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An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the kneel

Strand, V ; Conaghan, P. G. ; Lohmander, Stefan LU ; Koutsoukos, A. D. ; Hurley, F. L. ; Bird, H. ; Brooks, P. ; Day, R. ; Puhl, W. and Band, P. A. (2006) In Osteoarthritis and Cartilage 14(9). p.859-866
Abstract
Objective: Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. Method. Trials were similar in design, patient population and outcome measures - all included the Lequesne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety... (More)
Objective: Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. Method. Trials were similar in design, patient population and outcome measures - all included the Lequesne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety data from the five RCTs were summarized. Results: A total of 1155 patients with radiologically confirmed knee OA were enrolled: 619 received three or five IA-HA injections; 536 received. "placebo" saline injections. In the active and control groups, mean ages were 61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequesne scores 11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a statistically significant reduction (P < 0.001) in total Lequesne score with hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: -0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed robustness of the analyses. Conclusions: This integrated analysis demonstrates that multiple design factors influence the results of RCTs assessing efficacy of intra-articular (IA) therapies, and that integrated analyses based on primary data differ from meta-analyses using transformed data. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hyaluronic, hyaluronate, hyaluronan, intra-articular, osteoarthritis, knee, meta-analysis, viscosupplementation
in
Osteoarthritis and Cartilage
volume
14
issue
9
pages
859 - 866
publisher
Elsevier
external identifiers
  • wos:000239898500003
  • scopus:33746507275
ISSN
1063-4584
DOI
10.1016/j.joca.2006.02.012
language
English
LU publication?
yes
id
13058e9b-b1bf-42fe-8d3d-398e3fe3ccf4 (old id 397281)
date added to LUP
2016-04-01 12:08:34
date last changed
2020-12-01 02:50:21
@article{13058e9b-b1bf-42fe-8d3d-398e3fe3ccf4,
  abstract     = {Objective: Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. Method. Trials were similar in design, patient population and outcome measures - all included the Lequesne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety data from the five RCTs were summarized. Results: A total of 1155 patients with radiologically confirmed knee OA were enrolled: 619 received three or five IA-HA injections; 536 received. "placebo" saline injections. In the active and control groups, mean ages were 61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequesne scores 11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a statistically significant reduction (P &lt; 0.001) in total Lequesne score with hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: -0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed robustness of the analyses. Conclusions: This integrated analysis demonstrates that multiple design factors influence the results of RCTs assessing efficacy of intra-articular (IA) therapies, and that integrated analyses based on primary data differ from meta-analyses using transformed data. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.},
  author       = {Strand, V and Conaghan, P. G. and Lohmander, Stefan and Koutsoukos, A. D. and Hurley, F. L. and Bird, H. and Brooks, P. and Day, R. and Puhl, W. and Band, P. A.},
  issn         = {1063-4584},
  language     = {eng},
  number       = {9},
  pages        = {859--866},
  publisher    = {Elsevier},
  series       = {Osteoarthritis and Cartilage},
  title        = {An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the kneel},
  url          = {http://dx.doi.org/10.1016/j.joca.2006.02.012},
  doi          = {10.1016/j.joca.2006.02.012},
  volume       = {14},
  year         = {2006},
}