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. Clinical Trials 2011; 8: 699-704. http://ctj.sagepub.com