2,335 research outputs found

    Meta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ.

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    Meta-analysis using individual participant data (IPD) obtains and synthesises the raw, participant-level data from a set of relevant studies. The IPD approach is becoming an increasingly popular tool as an alternative to traditional aggregate data meta-analysis, especially as it avoids reliance on published results and provides an opportunity to investigate individual-level interactions, such as treatment-effect modifiers. There are two statistical approaches for conducting an IPD meta-analysis: one-stage and two-stage. The one-stage approach analyses the IPD from all studies simultaneously, for example, in a hierarchical regression model with random effects. The two-stage approach derives aggregate data (such as effect estimates) in each study separately and then combines these in a traditional meta-analysis model. There have been numerous comparisons of the one-stage and two-stage approaches via theoretical consideration, simulation and empirical examples, yet there remains confusion regarding when each approach should be adopted, and indeed why they may differ. In this tutorial paper, we outline the key statistical methods for one-stage and two-stage IPD meta-analyses, and provide 10 key reasons why they may produce different summary results. We explain that most differences arise because of different modelling assumptions, rather than the choice of one-stage or two-stage itself. We illustrate the concepts with recently published IPD meta-analyses, summarise key statistical software and provide recommendations for future IPD meta-analyses. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd

    Deriving percentage study weights in multi-parameter meta-analysis models: with application to meta-regression, network meta-analysis and one-stage individual participant data models.

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    Many meta-analysis models contain multiple parameters, for example due to multiple outcomes, multiple treatments or multiple regression coefficients. In particular, meta-regression models may contain multiple study-level covariates, and one-stage individual participant data meta-analysis models may contain multiple patient-level covariates and interactions. Here, we propose how to derive percentage study weights for such situations, in order to reveal the (otherwise hidden) contribution of each study toward the parameter estimates of interest. We assume that studies are independent, and utilise a decomposition of Fisher's information matrix to decompose the total variance matrix of parameter estimates into study-specific contributions, from which percentage weights are derived. This approach generalises how percentage weights are calculated in a traditional, single parameter meta-analysis model. Application is made to one- and two-stage individual participant data meta-analyses, meta-regression and network (multivariate) meta-analysis of multiple treatments. These reveal percentage study weights toward clinically important estimates, such as summary treatment effects and treatment-covariate interactions, and are especially useful when some studies are potential outliers or at high risk of bias. We also derive percentage study weights toward methodologically interesting measures, such as the magnitude of ecological bias (difference between within-study and across-study associations) and the amount of inconsistency (difference between direct and indirect evidence in a network meta-analysis)

    Simulation-based power calculations for planning a two-stage individual participant data meta-analysis

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    BACKGROUND Researchers and funders should consider the statistical power of planned Individual Participant Data (IPD) meta-analysis projects, as they are often time-consuming and costly. We propose simulation-based power calculations utilising a two-stage framework, and illustrate the approach for a planned IPD meta-analysis of randomised trials with continuous outcomes where the aim is to identify treatment-covariate interactions. METHODS The simulation approach has four steps: (i) specify an underlying (data generating) statistical model for trials in the IPD meta-analysis; (ii) use readily available information (e.g. from publications) and prior knowledge (e.g. number of studies promising IPD) to specify model parameter values (e.g. control group mean, intervention effect, treatment-covariate interaction); (iii) simulate an IPD meta-analysis dataset of a particular size from the model, and apply a two-stage IPD meta-analysis to obtain the summary estimate of interest (e.g. interaction effect) and its associated p-value; (iv) repeat the previous step (e.g. thousands of times), then estimate the power to detect a genuine effect by the proportion of summary estimates with a significant p-value. RESULTS In a planned IPD meta-analysis of lifestyle interventions to reduce weight gain in pregnancy, 14 trials (1183 patients) promised their IPD to examine a treatment-BMI interaction (i.e. whether baseline BMI modifies intervention effect on weight gain). Using our simulation-based approach, a two-stage IPD meta-analysis has < 60% power to detect a reduction of 1 kg weight gain for a 10-unit increase in BMI. Additional IPD from ten other published trials (containing 1761 patients) would improve power to over 80%, but only if a fixed-effect meta-analysis was appropriate. Pre-specified adjustment for prognostic factors would increase power further. Incorrect dichotomisation of BMI would reduce power by over 20%, similar to immediately throwing away IPD from ten trials. CONCLUSIONS Simulation-based power calculations could inform the planning and funding of IPD projects, and should be used routinely

    Association of maternal serum PAPP-A levels, nuchal translucency and crown rump length in first trimester with adverse pregnancy outcomes: Retrospective cohort study.

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    OBJECTIVE: Are first trimester serum pregnancy-associated plasma protein-A (PAPP-A), nuchal translucency (NT) and crown rump length (CRL) prognostic factors for adverse pregnancy outcomes? METHOD: Retrospective cohort women, singleton pregnancies (UK 2011-2015). Unadjusted and multivariable logistic regression, outcomes: small for gestational age (SGA), pre-eclampsia (PE), pre-term birth (PTB), miscarriage, stillbirth, perinatal mortality and neonatal death (NND). RESULTS: 12,592 pregnancies: 852 (6.8%) PTB, 352 (2.8%) PE, 1824 (14.5%) SGA, 73 (0.6%) miscarriages, 37(0.3%) stillbirths, 73 perinatal deaths (0.6%) and 38 (0.30%) NND. Multivariable analysis: lower odds of SGA [adjusted odds ratio (aOR) 0.88 (95% CI 0.85,0.91)], PTB [0.92 (95%CI 0.88,0.97)], PE [0.91 (95% CI 0.85,0.97)] and stillbirth [ 0.71 (95% CI 0.52,0.98)] as PAPP-A increases. Lower odds of SGA [aOR 0.79 (95% CI 0.70,0.89)] but higher odds of miscarriage [aOR 1.75 95% CI (1.12,2.72)] as NT increases, and lower odds of stillbirth as CRL increases [aOR 0.94 95% CI (0.89,0.99)]. Multivariable analysis of three factors together demonstrated strong associations: a) PAPP-A, NT, CRL and SGA, b) PAPP-A and PTB, c) PAPP-A, CRL and PE, d) NT and miscarriage. CONCLUSIONS: PAPP-A, NT and CRL independent prognostic factor for adverse pregnancy outcomes, especially PAPP-A and SGA with lower PAPP-A associated with increased risk

    A detailed analysis of a multi-agent diverse team

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    In an open system we can have many different kinds of agents. However, it is a challenge to decide which agents to pick when forming multi-agent teams. In some scenarios, agents coordinate by voting continuously. When forming such teams, should we focus on the diversity of the team or on the strength of each member? Can a team of diverse (and weak) agents outperform a uniform team of strong agents? We propose a new model to address these questions. Our key contributions include: (i) we show that a diverse team can overcome a uniform team and we give the necessary conditions for it to happen; (ii) we present optimal voting rules for a diverse team; (iii) we perform synthetic experiments that demonstrate that both diversity and strength contribute to the performance of a team; (iv) we show experiments that demonstrate the usefulness of our model in one of the most difficult challenges for Artificial Intelligence: Computer Go
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