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The use of data from multiple studies or centers for the validation of a clinical test or a multivariable prediction model allows researchers to investigate the test's/model's performance in multiple settings and populations. Recently, meta-analytic techniques have been proposed to summarize discrimination and calibration across study populations. Here, we rather consider performance in terms of net benefit, which is a measure of clinical utility that weighs the benefits of true positive classifications against the harms of false positives. We posit that it is important to examine clinical utility across multiple settings of interest. This requires a suitable meta-analysis method, and we propose a Bayesian trivariate random-effects meta-analysis of sensitivity, specificity, and prevalence. Across a range of chosen harm-to-benefit ratios, this provides a summary measure of net benefit, a prediction interval, and an estimate of the probability that the test/model is clinically useful in a new setting. In addition, the prediction interval and probability of usefulness can be calculated conditional on the known prevalence in a new setting. The proposed methods are illustrated by 2 case studies: one on the meta-analysis of published studies on ear thermometry to diagnose fever in children and one on the validation of a multivariable clinical risk prediction model for the diagnosis of ovarian cancer in a multicenter dataset. Crucially, in both case studies the clinical utility of the test/model was heterogeneous across settings, limiting its usefulness in practice. This emphasizes that heterogeneity in clinical utility should be assessed before a test/model is routinely implemented. [ABSTRACT FROM AUTHOR]

When combining results across related studies, a multivariate meta-analysis allows the joint synthesis of correlated effect estimates from multiple outcomes. Joint synthesis can improve efficiency over separate univariate syntheses, may reduce selective outcome reporting biases, and enables joint inferences across the outcomes. A common issue is that within-study correlations needed to fit the multivariate model are unknown from published reports. However, provision of individual participant data (IPD) allows them to be calculated directly. Here, we illustrate how to use IPD to estimate within-study correlations, using a joint linear regression for multiple continuous outcomes and bootstrapping methods for binary, survival and mixed outcomes. In a meta-analysis of 10 hypertension trials, we then show how these methods enable multivariate meta-analysis to address novel clinical questions about continuous, survival and binary outcomes; treatment-covariate interactions; adjusted risk/prognostic factor effects; longitudinal data; prognostic and multiparameter models; and multiple treatment comparisons. Both frequentist and Bayesian approaches are applied, with example software code provided to derive within-study correlations and to fit the models. © 2014 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Health outcomes throughout the life course have been linked to fetal growth restriction and low birthweight. A variety of measures exist to define low birthweight, with a lack of consensus regarding which predict adverse outcome.Objectives: To evaluate the relationship between birthweight standards and childhood and adult outcomes in term-born infants (≥37 weeks' gestation).Search Strategy: MEDLINE (1966-January 2011), EMBASE (1980-January 2011), and the Cochrane Library (2011:1) and MEDION were included.Selection Criteria: Studies comprising live term-born infants (gestation ≥37 completed weeks), with weight or other anthropometric measurements recorded at birth along with childhood and adult outcomes.Data Collection and Analysis: Data were extracted to populate 2 × 2 tables relating birthweight standard with outcome, and meta-analysis was performed where possible.Main Results: Fifty-nine articles (2 600 383 individuals) were selected. There was no significant relationship between birthweight <2.5 kg (odds ratio [OR] 0.98, 95% confidence intervals [CI] 0.87-1.10) and composite measure of childhood morbidity. Weight <10th centile on the population nomogram showed a small association (OR 1.49, 95% CI 1.02-2.19) for the same outcome. There was no significant association between either of the above measures and adult morbidity. The relationship between other measures and individual outcomes varied.Author's Conclusions: The association between low birthweight, by any definition, and childhood and adult morbidity was inconsistent. None of the current standards of low birthweight was a good predictor of adverse outcome. [ABSTRACT FROM AUTHOR]

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance.Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit.Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes.Conclusions: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Introduction: For tests reporting continuous results, primary studies usually provide test performance at multiple but often different thresholds. This creates missing data when performing a meta‐analysis at each threshold. A standard meta‐analysis (no imputation [NI]) ignores such missing data. A single imputation (SI) approach was recently proposed to recover missing threshold results. Here, we propose a new method that performs multiple imputation of the missing threshold results using discrete combinations (MIDC). Methods: The new MIDC method imputes missing threshold results by randomly selecting from the set of all possible discrete combinations which lie between the results for 2 known bounding thresholds. Imputed and observed results are then synthesised at each threshold. This is repeated multiple times, and the multiple pooled results at each threshold are combined using Rubin's rules to give final estimates. We compared the NI, SI, and MIDC approaches via simulation. Results: Both imputation methods outperform the NI method in simulations. There was generally little difference in the SI and MIDC methods, but the latter was noticeably better in terms of estimating the between‐study variances and generally gave better coverage, due to slightly larger standard errors of pooled estimates. Given selective reporting of thresholds, the imputation methods also reduced bias in the summary receiver operating characteristic curve. Simulations demonstrate the imputation methods rely on an equal threshold spacing assumption. A real example is presented. Conclusions: The SI and, in particular, MIDC methods can be used to examine the impact of missing threshold results in meta‐analysis of test accuracy studies. [ABSTRACT FROM AUTHOR]

The article reports on obstetrics which focuses on identification of pregnancies at risk of adverse outcomes to plan targeted intervention. Topics discussed include prognostic models provide individualized judge risk for clinically important outcomes in diseased patients, prediction model development for adverse outcomes in women with pre-eclampsia pose challenges in obstetrics and methods could address bias from treatment paradox such as standardization of treatment and predictor substitution.