2146 The Journal of Rheumatology 2006; 33:11
Personal non-commercial use only. The Journal of Rheumatology Copyright © 2006. All rights reserved.
An Index of Patient Reported Outcomes (PRO-Index)
Discriminates Effectively Between Active and Control
Treatment in 4 Clinical Trials of Adalimumab in
Rheumatoid Arthritis
THEODORE PINCUS, CECILIA CHUNG, OSCAR G. SEGURADO, INGRID AMARA, and GARY G. KOCH
ABSTRACT. Objective. To analyze 2 indices composed of the 3 patient reported outcomes (PRO) in the American
College of Rheumatology (ACR) Core Data Set — physical function, pain, and global estimate — with-
out joint count or laboratory data, for capacities to distinguish active from control treatments in 4
pivotal clinical trials.
Methods. Data from 4 clinical trials involving adalimumab, in combination with methotrexate or other
disease-modifying antirheumatic drugs (DMARD) or as monotherapy, versus control treatment were
made available to analyze properties of various indices. A categorical PRO-Index M was defined as
“majority” improvement in 2 of the 3 PRO measures at 20%, 50%, and 70% levels; results were eval-
uated to analyze agreement with ACR20, ACR50, ACR70 responses and an “all Core Data Set meas-
ures” index based on 4 of the 7 measures having such levels of improvement. A continuous PRO-Index
C was defined as the median or 2nd highest of 3 percentage differences from baseline to endpoint;
results were evaluated to analyze agreement with a continuous ACR-N, “all Core Data Set measures”
index, and Disease Activity Score 28 (DAS28).
Results. All indices distinguished active versus control treatment at similar levels, including PRO-Index
M versus ACR20, ACR50, and ACR70 responses, and PRO-Index C versus DAS28.
Conclusion. PRO indices based only on patient questionnaire data, without joint counts or laboratory
tests, may be useful quantitative measures of therapeutic efficacy for use in standard rheumatology clin-
ical care. (First Release Oct 15 2006; J Rheumatol 2006;33:2146–52)
Key Indexing Terms:
QUESTIONNAIRES RHEUMATOID ARTHRITIS RANDOMIZED CONTROLLED TRIAL
ADALIMUMAB PATIENT INDEX
From the Vanderbilt University Medical Center,Nashville, TN; Abbott
Laboratories, Abbott Park, IL; Quintiles, Inc., Durham, NC; and the
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
T. Pincus, MD, Professor of Medicine; C. Chung, MD, PhD, Vanderbilt
University Medical Center; O.G. Segurado, MD, PhD, Abbott
Laboratories; I. Amara, DrPH, Quintiles, Inc.; G.G. Koch, PhD,
University of North Carolina at Chapel Hill.
Address reprint requests to Dr. T. Pincus, Division of Rheumatology and
Immunology, Vanderbilt University School of Medicine, 203 Oxford
House, Box 5, Nashville, TN 37232-4500. E-mail:t.pincus@vanderbilt.edu
Accepted for publication June 6, 2006.
The American College of Rheumatology (ACR) Core Data
Set
1-3
and Disease Activity Score 28 (DAS28)
4,5
are major
advances to standardize measurement in rheumatoid arthritis
(RA) clinical trials and other clinical research. Criteria based
on 20%, 50%, and 70% improvement in ACR Core Data Set
measures (ACR20, 50, 70) have been developed for clinical
trials
6
. The ACR response criteria represent change scores
from baseline to endpoint, and cannot be used as an absolute
clinical measure. DAS scores have an absolute value rather
than being based on change, and are useful in both clinical tri-
als and standard clinical care.
These indices are advances used primarily to assess RA in
clinical trials and clinical research. Most standard rheumatol-
ogy clinical care, however, is conducted according to empiri-
cal qualitative impressions rather than quantitative clinical
measurement. Formal quantitative joint counts, although
regarded by rheumatologists as the most important means to
assess RA
5
, and needed to calculate ACR criteria or a DAS,
generally are not performed at most visits of patients with RA
to most rheumatologists
6
. The only quantitative measure
recorded at most visits is a laboratory test such as erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP), which
may be normal in 40% of patients
7
. Therefore, ACR criteria or
a DAS generally are not available in standard rheumatology
care, despite an excellent website (www.das-score.nl) and cal-
culators that simplify computation of the DAS.
A pragmatic quantitative measure that does not require
joint counts or laboratory tests, for which the patient does
almost all the work, might be of value to rheumatologists and
their patients in standard clinical care. Three of the 7 compo-
nents of the ACR Core Data Set, physical function, pain, and
global estimate, are patient reported outcome (PRO) meas-
ures. A quantitative index of only these 3 patient self-report
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