Jorgen Bauwens

Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women.

Vaccination during pregnancy is increasingly being used as an effective approach for protecting both young infants and their mothers from serious infections. Drawing conclusions from published studies in this area can be difficult because of the inability to compare vaccine trial results across different studies and settings due to the heterogeneity in the definitions of terms used to assess the safety of vaccines in pregnancy and the data collected in such studies. The guidelines proposed in this document have been developed to harmonize safety data collection in all phases of clinical trials of vaccines in pregnant women and apply to data from the mother, fetus and infant. Guidelines on the prioritization of the data to be collected is also provided to allow applicability in various geographic, cultural and resource settings, including high, middle and low-income countries.

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

BACKGROUND The variability of terms and definitions of Adverse Events Following Immunization (AEFI) represents a missed opportunity for optimal monitoring of safety of immunization in pregnancy. In 2014, the Brighton Collaboration Foundation and the World Health Organization (WHO) collaborated to address this gap. METHODS Two Brighton Collaboration interdisciplinary taskforces were formed. A landscape analysis included: (1) a systematic literature review of adverse event definitions used in vaccine studies during pregnancy; (2) a worldwide stakeholder survey of available terms and definitions; (3) and a series of taskforce meetings. Based on available evidence, taskforces proposed key terms and concept definitions to be refined, prioritized, and endorsed by a global expert consultation convened by WHO in Geneva, Switzerland in July 2014. RESULTS Using pre-specified criteria, 45 maternal and 62 fetal/neonatal events were prioritized, and key terms and concept definitions were endorsed. In addition recommendations to further improve safety monitoring of immunization in pregnancy programs were specified. This includes elaboration of disease concepts into standardized case definitions with sufficient applicability and positive predictive value to be of use for monitoring the safety of immunization in pregnancy globally, as well as the development of guidance, tools, and datasets in support of a globally concerted approach. CONCLUSIONS There is a need to improve the safety monitoring of immunization in pregnancy programs. A consensus list of terms and concept definitions of key events for monitoring immunization in pregnancy is available. Immediate actions to further strengthen monitoring of immunization in pregnancy programs are identified and recommended.

Global alignment of immunization safety assessment in pregnancy – The GAIA project

Immunization in pregnancy provides a promising contribution to globally reducing neonatal and under-five childhood mortality and morbidity. Thorough assessment of benefits and risks for the primarily healthy pregnant women and their unborn babies is required. The GAIA project was formed in response to the call of the World Health Organization for a globally concerted approach to actively monitor the safety of vaccines and immunization in pregnancy programs. GAIA aims to improve the quality of outcome data from clinical vaccine trials in pregnant women with a specific focus on the needs and requirements for safety monitoring in LMIC. In the first year of the project, a large and functional network of experts was created. The first outputs include a guidance document for clinical trials of immunization in pregnancy, a basic data collection guide, ten case definitions of key obstetric and neonatal health outcomes, an ontology of key terms and a map of pertinent disease codes. The GAIA Network is designed as an open and growing forum for professionals sharing the GAIA vision and aim. Based on the initial achievements, tools and services are developed to support investigators and strengthen immunization in pregnancy programs with specific focus on LMIC.

Methodology for computing the burden of disease of adverse events following immunization.

Composite disease burden measures such as disability‐adjusted life‐years (DALY) have been widely used to quantify the population‐level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden.

Immunization in pregnancy clinical research in low- and middle- income countries - study design, regulatory and safety considerations

Immunization of pregnant women is a promising public health strategy to reduce morbidity and mortality among both the mothers and their infants. Establishing safety and efficacy of vaccines generally uses a hybrid design between a conventional interventional study and an observational study that requires enrolling thousands of study participants to detect an unknown number of uncommon events. Historically, enrollment of pregnant women in clinical research studies encountered many barriers based on risk aversion, lack of knowledge, and regulatory ambiguity. Conducting research enrolling pregnant women in low- and middle-income countries can have additional factors to address such as limited availability of baseline epidemiologic data on disease burden and maternal and neonatal outcomes during and after pregnancy; challenges in recruiting and retaining pregnant women in research studies, variability in applying and interpreting assessment methods, and variability in locally acceptable and available infrastructure. Some measures to address these challenges include adjustment of study design, tailoring recruitment, consent process, retention strategies, operational and logistical processes, and the use of definitions and data collection methods that will align with efforts globally.

Vaccine Update: Recent Progress With Novel Vaccines, and New Approaches to Safety Monitoring and Vaccine Shortage

Vaccines are increasingly based on new constructs, new technologies, and new compounds. Novel immunization programs are rapidly implemented globally. In this article, we highlight selected hot topics of this highly dynamic and broad field of scientific and public health development. The first section focuses on novel vaccines including malaria, dengue, serogroup B meningococcal, and respiratory syncytial virus vaccines and antibodies. The second section is addressing emerging strategies and programmatic challenges including maternal immunization, integrated mother‐child safety monitoring, and finally coping strategies with vaccine shortages.