Efficient, Doubly Robust Estimation of the Effect of Dose Switching for Switchers in a Randomised Clinical Trial

Motivated by a clinical trial conducted by Janssen Pharmaceuticals in which a flexible dosing regimen is compared to placebo, we evaluate how switchers in the treatment arm (i.e., patients who were switched to the higher dose) would have fared had they been kept on the low dose. This in order to understand whether flexible dosing is potentially beneficial for them. Simply comparing these patients' responses with those of patients who stayed on the low dose is unsatisfactory because the latter patients are usually in a better health condition. Because the available information in the considered trial is too scarce to enable a reliable adjustment, we will instead transport data from a fixed dosing trial that has been conducted concurrently on the same target, albeit not in an identical patient population. In particular, we will propose an estimator which relies on an outcome model and a propensity score model for the association between study and patient characteristics. The proposed estimator is asymptotically unbiased if at least one of both models is correctly specified, and efficient (under the model defined by the restrictions on the propensity score) when both models are correctly specified. We show that the proposed method for using results from an external study is generically applicable in studies where a classical confounding adjustment is not possible due to positivity violation (e.g., studies where switching takes place in a deterministic manner). Monte Carlo simulations and application to the motivating study demonstrate adequate performance

A novel estimand to adjust for rescue treatment in clinical trials

The interpretation of randomised clinical trial results is often complicated by intercurrent events. For instance, rescue medication is sometimes given to patients in response to worsening of their disease, either in addition to the randomised treatment or in its place. The use of such medication complicates the interpretation of the intention-to-treat analysis. In view of this, we propose a novel estimand defined as the intention-to-treat effect that would have been observed, had patients on the active arm been switched to rescue medication if and only if they would have been switched when randomised to control. This enables us to disentangle the treatment effect from the effect of rescue medication on a patient's outcome, while avoiding the strong extrapolations that are typically needed when inferring what the intention-to-treat effect would have been in the absence of rescue medication. We develop an inverse probability weighting method to estimate this estimand under specific untestable assumptions, in view of which we propose a sensitivity analysis. We use the method for the analysis of a clinical trial conducted by Janssen Pharmaceuticals, in which chronically ill patients can switch to rescue medication for ethical reasons. Monte Carlo simulations confirm that the proposed estimator is unbiased in moderate sample sizes

The Persuasiveness of Child-Targeted Endorsement Strategies: A Systematic Review

Several European and U.S. reviews have established the link between food marketing and childhood obesity (EU Pledge, 2012; FTC, 2006; Persson, Soroko, Musicus & Lobstein, 2012), which has stimulated researchers to investigate the effects of the most prevalent child-targeted marketing technique: the use of endorsing characters. This systematic review of these studies (15 identified; participants age 3-12 years) focuses on three important questions: (a) Does a basic endorser effect exist?, (b) Is the strength of the endorsement effect influenced by endorser type?, and (c) Does the endorsement strength differ according to the type of food being promoted

Sexting in adolescents: Prevalence and behaviours

Sexting is among the practices used by young people to explore their sexuality. Although an educational response to all facets of this phenomenon is recommended, little research has been published to date in Spain that analyses its prevalence by differentiating between the different types of sexting behaviours: sending, receiving, third-party forwarding, and receiving via an intermediary. This gap in the research is addressed by exploring: 1) Sexting prevalence, differentiating between behaviours; 2) Relationships between sexting behaviours and gender, age, sexual orientation, having a romantic/sexual partner, social networking sites used, and the degree of normalisation and willingness to sext; 3) Gender-based differences. In total, 3,314 adolescents aged 12 to 16 years participated in the study. The most frequent sexting behaviours were identified as receiving and receiving via an intermediary, followed by third-party forwarding and the sending of sexual content. The relative importance of each analysed variable depended on the specific sexting behaviour and the participants’ gender. The results highlight the need to disentangle the diversity behind sexting behaviours and to address each one in an educational setting. This more detailed look at the different behaviours can be used as the basis for raising awareness and decision-making in education

Sexting in adolescents: Prevalence and behaviours

Sexting is among the practices used by young people to explore their sexuality. Although an educational response to all facets of this phenomenon is recommended, little research has been published to date in Spain that analyses its prevalence by differentiating between the different types of sexting behaviours: sending, receiving, third-party forwarding, and receiving via an intermediary. This gap in the research is addressed by exploring: 1) Sexting prevalence, differentiating between behaviours; 2) Relationships between sexting behaviours and gender, age, sexual orientation, having a romantic/sexual partner, social networking sites used, and the degree of normalisation and willingness to sext; 3) Gender-based differences. In total, 3,314 adolescents aged 12 to 16 years participated in the study. The most frequent sexting behaviours were identified as receiving and receiving via an intermediary, followed by third-party forwarding and the sending of sexual content. The relative importance of each analysed variable depended on the specific sexting behaviour and the participants’ gender. The results highlight the need to disentangle the diversity behind sexting behaviours and to address each one in an educational setting. This more detailed look at the different behaviours can be used as the basis for raising awareness and decision-making in education

Assassins, Gods, and Androids: How Narratives and Game Mechanics Shape Eudaimonic Game Experiences

Emerging research has suggested that digital games can generate entertainment experiences beyond hedonic enjoyment towards eudaimonic experiences: Being emotionally moved, stimulated to reflect on one’s self or a sense of elevation. Studies in this area have mainly focused on individual game characteristics that elicit singular and static eudaimonic game moments. However, such a focus neglects the interplay of multiple game aspects as well as the dynamic nature of eudaimonic experiences. The current study takes a novel approach to eudaimonic game research by conducting a qualitative game analysis of three games (Assassin’s Creed Odyssey, Detroit: Become Human, and God of War) and taking systematic notes on game experiences shortly after playing. Results reveal that emotionally moving, reflective, and elevating eudaimonic experiences were elicited when gameplay notes suggested a strong involvement with the game’s narrative and characters (i.e., narrative engagement) and, in some cases, narrative-impacting choices. These key aspects, in turn, are enhanced by clean player interfaces, graphically realistic characters, close camera perspectives, tone-appropriate soundtrack scores, and both narrative-enhancing (e.g., God of War’s health mechanic) and choice-enhancing mechanics (e.g., Detroit: Become Human’s flowchart). Eudaimonic experiences were also found to evolve throughout the game, with more powerful experiences occurring near the end of the game and some narrative themes fueling the eudaimonic flow of experiences throughout the overall game narrative. This study adds to academic research studying digital games by suggesting an innovative methodological approach that provides a detailed, integrative, and dynamic perspective on eudaimonic game experiences

Real-time dynamic modelling for the design of a cluster-randomized phase 3 Ebola vaccine trial in Sierra Leone.

BACKGROUND: Declining incidence and spatial heterogeneity complicated the design of phase 3 Ebola vaccine trials during the tail of the 2013-16 Ebola virus disease (EVD) epidemic in West Africa. Mathematical models can provide forecasts of expected incidence through time and can account for both vaccine efficacy in participants and effectiveness in populations. Determining expected disease incidence was critical to calculating power and determining trial sample size. METHODS: In real-time, we fitted, forecasted, and simulated a proposed phase 3 cluster-randomized vaccine trial for a prime-boost EVD vaccine in three candidate regions in Sierra Leone. The aim was to forecast trial feasibility in these areas through time and guide study design planning. RESULTS: EVD incidence was highly variable during the epidemic, especially in the declining phase. Delays in trial start date were expected to greatly reduce the ability to discern an effect, particularly as a trial with an effective vaccine would cause the epidemic to go extinct more quickly in the vaccine arm. Real-time updates of the model allowed decision-makers to determine how trial feasibility changed with time. CONCLUSIONS: This analysis was useful for vaccine trial planning because we simulated effectiveness as well as efficacy, which is possible with a dynamic transmission model. It contributed to decisions on choice of trial location and feasibility of the trial. Transmission models should be utilised as early as possible in the design process to provide mechanistic estimates of expected incidence, with which decisions about sample size, location, timing, and feasibility can be determined

Coping with distress among adolescents: Effectiveness of personal narratives on support websites

Compartir, leer y responder a narraciones personales en webs de apoyo entre iguales puede tanto fortalecer como amenazar la confianza de los adolescentes para hacer frente a los acontecimientos estresantes (es decir, la autoeficacia como estrategia de afrontamiento). Los principios de la escritura expresiva, el intercambio social de emociones, la persuasión narrativa y los efectos en uno mismo pueden proporcionar información sobre la forma en que esas acciones pueden relacionarse con la autoeficacia como estrategia de afrontamiento. Mediante una encuesta transversal en línea con 311 adolescentes de habla holandesa de entre 14 y 18 años, este artículo explora cómo estas acciones y los motivos del apoyo social (es decir, la búsqueda de información y la búsqueda de apoyo emocional) se relacionan con la autoeficacia de los adolescentes como estrategia de afrontamiento tras usar la web de apoyo entre iguales. Los resultados muestran que la experiencia de los usuarios al leer y responder a narraciones personales no estaba relacionada con su autoeficacia de afrontamiento. Sin embargo, se encontró una relación negativa entre la experiencia de compartir una narración personal y la autoeficacia, por lo que los usuarios no percibieron que el sitio web fuera útil para su confianza general a la hora de hacer frente a acontecimientos estresantes. No obstante, esta relación negativa se invirtió cuando también tenían el objetivo de encontrar apoyo emocional con sus igualesSharing, reading and responding to personal narratives on peer-to-peer support websites may provide adolescents with informational and emotional support to feel more confident in coping with stressful events. However, their use may also pose a threat to adolescents’ coping self-efficacy. Principles of expressive writing, social sharing of emotions, narrative persuasion and self-effects may provide insight in how these actions may both positively and negatively relate to coping self-efficacy. By using a cross-sectional online survey with 311 Dutch-speaking adolescents between the ages of 14 and 18, this article explores how these actions and social support motives (i.e. information-seeking and emotional supportseeking) are related to adolescents’ perceptions about the usefulness of these websites to their coping self-efficacy. The results showed a positive relation between adolescents’ social support motives and their belief in the usefulness of these websites to their coping self-efficacy. Therefore, we conclude that it may be an effective coping strategy for many adolescents. There was a negative relation between experience with sharing a personal narrative and coping self-efficacy, meaning that these users did not perceive the website to be helpful to their overall confidence in coping with stressful events. However, this negative relation was reversed when they were motivated to find emotional support with similar other