What ESMO grades D and E actually say
ESMO’s D and E grades mean evidence against efficacy or evidence of an adverse outcome. They do not mean merely that evidence is missing; that situation belongs to grade C.
Written retrospectively and published on August 3, 2026.
Background reading, not clinical guidance. This describes published research; it is not a recommendation for any individual case, and the cited studies may have been superseded.
ESMO Clinical Practice Guidelines attach a letter grade, A through E, to the strength of a recommendation and a separate Roman-numeral level, I through V, to the underlying evidence. The two labels answer different questions and should be read together.
Grade A means strong evidence for efficacy with substantial clinical benefit. Grade B describes efficacy with more limited benefit. Grade C is the middle category: evidence may be insufficient, or the likely benefit may not outweigh harms, costs or other disadvantages.
D and E are active negative findings
Grade D is moderate evidence against efficacy or for an adverse outcome, so the intervention is generally not recommended. Grade E is strong evidence against efficacy or for an adverse outcome, so it is never recommended. Demonstrated harm can therefore matter even if some efficacy signal exists.
“Moderate” and “strong” here describe the strength of the negative evidence, not a percentage probability that a treatment does not work. The ESMO Magnitude of Clinical Benefit Scale is separate again: it asks how much benefit a positive study provides, not whether to recommend an intervention.
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