Article Figures & Data
Tables
- Table 1.
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.
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↵† 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.
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- Table 2.
Summary results of 3-stage Delphi consensus exercise addressing minimum standards for longitudinal study design for validation of biomarker reflecting damage endpoints in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Items lacking consensus are indicated in bold type (percentage of respondents voting in support of the item is indicated in parentheses).
RA PsA AS Inclusion Criteria ACR (48%)17, EULAR early referral criteria (26%)18, ANTI-CCP arthritis (25%) CASPAR19 Modified New York (67%)20 Pre-radiographic axial (24%)21 Treatment strategy All treatments (68%) All treatments All treatments Selection of patient cohort Consecutive cases Consecutive cases (67%) Consecutive cases Inception cohort (33%) Study duration 2 yrs 4 yrs (69%) 4 yrs 2 yrs (27%) Frequency of assessment Every 3 mo Every 6 mo Every 6 mo Analysis of radiographic endpoint Blinded to timepoint Blinded to timepoint Blinded to timepoint Allow steroid Yes Not considered Not considered Rules for changes in treatment By predetermined DAS every 3 mo Not considered Not considered Frequency of biomarker collection Q6 mo and prior to new DMARD/anti-TNF Q6 mo and prior to new DMARD/anti-TNF Q6 mo and prior to new DMARD/anti-TNF Symptoms Pain, patient global, fatigue (50%), stiffness (51%) Pain, skin global, patient global, stiffness (61%), fatigue (40%) Pain, stiffness, patient global, fatigue (38%) Physical function Patient self-reported function, objective measures of function (47%) Patient self-reported function Patient self-reported function, metrology Psychosocial function Quality of life Quality of life Quality of life Other Work status, work productivity (53%), participation (42%) Work status, work productivity (33%), participation (40%) Work status Disease activity Joint inflammation, global disease activity (patient/physician), general labs (ESR, CRP), imaging/MRI (62%), imaging/US (31%) Joint inflammation, global disease activity, (patient/physician), clinical enthesitis, dactylitis, spinal, skin, general labs (ESR, CRP), nail (56%), extraarticular disease (67%) Joint inflammation, global disease activity (patient/physician), clinical enthesitis, metrology, general labs (ESR, CRP), extraarticular disease, imaging/MRI Radiographic damage endpoint Modified Sharp Modified Sharp mSASSS -
ACR: American College of Rheumatology; EULAR: European League Against Rheumatism; CCP: cyclic citrullinated peptide; CASPAR: CASPAR Study Group Criteria; DAS: Disease Activity Score; DMARD: disease modifying antirheumatic drugs; TNF: tumor necrosis factor; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; MRI: magnetic resonance imaging; mSASSS: modified Stoke AS Spinal Score; US: ultrasonography.
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- Table 3.
OMERACT 9 Soluble Biomarker Working Group minimum standards for the handling and processing of biomarker samples.
Recommendation Comment Type of sample Serum, urine Standardized sample collection (e.g., tubes) Fasting sample Time of collection 2–4 hours after rising Diurnal variation is common with musculoskeletal biomarkers22 Time of sample processing Within 2 hours of collection Standardized centrifugation procedure. Keep sample at 4°C prior to centrifugation23 Storage of samples Sample storage in 300–400 μl aliquots in −70°C freezer Avoid use of sample after 3 freeze/thaw cycles Sample transport Express delivery on dry ice Use ample dry ice
