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Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision‐making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls from one or more sources of historical trial data [HTD]) can be used to increase statistical precision. Here we assess combining two sources of Roche HTD to construct a hybrid control in targeted therapy for decision‐making via an extensive simulation study. Our simulations are based on the real data of one of the experimental arms and the control arm of the MORPHEUS‐UC Phase Ib/II study and two Roche HTD for atezolizumab monotherapy. We consider potential complications such as model misspecification, unmeasured confounding, different sample sizes of current treatment groups, and heterogeneity among the three trials. We evaluate two frequentist methods (with both Cox and Weibull accelerated failure time [AFT] models) and three different commensurate priors in Bayesian dynamic borrowing (with a Weibull AFT model), and modifications within each of those, when estimating the effect of treatment on survival outcomes and measures of effect such as marginal hazard ratios. We assess the performance of these methods in different settings and the potential of generalizations to supplement decisions in early‐phase oncology trials. The results show that the proposed joint frequentist methods and noninformative priors within Bayesian dynamic borrowing with no adjustment on covariates are preferred, especially when treatment effects across the three trials are heterogeneous. For generalization of hybrid control methods in such settings, we recommend more simulation studies. [ABSTRACT FROM AUTHOR]

Maternal depression in the peri-natal period is associated with increased risk for young adult depression in offspring. This study explored mediation of these links via trajectories of child conduct and emotional problems (Strengths and Difficulties Questionnaire) from ages 4-16 years old in data from the Avon Longitudinal Study of Parents and Children cohort ( n = 13373). Through gender-specific structural equation models, a composite measure of exposure to early maternal depression (Edinburgh Postnatal Depression Scale), predicted young adult depression at age 18 (Revised Clinical Interview Schedule - distal outcome). Mediational effects were then estimated by testing which parts of joint piecewise latent trajectory models for child/adolescent conduct and emotional problems were associated with both exposure and distal outcome. For girls, only conduct problems in early childhood were consistently indicated to mediate effects of early maternal depression on risk of young adulthood depression. Some evidence for a pathway via changing levels of childhood and adolescent emotional difficulties was also suggested. For boys, by contrast, the differing models gave less consistent findings providing some evidence for a small time-specific indirect effect via early childhood conduct problems. In addition to its practice implications the current methodological application offers considerable potential in exploratory longitudinal developmental mediation studies. © 2016 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

Background The global impact of the 2009 influenza A( H1 N1) pandemic ( H1 N1pdm) is not well understood. Objectives We estimate overall and age-specific prevalence of cross-reactive antibodies to H1 N1pdm virus and rates of H1 N1pdm infection during the first year of the pandemic using data from published and unpublished H1 N1pdm seroepidemiological studies. Methods Primary aggregate H1 N1pdm serologic data from each study were stratified in standardized age groups and evaluated based on when sera were collected in relation to national or subnational peak H1 N1pdm activity. Seropositivity was assessed using well-described and standardized hemagglutination inhibition ( HI titers ≥32 or ≥40) and microneutralization ( MN ≥ 40) laboratory assays. The prevalence of cross-reactive antibodies to the H1 N1pdm virus was estimated for studies using sera collected prior to the start of the pandemic (between 2004 and April 2009); H1 N1pdm cumulative incidence was estimated for studies in which collected both pre- and post-pandemic sera; and H1 N1pdm seropositivity was calculated from studies with post-pandemic sera only (collected between December 2009- June 2010). Results Data from 27 published/unpublished studies from 19 countries/administrative regions - Australia, Canada, China, Finland, France, Germany, Hong Kong SAR, India, Iran, Italy, Japan, Netherlands, New Zealand, Norway, Reunion Island, Singapore, United Kingdom, United States, and Vietnam - were eligible for inclusion. The overall age-standardized pre-pandemic prevalence of cross-reactive antibodies was 5% (95% CI 3-7%) and varied significantly by age with the highest rates among persons ≥65 years old (14% 95% CI 8-24%). Overall age-standardized H1 N1pdm cumulative incidence was 24% (95% CI 20-27%) and varied significantly by age with the highest in children 5-19 (47% 95% CI 39-55%) and 0-4 years old (36% 95% CI 30-43%). Conclusions Our results offer unique insight into the global impact of the H1 N1 pandemic and highlight the need for standardization of seroepidemiological studies and for their inclusion in pre-pandemic preparedness plans. Our results taken together with recent global pandemic respiratory-associated mortality estimates suggest that the case fatality ratio of the pandemic virus was approximately 0·02%. [ABSTRACT FROM AUTHOR]