Global Research in Paediatrics

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Epidemiological and post marketing drug studies


Work Package 2 - Integrated infrastructure for paediatric epidemiological and post marketing drug studies


GRiP Epidemiological and post-marketing drug studiesThe currently available pharmacoepidemiologic data on infants, children, and adolescents are not adequately utilised due to hindrances including: 


1. the lack of a federation of databases for meaningful investigations

2. the lack of shared methodologies to specifically retrieve paediatric information 

3. a lack of standardized methods and study designs. New methodologies and guidelines regarding the scope of pharmacoepidemiology in paediatric clinical drug and vaccine development are urgently needed.


To answer the call, Work Package 2 will target the following key areas:

  • Build an online platform for real time data sharing and scientific collaboration as a basis of an integrated research infrastructure.
  • Identify healthcare databases with population based information on drug use and vaccine outcomes in children and to describe their characteristics. 
  • Describe the governance and ethical issues related to the use and linking of the healthcare databases.
  • Map disease and drug/vaccine coding terminologies across the healthcare and adverse events databases 
  • Create a common methodology for drug and vaccine utilization studies, for disease incidence and prevalence studies, and for epidemiological ascertainment of drug and vaccine safety. All of which using a distributed data model.



Please see the latest results delivered by the GRiP Network under Work Package 2. Where possible, abstracts of the reports have been provided on this page. To obtain more detailed information, you can download the available materials by clicking on the links at the bottom of the page (only public documents will be made available).


WP2 – Integrated Infrastructure For Paediatric Epidemiological And Post Marketing Drug Studies                 


Report on methods of retrospective safety signal generation in paediatrics from longitudinal Healthcare DBs


Traditional drug safety surveillance activities do not focus specifically on children, also signal detection is often done with spontaneous reporting databases. Based on the VIOXX scandal several projects were initiated that investigated whether signal detection based on electronic health care databases would be feasible. One of them was the EU-ADR project, which did not target pediatrics. Since EU-ADR was coordinated from Erasmus as well as GRiP WP2, a collaboration was created with specific questions from the GRiP NoE that were addressed with the EU-ADR data. In this deliverable we provide an overview of the initiatives that use EHR data for signal detection and present two studies that focused on signal detection in pediatrics using data from the EU-ADR network in study 1 and using data from NL and Italy in study 2.


Comparison of methods for safety signal generation from pharmacovigilance databases and longitudinal healthcare DBs


Safety signal detection has relied since the 1950s initially on manual inspection of case reports, case series and in the last 20 years mostly on statistical detection algorithms due to the large volume of reports. Each country has a spontaneous reporting system, which also feed into international systems.

For the GRiP initiative, we created paediatric specific reference sets and a vaccine and drug reference set of positive and negative controls has been created and published. These reference sets were used on the FAERS and EUDRAVIGILANCE data to compare signal detection methods in paediatrics and to explore whether age stratification is necessary. This document compares the signal detection methods in spontaneous reporting systems and electronic health care records, and shows the results of GRiP analysis in FAERS and EUDRAVIGILANCE.


Proof of concept studies: comparative effectiveness (drug/vaccine utilization)

In children, drugs are often used off label because of lack of appropriate efficacy evidence. Data regarding drug prescriptions and health outcomes, captured as part of routine healthcare can be analysed to provide evidence of drug effectiveness but several methodological challenges should be overcome. Children are peculiar in terms of anatomy, physiology, drug pharmacokinetics and pharmacodynamics as well as drug utilization. Using existing health care data provides an enormous opportunity to generate evidence on the effects of drugs in children. However comparative effectiveness research in children is underdeveloped. Modern methods should be applied to control confounding, where this is feasible.


Integrated online research infrastructure


This deliverable of the GRIP project describes the research infrastructure that will allow for collaborative work on aggregated healthcare data on paediatrics. The electronic infrastructure that has been built will allow for virtually linking existing healthcare databases across the globe to assess incidence/prevalence of diseases in children, plus the use and effects of drugs (including vaccines) on a large scale and in a standardized manner. The preferred work model in GRIP is a distributed approach, with standardized data elaboration nationally based on validated analytical scripts (JERBOA or SAS). The aggregated data will be shared on the remote research environment which is located within the firewalls of the Erasmus University Medical Center. Remote access and use is secured by personal tokens, use of the data will be under supervision of a data manager. This will allow all partners to analyse the data.


Description of Data Sources


Report on international adverse drug events (ADE) databases


Report on terminology mapping and AEFI/ADE definitions


Report and demonstrator for safety evaluation designs


Report on methods of safety signal generation in paediatrics from pharmacovigilance databases


Report on ethical and governance issues related to processing of healthcare data


Developing training material on pharmaco-epidemiology and pharmacovigilance


Report and Jerboa demonstrator for incidence and prevalence calculations


Report on confounding adjustment for comparative effectiveness research in electronic medical records and claims DBs


Proof of concept studies: drug/vaccine utilization


The aim of this proof of concept collaborative study that was initiated by WHO was co-funded by USFDA and GRiP is to assess the feasibility, quality and potential for sustainability of an international hospital-based active surveillance system for the evaluation of vaccine safety.