Joint Data Analyses Of European Birth Cohorts: Two Different Approaches

Background: Combined data analyses of birth cohorts can overcome the fragmentation of individual and inconclusive results obtained by analyses based upon single cohorts only. The European project Environmental Health Risks in European Birth Cohorts (ENRIECO) undertook four combined studies to evaluate the concept of added scientific value through harmonisation and exchange of birth cohort data for common analyses on environmental health risks. Objectives: Two alternative analytical approaches were evaluated regarding their feasibility, benefits and limitations: (1) the centralised approach (pooled and non-pooled analyses which were centrally conducted by a single case study leader) and (2) the decentralised approach (meta-analysis of summary statistics derived by uniform methods conducted in each cohort). Methods: Four main steps were identified for database building and analyses: (I) eligibility of cohorts, (II) collection of individual participant data, (III) data verification and (IV) analyses and manuscript preparation. Discussion: The decentralised approach is recommended if cross-border data transfer is difficult and/or a solid basis of trust and experience still has to be established among partners. The centralised approach is recommended for combined analyses addressing variables with very heterogeneous assessments across cohorts, where a flexible handling of data is essential and trust and work experience between participating partners already exists. Conclusion: Both approaches were successful, albeit laborious and time-consuming. Transparency through regular updates, presentation of results from interim analyses and the possibility for birth cohort researchers to comment and agree to each step of the analysis process builds trust and forms the basis for a sustainable collaboration. Background Collaboration of Birth Cohorts Over the past 30 years a large number of mother-child cohorts (birth cohorts) with various objectives have been established across Europe [1]. Although these birth cohorts were originally designed for stand-alone analyses, on a whole they build a unique data resource for investigating risk factors and determinants of pregnancy outcomes and child health. Recently, there has been a focus on collaboration between cohorts and networks have been established and maintained by projects such as GALEN (Global Allergy and Asthma European Network) [2-3], OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) [4], ENRIECO (Environmental Health Risks in European Birth Cohorts) [1] or CHICOS (Developing a Child Cohort Research Strategy for Europe) (http://www.chicosproject.eu/). An overview of avai lab le cohort data is avai lab le under www.birthcohorts.net. Combined data analyses of birth cohorts can overcome the fragmentation of individual and inconclusive results obtained by analyses based upon single cohorts only. The sample size of many cohorts is often not sufficient for analysing exposures and outcomes with low prevalences. Harmonising and combining their datasets increases statistical power allowing examination of exposure-response relationships and regional differences. Consistent findings across cohorts may add to the credibility of results and robust findings are expected to have a greater impact on clinical practice and public health. Reporting bias may be reduced by promoting the reporting of results from all cohorts regardless if an effect is observed or not. Expensive laboratory analyses of xenobiotic exposures and/or advanced outcome measures are often determined in subsets of birth cohorts only and may provide added value if combined with similar data in other cohorts. Given these advantages and a general positive attitude towards collaborating, the above listed existing European birth cohort networks as well as already published and numerous ongoing combined analyses WebmedCentral > Review articles Page 2 of 14 WMC003869 Downloaded from http://www.webmedcentral.com on 12-Dec-2012, 04:48:13 PM within these networks reflect the growing interest of birth cohort study teams to participate in combined data analyses. The ENRIECO project was a coordination project with the aim of enhancing the collaboration and networking between birth and pregnancy cohorts in Europe with a focus on exposure-response relationships between environmental exposures and health outcomes in childhood. Within the ENRIECO-framework four case studies were undertaken to evaluate the concept of added scientific value through harmonisation and exchange of birth cohort data for common analyses on environmental health risks. Two alternative analytical approaches were evaluated: (1) The first was based on the central storage of data from different birth cohorts following which pooled and non-pooled analyses were centrally conducted by a single case study leader (in the following the centralised approach) and (2) the second was based on the meta-analysis of summary statistics derived by uniform methods conducted in each cohort (in the following the decentralised approach). In this paper we report and compare feasibility, benefits and limitations of these two approaches to combine analysis. Centralised Approach in three Case Studies: Dampness/Mould or Tobacco Smoke Exposure and Respiratory Health and Allergy Each of the three case studies aimed to examine the association between certain environmental exposures and paediatric health outcomes. The scientific background of the first case study was suggestive evidence for an association between mould or mould spores and respiratory tract infections, bronchitis, early wheeze and physician-diagnosed al le rg ic rh in i t i s [5 ] and between indoor dampness/mould and cough, wheeze, upper respiratory tract symptoms or physician-diagnosed asthma [6]. The first ENRIECO case study analysed data from 31,000 children from 11 birth cohorts and found early exposure to visible mould and dampness to be associated with asthma symptoms in the first two years of life and allergic rhinitis in children up to 10 years of age [7]. Exemplarily, Figure 1 shows already published results of this combined data analysis.