Overcoming the challenges to developing new antibiotics.

Area of Science:

• Infectious Diseases
• Clinical Trial Design
• Pharmacometrics

Background:

• Addressing the urgent medical need for treatments against highly resistant pathogens.
• Recognizing the limitations of current approaches in evaluating new antimicrobial therapies.

Purpose of the Study:

• To propose novel superiority trial designs for evaluating treatments against resistant pathogens.
• To outline strategies for incorporating historical or active controls in these trials.

Main Methods:

• Discussing the potential use of statistically powered or unpowered superiority trials.
• Proposing two methods for historically controlled trials: pharmacometrics and concurrent observational studies.
• Detailing two approaches for active controlled trials: standard of care plus test versus standard of care, or standard of care versus test article.

Main Results:

• The proposed designs offer flexibility in control group selection and response rate definition.
• Specific methodologies are presented for both historically and actively controlled superiority trials.
• Emphasis is placed on the need for extensive preclinical justification for all proposed designs.

Conclusions:

• Superiority trial designs present a viable strategy to address the challenges posed by drug-resistant infections.
• The proposed methodologies provide a framework for robust clinical evaluation of novel therapeutics.
• Further research and validation of these designs are warranted to advance antimicrobial drug development.