Sample size for binary logistic prediction models: Beyond events per variable criteria.

Binary logistic regression is one of the most frequently applied statistical approaches for developing clinical prediction models. Developers of such models often rely on an Events Per Variable criterion (EPV), notably EPV ≥10, to determine the minimal sample size required and the maximum number of candidate predictors that can be examined. We present an extensive simulation study in which we studied the influence of EPV, events fraction, number of candidate predictors, the correlations and distributions of candidate predictor variables, area under the ROC curve, and predictor effects on out-of-sample predictive performance of prediction models.

Standardized mean differences cause funnel plot distortion in publication bias assessments.

Meta-analyses are increasingly used for synthesis of evidence from biomedical research, and often include an assessment of publication bias based on visual or analytical detection of asymmetry in funnel plots. We studied the influence of different normalisation approaches, sample size and intervention effects on funnel plot asymmetry, using empirical datasets and illustrative simulations. We found that funnel plots of the Standardized Mean Difference (SMD) plotted against the standard error (SE) are susceptible to distortion, leading to overestimation of the existence and extent of publication bias.

A generic nomogram for multinomial prediction models: theory and guidance for construction.

Background: The use of multinomial logistic regression models is advocated for modeling the associations of covariates with three or more mutually exclusive outcome categories. As compared to a binary logistic regression analysis, the simultaneous modeling of multiple outcome categories using a multinomial model often better resembles the clinical setting, where a physician typically must distinguish between more than two possible diagnoses or outcome events for an individual patient (e.g.

Effect of Fibrinogen Concentrate on Intraoperative Blood Loss Among Patients With Intraoperative Bleeding During High-Risk Cardiac Surgery: A Randomized Clinical Trial.

Importance: Fibrinogen concentrate might partly restore coagulation defects and reduce intraoperative bleeding.

Objective: To determine whether fibrinogen concentrate infusion dosed to achieve a plasma fibrinogen level of 2.5 g/L in high-risk cardiac surgery patients with intraoperative bleeding reduces intraoperative blood loss.

No rationale for 1 variable per 10 events criterion for binary logistic regression analysis.

Background: Ten events per variable (EPV) is a widely advocated minimal criterion for sample size considerations in logistic regression analysis. Of three previous simulation studies that examined this minimal EPV criterion only one supports the use of a minimum of 10 EPV. In this paper, we examine the reasons for substantial differences between these extensive simulation studies.

Predicting stillbirth in a low resource setting.

Background: Stillbirth is a major contributor to perinatal mortality and it is particularly common in low- and middle-income countries, where annually about three million stillbirths occur in the third trimester. This study aims to develop a prediction model for early detection of pregnancies at high risk of stillbirth.

Methods: This retrospective cohort study examined 6,573 pregnant women who delivered at Federal Medical Centre Bida, a tertiary level of healthcare in Nigeria from January 2010 to December 2013.

External Validation of Prediction Models for Pneumonia in Primary Care Patients with Lower Respiratory Tract Infection: An Individual Patient Data Meta-Analysis.

Background: Pneumonia remains difficult to diagnose in primary care. Prediction models based on signs and symptoms (S&S) serve to minimize the diagnostic uncertainty. External validation of these models is essential before implementation into routine practice.

Anticipating missing reference standard data when planning diagnostic accuracy studies.

Results obtained using a reference standard may be missing for some participants in diagnostic accuracy studies. This paper looks at methods for dealing with such missing data when designing or conducting a prospective diagnostic accuracy study

Problems in detecting misfit of latent class models in diagnostic research without a gold standard were shown.

Objectives: The objective of this study was to evaluate the performance of goodness-of-fit testing to detect relevant violations of the assumptions underlying the criticized "standard" two-class latent class model. Often used to obtain sensitivity and specificity estimates for diagnostic tests in the absence of a gold reference standard, this model relies on assuming that diagnostic test errors are independent. When this assumption is violated, accuracy estimates may be biased: goodness-of-fit testing is often used to evaluate the assumption and prevent bias.

Small-study effects and time trends in diagnostic test accuracy meta-analyses: a meta-epidemiological study.

Background: Small-study effects and time trends have been identified in meta-analyses of randomized trials. We evaluated whether these effects are also present in meta-analyses of diagnostic test accuracy studies.

Methods: A systematic search identified test accuracy meta-analyses published between May and September 2012.

The impending epidemic of chronic cardiopulmonary disease and multimorbidity: the need for new research approaches to guide daily practice.

Mortality caused by acute cardiopulmonary disease is decreasing, and in many countries the population is aging rapidly. Yet, the life-years gained are often spent with multiple chronic and slowly progressive conditions, and this particularly applies to patients with cardiopulmonary disease. Affected individuals often have multiple diagnoses related to the cardiopulmonary-metabolic axis with accelerated aging and gradually progressive failure of organs that provide the body with oxygen and nutrients.

The added diagnostic value of five different C-reactive protein point-of-care test devices in detecting pneumonia in primary care: A nested case-control study.

Background: The results obtained from various point-of-care (POC) test devices for estimating C-reactive protein (CRP) levels in a laboratory setting differ when compared to a laboratory reference test. We aimed to determine whether such differences meaningfully affect the accuracy and added diagnostic value in predicting radiographic pneumonia in adults presenting with acute cough in primary care.

Methods: A nested case control study of adult patients presenting with acute cough in 12 different European countries (the Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe [GRACE] Network).

[Reference standards in diagnostic research: problems and solutions].

The accuracy of diagnostic tests is of utmost importance as biased test results may lead to wrong decisions in clinical practice. In diagnostic accuracy research the results of a diagnostic test, model or strategy are compared to those of the reference standard, i.e.

Critical appraisal and data extraction for systematic reviews of prediction modelling studies: the CHARMS checklist.

Carl Moons and colleagues provide a checklist and background explanation for critically appraising and extracting data from systematic reviews of prognostic and diagnostic prediction modelling studies. Please see later in the article for the Editors' Summary.

Added value of hybrid myocardial perfusion SPECT and CT coronary angiography in the diagnosis of coronary artery disease.

Aims: Hybrid single photon emission computed tomography (SPECT)/coronary computed tomography angiography (CCTA) has only been evaluated for its diagnostic accuracy as a single test in patients suspected of significant coronary artery disease (CAD). Added value of hybrid SPECT/CCTA beyond usual clinical work-up, or use of each of these tests separately, remains unclear. We evaluated the added value of hybrid myocardial perfusion SPECT (SPECT) and CCTA, beyond pre-test likelihood and exercise stress ECG (X-ECG), in the diagnosis of CAD.

Systematic overview finds variation in approaches to investigating and reporting on sources of heterogeneity in systematic reviews of diagnostic studies.

Objectives: To examine how authors explore and report on sources of heterogeneity in systematic reviews of diagnostic accuracy studies.

Study Design And Setting: A cohort of systematic reviews of diagnostic tests was systematically identified. Data were extracted on whether an exploration of the sources of heterogeneity was undertaken, how this was done, the number and type of potential sources explored, and how results and conclusions were reported.

External validation of multivariable prediction models: a systematic review of methodological conduct and reporting.

Background: Before considering whether to use a multivariable (diagnostic or prognostic) prediction model, it is essential that its performance be evaluated in data that were not used to develop the model (referred to as external validation). We critically appraised the methodological conduct and reporting of external validation studies of multivariable prediction models.

Methods: We conducted a systematic review of articles describing some form of external validation of one or more multivariable prediction models indexed in PubMed core clinical journals published in 2010.

Incorporating quality assessments of primary studies in the conclusions of diagnostic accuracy reviews: a cross-sectional study.

Background: Drawing conclusions from systematic reviews of test accuracy studies without considering the methodological quality (risk of bias) of included studies may lead to unwarranted optimism about the value of the test(s) under study. We sought to identify to what extent the results of quality assessment of included studies are incorporated in the conclusions of diagnostic accuracy reviews.

Methods: We searched MEDLINE and EMBASE for test accuracy reviews published between May and September 2012.

Latent class models in diagnostic studies when there is no reference standard--a systematic review.

Latent class models (LCMs) combine the results of multiple diagnostic tests through a statistical model to obtain estimates of disease prevalence and diagnostic test accuracy in situations where there is no single, accurate reference standard. We performed a systematic review of the methodology and reporting of LCMs in diagnostic accuracy studies. This review shows that the use of LCMs in such studies increased sharply in the past decade, notably in the domain of infectious diseases (overall contribution: 59%).

Analytical performance, agreement and user-friendliness of five C-reactive protein point-of-care tests.

Background: Point-of-care (POC) C-reactive protein (CRP) testing is increasingly used in primary care to assist general practitioners (GPs) in the diagnostic workup for various complaints. The present study compares analytical performance, agreement and user-friendliness of five of these POC CRP tests.

Methods: The following five POC CRP tests were evaluated: Afinion and NycoCard Reader II (both Alere), Eurolyser Smart 700/340 (Eurolyser), QuikRead go and QuikRead 101 (both Orion Diagnostica).

Evaluating diagnostic accuracy in the face of multiple reference standards.

A universal challenge in studies that quantify the accuracy of diagnostic tests is establishing whether each participant has the disease of interest. Ideally, the same preferred reference standard would be used for all participants; however, for practical or ethical reasons, alternative reference standards that are often less accurate are frequently used instead. The use of different reference standards across participants in a single study is known as differential verification.

Effectiveness of a cardiac surgery-specific transfusion protocol.

Background: Cardiac surgery is often complicated by excessive bleeding that is commonly treated with blood products. In the year 2009 a transfusion protocol was introduced specifically designed for cardiac surgery procedures. This study aims to evaluate the effect of this protocol on transfusion of blood products and the occurrence of clinical events.