Overcoming the challenges to developing new antibiotics.

In order to meet the challenges of our current medical need to address infections caused by highly resistant pathogens, we propose the use of superiority trial designs. The proposed trials may or may not be statistically powered. All require extensive preclinical justification. The designs could use either historical or active controls. For historically controlled trials we propose two approaches for defining the control response rate to therapy; (1) the use of pharmacometrics from modern trials and (2) the use of a concurrent observational study. Designs for active controlled trials could be (1) standard of care+test vs. standard of care alone or (2) standard of care vs. test article. The second approach requires extensive justification to show that the test article will be of sufficient efficacy to allow ethical use as a single agent.