Modifications of sequential designs in bioequivalence trials

Bioequivalence (BE) studies are designed to show that two formulations of one drug are equivalent and they play an important role in drug development. When in a design stage, it is possible that there is a high degree of uncertainty on variability of the formulations and the actual performance of the test versus reference formulation. Therefore, an interim look may be desirable to stop the study if there is no chance of claiming BE at the end (futility), or claim BE if evidence is sufficient (efficacy), or adjust the sample size. Sequential design approaches specially for BE studies have been proposed previously in publications. We applied modification to the existing methods focusing on simplified multiplicity adjustment and futility stopping. We name our method modified sequential design for BE studies (MSDBE). Simulation results demonstrate comparable performance between MSDBE and the original published methods while MSDBE offers more transparency and better applicability. The R package MSDBE is available at https://sites.google.com/site/modsdbe/ . Copyright © 2015 John Wiley & Sons, Ltd.     

Maternal and paternal reactions to child sadness predict children's psychosocial outcomes: A family‐centered approach

Parents' reactions to children's emotions shape their psychosocial outcomes. Extant research on emotion socialization primarily uses variable‐centered approaches. This study explores family patterns of maternal and paternal responses to children's sadness in relation to psychosocial outcomes in middle childhood. Fifty‐one families with 8‐ to 12‐year‐old children participated. Mothers and fathers reported their reactions to children's sadness and children's social competence and psychological adjustment. Cluster analyses revealed three family patterns: Supportive (high supportive and low non‐supportive reactions from both parents), Not Supportive (low supportive reactions from both parents), and Father Dominant (high paternal supportive and non‐supportive reactions, low maternal supportive and non‐supportive reactions). Supportive families had children with higher social competence and more internalizing symptoms whereas Father Dominant families had children with lower social competence and fewer internalizing symptoms. Not Supportive families had children with average social competence and fewer internalizing symptoms. Findings are discussed in relation to the “divergence model” which proposes that a diverse range of parental responses to children's sadness, rather than a uniformly supportive approach, may facilitate children's psychosocial adjustment.     

Land markets and migration trends in Tanzania: A qualitative‐quantitative analysis

While migration has been found to enhance welfare across a range of settings, most of the literature focuses on rural‐to‐urban migrant flows. Using a unique dataset from north‐western Tanzania, this article probes an important, yet overlooked, link between land markets and rural‐to‐rural migration. A mixed‐methods approach is used to discern how these two forces are intertwined in village life. Results indicate that household decisions to migrate are particularly influenced by the ease of market‐based land access in their new communities. This suggests that labour mobility may be facilitated through the development of a well‐functioning land market.     

Journey towards independent living: a grounded theory investigation of leaving the care of Girls & Boys Town,South Africa

The journey out of care and towards independent living is a challenge for many care-leavers. There has been little research into the social processes involved in this care-leaving journey. This paper presents the results of a grounded theory investigation into the care-leaving journeys of nine young men who had, several years previously, been in the care of Girls & Boys Town in South Africa. Working from a resilience perspective, with an ecological emphasis, four central social processes emerged that together explain the care-leaving experiences of the participants. These processes are striving for authentic belonging; networking people for goal attainment; contextualised responsiveness and building hopeful and tenacious self-confidence. These four processes are located within contextual boundaries and at the social environmental interface. The paper presents these processes in detail, drawing on selected narratives of the participants and integrated with additional theory. It is hoped that this paper may contribute to theory building concerning care-leaving processes and enhance youth care practices for youth in care and leaving care.     

Parental Divorce and Interpersonal Trust in Adult Offspring

It has been proposed that recent increases in parental divorce have inhibited the development of trust among offspring. This proposition is tested by examining whether parental divorce is associated with offspring trust in parents, intimate partners, and others. Data come from the Marital Instability Over the Life Course Study. Results reveal that although parental divorce is negatively associated with trust, these effects largely disappear once the quality of the past parent‐teen relationship is taken into account. The one exception is trust in fathers where children of divorce remain at higher risk of mistrust. Trust in parents, intimates, and others is strongly linked to positive parent‐teen relationships regardless of parental divorce. Contemporary relationship experiences also influence trusting intimates and others.     

Open Road or Blind Alley? Welfare Reform, Mothers, and Children with Disabilities

Welfare reform was examined for 39 Michigan families whose children have significant health or intellectual and behavioral disabilities. As a group, these families received little specialized assistance or services to address their unique needs. Family-cited barriers to self-sufficiency included poorly trained welfare caseworkers, limited public transportation, and inadequate child care. Having an older child was the only discriminating variable between working and non-working mothers. However, working mothers only had temporary positions with no benefits and low pay. All families, whether employed or not, lived below the poverty line.     

校园网与现代教育

探讨了校园网和现代教育的关系 ,校园网络可以成为现代教育的平台和核心 ,围绕着校园网建设面向未来的现代教育 ,着重阐述了校园网络建设应该注意的问题。     

Type I error rates from likelihood‐based repeated measures analyses of incomplete longitudinal data

The last observation carried forward (LOCF) approach is commonly utilized to handle missing values in the primary analysis of clinical trials. However, recent evidence suggests that likelihood‐based analyses developed under the missing at random (MAR) framework are sensible alternatives. The objective of this study was to assess the Type I error rates from a likelihood‐based MAR approach – mixed‐model repeated measures (MMRM) – compared with LOCF when estimating treatment contrasts for mean change from baseline to endpoint (Δ). Data emulating neuropsychiatric clinical trials were simulated in a 4 × 4 factorial arrangement of scenarios, using four patterns of mean changes over time and four strategies for deleting data to generate subject dropout via an MAR mechanism. In data with no dropout, estimates of Δ and SE_Δ from MMRM and LOCF were identical. In data with dropout, the Type I error rates (averaged across all scenarios) for MMRM and LOCF were 5.49% and 16.76%, respectively. In 11 of the 16 scenarios, the Type I error rate from MMRM was at least 1.00% closer to the expected rate of 5.00% than the corresponding rate from LOCF. In no scenario did LOCF yield a Type I error rate that was at least 1.00% closer to the expected rate than the corresponding rate from MMRM. The average estimate of SE_Δ from MMRM was greater in data with dropout than in complete data, whereas the average estimate of SE_Δ from LOCF was smaller in data with dropout than in complete data, suggesting that standard errors from MMRM better reflected the uncertainty in the data. The results from this investigation support those from previous studies, which found that MMRM provided reasonable control of Type I error even in the presence of MNAR missingness. No universally best approach to analysis of longitudinal data exists. However, likelihood‐based MAR approaches have been shown to perform well in a variety of situations and are a sensible alternative to the LOCF approach. MNAR methods can be used within a sensitivity analysis framework to test the potential presence and impact of MNAR data, thereby assessing robustness of results from an MAR method. Copyright © 2004 John Wiley & Sons, Ltd.     

The potential of integrated modelling in conservation biology: A case study of the black‐footed albatross (Phoebastria nigripes)

Conservation biology aims at assessing the status of a population, based on information which is often incomplete. Integrated population modelling based on state‐space models appears to be a powerful and relevant way of combining into a single likelihood several types of information such as capture‐recapture data and population surveys. In this paper, the authors describe the principles of integrated population modelling and they evaluate its performance for conservation biology based on a case study, that of the black‐footed albatross, a northern Pacific albatross species suspected to be impacted by longline fishing     

Dementia Problem Behavior and the Production of Informal Caregiving Services

Informal caregivers of individuals with Alzheimer's disease spend a considerable amount of time providing care. In this paper, we use Grossman's health production and Becker's time allocation models to develop a model of informal care provision to elderly dementia patients. In our model, time inputs produce caregiving services, which provides utility to the caregiver, but reduces leisure. We assume that time is less productive of services on the margin as the disease progresses. In this framework, an increase in patients' disease severity does not necessarily increase informal caregiver time input. The cost of formal care establishes a reservation price for informal caregiving. When the costs of informal caregiving rise above this reservation level, the patient is institutionalized. We test empirically the effect of deterioration in the patients' condition, proxied by both disease severity and dementia problem behavior, on informal caregiving time. We find that dementia-related problem behaviors and functional limitations significantly increase inputs of informal caregiving time. Patients' problem behavior exerts a modifying effect on functional limitations, and patients' comorbidities have no effect on informal caregiving time.