About Immunization in Pregnancy
Immunization in pregnancy is a promising public health strategy to reduce illness and death among pregnant women and young infants. This is particularly true in low and middle-income countries (LMICs), where there is the greatest burden of vaccine-preventable diseases and limited access to basic health services. The aim of vaccinating pregnant women is to increase the mother’s antibody levels against particular infections so that high and protective levels of antibody are transferred to the infant. Immunization in pregnancy has the potential to provide protection against infectious diseases in the mother, her developing fetus and the newborn infant. The success of maternal tetanus vaccination demonstrates this principle and is part of routine care in many countries. Influenza and pertussis vaccines are being increasingly recommended as an integral part of immunization in pregnancy programs. Promising new vaccines are being considered and developed to prevent infections in pregnant women and young infants, including against Group B streptococcus, respiratory syncytial virus, cytomegalovirus (CMV), hepatitis E, and Zika virus.
The safety of vaccines administered during pregnancy is a key consideration for pregnant women, healthcare providers, vaccine manufacturers, investigators, regulators, ethics committees and communities. There is a need for a globally harmonized approach to actively monitoring the safety of vaccines used in immunization programs for pregnant women.
About GAIA
The GAIA (Global Alignment of Immunization Safety Assessment in Pregnancy) project, coordinated by the Brighton Collaboration and funded by the Bill & Melinda Gates Foundation, was initiated in 2015 for an initial period of 2 years (2015-2016). This was in response to the call of the World Health Organization for a globally harmonized approach to actively monitor the safety of vaccines and immunization in pregnancy programs with a specific focus on LMICs needs and requirements. In the GAIA project, experts from 13 organizations (the BCF, US National Institute of Health, World Health Organization, Global Healthcare Consulting, University of Washington, Baylor College of Medicine, Monash Institute of Medical Research, St. George’s University of London, Erasmus University Medical Center, Cincinnati Children’s Hospital, Public Health Agency Canada, Synapse Research Management Partners and International Alliance for Biological Standardization) collaborated with over 200 volunteers worldwide who participated in 25 working groups.
The GAIA project achieved its three objectives:
Improve data
Create a common understanding
Develop standards, guidance, and tools
Improve data generated for strengthening programs of immunization in pregnancy by harmonizing maternal, pregnancy, fetal, and neonatal health outcome assessment with specific focus on LMICs.
Create a common understanding of the outcomes monitored by developing a common language for effective scientific communication about outcomes and by improving data comparability between studies to allow for better synthesis and pooling.
Develop GAIA standards, guidance, and tools for the benefit of all concerned with investigating or monitoring the safety of immunization programs in pregnancy around the world.Â
GAIA Achievements
During the GAIA project, a global functional network of experts was set up and the Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women was developed. Based on a landscape analysis of available standards and guidance documents including regulatory guidance available for immunization in pregnancy from the Food and Drug Administration (FDA), European Medicines Agency (EMA) and International Conference on Harmonization (ICH), through the standard Brighton Collaboration process, GAIA partners developed a core set of over 21 globally standardized case definitions of selected key obstetric and neonatal terms. A glossary of enabling terms critical to these obstetric and neonatal case definitions was developed (e.g., an algorithm for determination of gestational age) to support stakeholders using the definitions. A searchable database of terms, concept definitions and ontology of over 3000 terms related to key events for monitoring immunization in pregnancy was developed. A map of disease codes across coding terminologies, including MedDRA and ICD, was created to enable pooling of data from various sources. An online tool for automated case classification (single case or batch cases classification) of events according to the standardized case definitions has also been developed.
GAIA has developed two guideline documents for the standardized conduct of clinical trials of vaccines in pregnant women, including recommendations on the collection, analysis and presentation of safety data, to provide guidance on the prioritization and classification of the data to be collected in such studies, and to facilitate their applicability in various settings, including LMICs. These guidelines may also assist in the safety surveillance of vaccines already recommended for pregnant women (tetanus, influenza and pertussis). Guidance on study design and the standardization of data collection will help to promote the collection of a minimal set of high priority parameters in various settings, including LMICs.
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GAIA Guidance & Study Design Documents
- Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women
- Guidance for the collection of case report form variables to assess safety in clinical trials of vaccines in pregnancy
- A systematic review of adverse events following immunization during pregnancy and the newborn period
- Key terms for the assessment of the safety of vaccines in pregnancy: Results of a global consultative process to initiate harmonization of adverse event definitions
- Immunization in Pregnancy Clinical Research in Low- And Middle-Income Countries – Study Design, Regulatory and Safety Considerations
- Data collection matrix for clinical trials and program monitoring
GAIA Case Definitions
Neonatal Case Definitions
Obstretric Case Definitions
Support for GAIA Products
The GAIA outputs are developed based on the standard Brighton Collaboration consensus process including global consultation of professionals from key regulatory organizations, public health institutes, investigators, vaccine manufacturers and academia to ensure their applicability, usefulness and acceptability, especially in LMICs. The WHO Global Advisory Committee on Vaccine Safety (GACVS) provided a highly supportive assessment of the key GAIA guidance document and considered them to be timely and useful.
A special December 2016 issue of Vaccine includes the first 10 globally standardized case definitions of key obstetric and neonatal term and the two guideline documents. The next set of 11 case definitions and feedback from investigators and stakeholders on the GAIA outputs was published in a special December 2017 issue of Vaccine. This aims to aid in the dissemination and use of the GAIA project outputs globally.
The GAIA outputs are being increasingly utilized in the field of Immunization in Pregnancy and Maternal and Child Health by key stakeholders such as clinical investigators, regulators, and industry.
The GAIA case definitions, study design and data collection guidelines and tools will be applicable in immunization in pregnancy pre-and post-licensure safety and pharmacovigilance surveillance systems and will help support enhanced surveillance and collection of safety data that can be consolidated and compared across sites, countries, and programs worldwide. A standardized approach to safety data collection and reporting is likely to improve the acceptability and implementation of immunizations in pregnancy and subsequently help reduce illness and death among pregnant women and young infants globally.
International Consensus Conference: Harmonized Safety Monitoring of Immunization in Pregnancy
The International Alliance for Biological Standardization (IABS) organized this meeting that was inspired by the work performed by GAIA project partners and volunteers worldwide. It brought together 142 registered participants coming from regulatory authorities, public health institutes, academia and industry to help resolve existing challenges of safety monitoring of immunization in pregnancy and to reach conclusions that will be valuable to a globally concerted approach. Â
The objectives of the meeting were to discuss new safety data from immunization in pregnancy studies, to identify converging stakeholder needs and requirements for high quality data, to review new standards and tools for safety monitoring, including terminology, and to build consensus on the best practice guidance for monitoring vaccine safety in pregnancyÂ
As a result of 32 presentations and 7 panel discussions in 7 sessions, this meeting has enhanced a shared understanding of the challenges of monitoring immunization in pregnancy. It allowed for in depth discussion on solutions for a collaborative way forward and yielded consensus on the need for a globally concerted approach.Â
The need for systems for prompt identification and response to adverse events following immunization (AEFI) in pregnancy was generally agreed on. This primarily rests on moving from minimal to enhanced safety monitoring throughout the vaccine life cycle. Â
The conference was made possible by the support of Sanofi Pasteur, Novavax, GSK, and the Bill & Melinda Gates Foundation.
