About FDA

Description: The cooperative agreement remains a successful scientific public health collaboration between FDA and WHO, in furthering vaccine safety through global pharmacovigilance capacity building. Year 2 funding supports development of a network of sentinel sites for vaccine signal detection, and a pharmacovigilance training course in coordination with the Uppsala Monitoring Centre in Sweden. Public health outcome: These activities support the public health goal of enhancing access of the global population to safe and effective vaccines.

Accomplishment: These activities supported the public health goal of enhancing access of the global population to safe and effective vaccines. Project accomplishments of Year 2 include:

• Continued development of the Global Vaccine Safety Multi-country Collaboration (GVS-MCC) for signal evaluation and hypothesis testing;
• FDA/CBER training course in pharmacovigilance at Uppsala Monitoring Center (UMC)

Description: The cooperative agreement remains a successful scientific public health collaboration between FDA and WHO, in furthering vaccine safety through global pharmacovigilance capacity building. Public Health outcome: These activities support the public health goal of enhancing access of the global population to safe and effective vaccines.

Accomplishment: These activities supported the public health goal of enhancing access of the global population to safe and effective vaccines. Project accomplishments of Year 3 include continuation of a proof of concept study for an international hospital-based active surveillance system to investigate the association between measles-containing vaccines and two specific adverse events. The work supports continued development of a network of hospital-based sentinel sites in low-and-middle-income countries to allow for signal evaluation and hypothesis testing.

Description: Year 4 funding supports continued development of a network of hospital-based sentinel sites and the conduct of a proof-of-concept study to evaluate feasibility and sustainability of an international hospital-based active surveillance system for monitoring vaccine safety. This project advances the strategic goal of strengthening global pharmacovigilance capacity.

Accomplishment: Large-scale immunization programs now reach millions of people in developing countries. The number of vaccine doses administered worldwide is increasing as new vaccines are developed and made available to the global population. Some new vaccines are developed specifically for low-and-middle-income countries (LMICs) or become available in LMICs at the same time as developed countries. Monitoring of vaccines after they are licensed and in wide-spread use is critical for detecting a potential safety signal that may not have been identified during clinical trials. Because most potential adverse events of interest, not already identified in clinical trials, are rare, their assessment requires the use of well-controlled studies in very large populations. This is impractical, too expensive or simply unfeasible in most countries. For this reason, the use of international networks of hospitals for active adverse event surveillance is an attractive, efficient, and less costly alternative.

A Global network for Post-marketing Surveillance (PMS) of vaccines was established by WHO in early 2008 to monitor the safety of vaccines, and involved twelve LMICs from all WHO regions. A proof of concept study was conducted to investigate a possible association between Guillain-Barre Syndrome (GBS) and the 2009-2010 H1N1 pandemic influenza vaccine. That pilot project was highly successful with over 700 carefully documented cases of GBS, demonstrating that multinational studies are feasible and can provide a useful platform to evaluate future vaccine safety concerns especially for rare, serious events.

The main project supported by the CoAg was expansion of the initial pilot project to conduct a WHO Global Vaccine Safety-Multi Country Collaboration (GVS-MCC) to assess the feasibility, quality and sustainability of an international hospital-based active surveillance system for vaccine safety monitoring. The CoAg supported a second proof-of-concept study to investigate the association between measles- containing vaccines and immune thrombocytopenic purpura (ITP) and aseptic meningitis (AP). This was a multi-year project with several objectives including development of active surveillance hospital-based sentinel sites for adverse event following immunization (AEFI) monitoring in different regions of the world, and providing independent and timely risk-benefit information to WHO and the member countries on vaccine safety issues with the potential to affect national immunization programs. Activities carried out by the investigators included assessment of site capacities; development and translation of the study protocol, data collection tool, data management and analysis plan; development and maintenance of a secured web-based platform for data sharing; identifying study sites among eligible institutions; finalizing and ethical clearance of the study protocol; training of staff on study procedures (field procedures, data collection and data sharing); data collection and validation; study-specific data quality checks; data cleaning and analysis; discussion of study results with participants and coordination team and; publication. The study is almost completed and dissemination of results is pending.

Additional projects supported by the CBER-WHO CoAg included:

• Training seminars in “Application of Pharmacovigilance to Regulatory Decisions for Vaccines”: Each year, the Uppsala Monitoring Centre (UMC) presents a pharmacovigilance training course to regulatory and public health staff from multiple countries. CBER staff leveraged the UMC training to present a series of lectures on “Application of Pharmacovigilance to U.S. FDA Regulatory Decisions for Vaccines”. Through formal presentations and interactive discussions, CBER lecturers introduced the methods used by FDA/CBER scientists to assess post-marketing safety data and to inform subsequent regulatory actions taken for vaccines. Class participants joined in the conversations on the agenda topics and shared their perspective of the issue as it related to their own country and pharmacovigilance system. CBER experts gave presentations on FDA overview and review of publicly available resources; challenges in evaluating vaccine exposure; adverse event reporting systems; pre-licensure safety assessments and pharmacovigilance planning; required post-marketing studies and led case-based discussions on a vaccine and associated adverse event (practical application of the concepts learned during the lectures). This training was given in multiple years. ;
• Case definition for narcolepsy as an adverse event of special interest following influenza vaccines: Narcolepsy was one of the most prominent adverse events following immunization (AEFI) that has been investigated. A working case definition of “narcolepsy” was developed by a Brighton Collaboration Working group in conjunction with other experts. A standard Brighton Collaboration case definition with guidelines for data collection, analysis, and presentation was developed according to the standard process and published in a peer-reviewed journal [Narcolepsy as an adverse event following immunization: Case definition and guidelines for data collection, analysis and Presentation: Vaccine 31 (2013) 994-1007]). This work was supported in part by funding from the CoAg. ;
• Development of data management tools (e.g., Automatic Brighton Classification tool) for AEFI reports and reporting: The first step of investigating a safety signal is usually the verification of the validity of a reported event (i.e., verify the diagnosis). Determining the diagnostic certainty of reported events and identification of missing information according to Brighton Collaboration Case Definitions electronically and automatically would significantly enhance the ability of investigators to determine whether a reported event meets a standardized case definition, and whether the degree of diagnostic certainty is sufficient for further signal evaluation or whether additional information is needed. The CoAg supported development of the Automatic Brighton Classification tool (ABC) (including development of software) which could he use to improve the information gathered by individual case investigations or safety assessments on a national level and also promote data comparability between different countries.> ;
• Global Advisory Committee on Vaccine Safety (GACVS) sub-group activities on influenza vaccines: The GACVS subgroup on influenza vaccines safety reviews the available evidence about reactions to various seasonal and pandemic influenza vaccines. During the Pandemic in 2009, the subgroup focused on global monitoring of the safety of pandemic influenza vaccines but its scope has expanded since then to cover other influenza vaccine-related issues. The CoAg supported activities of this sub-group including: Assessment of results of ongoing experimental research efforts investigating potential immunologic links between narcolepsy and Pandemrix and provide scientific guidance; provide scientific advice to the development, implementation and evaluation of results of a pilot network of sentinel organizations in developing countries on issues related to Influenza vaccine (a project that was funded by the CoAg) and; contribute to the development of written guidance outlining the safety of use of influenza vaccines during pregnancy.