Data from phase 3 trials can provide key input into the determination of “breakpoints” for new antibiotics – the concentration of antibiotic associated with treatment success for a particular strain of pathogen.
Breakpoints can be used to predict whether isolates are likely to be susceptible, resistant or intermediate to a new antibiotic. They are therefore critical tools in clinical practice, providing an indication of whether an antibiotic is likely to be suitable for particular infections.
Breakpoints can be estimated at earlier stages of clinical development, but phase 3 trials generate much more data on pathogens and clinical responses to inform breakpoint analyses.
Typically, breakpoint development is an iterative process, integrating data from microbiological analyses on the infectious organism and responses to treatment and pharmacokinetic data, which provides a measure of antibiotic concentration in critical body compartments.
Instructions for developing breakpoints can be found in the Clinical Laboratory Standards Institute (CLSI) document M23 and in the microbiologic investigations section of the EMA guidance for studying bacterial infections.