Toxicology Letters206 (2011) 144– 151 Contentslists availableat ScienceDirect Toxicology Letters j o u r n a l h o me p a g e : w w w . e l s e v i e r . c o m / l o c a t e / t o x l e t Statisticalmeansto enhancethe comparability of data within a pooled analysisof individual data in neurobehavioral toxicology Monika Meyer-Baron a,∗ , Michael Schäper a , Guido Knapp b , Roberto Lucchini c , Elisa Albini c , Rita Bast-Pettersen d , ShuchangHe e , Hong Yuan e , Qiao Niu f , Xian-Liang Wang g , Yong-Jian Yang h , Anders Iregren i , Bengt Sjögren j , Morten Blond k , Peter Laursen l , Bo Netterstrom m , Donna Mergler n , RosemarieBowler o , Christoph van Thriel a a IfADo– LeibnizResearch Centre for WorkingEnvironment and HumanFactors, Ardeystr. 67,Dortmund, Germany b TU DortmundUniversity, Department of Statistics, Dortmund, Germany c Occupational Healthand IndustrialHygiene, University of Brescia, Italy d NationalInstituteof Occupational Health, Oslo,Norway e Department of Psychology, PekingUniversity, China f Department of Occupational Health, Shanxi MedicalUniversity, Taiyuan, China g StateKeyLaboratory of Environmental Criteriaand RiskAssessment, Chinese Research Academy of Environmental Sciences, Beijing, China h School of PublicHealth, Anhui MedicalUniversity, Hefei, China i Toxicological RiskAssessment, Swedish Work Environment Authority, Stockholm, Sweden j Work Environment Toxicology, Institute of Environmental Medicine, KarolinskaInstitutet, Stockholm, Sweden k Clinicof Occupational Medicine, Nykoebing, Denmark l DanishWorkingEnvironment Authority, Copenhagen, Denmark m Clinicof Occupational Medicine, Copenhagen, Denmark n University of Quebec, Montreal,Canada o SanFrancisco StateUniversity, SanFrancisco, USA a r t i c l e i n f o Articlehistory: Received28 April 2011 Receivedin revisedform 29 June 2011 Accepted1 July 2011 Available online 7 July 2011 Keywords: Systematic review Meta-analysis Manganese Cross-cultural comparison Confounder a b s t r a c t Meta-analysesof individual participant data (IPD) provide important contributions to toxicologicalrisk assessments. However, comparabilityof individual data cannot be taken for grantedwhen information from different studies has to be summarized. By means of statistical standardization approachesthe comparabilityof data might be increased. An analysisof individual data on the neurobehavioral impact of manganese (Mn) exemplifieschallenges and effectsof a multilevel statisticalprocedure. Confoundingfrom individual-level and study-level covariates was shown by analyses of variance, but could be reducedby linear regressions and z-normalization using data of the respectivecontrol groups. Fixed models that were used to estimate the impact of the neurotoxic exposure, provided evidence that the employed procedures, especially the z-normalization, effectively reduced variance that was unrelatedto the neurotoxicexposure. Evenafterthis statistical treatment the fixed effectmodelsrevealed differencesamong studies that did not seemto be exhaustivelyexplicableby concentrationdifferences obvious from the Mn biomarker at hand. IPD studiesusingconfoundedendpointsaseffectsmarkerscanbereasonably summarizedwhen appro- priate statisticaloperationsare employed. For the dataat hand the proposednormalization allowed new insights into exposure–effect relationships,in generalit appearsappropriateto investigatethe effect of the independentvariablemore closely. © 2011 Elsevier Ireland Ltd. All rights reserved. Abbreviations: AD, aggregated data; IPD, individual patient/participant data; Mn, manganese; MnB, manganesein blood; SRT, simple reaction task; SPES, Swedish performanceevaluationsystem. ∗ Correspondingauthor. Tel.: +49231 1084416; fax: +49231 1084308. E-mail address: meyerbaron@ifado.de (M. Meyer-Baron). 1. Introduction Meta-analysesof aggregated data (AD) provide important con- tributions to risk assessment, but the analyses of dose–response relationships, person-specific risk factors, and covariates often remain dissatisfying (Meyer-Baron et al., 2008, 2009). Meta- analysesof IPD (individual patient data) are considered as having 0378-4274/$– seefront matter ©2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2011.07.003