Tracy A. Lieu

The Vaccine Safety Datalink: A Model for Monitoring Immunization Safety

The Vaccine Safety Datalink (VSD) project is a collaborative project between the Centers for Disease Control and Prevention and 8 managed care organizations (MCOs) in the United States. Established in 1990 to conduct postmarketing evaluations of vaccine safety, the project has created an infrastructure that allows for high-quality research and surveillance. The 8 participating MCOs comprise a large population of 8.8 million members annually (3% of the US population), which enables researchers to conduct studies that assess adverse events after immunization. Each MCO prepares computerized data files by using a standardized data dictionary containing demographic and medical information on its members, such as age and gender, health plan enrollment, vaccinations, hospitalizations, outpatient clinic visits, emergency department visits, urgent care visits, and mortality data, as well as additional birth information (eg, birth weight) when available. Other information sources, such as medical chart review, member surveys, and pharmacy, laboratory, and radiology data, are often used in VSD studies to validate outcomes and vaccination data. Since 2000, the VSD has undergone significant changes including an increase in the number of participating MCOs and enrolled population, changes in data-collection procedures, the creation of near real-time data files, and the development of near real-time postmarketing surveillance for newly licensed vaccines or changes in vaccine recommendations. Recognized as an important resource in vaccine safety, the VSD is working toward increasing transparency through data-sharing and external input. With its recent enhancements, the VSD provides scientific expertise, continues to develop innovative approaches for vaccine-safety research, and may serve as a model for other patient safety collaborative research projects.

Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants.

Objectives. To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies—RSVIG, palivizumab, and no prophylaxis—among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente–Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%. Results. Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was ≤32 weeks, who required ≥28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost

Population-based study of rotavirus vaccination and intussusception

12 000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or

Real-time vaccine safety surveillance for the early detection of adverse events.

33 000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from

Intussusception Risk after Rotavirus Vaccination in U.S. Infants

39 000 to

Healthcare utilization and cost of pneumococcal disease in the United States

420 000 per hospitalization averted or

Cost-effectiveness of pneumococcal conjugate vaccination in the prevention of child mortality: an international economic analysis

110 000 to

Societal Costs and Morbidity of Pertussis in Adolescents and Adults

1 200 000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization. Conclusion. In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.

A Maximized Sequential Probability Ratio Test for Drug and Vaccine Safety Surveillance

Background. During the first year that the rhesus rotavirus tetravalent vaccine (RRV-TV) was licensed, the Vaccine Adverse Event Reporting System received several reports of intussusception after vaccination. To evaluate the risk of intussusception, we conducted a retrospective cohort study in ten managed care organizations. Methods. Cases of intussusception were identified by searching electronic databases for diagnoses of intussusception (ICD-9 Code 560.0) in infants 1 to 11 months of age and confirmed by medical chart review. Vaccination and enrollment data were obtained from administrative databases. Incidence rate ratios (RR) of intussusception were computed by dividing incidence rates in prespecified risk intervals after vaccination by the background rate of intussusception and adjusted for age by Poisson regression. Cox proportional hazard regression was used to evaluate risk by vaccine dose. Results. Of 463 277 children 56 253 had been vaccinated with a total of 91 371 doses of RRV-TV. The incidence rate of intussusception was 25/100 000 person years among unexposed infants and 340/100 000 person years 3 to 7 days postvaccination. In the interval 3 to 7 days after vaccination, the age-adjusted RR was 16.0 (95% confidence interval, 5.5 to 46.7) for all doses combined and 30.4 (95% confidence interval, 8.8 to 104.9) after the first dose. RRs for the 8- to 14- and 15- to 21-day risk intervals were >1.0, but the confidence intervals substantially overlapped 1.0. The attributable risk was one case of intussusception per 11 073 children vaccinated. Conclusions. RRV-TV is associated with an increased risk of intussusception. The risk is greatest 3 to 7 days after the first vaccination dose.

Real-time surveillance to assess risk of intussusception and other adverse events after pentavalent, bovine-derived rotavirus vaccine.

Background:Rare but serious adverse events associated with vaccines or drugs are often nearly impossible to detect in prelicensure studies and require monitoring after introduction of the agent in large populations. Sequential testing procedures are needed to detect vaccine or drug safety problems as soon as possible after introduction. Objective:To develop and evaluate a new real-time surveillance system that uses dynamic data files and sequential analysis for early detection of adverse events after the introduction of new vaccines. Research Design:The Centers for Disease Control and Prevention (CDC)-sponsored Vaccine Safety Datalink Project developed a real-time surveillance system and initiated its use in an ongoing study of a new meningococcal vaccine for adolescents. Dynamic data files from 8 health plans were updated and aggregated for analysis every week. The analysis used maximized sequential probability ratio testing (maxSPRT), a new signal detection method that supports continuous or time-period analysis of data as they are collected. Results:Using the new real-time surveillance system, ongoing analyses of meningococcal conjugate vaccine (MCV) safety are being conducted on a weekly basis. Two forms of maxSPRT were implemented: an analysis using concurrent matched controls, and an analysis based on expected counts of the outcomes of interest, which were estimated based on historical data. The analysis highlights both theoretical and operational issues, including how to (1) choose appropriate outcomes and stopping rules, (2) select control groups, and (3) accommodate variation in exposed:unexposed ratios between time periods and study sites. Conclusions:Real-time surveillance combining dynamic data files, aggregation of data, and sequential analysis methods offers a useful and highly adaptable approach to early detection of adverse events after the introduction of new vaccines.