The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement.
OBJECTIVE
To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE).


METHODS
Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic.


RESULTS
The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%.


CONCLUSIONS
PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.
Ruperto
Nicolino
N
Pediatric Rheumatology International Trials Organization, IRCCS G. Gaslini, Università di Genova Pediatria II-Reumatologia, 5 Largo Gaslini, 16147 Genoa, Italy. nicolaruperto@ospedale-gaslini.ge.it
Ravelli
Angelo
A
Oliveira
Sheila
S
Alessio
Maria
M
Mihaylova
Dimitrina
D
Pasic
Srdjan
S
Cortis
Elisabetta
E
Apaz
Maria
M
Burgos-Vargas
Ruben
R
Kanakoudi-Tsakalidou
Florence
F
Norambuena
Ximena
X
Corona
Fabrizia
F
Gerloni
Valeria
V
Hagelberg
Stefan
S
Aggarwal
Amita
A
Dolezalova
Pavla
P
Saad
Claudia Magalhaes
CM
Bae
Sang-Cheol
SC
Vesely
Richard
R
Avcin
Tadej
T
Foster
Helen
H
Duarte
Carolina
C
Herlin
Troels
T
Horneff
Gerd
G
Lepore
Loredana
L
van Rossum
Marion
M
Trail
Lucia
L
Pistorio
Angela
A
Andersson-Gäre
Boel
B
Giannini
Edward H
EH
Martini
Alberto
A
D002648:Child; D032921:Consensus; D023381:Endpoint Determination / Q000379:methods* / Q000592:standards; D005260:Female; D006304:Health Status; D006801:Humans; D007391:International Cooperation; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D017063:Outcome Assessment, Health Care; D010372:Pediatrics / Q000379:methods*; D015203:Reproducibility of Results; D012219:Rheumatology / Q000379:methods*; D012720:Severity of Illness Index; D012955:Societies, Medical; D016896:Treatment Outcome