Table 3.

Performance of serum urate as a surrogate for gout flares according to the BSES 3 framework (S is the surrogate and T is the target outcome) [19].

		BIOMARKER-SURROGATE EVALUATION SCHEMA (BSES) 3	SU score
Biomarker-surrogate domains	Score
Study design	0	Biological plausibility & lower quality clinical studies e.g. cross-sectional observational studies
	1	Rank 0 and at least 2 good quality prospective observational cohort studies measuring S and T
	2	Rank 1 and at least 2 high quality adequately powered RCTs measuring S and T
	3	Rank 1 and all, and at least 5 high quality adequately powered, RCTs measuring S and T	X
Target outcome	0	Target is reversible disease-centered biomarker of harm
	1	Target is irreversible disease-centered biomarker of harm
	2	Target is patient-centered endpoint of reversible organ morbidity or clinical burden of disease or clinical harm	X
	3	Target is patient-centered endpoint of irreversible organ morbidity or clinical burden of disease or severe irreversible clinical harm or death
Statistical Evaluation of biosurrogate — Target (B-T) domai	0	Poor: Does not meet the criteria for Rank 1	X
	1	Fair: RCT R2trial≥0.2 AND STEP* ≥ 0.1 AND R2ind ≥ 0.2 OR cohort data R2ind ≥ 0.4
	2	Good: RCT R2trial ≥ 0.4 AND STEP ≥ 0.2 AND R2ind ≥ 0.4
	3	Excellent: RCT R2trial ≥ 0.6 AND STEP ≥ 0.3 AND R2ind ≥ 0.6 (without data subdivision)**
Generalizability	0	No clinical or pharmacologic evidence
	1	Clinical OR pharmacologic evidence
	2	Clinical AND pharmacologic evidence
	3	Consistent Clinical RCT AND pharmacologic RCT evidence	X
TOTAL

Score: Level A 12, Level B+, B, B− 11-9, Level C+, C, C−, D+, D, D− 8-6, Level D+, D, D−, E+, E, E− 5-3, Level E+, E, E−, F+, F, F-2-0