Designing Development Programs for Non-Traditional Antibacterial Agents

Holly Fernandez Lynch, JD, MBe, is an author on this research publicated in Nature Communications:

"First, and most fundamental, is the question of whether it is ethically acceptable to carry out non-inferiority trials when developing new antimicrobial agents. Outside a trial, those who might be asked to enroll would be treated with a reliable drug, i.e., an existing effective agent (assuming their infection is not resistant to all available therapies). Within the trial, they would be randomized either to the novel intervention or the reliable standard-of-care drug. However, in a non-inferiority trial, that novel intervention is not hypothesized to leave the participant better off than he or she would have been outside the trial, given that superiority is not expected. Instead, the only hypotheses are that participants randomized to the intervention arm of the trial could do as well as they would have done outside the study (best case) or potentially worse. Equipoise may still be satisfied in this scenario, as the expectation is that the novel intervention will be an acceptable clinical substitute for the established older drug such that no participant is made knowingly worse off as a result of randomization39. Nonetheless, except for those individual participants who turn out to be infected with a resistant pathogen, enrollment entails an entirely risk-based proposition compared to accepting standard care outside the study."