Why study design matters: evaluating bias and generalizability in contrast-enhanced mammography research

We read with great interest the study by Pediconi et al, which evaluated the diagnostic performance of contrastenhanced mammography (CEM) using a highconcentration iodinated contrast medium (HCCM) [1].The study aimed to determine whether a reduced iodine volume-achieved through higher contrast concentration and lower injection volume-could provide a more sustainable alternative to conventional CEM protocols employing lower-concentration contrast media.The authors concluded that reducing the volume of iodinated contrast agent allows for a more sustainable approach to CEM without compromising diagnostic performance.This research question is of considerable importance, as reducing iodine load may benefit both patient safety and ecological impact.However, we believe that the study design imposes important limitations that affect the generalizability of the findings and preclude the definitive conclusions drawn by the authors regarding the applicability of an HCCM protocol.In medical practice, diagnostic testing plays a vital role, and physicians rely on it to refine their clinical assessment.This reliance assumes that the tests yield dependable information about a patient's health status.However,