Design of clinical trials of antibacterial agents for community-acquired bacterial pneumonia.

Standards for the conduct of clinical trials of antibacterial agents for community-acquired bacterial pneumonia (CABP) have changed dramatically in recent years. A draft guidance from the US FDA on the conduct of such trials was issued in March 2009. However, the guidance has already faced substantial criticism during the open public comment period, resulting in uncertainty regarding the appropriate design of such studies from a regulatory perspective. Controversies regarding the magnitude of the treatment effect associated with antibacterial therapy versus placebo/no therapy, the appropriate timing, nature and noninferiority margin for the primary efficacy end point, and other clinical and statistical issues have complicated efforts to reach consensus on appropriate trial design of antibacterial therapy for CABP. It is critical that studies of new drugs for CABP are designed to ensure that they are feasible to conduct and that their results are scientifically valid, statistically rigorous and clinically meaningful. Based on 3 years of active dialog between clinical, statistical, and regulatory experts, this article proposes an approach to enable a balance of clinical trial feasibility with appropriate scientific, statistical and clinical rigor.