Global Alignment of Immunization safety Assessment in pregnancy (GAIA) project

Vaccination during pregnancy offers mothers and their infants effective protection against infectious diseases. However, due to the heterogeneity in the definitions of terms used to assess vaccine safety, data collection methods and their presentation, comparing results across studies and settings presents challenges. Thus, the harmonization of terms, disease concepts and the use of standardized case definitions of key events related to safety monitoring of vaccines will facilitate comparability of outcomes across studies.

In 2014, WHO convened an expert consultation to a) review existing obstetrical and paediatric adverse event case definitions and guidance documents; b) prioritize terms for key events for continuous monitoring of vaccine safety in pregnancy; c) develop concept definitions for these events; and d) recommend a core data set of key terms of events to be collected when monitoring safety of vaccines used in pregnancy. The consultation also recommended developing a guidance document for data collection, analysis and presentation of safety data, tools for harmonized data collection, data sharing, and the use of health-care data sets to strengthen safety surveillance.

The Global Alignment of Immunization safety Assessment in pregnancy (GAIA) network was formed to help establish a global, common understanding of outcomes and approaches to monitoring safety of vaccines used in pregnancy with particular focus on LMICs. GAIA has prepared draft guidelines – “Guidelines for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women” on prioritizing data to be collected in studies of the use of vaccines in pregnancy, and to assist their applicability in various geographical, cultural and resource settings, including LMICs. The intention is also to optimize the use of data obtained from participants in clinical trials by improving data accuracy and comparability.

The guidelines are intended for all entities involved in the planning, evaluation, and implementation of studies on vaccines used in pregnancy. However, they are not regulatory in nature, and are not intended to replace established or mandated processes of adverse event reporting. In their current form, applying all recommended standards may thus prove complex for some settings.

The guideline document emphasizes 5 aspects of data collection for pregnancy vaccine trials: (i) collection of background data; (ii) pre-vaccination screening data; (iii) vaccine- and immunization-related data; (iv) follow-up monitoring data (including birth-related and neonatal data); and (v) adverse event monitoring data (including maternal, fetal and infant). While it may not be practical to pre-define and solicit all possible clinical and laboratory outcomes, a core dataset should be collected in all vaccine trials in pregnancy, where feasible. Two levels of priority for data collection have been defined: priority 1– data considered important for the understanding of the trial results and/or required by national and/or international regulatory authorities; and priority 2 – data considered less important but helpful.

The guidelines prepared by GAIA were reviewed and discussed by the pregnancy subgroup of GACVS and at the IABS⁴ “Harmonized Safety Monitoring of Immunization in Pregnancy International Consensus Conference” in March 2016, following which they were revised. GACVS reviewed the revised version and agreed that a global concerted approach was needed towards harmonized safety data collection in vaccine trials in pregnancy

The Committee considered the GAIA guidelines timely and useful and noted that they should provide for flexibility regarding core data collection requirements as data collection in certain settings may not be feasible. Challenges related to infrastructure, availability of background data, changes in background rates or clinical standards in various settings should also be acknowledged, including the fact that the presence of researchers will affect some pregnancy-related outcomes. GACVS also noted the possibility of updating these guidelines which may also be applicable for safety monitoring in the context of observational studies. Furthermore, to test and facilitate their implementation, the Committee stressed the need for field testing and review, the generation of practical tools for investigators, capacity-building/training and a dissemination strategy.

⁴ The International Alliance for Biological Standardization.

Full report of GACVS meeting of 15-16 June 2016, published in the WHO Weekly Epidemiological Record of 15 July 2016