Statistical design and analysis in trials of proportionate interventions: a systematic review

Background: In proportionate or adaptive interventions, the dose or intensity can be adjusted based on individual need at predefined decision stages during the delivery of the intervention. The development of such interventions may require an evaluation of the effectiveness of the individual stages in addition to the whole intervention. However, evaluating individual stages of an intervention has various challenges, particularly the statistical design and analysis. This review aimed to identify the use of trials of proportionate interventions and how they are being designed and analysed in current practice. Methods: We searched MEDLINE, Web of Science and PsycINFO for articles published between 2010 and 2015 inclusive. We considered trials of proportionate interventions in all fields of research. For each trial, its aims, design and analysis were extracted. The data synthesis was conducted using summary statistics and a narrative format. Results: Our review identified 44 proportionate intervention trials, comprising 28 trial results, 13 protocols and three secondary analyses. These were mostly described as stepped care (n=37) and mainly focussed on mental health research (n=30). The other studies were aimed at finding an optimal adaptive treatment strategy (n=7) in a variety of therapeutic areas. Further terminology used included adaptive intervention, staged intervention, sequentially multiple assignment trial or a two-phase design. The median number of decision stages in the interventions was two and only one study explicitly evaluated the effect of the individual stages. Conclusions: Trials of proportionate staged interventions are being used predominantly within the mental health field. However, few studies consider the different stages of the interventions, either at the design or the analysis phase, and how they may interact with one another. There is a need for further guidance on the design, analyses and reporting across trials of proportionate interventions

Reading Genesis–Joshua as a Unified Document from an Early Date: A Settler Colonial Perspective

This essay proposes based on literary-compositional considerations how two authors working together could have composed Genesis–Joshua. After this, it suggests that Genesis–Joshua can be seen to reflect a sociopolitical transformation of ancient Canaanite societies into an Israelite one(s) through a process that can be labeled as ancient settler colonialism, and that the document could have been written concomitantly. Subsequently, relevant ancient Near Eastern and archaeological evidence will be considered, suggesting compatibility with the idea that Genesis–Joshua has reused and readapted existing traditions together with creative narrative retelling for its socio-political purposes, and that this could have already taken place from the late second millennium Bce on. The essay concludes by drawing out some explicit contemporary implications of such a reading of Genesis–Joshua

Tailored implementation of internet-based cognitive behavioural therapy in the multinational context of the ImpleMentAll project: a study protocol for a stepped wedge cluster randomized trial

Background: Internet-based Cognitive Behavioural Therapy (iCBT) is found effective in treating common mental disorders. However, the use of these interventions in routine care is limited. The international ImpleMentAll study is funded by the European Union’s Horizon 2020 programme. It is concerned with studying and improving methods for implementing evidence-based iCBT services for common mental disorders in routine mental health care. A digitally accessible implementation toolkit (ItFits-toolkit) will be introduced to mental health care organizations with the aim to facilitate the ongoing implementation of iCBT services within local contexts. This study investigates the effectiveness of the ItFits-toolkit by comparing it to implementation-as-usual activities. Methods: A stepped wedge cluster randomized controlled trial (SWT) design will be applied. Over a trial period of 30 months, the ItFits-toolkit will be introduced sequentially in twelve routine mental health care organizations in primary and specialist care across nine countries in Europe and Australia. Repeated measures are applied to assess change over time in the outcome variables. The effectiveness of the ItFits-toolkit will be assessed in terms of the degree of normalization of the use of the iCBT services. Several exploratory outcomes including uptake of the iCBT services will be measured to feed the interpretation of the primary outcome. Data will be collected via a centralized data collection system and analysed using generalized linear mixed modelling. A qualitative process evaluation of routine implementation activities and the use of the ItFits-toolkit will be conducted within this study. Discussion: The ImpleMentAll study is a large-scale international research project designed to study the effectiveness of tailored implementation. Using a SWT design that allows to examine change over time, this study will investigate the effect of tailored implementation on the normalization of the use of iCBT services and their uptake. It will provide a better understanding of the process and methods of tailoring implementation strategies. If found effective, the ItFits-toolkit will be made accessible for mental health care service providers, to help them overcome their context-specific implementation challenges. Trial registration: ClinicalTrials.gov NCT03652883. Retrospectively registered on 29 August 201

Screening for depression in the general population with the Center for Epidemiologic Studies Depression (CES-D): a systematic review with meta-analysis

OBJECTIVE: We aimed to collect and meta-analyse the existing evidence regarding the performance of the Center for Epidemiologic Studies Depression (CES-D) for detecting depression in general population and primary care settings./nMETHOD: Systematic literature search in PubMed and PsychINFO. Eligible studies were: a) validation studies of screening questionnaires with information on the accuracy of the CES-D; b) samples from general populations or primary care settings; c) standardized diagnostic interviews following standard classification systems used as gold standard; and d) English or Spanish language of publication. Pooled sensitivity, specificity, likelihood ratios and diagnostic odds ratio were estimated for several cut-off points using bivariate mixed effects models for each threshold. The summary receiver operating characteristic curve was estimated with Rutter and Gatsonis mixed effects models; area under the curve was calculated. Quality of the studies was assessed with the QUADAS tool. Causes of heterogeneity were evaluated with the Rutter and Gatsonis mixed effects model including each covariate at a time. RESULTS: 28 studies (10,617 participants) met eligibility criteria. The median prevalence of Major Depression was 8.8% (IQ range from 3.8% to 12.6%). The overall area under the curve was 0.87. At the cut-off 16, sensitivity was 0.87 (95% CI: 0.82-0.92), specificity 0.70 (95% CI: 0.65-0.75), and DOR 16.2 (95% CI: 10.49-25.10). Better trade-offs between sensitivity and specificity were observed (Sensitivity = 0.83, Specificity = 0.78, diagnostic odds ratio = 16.64) for cut-off 20. None of the variables assessed as possible sources of heterogeneity was found to be statistically significant. CONCLUSION: The CES-D has acceptable screening accuracy in the general population or primary care settings, but it should not be used as an isolated diagnostic measure of depression. Depending on the test objectives, the cut-off 20 may be more adequate than the value of 16, which is typically recommended.This study is supported by a grant from Instituto de Salud Carlos III FEDER, (PI08/90724) and from the DIUE of the Generalitat de Catalunya, Spain (2014 SGR 748; 2009 SGR 1095). Gemma Vilagut was supported by “Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (ISCIII)” (ECA07/059); Carlos G. Forero was supported by “Ministerio de Ciencia e Innovación”, FSE (JCI-2009-05486); Gabriela Barbaglia was supported by “Ministerio de Ciencia e Innovación” Rio Hortega grant (CM 10-00099), Spain