This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.

The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.

In children followed up to 3.5 years, PCV provided a moderate amount of protection against ear infections while reducing frequent otitis media and tube procedures by greater amounts.

WHAT'S KNOWN ON THIS SUBJECT:We previously alerted the ACIP to preliminary evidence of a twofold increased risk of febrile seizures after MMRV when compared with separate MMR and varicella vaccines after monitoring with the VSD RCA surveillance system. WHAT THIS STUDY ADDS:Using VSD data on twice as many vaccines, we examined the effect of MMRV on risk of seizure and describe here the postvaccination risk interval for increased fever and febrile seizures after vaccination. abstract OBJECTIVE: In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine. METHODS: Using 2000 -2008Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR ϩ varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR ϩ varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses. RESULTS:MMRV vaccine recipients (83 107) were compared with recipients of MMR ϩ varicella vaccines (376 354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR ϩ varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR ϩ varicella vaccination was 4.3 per 10 000 doses (95% confidence interval: 2.6 -5.6). CONCLUSIONS:Among 12-to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR ϩ varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.

Because of rare but serious adverse events, pharmaceutical drugs and vaccines are sometimes withdrawn from the market, either by a government agency such as the Food and Drug Administration (FDA) in the United States or by the manufacturing pharmaceutical company. In other cases, a drug may be generally safe but increase the risk for serious adverse events for certain subpopulations such as pregnant women or people with heart problems. Due to limited sample size and selected study populations, rare adverse events are often impossible to detect during phase 3 trials conducted before the drug is approved for general use. It is then important to conduct post-approval drug safety surveillance, using, for example, health insurance claims data. In such surveillance, the goal should be to detect serious adverse events as early as possible without too many false alarms, and it is then natural to use a continuous or near-continuous sequential test procedure that reevaluates the data on a daily or weekly basis.In this article, we first show that Wald's classical sequential probability ratio test (SPRT) for continuous surveillance is very sensitive to the choice of relative risk required in the specification of the alternative hypothesis, making it difficult to use for drug and vaccine safety surveillance. We instead propose the use of a maximized sequential probability ratio test (MaxSPRT) based on a composite alternative hypothesis, which works well across a range of relative risks. We illustrate the use of this method on vaccine safety surveillance and compare it with the classical SPRT. † Deceased.Received January 22, 2010, Revised September 24, 2010, October 28, 2010, Accepted October 30, 2010 Recommended by Nitis Mukhopadhyay Address correspondence to Martin Kulldorff, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA 02215, USA; E-mail: martin_kulldorff@hms.harvard.edu Drug and Vaccine Safety Surveillance 59A table of critical values for the MaxSPRT is provided, covering most parameter choices relevant for vaccine and drug safety surveillance. The critical values are based on exact numerical calculations. We also calculate the statistical power, the expected time until the null hypothesis is rejected, and the average length of surveillance.