Vaccine Safety Datalink Project (VSD)

The Vaccine Safety Datalink (VSD) project is a collaborative effort between CDC's Immunization Safety Office and eight large managed care organizations (MCO). The VSD project was established in 1990 to monitor immunization safety and address the gaps in scientific knowledge about rare and serious adverse events following immunization.

The VSD project includes a large linked database that uses administrative data sources at each MCO. Each participating site gathers data on vaccination (vaccine type, date of vaccination, concurrent vaccinations), medical outcomes (outpatient visits, inpatient visits, urgent care visits), birth data, and census data.

The VSD project allows for planned immunization safety studies as well as timely investigations of hypotheses that arise from review of medical literature, reports to the Vaccine Adverse Event Reporting System (VAERS), changes in immunization schedules, or the introduction of new vaccines.

Since 1990, investigators from the VSD project have published more than 75 scientific articles. The VSD project has addressed the following immunization safety concerns:

• A study that quantifies the risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella (MMR) vaccine
• An investigation of MMR and other measles-containing vaccines, which found no increased risk for inflammatory bowel disease
• An examination of the safety of revaccination with the pneumococcal polysaccharide vaccine
• An evaluation of the VSD data to examine the safety of thimerosal-containing vaccines

The VSD project has proven to be a highly effective tool for evaluating immunization safety.

Managed Care Organization Sites

• Group Health Cooperative of Puget Sound, Seattle, WA
• Kaiser Permanente Northwest, Portland, OR
• Kaiser Permanente Medical Care Program of Northern California, Oakland, CA
• Southern California Kaiser Permanente Health Care Program, Los Angeles, CA
• HealthPartners Research Foundation, Minneapolis, MN
• Marshfield Clinic Research Foundation, Marshfield, WI
• Kaiser Permanente Colorado, Denver, CO
• Harvard Pilgrim Health Care, Boston, MA

Objectives

• To conduct population-based research on immunization safety questions
• To evaluate immunization safety hypotheses that arise from medical literature, passive surveillance systems, adjustments to immunization schedules, and introduction of new vaccines
• To guide national immunization policy decisions
• To partner with healthcare providers, public health officials, and others to ensure the public has the best available information regarding the risks and benefits of immunizations

Priority Studies

• Hair Loss
• Flu Vaccine and Bell's Palsy
• MMR Vaccine and ITP
• Rapid Cycle Analysis (RCA) Project
• Thimerosal and Autism
• Thimerosal and Neurodevelopment
• Yellow Fever Vaccine
• Diphtheria-Containing Vaccines

Rapid Cycle Analysis (RCA)

Rapid Cycle Analysis (RCA) is an active surveillance system designed to detect adverse events (possible side effects) following vaccination in near real time, so the public can be informed quickly of possible risks.

Read the VSD 2004–2005 Annual Report.

Hair Loss

Recent studies suggest that alopecia areata (hair loss) may occur rarely in persons who have received hepatitis B vaccine. While the mechanisms responsible for alopecia following vaccination are not certain, the condition may be caused by an immune disorder. Researchers at two VSD sites are conducting two studies using different study designs to assess the association between receipt of hepatitis B vaccine and the risk of alopecia in adults and adolescents.

For one site, the final analyses are complete. The other site is completing their final analysis for the study.

Flu Vaccine and Bell’s Palsy

Bell's palsy is a common neurologic disorder that accounts for up to 75% of all peripheral facial palsies. Although the etiology of Bell's palsy is not clear, one of the theories put forward involves an autoimmune etiology. Following the introduction of newly licensed intranasal influenza vaccine in Switzerland in October 2000, 46 cases of Bell's palsy were noted among people who received the vaccine. The situation warranted a thorough investigation to determine if there is any association between influenza vaccine and Bell's palsy in which VSD researchers are currently conducting a case-control study. As part of the study, researchers will identify people with Bell's palsy who are members of HMOs participating in the VSD project. At each participating site, medical records of persons will Bell's palsy will be reviewed to assess exposure to influenza vaccine, hepatitis B vaccine, Td vaccine, and other vaccines.

Final analyses calculating the relative risk of Bell's palsy following vaccination as well as the incidence of Bell's palsy among vaccinated and unvaccinated populations have been conducted. The manuscript for this study is currently under development.

MMR Vaccine and ITP

Idiopathic thrombocytopenia purpura (ITP) is an acquired disease that is caused by the destruction or impaired production of platelets. In children who are otherwise healthy, the acute onset of thrombocytopenia is commonly characterized as ITP. Over the last several years, there has been growing concern that the live virus MMR vaccination is associated with an increased incidence of ITP. Previous studies have demonstrated a significant risk of ITP following receipt of MMR vaccination, however, they were based on small populations. To better quantify the relationship between MMR vaccination and ITP, VSD researchers are currently investigating the association in a large cohort of children. Researchers will use inpatient, outpatient, and laboratory data to identify children with a diagnosis of ITP during a specific period of time. Medical charts will then be reviewed to verify cases of ITP and collect information on vaccination history. Analyses will be performed to assess the risk of ITP following MMR vaccination.

Final analyses are currently being conducted for this study.

Thimerosal and Autism

In response to public concerns, VSD researchers have begun a case-control study to examine the association between thimerosal and autism rigorously. The study aims to determine whether exposure to thimerosal in infancy or in utero is related to development of autism. The study will also evaluate whether exposure to thimerosal in infancy is related to development of the subclass of autism predominantly associated with regression. As part of the study, researchers will use automated data and registries to identify children with autism (cases) and without autism (controls). In-person examinations, telephone interviews, medical chart reviews, and immunization tracking systems will be used to collect information on vaccine history and other possible covariates. Recommended by the Institute of Medicine, this VSD study will be the first rigorous, epidemiological study conducted on the issue of thimerosal and autism. Data from this VSD study should provide the best available scientific information on whether a causal association between exposure to thimerosal and the development of autism is possible.

This study is in the data collection phase.

Thimerosal and Neurodevelopment

CDC conducted the Infant and Environmental Exposures to Thimerosal and Neuropsychological Outcomes at Ages 7 to 10 Years study to investigate possible associations between prenatal and early childhood exposure to thimerosal-containing vaccines and/or immunoglobulins and deficits in neuropsychological functioning. Thimerosal is a preservative that contains ethyl mercury and is used in some vaccines and immunoglobulins. This study was not designed to assess possible association between thimerosal and autism.

Yellow Fever Vaccine

In June 2001, seven cases of yellow fever vaccine-associated viscerotropic disease (previously called multiple organ system failure) in recipients of 17D-derived yellow fever vaccine were reported. The ACIP reviewed these cases, recommended enhanced surveillance for adverse events, and updated the ACIP statement on yellow fever vaccine. An additional report in MMWR provided two new suspected cases of yellow fever-associated viscerotropic disease and four suspected cases of yellow fever-associated neurotropic disease (previously called past-vaccinal encephalitis). Although yellow fever vaccine remains essential for travelers to yellow fever endemic areas, these findings underscore the need for enhanced surveillance and timely clinical assessment of yellow fever vaccine-associated disease.

In collaboration with the Department of Defense, VSD investigators are conducting epidemiologic studies involving the databases and records systems of the VSD, the Air Force and the Navy to study hospitalized viscerotropic and neurotropic events associated with yellow fever vaccine.

Data collection is currently underway for this study.

Diphtheria-Containing Vaccines

Three vaccines currently recommended for adolescents (Tdap, Td, and Menactra meningococcal conjugate vaccine) contain diphtheria toxoid and result in a diphtheria antibody response. While the safety of individual diphtheria-containing vaccines has been evaluated, less is known regarding the safety of administration of two or more of these vaccines, either simultaneously or sequentially. Local injection site reactions are the primary adverse event of concern with administration of multiple diphtheria toxoid-containing vaccines. The primary aim of this VSD study is to assess the occurrence of relatively severe local reactions, defined as medically-attended reactions, in adolescents and young adults with varying patterns of receipt of diphtheria toxoid-containing vaccines. In addition, the occurrence of illnesses possibly indicative of a hypersensitivity response to vaccination will be identified. The study will involve collection of information from administrative data, with chart review confirmation of presumptive cases.

Data collection is currently underway for this study.

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