Proposal for levels of evidence schema for validation of a soluble biomarker reflecting damage endpoints in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, and recommendations for study design.
OBJECTIVE
At OMERACT 8 a framework for levels of evidence was proposed for the validation of biomarkers as surrogate outcome measures. We aimed to adapt this scheme in order to apply it in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We also aimed to generate consensus on minimum standards for the design of longitudinal studies aimed at validating biomarkers.


METHODS
Before the meeting, the Soluble Biomarker Working Group prepared a preliminary framework and discussed various models for association and prediction related to the statistical strength domain. In addition, 3 Delphi exercises addressing longitudinal study design for RA, PsA, and AS were conducted within the working group and members of the Assessments in SpondyloArthritis International Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). This formed the basis for discussions among OMERACT 9 participants.


RESULTS
The proposed framework was accepted by consensus. In the study design domain a requirement for both prospective observational studies and randomized controlled trials (RCT) in different drug classes was noted. A template for determining the level of statistical strength was proposed. The addition of a new domain on biomarker assay performance was considered essential, and participants suggested that for any biomarker this domain should be addressed first, i.e., before starting clinical validation studies. Participants agreed on most elements of a longitudinal study design template. Where consensus was lacking the working group has drafted solutions that constitute a basis for prospective validation studies.


CONCLUSIONS
The OMERACT 9 Soluble Biomarker Group has successfully formulated a levels of evidence scheme and a study design template that will provide guidance to conduct validation studies in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in RA, PsA, and AS.
Maksymowych
Walter P
WP
Heritage Medical Research Building, University of Alberta, Edmonton, Alberta, Canada. walter.maksymowych@ualberta.ca
Fitzgerald
Oliver
O
Wells
George A
GA
Gladman
Dafna D
DD
Landewé
Robert
R
Ostergaard
Mikkel
M
Taylor
William J
WJ
Christensen
Robin
R
Tak
Paul-Peter
PP
Boers
Maarten
M
Syversen
Silje W
SW
Bathon
Joan M
JM
Ritchlin
Christopher J
CJ
Mease
Philip J
PJ
Bykerk
Vivien P
VP
Garnero
Patrick
P
Geusens
Piet
P
El-Gabalawy
Hani
H
Aletaha
Daniel
D
Inman
Robert D
RD
Kraus
Virginia Byers
VB
Kvien
Tore K
TK
van der Heijde
Désirée
D
D001168:Arthritis / Q000097:blood* / Q000473:pathology*; D015535:Arthritis, Psoriatic / Q000097:blood / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D019317:Evidence-Based Medicine / Q000592:standards*; D006801:Humans; D007596:Joints / Q000473:pathology*; D008137:Longitudinal Studies; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000473:pathology
D015415:Biomarkers