Issues of Noninferiority: The Significance Fallacy.

This letter addresses a study on the use of reduced-dose trimethoprim-sulfamethoxazole (TMP-SMX) for treating mild to moderate Pneumocystis jirovecii pneumonia (PJP) in patients with hematologic malignancies. The authors argue that the original study's conclusion of noninferiority for reduced-dose TMP-SMX was based on statistically nonsignificant results, which should be interpreted as inconclusive rather than proof of equivalence. They emphasize the need for properly designed noninferiority trials with appropriate sample size calculations to confirm effectiveness. The letter acknowledges that the observational study provides partial support for the potential efficacy of reduced-dose TMP-SMX but calls for randomized controlled trials to establish definitive evidence.