Established Safety Surveillance for Smallpox Vaccine

General Steps to Establishing Vaccine Safety Surveillance (22:V7:4)

If there is no system in place for monitoring adverse events that could handle the addition of surveillance for smallpox, VIG, and Cidofovir, the following activities should be taken:

  1. Clarify the roles of the national regulatory authority and public health epidemiology and agree on objectives for the system.
  2. Identify the resources available and needed and establish political commitment to immunization safety surveillance.
  3. Appoint or designate regional and/or national assessors for immunization safety.
  4. Establish an expert panel on immunization safety.
  5. Develop and disseminate a list of events to be reported and their case definitions; a standard investigation procedure; and report and investigation forms.
  6. Designate and train staff to prepare the reports, complete the report forms, investigate adverse events, and conduct analyses of the data as appropriate.
  7. Inform all healthcare workers and clinicians of the need to report an adverse event immediately and clarify which ones should be reported.
  8. Consider the establishment of a compensation scheme for specified adverse events.

What to Report

Reportable adverse events must include any deaths or serious adverse events believed by the public or healthcare workers to be caused by immunization. Some events like abscess, toxic shock syndrome, and sepsis, are indicators of program error and need to be monitored at a minimum to identify and correct program errors. In addition, providers must be encouraged to report even if the causality of the adverse event is uncertain (i.e., temporal association is sufficient for reporting).

More information can be found in the World Health Organization guidelines on “Immunization Safety Surveillance.” (You need Adobe Acrobat Reader to view this link.)

Current General Vaccine Safety Infrastructure in the United States

VAERS (The Vaccine Adverse Event Reporting System) is the national surveillance system for adverse events following the administration of U.S. licensed vaccines. VAERS is administered by the CDC and the Food and Drug Administration (FDA). VAERS data is routinely analyzed by the CDC and the FDA to identify new or rare vaccine side effects, increases in rates of known side effects, associations with specific vaccine lots and patient risk factors. All smallpox adverse event reports are also delivered to this system.

The VAERS Reporting Form (22:V7:10) can be downloaded from the internet for physician or patient access and reporting. The internet site address for the form is https://secure.vaers.org/VaersDataEntryintro.htm. The form is designed to obtain basic information about the adverse event and its management. Additional follow-up is done to determine long-term sequelae.

VAERS Role in Smallpox Vaccine Response (22:V7:11)

The VAERS system is useful as a mechanism for monitoring smallpox vaccine adverse events because it’s national and known to healthcare providers. It allows the CDC to get an indication of what is occurring with the vaccine. However, since it is simply a gathering point of information, it cannot determine whether or not a vaccine caused the adverse events.

While VAERS provides useful information on vaccine safety, the data are somewhat limited. Judgments about causality (whether the vaccine was truly responsible for an adverse event) cannot be made from VAERS reports because of incomplete information. VAERS reports often lack important information such as laboratory results. As a result, researchers have turned more recently to large-linked databases (LLDBs) in order to further study vaccine safety. LLDBs provide scientists with access to the complete medical records of millions of individuals receiving vaccines (all identifying information is deleted to protect the confidentiality of the patient).

Role of the Institute of Medicine (22:V7:12)

As concerns about vaccine safety or a particular AE association are raised by VAERS data or by other studies, the Institute of Medicine can convene expert committees to review the hypotheses and supporting information to determine their significance to public health. The mission of the Institute of Medicine is to advance and disseminate scientific knowledge to improve human health. The Institute provides objective, timely, authoritative information and advice concerning health and science policy to government, the corporate sector, the professions and the public. The web address for the Institute of Medicine is: http://www.iom.edu/.

Clinical Immunization Safety Assessment (CISA) Network (22:V7:13)

The Clinical Immunization Safety Assessment Network, or CISA, was established to provide clinical evaluation of the data collected by VAERS in order to help determine whether or not a particular vaccine caused an adverse event. Many of the top academic centers in the U.S. are part of this network. CISA is composed of academic centers of excellence (4) in partnership with CDC serving as a source of clinical expertise in adverse events following immunization. The four academic centers are: Johns Hopkins with University of Maryland, Boston Medical Center, Kaiser Research Institute Foundation with Stanford University and Vanderbilt University and New York Presbyterian-Columbia.

Vaccine Safety Datalink

The gaps that exist in the scientific knowledge of rare vaccine side effects prompted the CDC to develop the Vaccine Safety Datalink (VSD) project in 1990. This project involves partnerships with seven large health maintenance organizations (HMOs) to continually monitor vaccine safety. VSD is an example of a large-linked database (LLDB) and includes information on more than six million people. All vaccines administered within the study population are recorded. Available data include vaccine type, date of vaccination, concurrent vaccinations (those given during the same visit), the manufacturer, lot number, and injection site. Medical records are then monitored for potential adverse events resulting from immunization. The VSD project allows for planned vaccine safety studies as well as timely investigations of hypotheses. The web address for the home page for the Vaccine Safety Datalink is: http://www.cdc.gov/nip/vacsafe/vsd/default.htm.

Importance of Monitoring Smallpox Vaccine Safety (22:V7:16)

Although we have a great deal of information already on the expected adverse events associated with smallpox vaccine, monitoring for these and other adverse events is still essential (in both a pre- and post- event vaccination campaign). Several issues arise that support the need for organized monitoring for adverse events:

  1. Smallpox vaccination hasn’t been used on a large scale in quite some time, therefore, primary vaccine recipient populations will generally be older than during the eradication period.
  2. More people exist today with disease or medication altered immune systems than existed when the vaccine was used on a wide-scale.
  3. Because the make-up and health status of today’s population is different than previously, while we can make intelligent guesses as to what to expect in terms of adverse events, we really do not have a modern day safety profile.

In addition, it is extremely important to actively track serious vaccine adverse events that may require specialized and/or limited treatment resources in order to gauge and address those resource needs to support vaccination. 

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