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.