (SIRT), transarterial chemoembolization, and placebo or best supportive care. Randomized controlled trials published from January 1, 2007, to March 12, 2020, were retrieved from MEDLINE and Embase. Qualitative assessment of heterogeneity evaluated study designs, populations, and outcomes. Indirect comparisons used generalized linear models with random effects within a Bayesian framework and informative priors. We calculated relative efficacy estimates with 95% credible intervals (CrIs) and Bayesian posterior probability estimates of atezolizumab-bevacizumab being superior to other treatments. Nine clinical studies with a total of 3,897 participants were identified from 8,783 records and used to build the all-trials evidence network. Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39-1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41-1.14]; 94%), sorafenib (0.59 [95% CrI 0.39-0.87]; 99%), SIRT (0.51 [95% CrI 0.32-0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25-0.64]; 100%). KEY MESSAGES: Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.