Assessment of the information theory approach to evaluating time-to-event surrogate and true endpoints in a meta-analytic setting

In many disease areas, commonly used long-term clinical endpoints are becoming increasingly difficult to implement due to long follow-up times and/or increased costs. Shorter-term surrogate endpoints are urgently needed to expedite drug development, the evaluation of which requires robust and reliable statistical methodology to drive meaningful clinical conclusions about the strength of relationship with the true long-term endpoint. This paper uses a simulation study to explore one such previously proposed method, based on information theory, for evaluation of time to event surrogate and long-term endpoints, including the first examination within a meta-analytic setting of multiple clinical trials with such endpoints. The performance of the information theory method is examined for various scenarios including different dependence structures, surrogate endpoints, censoring mechanisms, treatment effects, trial and sample sizes, and for surrogate and true endpoints with a natural time-ordering. Results allow us to conclude that, contrary to some findings in the literature, the approach provides estimates of surrogacy that may be substantially lower than the true relationship between surrogate and true endpoints, and rarely reach a level that would enable confidence in the strength of a given surrogate endpoint. As a result, care is needed in the assessment of time to event surrogate and true endpoints based only on this methodology.     

Effect of Pet Dogs on Children's Perceived Stress and Cortisol Stress Response

The present study tested whether pet dogs have stress‐buffering effects for children during a validated laboratory‐based protocol, the Trier Social Stress Test for Children (TSST‐C). Participants were 101 children aged 7–12 years with their primary caregivers and pet dogs. Children were randomly assigned in the TSST‐C to a pet present condition or one of two comparison conditions: parent present or no support figure present. Baseline, response, and recovery indices of perceived stress and cortisol levels were computed based on children's self‐reported feelings of stress and salivary cortisol. Results indicated that in the alone (no social support) condition, children showed the expected rise for both perceived stress and cortisol response to stress. Pet dog presence significantly buffered the perceived stress response in comparison to children in the alone and parent present conditions. No main condition effect was observed for cortisol; however, for children experiencing the stressor with their pet present, lower cortisol response to stress was associated with more child‐initiated petting and less dog proximity‐seeking behavior. The results support the notion that pet dogs can provide socio‐emotional benefits for children via stress buffering.     

Relations over Time among Children's Shyness,Emotionality, and Internalizing Problems

Data regarding children's shyness and emotionality were collected at three time points, two years apart (T1: N = 214, M = 6.12 years; T2: N = 185, M = 7.67 years; T3: N = 185, M = 9.70 years), and internalizing data were collected at T1 and T3. Relations among parent‐rated shyness, emotionality [parent‐ and teacher‐rated anger, sadness, and positive emotional intensity (EI)], and mother‐rated internalizing were examined in panel models. In some cases, shyness predicted emotionality two years later (teacher‐rated anger, parent‐rated sadness, and teacher‐rated positive EI) and emotionality sometimes predicted shyness two years later (teacher‐rated sadness, parent‐rated positive EI, and teacher‐rated positive EI). Parent‐rated shyness and/or emotionality (parent‐rated anger and parent‐rated sadness) predicted internalizing at T3. Results shed light on developmental relations between emotionality and shyness, as well as processes of risk for, or protection against, the development of internalizing problems.