Table 4.

Determination of LOE Using Elements of Tumor Marker Studies

LOE	LOE Category	Study Design	Validation Studies Available
I	A	Prospective	None required
	B	Prospective using archive samples	≥1 with consistent results
II	B	Prospective using archive samples	None or inconsistent results
	C	Prospective/observational	≥2 with consistent results
III	C	Prospective/observational	None or 1 with consistent results or inconsistent results
IV–V	D	Prospective/observational	Not applicablea

^aNot applicable because LOE IV and V studies will never be satisfactory for the determination of medical utility. LOE, level of evidence.

Reproduced from Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst. 2009;101:1446–1452, by permission of Oxford University Press.²⁰