Determining individual trajectories of joint space loss: improved statistical methods for monitoring knee osteoarthritis disease progression

C M Parsons, A Judge, R Meyer, O Bruyere, F Petit-Dop, R Chapurlat, J-Y Reginster, C Cooper, H Inskip

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Abstract

OBJECTIVES: Knee osteoarthritis (KOA) progression is frequently monitored by calculating the change in knee joint space width (JSW) measurements. Such differences are small and sensitive to measurement error. We aimed to assess the utility of two alternative statistical modelling methods for monitoring KOA.

MATERIAL AND METHODS: We used JSW on radiographs from both the control arm of the Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA), a 3-year multicentre, double-blind, placebo-controlled phase three trial, and the Osteoarthritis Initiative (OAI), an open-access longitudinal dataset from the USA comprising participants followed over 8 years. Individual estimates of annualised change obtained from frequentist linear mixed effect (LME) and Bayesian hierarchical modelling, were compared with annualised crude change, and the association of these parameters with change in WOMAC pain was examined.

RESULTS: Mean annualised JSW changes were comparable for all estimates, a reduction of around 0.14 mm/y in SEKOIA and 0.07 mm/y in OAI. The standard deviation (SD) of change estimates was lower with LME and Bayesian modelling than crude change (SEKOIA SD = 0.12, 0.12 and 0.21 respectively; OAI SD = 0.08, 0.08 and 0.11 respectively). Estimates from LME and Bayesian modelling were statistically significant predictors of change in pain in SEKOIA (LME P-value = 0.04, Bayes P-value = 0.04), while crude change did not predict change in pain (P-value = 0.10).

CONCLUSIONS: Implementation of LME or Bayesian modelling in clinical trials and epidemiological studies, would reduce sample sizes by enabling all study participants to be included in analysis regardless of incomplete follow up, and precision of change estimates would improve. They provide increased power to detect associations with other measures.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalOsteoarthritis and Cartilage
Volume29
Issue number1
Early online date24 Nov 2020
DOIs
Publication statusPublished - 1 Jan 2021

Bibliographical note

Funding Information:
We acknowledge the directors and personnel of the 98 investigating centres, all members of the SEKOIA management team (appendix 1) and the study participants. We would also like to express our gratitude to the participants of the OAI. The OAI is a public-private partnership comprised of five contracts ( NO1-AR-2-2258 , NO1-AR-2-2259 , NO1-AR-2-2260 , NO1-AR-2-2261 , NO1-AR-2-2262 ) funded by the National Institutes of Health , a branch of the U.S. Department of Health and Human Services, in four clinical sites and conducted by the OAI study investigators. Work in part supported by a World Universities Network Research Mobility Programme Grant .

Funding Information:
CP and RM has no conflicts of interest to report. Outside of the submitted work, AJ has recived consultancy fees from Freshfields Bruckhaus Derringer and Anthera Phramaceuticals LTD. Outside the submitted work, OB reports grants from Biophytis, IBSA, MEDA, Servier, and SMB, personal fees from Amgen, Aptissen, Biophytis, IBSA, MEDA, Sanofi, Servier, SMB, and UCB. Outside of the submitted work, J-YR reports consultanty fees from IBSA Genevrier, Mylan, Radius Health, and Pierre Fabre, grants from IBSA Genevrier, Mylan, CNIEL, and Radius Health, and payment for lectures from IBSA Genevrier, Mylan, CNIEL, Dairy Research Council (DRC). HMI salary is provided from the UK Medical Research Council, and outside of the submitted work HMI's institution has received grants from NIHR and the British Heart Foundation. FP-D salary if provided by Servier. Outside of the submitted work, CC reports personal fees from Alliance for Better Bone Health, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB. Outside of the submitted work, RC reports board membership and consultancy fees from Pfizer.

Publisher Copyright:
© 2020 Osteoarthritis Research Society International

Keywords

  • Longitudinal
  • Osteoarthritis
  • Progression

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