Search

Additional file 4. Published trial data used in reviews of overall survival.

Additional file 2. PRISMA Flow diagram showing results of systematic literature search.

Individual participant data (IPD) meta-analyses of randomised trials are considered a reliable way to assess participant-level treatment effect modifiers but may not make the best use of the available data. Traditionally, effect modifiers are explored one covariate at a time, which gives rise to the possibility that evidence of treatment-covariate interaction may be due to confounding from a different, related covariate. We aimed to evaluate current practice when estimating treatment-covariate interactions in IPD meta-analysis, specifically focusing on involvement of additional covariates in the models. We reviewed 100 IPD meta-analyses of randomised trials, published between 2015 and 2020, that assessed at least one treatment-covariate interaction. We identified four approaches to handling additional covariates: (1) Single interaction model (unadjusted): No additional covariates included (57/100 studies); (2) Single interaction model (adjusted): Adjustment for the main effect of at least one additional covariate (35/100); (3) Multiple interactions model: Adjustment for at least one two-way interaction between treatment and an additional covariate (3/100); and (4) Three-way interaction model: Three-way interaction formed between treatment, the additional covariate and the potential effect modifier (5/100). IPD is not being utilised to its fullest extent. In an exemplar dataset, we demonstrate how these approaches can lead to different conclusions. Researchers should adjust for additional covariates when estimating interactions in IPD meta-analysis providing they adjust their main effects, which is already widely recommended. Further, they should consider whether more complex approaches could provide better information on who might benefit most from treatments, improving patient choice and treatment policy and practice., Comment: 23 pages, 3 figures, 4 tables

Additional file 1. Search Strategy for literature review.

Additional file 3. Summary of characteristics of included reviews.

Additional file 5. Published trial data used in reviews of intermediate composite outcomes.

This project will provide an addendum to currently existing guidelines for reporting evidence syntheses to support authors who report the results of their time-to-event meta-analyses based on aggregate data from RCTs.

INTRODUCTION: Trauma-focused cognitive behavioural therapies are the first-line treatment for posttraumatic stress disorder (PTSD) in children and adolescents. Nevertheless, open questions remain with respect to efficacy: why does this first-line treatment not work for everyone? For whom does it work best? Individual clinical trials often do not provide sufficient statistical power to examine and substantiate moderating factors. To overcome the issue of limited power, an individual participant data meta-analysis of randomised trials evaluating forms of trauma-focused cognitive behavioural therapy in children and adolescents aged 6-18 years will be conducted. METHODS AND ANALYSIS: We will update the National Institute for Health and Care Excellence guideline literature search from 2018 with an electronic search in the databases PsycINFO, MEDLINE, Embase, Cochrane Central Register of Controlled Trials and CINAHL with the terms (trauma* OR stress*) AND (cognitive therap* OR psychotherap*) AND (trial* OR review*). Electronic searches will be supplemented by a comprehensive grey literature search in archives and trial registries. Only randomised trials that used any manualised psychological treatment-that is a trauma-focused cognitive behavioural therapy for children and adolescents-will be included. The primary outcome variable will be child-reported posttraumatic stress symptoms (PTSS) post-treatment. Proxy-reports (teacher, parent and caregiver) will be analysed separately. Secondary outcomes will include follow-up assessments of PTSS, PTSD diagnosis and symptoms of comorbid disorders such as depression, anxiety-related and externalising problems. Random-effects models applying restricted maximum likelihood estimation will be used for all analyses. We will use the Revised Cochrane Risk of Bias tool to measure risk of bias. ETHICS AND DISSEMINATION: Contributing study authors need to have permission to share anonymised data. Contributing studies will be required to remove patient identifiers before providing their data. Results will be published in a peer-reviewed journal and presented at international conferences. PROSPERO REGISTRATION NUMBER: CRD42019151954.

Background: Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC). Objective: To systematically review trials of prostate radiotherapy. Design, setting, and participants: Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known. We searched extensively for eligible trials and asked investigators when results would be available. We could then anticipate that a definitive meta-analysis of the effects of prostate radiotherapy was possible. We obtained prepublication, unpublished, and harmonised results from investigators. Intervention: We included trials that randomised men to prostate radiotherapy and androgen deprivation therapy (ADT) or ADT only. Outcome measurements and statistical analysis: Hazard ratios (HRs) for the effects of prostate radiotherapy on survival, progression-free survival (PFS), failure-free survival (FFS), biochemical progression, and subgroup interactions were combined using fixed-effect meta-analysis. Results and limitations: We identified one ongoing (PEACE-1) and two completed (HORRAD and STAMPEDE) eligible trials. Pooled results of the latter (2126 men; 90% of those eligible) showed no overall improvement in survival (HR = 0.92, 95% confidence interval [CI] 0.81–1.04, p = 0.195) or PFS (HR = 0.94, 95% CI 0.84–1.05, p = 0.238) with prostate radiotherapy. There was an overall improvement in biochemical progression (HR = 0.74, 95% CI 0.67–0.82, p = 0.94 × 10 −8 ) and FFS (HR = 0.76, 95% CI 0.69–0.84, p = 0.64 × 10 −7 ), equivalent to ∼10% benefit at 3 yr. The effect of prostate radiotherapy varied by metastatic burden—a pattern consistent across trials and outcome measures, including survival (

Cyber security experts agree that insider threats are and will continue to be a threat to every organization. These threats come from trusted co-workers who, for one reason or another, betray their organizations and steal data, disrupt information systems, or corrupt the data. Millennials are commonly thought of as entitled, high maintenance, and less trustworthy than the older generations; in other words, they have personality traits associated with insider threats, making the insider threat and the Millennial a dangerous combination. But are the Millennials truly any more likely to become insider threats than members Generation X (GenX) or Baby Boomers? This study shows that, contrary to conventional wisdom and societal belief, Millennials are no more likely to become insider threats than other generations; in fact, data shows they are less likely to do so than members of GenX. http://archive.org/details/themillennialgen1094547256 Program Manager, Department of Homeland Security Approved for public release; distribution is unlimited.