Cardiovascular medicine has the largest and hardest outcome literature in this field: mortality, myocardial infarction, stroke. That makes it the topic where the hard-outcome route to Grade A is most often available, and it also makes the gap between a hard endpoint An outcome that matters directly to a person and is counted without judgment, such as death, heart attack, stroke or fracture. and a moved biomarker A measurable sign in the body, such as a blood test value, used to track a condition or the effect of a treatment. unusually visible. Grade A is reachable elsewhere too, by the other two routes: an objectively measured function, or a validated scale scored by a clinician blinded to treatment.
Two features of the grading system matter on a page like this. A grade attaches to a use, not to a molecule, so the same compound can carry different letters for different questions. And a grade is capped by the kind of outcome the trials measured: a surrogate marker A lab value or measurement used in place of the outcome that matters, such as LDL cholesterol standing in for heart attacks. Moving a surrogate does not always move the outcome. or a self-reported score cannot reach Grade A under the EBL rubric no matter how well the trial was run.
Every letter below links to its own page, where the trials, the PMIDs PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. and the reasons for the ceiling are set out in full.