OMERACT 9 Levels of Evidence framework for validation of a soluble biomarker reflecting damage endpoints in rheumatoid arthritis, psoriatic arthritis, and ankylosing arthritis (adapted from the generic biomarker framework at OMERACT 81).
| Domain Components |
|---|
| 1. Target outcome |
| 0 Disease-centered, reversible |
| 1 Disease-centered, irreversible |
| 2 Patient-centered, reversible |
| 3 Patient-centered, irreversible, minor organ/clinical morbidity (radiography) |
| 2. Study design |
| 1 Prospective, non-population, observational |
| 2 Prospective, population observational or 1 RCT |
| 3 ≥ 2 RCT and/or ≥ 2 prospective observational studies, same drug class (total of any 2) |
| 4 ≥ 2 RCT and/or ≥ 2 prospective observational studies, each of different drug class (total of any 2) |
| 5 ≥ 3 studies, ≥ 1 RCT and ≥ 1 prospective observational study (at least one of each study design), different drug class studies |
| 3. Penalties* |
| –1 No evidence in ≥ 1 powered RCT |
| –1 Opposite assertion in epidemiological study |
| –1 No evidence in ≥ 1 epidemiological powered study |
| –1 ≥ 1 RCT demonstrating clinical heterogeneity |
| –2 ≥ 1 RCT supports opposite assertion |
| –3 ≥ 1 RCT use of marker confers patient harm |
| 4. Performance criteria† |
| Reproducibility |
| Feasibility (readily accessible, availability of international standards, reasonable costs) |
| Confounders (assay related, non-assay related) |
| Stability |
↵* Penalties are not additive. The highest penalty ranking is applied. Studies should meet minimum standards for longitudinal study design.
↵† 1. Performance criterion domain meets criteria 1, 2, 4, and 5 of OMERACT 9 v2 criteria. 2. Performance criteria should be met in their entirety before clinical validation studies. RCT: randomized controlled trial.