OARSI-OMERACT initiative: Defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials

Rebecca Manno, Clifton Bingham, S. Paternotte, L. Gossec, H. Halhol, G. Giacovelli, L. Rovati, S. A. Mazzuca, D. O. Clegg, H. Shi, E. Tajana Messi, A. Lanzarotti, M. Dougados

Research output: Contribution to journalArticle

Abstract

Objective: Total joint replacement has been proposed as an endpoint in disease modifying osteoarthritis drug (DMOAD) randomized clinical trials (RCTs); however, disparities have generated concerns regarding this outcome. A combined Osteoarthritis Research Society International (OARSI)/Outcome Measures in Rheumatology (OMERACT) initiative was launched in 2004 to develop a composite index ['virtual total joint replacement' (VJR)] as a surrogate outcome for osteoarthritis (OA) progression in DMOAD RCTs. Our objective was to evaluate the prevalence of patients fulfilling different thresholds of sustained pain, reduced function, and X-ray change in existing DMOAD RCTs. Design: Post hoc analysis of summary data from the. placebo arm of eight DMOAD RCTs. Results: Eight OA RCTs representing 1379 patients were included. Pain was assessed by WOMAC and/or VAS and function by WOMAC and/or Lequesne. Among six knee and two hip studies, 248 (22%) and 132 (51%) patients respectively had X-ray progression [decrease joint space width (JSW) ≥0.5mm]. The prevalence of patients fulfilling clinical and radiographic criteria was highest (n=163, 12%) in the least stringent scenario (pain+function ≥80 at ≥2 visits); with few patients (n=129, 2%) in the most stringent scenario (pain+function ≥80 at ≥4 visits). Using these prevalence data, a sample size of 352-2144 per group would be needed to demonstrate a 50% difference between groups. Conclusions: The prevalence of patients with sustained symptomatic OA of at least a moderate degree with X-ray progression is low. Even using lenient criteria to define VJR, large patient numbers would be required to detect differences between groups in DMOAD RCTs. Investigation of the optimal cutoff threshold and combination of symptoms and radiographic change should be pursued.

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalOsteoarthritis and Cartilage
Volume20
Issue number2
DOIs
StatePublished - Feb 2012

Fingerprint

Osteoarthritis
Clinical Trials
Replacement Arthroplasties
Randomized Controlled Trials
Research
Pharmaceutical Preparations
X rays
X-Rays
Pain
Pain Threshold
Rheumatology
Sample Size
Disease Progression
Composite materials
Hip
Knee
Arm
Joints
Placebos
Outcome Assessment (Health Care)

Keywords

  • Osteoarthritis
  • Outcomes
  • Randomized clinical trials

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

OARSI-OMERACT initiative : Defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials. / Manno, Rebecca; Bingham, Clifton; Paternotte, S.; Gossec, L.; Halhol, H.; Giacovelli, G.; Rovati, L.; Mazzuca, S. A.; Clegg, D. O.; Shi, H.; Tajana Messi, E.; Lanzarotti, A.; Dougados, M.

In: Osteoarthritis and Cartilage, Vol. 20, No. 2, 02.2012, p. 93-101.

Research output: Contribution to journalArticle

Manno, R, Bingham, C, Paternotte, S, Gossec, L, Halhol, H, Giacovelli, G, Rovati, L, Mazzuca, SA, Clegg, DO, Shi, H, Tajana Messi, E, Lanzarotti, A & Dougados, M 2012, 'OARSI-OMERACT initiative: Defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials', Osteoarthritis and Cartilage, vol. 20, no. 2, pp. 93-101. https://doi.org/10.1016/j.joca.2011.11.013
Manno, Rebecca ; Bingham, Clifton ; Paternotte, S. ; Gossec, L. ; Halhol, H. ; Giacovelli, G. ; Rovati, L. ; Mazzuca, S. A. ; Clegg, D. O. ; Shi, H. ; Tajana Messi, E. ; Lanzarotti, A. ; Dougados, M. / OARSI-OMERACT initiative : Defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials. In: Osteoarthritis and Cartilage. 2012 ; Vol. 20, No. 2. pp. 93-101.
@article{f74893c25b3e4b3f882caa733975c8bb,
title = "OARSI-OMERACT initiative: Defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials",
abstract = "Objective: Total joint replacement has been proposed as an endpoint in disease modifying osteoarthritis drug (DMOAD) randomized clinical trials (RCTs); however, disparities have generated concerns regarding this outcome. A combined Osteoarthritis Research Society International (OARSI)/Outcome Measures in Rheumatology (OMERACT) initiative was launched in 2004 to develop a composite index ['virtual total joint replacement' (VJR)] as a surrogate outcome for osteoarthritis (OA) progression in DMOAD RCTs. Our objective was to evaluate the prevalence of patients fulfilling different thresholds of sustained pain, reduced function, and X-ray change in existing DMOAD RCTs. Design: Post hoc analysis of summary data from the. placebo arm of eight DMOAD RCTs. Results: Eight OA RCTs representing 1379 patients were included. Pain was assessed by WOMAC and/or VAS and function by WOMAC and/or Lequesne. Among six knee and two hip studies, 248 (22{\%}) and 132 (51{\%}) patients respectively had X-ray progression [decrease joint space width (JSW) ≥0.5mm]. The prevalence of patients fulfilling clinical and radiographic criteria was highest (n=163, 12{\%}) in the least stringent scenario (pain+function ≥80 at ≥2 visits); with few patients (n=129, 2{\%}) in the most stringent scenario (pain+function ≥80 at ≥4 visits). Using these prevalence data, a sample size of 352-2144 per group would be needed to demonstrate a 50{\%} difference between groups. Conclusions: The prevalence of patients with sustained symptomatic OA of at least a moderate degree with X-ray progression is low. Even using lenient criteria to define VJR, large patient numbers would be required to detect differences between groups in DMOAD RCTs. Investigation of the optimal cutoff threshold and combination of symptoms and radiographic change should be pursued.",
keywords = "Osteoarthritis, Outcomes, Randomized clinical trials",
author = "Rebecca Manno and Clifton Bingham and S. Paternotte and L. Gossec and H. Halhol and G. Giacovelli and L. Rovati and Mazzuca, {S. A.} and Clegg, {D. O.} and H. Shi and {Tajana Messi}, E. and A. Lanzarotti and M. Dougados",
year = "2012",
month = "2",
doi = "10.1016/j.joca.2011.11.013",
language = "English (US)",
volume = "20",
pages = "93--101",
journal = "Osteoarthritis and Cartilage",
issn = "1063-4584",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - OARSI-OMERACT initiative

T2 - Defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials

AU - Manno, Rebecca

AU - Bingham, Clifton

AU - Paternotte, S.

AU - Gossec, L.

AU - Halhol, H.

AU - Giacovelli, G.

AU - Rovati, L.

AU - Mazzuca, S. A.

AU - Clegg, D. O.

AU - Shi, H.

AU - Tajana Messi, E.

AU - Lanzarotti, A.

AU - Dougados, M.

PY - 2012/2

Y1 - 2012/2

N2 - Objective: Total joint replacement has been proposed as an endpoint in disease modifying osteoarthritis drug (DMOAD) randomized clinical trials (RCTs); however, disparities have generated concerns regarding this outcome. A combined Osteoarthritis Research Society International (OARSI)/Outcome Measures in Rheumatology (OMERACT) initiative was launched in 2004 to develop a composite index ['virtual total joint replacement' (VJR)] as a surrogate outcome for osteoarthritis (OA) progression in DMOAD RCTs. Our objective was to evaluate the prevalence of patients fulfilling different thresholds of sustained pain, reduced function, and X-ray change in existing DMOAD RCTs. Design: Post hoc analysis of summary data from the. placebo arm of eight DMOAD RCTs. Results: Eight OA RCTs representing 1379 patients were included. Pain was assessed by WOMAC and/or VAS and function by WOMAC and/or Lequesne. Among six knee and two hip studies, 248 (22%) and 132 (51%) patients respectively had X-ray progression [decrease joint space width (JSW) ≥0.5mm]. The prevalence of patients fulfilling clinical and radiographic criteria was highest (n=163, 12%) in the least stringent scenario (pain+function ≥80 at ≥2 visits); with few patients (n=129, 2%) in the most stringent scenario (pain+function ≥80 at ≥4 visits). Using these prevalence data, a sample size of 352-2144 per group would be needed to demonstrate a 50% difference between groups. Conclusions: The prevalence of patients with sustained symptomatic OA of at least a moderate degree with X-ray progression is low. Even using lenient criteria to define VJR, large patient numbers would be required to detect differences between groups in DMOAD RCTs. Investigation of the optimal cutoff threshold and combination of symptoms and radiographic change should be pursued.

AB - Objective: Total joint replacement has been proposed as an endpoint in disease modifying osteoarthritis drug (DMOAD) randomized clinical trials (RCTs); however, disparities have generated concerns regarding this outcome. A combined Osteoarthritis Research Society International (OARSI)/Outcome Measures in Rheumatology (OMERACT) initiative was launched in 2004 to develop a composite index ['virtual total joint replacement' (VJR)] as a surrogate outcome for osteoarthritis (OA) progression in DMOAD RCTs. Our objective was to evaluate the prevalence of patients fulfilling different thresholds of sustained pain, reduced function, and X-ray change in existing DMOAD RCTs. Design: Post hoc analysis of summary data from the. placebo arm of eight DMOAD RCTs. Results: Eight OA RCTs representing 1379 patients were included. Pain was assessed by WOMAC and/or VAS and function by WOMAC and/or Lequesne. Among six knee and two hip studies, 248 (22%) and 132 (51%) patients respectively had X-ray progression [decrease joint space width (JSW) ≥0.5mm]. The prevalence of patients fulfilling clinical and radiographic criteria was highest (n=163, 12%) in the least stringent scenario (pain+function ≥80 at ≥2 visits); with few patients (n=129, 2%) in the most stringent scenario (pain+function ≥80 at ≥4 visits). Using these prevalence data, a sample size of 352-2144 per group would be needed to demonstrate a 50% difference between groups. Conclusions: The prevalence of patients with sustained symptomatic OA of at least a moderate degree with X-ray progression is low. Even using lenient criteria to define VJR, large patient numbers would be required to detect differences between groups in DMOAD RCTs. Investigation of the optimal cutoff threshold and combination of symptoms and radiographic change should be pursued.

KW - Osteoarthritis

KW - Outcomes

KW - Randomized clinical trials

UR - http://www.scopus.com/inward/record.url?scp=84855825067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855825067&partnerID=8YFLogxK

U2 - 10.1016/j.joca.2011.11.013

DO - 10.1016/j.joca.2011.11.013

M3 - Article

C2 - 22178465

AN - SCOPUS:84855825067

VL - 20

SP - 93

EP - 101

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

SN - 1063-4584

IS - 2

ER -