Pneumococcal conjugate vaccines as maternal and infant immunogens: challenges of maternal recruitment.

Maternal pneumococcal immunization may be a strategy for the prevention of pneumococcal disease during the first months of life before infant-administered pneumococcal conjugate vaccine (PCV) becomes protective. Preparatory to a Phase III efficacy trial to investigate this strategy for preventing early infant otitis media (OM), we are conducting a Phase I-II randomized, double-masked trial to determine if maternal 9-valent PCV immunization alters active antibody production in infants who are immunized with PCV-7 and to compare local and systemic adverse events among women immunized with PCV-9 or placebo. A pilot study was conducted in 1997 in a Minneapolis-St. Paul health maintenance organization, HealthPartners (HP), to estimate enrollment rate for the proposed Phase III trial. A total of 154 pregnant women were selected of whom 122 appeared to be eligible from ICD codes in the HP claims database; 76 responded, and 46 of these were eligible for participation. Four of the 46 reported that they would be very likely and 21 somewhat likely to participate; an estimated 20% (25/122) participation rate. The records of 4,289 women in their second trimester have been reviewed to date for the Phase I/II trial; 2,589 (60%) were found not to be eligible; and an additional 1,015 (24%) could not be contacted. Of the 685 remaining, 558 (81%) were not interested in participating when interviewed, and 127 (19%) have consented. Most (46%) of those who declined participation have cited concern about the safety of vaccination during pregnancy. While the overall participation rate of second trimester women is only 3% (127/4,289), maternal attrition (2.8%) and infant attrition from the study before age 7 months (3.9%) are lower than projected (25%). Differences in study design could explain the difference in participation rates estimated in the pilot study and experienced in the Phase I/II study. Reports of safety from large-scale studies of maternal PCV immunization in industrialized countries are needed before women are receptive to maternal immunization to protect their infants against pneumococcal disease.

RCT Entities:   Population Interventions Outcomes