Comparison of Hospitalization Incidence in Influenza Outpatients Treated With Baloxavir Marboxil or Neuraminidase Inhibitors: A Health Insurance Claims Database Study.

BACKGROUND: Baloxavir marboxil (baloxavir) is a single-dose, oral antiinfluenza drug with a novel mechanism of action. We compared the incidence of hospitalization in patients treated with baloxavir vs neuraminidase inhibitors. METHODS: In this retrospective, observational, cohort study, we used real-world patient data extracted from a Japanese health insurance claims database. The enrollment period was 1 October 2018 to 17 April 2019. On day 1, eligible patients (N = 339 007) received baloxavir, oseltamivir, zanamivir, or laninamivir. Baseline characteristics were standardized using the inverse probability of treatment weighting method. The primary end point was the incidence of hospitalization (days 2-14). Secondary end points included antibacterial use, secondary pneumonia, and additional antiinfluenza drug use. RESULTS: Compared with the baloxavir group, the incidence of hospitalization was greater in the oseltamivir group (risk ratio [RR] and 95% confidence interval [CI], 1.41 [1.00-2.00]; risk difference [RD] and 95% CI, 0.06 [.01-.12]) and zanamivir group (RR, 1.85 [1.23-2.78]; RD, 0.11 [.02-.20]). Oseltamivir-treated patients were less likely to require antibacterials than baloxavir-treated patients (RR, 0.87 [.82-.91]). However, oseltamivir-treated patients were more likely to be hospitalized with antibacterials (RR, 1.70 [1.21-2.38]) or antibacterial injection (RR, 1.67 [1.17-2.38]) than baloxavir-treated patients (post hoc analysis). Compared with baloxavir-treated patients, additional antiinfluenza drug use was greater in oseltamivir-, zanamivir-, and laninamivir-treated patients (RR, 1.51 [1.05-2.18], 2.84 [2.04-3.96], and 1.68 [1.35-2.10], respectively). CONCLUSIONS: Baloxavir is an efficacious antiinfluenza treatment that may reduce hospitalization compared with oseltamivir and zanamivir. CLINICAL TRIALS REGISTRATION: University hospital Medical Information Network Clinical Trials Registry (UMIN000038159).

Comparison of Household Transmission of Influenza Virus From Index Patients Treated With Baloxavir Marboxil or Neuraminidase Inhibitors: A Health Insurance Claims Database Study.

BACKGROUND: Baloxavir marboxil (baloxavir) is expected to reduce influenza transmission by rapid reduction of viral load. The incidence of household transmission was compared between index patients (IPs) treated with baloxavir and those treated with neuraminidase inhibitors. METHODS: Using a Japanese claims database, the first family members with influenza diagnosis during the 2018-2019 influenza season were identified as IPs, and the diagnosis date was designated day 1. According to the anti-influenza drug dispensed to the IP, their families were classified into the oral baloxavir group and 3 controls: oral oseltamivir group (a primary control), inhaled zanamivir group, and inhaled laninamivir group. A household transmission was defined as influenza diagnosed for any non-IP family members during days 3-8. The incidence of household transmission was compared between groups using a logistic regression model adjusting backgrounds of IPs. RESULTS: The proportion of families with household transmission was 17.98% (15 226 of 84 672) in the baloxavir group and 24.16% (14 983 of 62 004) in the oseltamivir group. The covariate-adjusted odds ratio (oseltamivir/baloxavir) was 1.09 (95% confidence interval [95% CI], 1.05-1.12), which indicated significantly lower incidence in the baloxavir group. The adjusted odds ratios (controls/baloxavir) against zanamivir and laninamivir were 0.93 (95% CI, .89-.97) and 0.99 (95% CI, .96-1.02), respectively. CONCLUSIONS: Baloxavir may contribute to reduction in household transmission compared with oseltamivir. In comparison between baloxavir and inhalants, a similar reduction was not shown and it might be due to unmeasured confounding by administration route differences.

The Relationship Between Baseline Clinical Symptom Characteristics and Working Ability in Japanese Patients Treated for Major Depressive Disorder and Painful Physical Symptoms.

PURPOSE: The objective of this post hoc analysis was to explore the relationship, including changes over time, between baseline clinical symptom characteristics and working ability, judged by investigators, after 12 weeks of antidepressant monotherapy in Japanese patients with major depressive disorder (MDD) and painful physical symptoms (PPS) in a real-world clinical setting. PATIENTS AND METHODS: This prospective, observational study in patients treated with duloxetine or selective serotonin reuptake inhibitors was conducted from 2014 to 2016. Both treatment groups were pooled and divided into 2 groups, "working ability recovered" or "working ability not recovered," based on working ability at the end of the study. Patients were also divided into 4 subgroups by the presence or absence of previous depressive episodes and working ability. Main outcome measures included baseline demographics and clinical characteristics, and the 17-item Hamilton Rating Scale for Depression (HAM-D17). RESULTS: Comparison between "working ability recovered" (n=122) and "working ability not recovered" (n=91) showed that the percentage of patients with complications and psychotherapy at baseline, and baseline HAM-D17 total, insomnia, somatic, and anxiety scores, were significantly different. The results of subgroup analyses were mostly the same as the results analyzed by working ability alone. Although statistical differences were observed for some outcome measures, the differences at baseline, except use of psychotherapy, may not be applicable clinically, and there were no specific trends observed that could predict working ability. CONCLUSION: This post hoc analysis suggested that most baseline clinical characteristics, including the presence or absence of previous depressive episodes, were not predictive of working ability recovery. However, the use of psychotherapy in parallel with antidepressant monotherapy may be positively associated with working ability recovery. All outcome measures improved over time, reinforcing the importance of continuous treatment and observation to improve and accurately judge working ability in patients with MDD and PPS.

Study Designs in Multi-arm Trials for Breast Cancer: A Systematic Literature Review of Major Journals.

BACKGROUND: Several articles showed that statistical efficiency of multi-arm randomized clinical trials (RCTs) is much better than conventional two-arm RCTs. Multi-arm RCTs attract interest mainly when the experimental treatment regimen is not optimized or several pipelines under development exist. Breast cancer is a possible candidate disease. Our aim was to elucidate the current study designs and multiplicity adjustment methods in multi-arm RCTs. METHODS: A search of the PubMed database revealed 468 articles on breast cancer RCTs published from 2010 to 2016. Information on study designs and analysis methods was collected from 4 major journals. RESULTS: A total of 202 RCTs were selected, 48 were multi-arm and 29 were three-arm RCTs. In two of the target journals, multi-arm RCTs have been increasingly reported since 2013. Compared with two-arm RCTs, three-arm RCTs were frequently conducted in neoadjuvant settings (7.7% vs 33.3%). The number of trials performed in perioperative settings was 46 in two-arm and 15 in three-arm RCTs. Of these, the proportion of industry-sponsored trials in two-arm and three-arm RCTs was 26.1% and 53.3%, respectively. Shared control designs (SCDs) which randomized to a common control arm and multiple experimental arms comprised 54.2% of 48 multi-arm RCTs. For SCDs, detailed information on multiplicity adjustment methods was seldom reported. The Bonferroni adjustment method together with alpha-spending functions was commonly used. CONCLUSION: Breast cancer multi-arm RCTs have been increasingly reported. The majority of multi-arm RCTs are industry-sponsored trials using SCDs in neoadjuvant settings. Detailed description about multiplicity adjustment methods is required for multi-arm RCTs.