Open-Label Pilot Study to Compare the Safety and Immunogenicity of Pentavalent Rotavirus Vaccine (RV5) Administered on an Early Alternative Dosing Schedule with Those of RV5 Administered on the Recommended Standard Schedule.

This study compares the safety and immunogenicity of pentavalent rotavirus vaccine (RV5) administered on an alternative schedule (initiated at 2-5 weeks of age) with those of RV5 administered on the recommended standard schedule. Our findings support the future conduct of larger clinical trials to confirm the safety and efficacy of rotavirus vaccination in the neonatal period.

Background incidence of liver chemistry abnormalities in a clinical trial population without underlying liver disease.

BACKGROUND: The FDA has recently proposed pre-marketing liver chemistry subject stopping criteria. The study was undertaken to determine the background rates of liver chemistry abnormalities in clinical trial populations without underlying liver disease. METHODS: Data from 28 Phase II-IV trials in diseases with normal risk of underlying liver abnormalities were included. Information on 18,672 subjects, mean age of 44.3 years and 92.3% female was available. Prevalence and incidence of abnormal liver chemistries were calculated. RESULTS: At baseline, the overall prevalence of alanine aminotransferase (ALT) elevations of 3 x ULN (upper limit of normal) and 5 x ULN was 0.08% and 0.01%, respectively. The prevalence of liver chemistry abnormalities was similar at study entry and exit. Overall, elevated liver chemistry incidence rates per 10,000 person months were 6.5 (95% CI 4.8; 8.5) for ALT 3 x ULN, 2.6 (1.6; 4.0) for ALT 5 x ULN, 0.3 (0.03; 0.9) for ALT 8 x ULN, 0.09 (0.04; 0.2) for alkaline phosphatase (ALP) 2 x ULN, and 0 for combined ALT+bilirubin elevation. CONCLUSION: Elevations of ALT (3 x ULN) and ALP (2 x ULN) are rare in clinical trial populations without underlying liver disease and can be considered a safety signal. No events of ALT 3 x ULN with concomitant bilirubin 1.5 x ULN were noted. These analyses create a liver chemistry evidence base in normal risk clinical trial populations.

Evaluation of the General Practice Research Database congenital heart defects prevalence: comparison to United Kingdom national systems.

BACKGROUND: As part of an effort to validate the General Practice Research Database (GPRD) for future studies of medication use in pregnancy, this study examined whether the rates of all, and specific types of, congenital heart defects obtained from the GPRD are similar to those obtained from UK national systems. METHODS: The prevalence rates of heart defects for 2001-2003 were determined from the GPRD and compared with both the National Congenital Anomaly System (NCAS) and the European Concerted Action of Congenital Anomalies and Twins (EUROCAT). Rate ratios (RRs) and 95% CIs were calculated comparing the prevalence of all congenital heart defects as well as specific types of heart defects in the three data sources. In addition, the effect of the child's age on the frequency of heart defects in the GPRD was determined. RESULTS: The prevalence of heart defects in the GPRD was more than twice as high as in the NCAS and slightly higher than in the EUROCAT. All differences were statistically significant. The prevalence of specific heart defects varied across the GPRD, NCAS, and EUROCAT. The measured prevalence of congenital heart defects in the GPRD was higher if calculated including children up to age 6. CONCLUSIONS: The comparisons of the GPRD prevalence rates to national prevalence estimates demonstrate that the GPRD can serve as a more complete source of background prevalence for the most commonly occurring congenital heart defects, which is essential to properly assess possible associations between maternal exposures and congenital heart defects.