Table 1.

Summary of definitions of LOE [98]

LOE	Type of study	Validation
I-A	RCT specifically to assess the utility of the biomarker. The samples are collected and analysed in real-time	Not necessary but could be useful
I-B	RCT not specifically to assess the utility of the biomarker. The samples are stored during the study and analysed after the study is finished, following a protocol	One or more studies with consistent results
II-B	RCT not specifically to assess the utility of the biomarker. The samples are stored during the study and analysed after the study is finished, following a protocol	Only one study, or several studies with inconsistent results
II-C	Non-randomized retrospective study aimed to assess the utility of the biomarker using samples from patients in an observational setting (standard treatment and follow-up)	Two or more studies with consistent results
III-C	Non-randomized retrospective study aimed to assess the utility of the biomarker using samples from patients in an observational setting (standard treatment and follow-up)	Only one study, or several studies with inconsistent results
IV–V-D	No aspect of the study is prospective	Not necessary because these types of studies do not enable the clinical utility of the biomarker to be assessed