Strategies for successful rapid trials of influenza vaccine.

BACKGROUND: In contrast to the gradual pace of conventional vaccine trials, evaluation of influenza vaccines often must be accelerated for use in a pandemic or for annual re-licensure. Descriptions of how best to design studies for rapid completion are few. PURPOSE: In August, 2010, we conducted a rapid trial with a seasonal influenza vaccine for 2010-2011 given to persons vaccinated with an adjuvanted H1N1 vaccine in 2009, to determine whether re-exposure to the H1N1(2009) component of the seasonal vaccine would cause increased reactions. We describe the strategies that we believe were responsible for success in meeting the desired timeline. METHODS: The key means for expediting the study were: use of a few experienced, well-staffed centers; efficient completion of administrative approvals; advance recruitment of volunteers; synchronized start among centers with rapid completion (≤1 week) of first visits; rapid data assembly via the Internet; and a well-prepared data analysis plan. We chose to use a randomized, blinded, cross-over design to allow estimation of vaccine-attributable adverse event rates, with sufficient power (320 participants) to detect events occurring at true rates ≥1% with ≥90% probability. RESULTS: Planned enrollment numbers, center synchronization, and timelines, including review by a safety board prior to the cross-over step (second doses), were achieved. A detailed safety report was delivered to federal health officials just 32 days after study initiation and was used to fine-tune public messaging prior to the mass vaccination programs across Canada. LIMITATIONS: This aggressive timeline could not have been met without opportunities for careful planning and the prior existence of a network of experienced, collaborating trial centers. CONCLUSIONS: The means used to accelerate this study timeline were successful and could be used in other urgent situations but the mechanics of collaborative trials must be well rehearsed as a precondition.

Measuring hepatitis B uptake in a new universal infant program.

BACKGROUND: Vancouver-Richmond Health Board has the highest reported rate of hepatitis B in Canada, including an annual average of 25 cases in children under 12 years of age, based on reports from 1994-1997 inclusive. The current provincial adolescent grade-six hepatitis B immunization program does not protect against childhood infection. The regional health board implemented universal infant hepatitis B immunization in September 1998. METHOD: Immunization coverage data were obtained on a random sample of 191 infants born in March 1999 one year after initiation of the program. RESULTS: By eight months of age, 97.9% of children had received some vaccinations. 73.8% of infants had received three doses of hepatitis B vaccine and 12.6% had received two doses. In comparison, 89% had received three doses and 7.9% two doses of DPTP-Hib vaccine. 13.1% of infants had not received any hepatitis B vaccine. For a majority (67%) of these children, their physician's lack of awareness or lack of acceptance of the program constituted the reason for no hepatitis B vaccine uptake. Only one parent cited adverse publicity as the reason for refusing vaccination. INTERPRETATION: This survey reveals a successful first year of the program without harm to the pre-existing childhood vaccination programs. Hepatitis B vaccine uptake can be improved by increased awareness among physicians and parents.