Double-Blind Placebo-Controlled Clinical Effectiveness Trial of the 23-Valent Pneumococcal Vaccine Among Military Trainees At Increased Risk of Respiratory Disease

Study participants. Given their documented high rates of respiratory illness, US military trainees were selected for participation. A sample size of 166,744 person-years was calculated based on the following assumptions: 12% attrition from military training, clinical pneumonia attack rate of 11 cases per 1000 person-years, 20% of captured pneumonias caused by Sp, 90% of captured Sp pneumonias caused by a vaccine-covered Sp strain, and 70% vaccine efficacy.

Enrollment and follow-up. This study was approved by multiple Department of Defense (DoD) institutional review boards. Using an informed consent process, basic training recruits at 5 recruit training centers (in South Carolina, Missouri, Illinois, and California) were invited to participate during their first week of training. Pregnancy screening was performed on all women, and those with positive results were not enrolled. Exclusion criteria included having previously received the a 23-valent pneumococcal vaccine during the previous 5 years or having a medical condition that either required or precluded pneumococcal vaccination. Study participants completed a study questionnaire and were administered a pre-packaged, blinded, and randomized injection containing either the 23-valent pneumococcal vaccine (Wyeth Pharmaceuticals or Merck & Company, Inc.) or saline in a 1:1 ratio. Study injections were administered at the same time as other recruit in-processing vaccinations, which may have included vaccines against polio, measles-mumps-rubella, varicella, tetanus-diphtheria, hepatitis A virus, hepatitis B virus, meningococcal disease (A/C/Y/W135), and influenza. At the end of recruit training, a questionnaire was administered to capture symptoms and signs of illnesses which might have been missed captured by the active and passive surveillance.

As enrollment continued for more than two years, the person-year contributions of those first enrolled were greater than those enrolled near the trial's end. The original planned surveillance period was 1.7 years. This was later extended to 6.7 years from enrollment of the first participant, for continued monitoring of impact in this large double-blinded trial.

Specimen collection. During the active surveillance period, study participants with suspect pneumonia were identified by the attending physician. Study personnel obtained three throat swabs, blood cultures (aerobic and anaerobic), sputum sample (if producible), and acute serum samples from participants. Attempts were made to also capture a convalescent serum sample 2 weeks after the acute presentation on all radiographically-confirmed pneumonia cases. These attempts were not always successful. Barriers included: trainee discharge from military service, difficulty in obtaining access to the recruits when they were in field exercises, and recruits graduating and moving to new duty stations.

Laboratory methods. Specimens collected from study participants were examined using classic, molecular, and serologic laboratory methods at the Naval Health Research Center (NHRC) Respiratory Disease Laboratory, a College of American Pathologist (CAP) accredited laboratory.