Estimand framework: Are we asking the right questions? A case study in the solid tumor setting

The estimand framework requires a precise definition of the clinical question of interest (the estimand) as different ways of accounting for “intercurrent” events post randomization may result in different scientific questions. The initiation of subsequent therapy is common in oncology clinical trials and is considered an intercurrent event if the start of such therapy occurs prior to a recurrence or progression event. Three possible ways to account for this intercurrent event in the analysis are to censor at initiation, consider recurrence or progression events (including death) that occur before and after the initiation of subsequent therapy, or consider the start of subsequent therapy as an event in and of itself. The new estimand framework clarifies that these analyses address different questions (“does the drug delay recurrence if no patient had received subsequent therapy?” vs “does the drug delay recurrence with or without subsequent therapy?” vs “does the drug delay recurrence or start of subsequent therapy?”). The framework facilitates discussions during clinical trial planning and design to ensure alignment between the key question of interest, the analysis, and interpretation. This article is a result of a cross-industry collaboration to connect the International Council for Harmonisation E9 addendum concepts to applications. Data from previously reported randomized phase 3 studies in the renal cell carcinoma setting are used to consider common intercurrent events in solid tumor studies, and to illustrate different scientific questions and the consequences of the estimand choice for study design, data collection, analysis, and interpretation.     

Dengue Disease Risk Mental Models in the City of Dhaka,Bangladesh: Juxtapositions and Gaps Between the Public and Experts

Worldwide, more than 50 million cases of dengue fever are reported every year in at least 124 countries, and it is estimated that approximately 2.5 billion people are at risk for dengue infection. In Bangladesh, the recurrence of dengue has become a growing public health threat. Notably, knowledge and perceptions of dengue disease risk, particularly among the public, are not well understood. Recognizing the importance of assessing risk perception, we adopted a comparative approach to examine a generic methodology to assess diverse sets of beliefs related to dengue disease risk. Our study mapped existing knowledge structures regarding the risk associated with dengue virus, its vector (Aedes mosquitoes), water container use, and human activities in the city of Dhaka, Bangladesh. “Public mental models” were developed from interviews and focus group discussions with diverse community groups; “expert mental models” were formulated based on open‐ended discussions with experts in the pertinent fields. A comparative assessment of the public's and experts’ knowledge and perception of dengue disease risk has revealed significant gaps in the perception of: (a) disease risk indicators and measurements; (b) disease severity; (c) control of disease spread; and (d) the institutions responsible for intervention. This assessment further identifies misconceptions in public perception regarding: (a) causes of dengue disease; (b) dengue disease symptoms; (c) dengue disease severity; (d) dengue vector ecology; and (e) dengue disease transmission. Based on these results, recommendations are put forward for improving communication of dengue risk and practicing local community engagement and knowledge enhancement in Bangladesh.     

Acts of Social Perspective Taking: A Functional Construct and the Validation of a Performance Measure for Early Adolescents

To understand and assess how early adolescents use their social perspective taking (SPT) skills in their consideration of social problems, we conducted two studies. In study 1, we administered a hypothetical SPT scenario to 359 fourth to eighth graders. Modeled on the linguistic pragmatics of speech acts, we used grounded theory to develop a functional approach that identified three types of SPT acts: (1) the acknowledgment of different actors, (2) the articulation of their thoughts and feelings, and (3) the positioning of the roles, experiences, or circumstances that influence how they resolve problems. Study 2 tested the validity of an expanded instrument, the Social Perspective Taking Acts Measure, with 459 fourth to eighth graders. We confirmed the structure of the construct with a fully saturated confirmatory factor analysis, with factor loadings in the range of .62 and .71, and a factor determinacy of .90. We obtained evidence of criterion‐related validity by successfully predicting that girls and older participants would exhibit better performance than boys and younger students, and that SPT would exhibit a negative association with aggressive interpersonal strategies, a positive but moderate association with writing, and non‐significant associations with academic language, complex reasoning, and reading skills.     

Housing and Accommodation of Irish Travellers: From Assimilationism to Multiculturalism and Back Again

This article charts the changing conceptualization of Travellers in relevant Irish central government policy statements since the 1960s, together with the accommodation policy initiatives devised on this basis. It interprets developments in this regard as a movement from assimilationism to integrationism to (weak) multiculturalism. The article also reveals a significant “policy implementation deficit”, which is manifested in two ways. Firstly, accommodation output has generally failed to meet central government targets and has consistently failed to reduce the numbers of Travellers living in unofficial encampments. Secondly, the type of accommodation provided has often been at variance with central government recommendations. Thus, an assimilationist policy statement has effected multicultural policy outcomes, while a multiculturalist policy statement has effected assimilationist policy outcomes. These patterns of accommodation output are related to various implementation variables—some long‐standing, others new—which have impeded the implementation of national policy by actors on the ground.