OARSI Clinical Trials Recommendations: Key analytic considerations in design, analysis, and reporting of randomized controlled trials in osteoarthritis

doi:10.1016/j.joca.2015.03.011

Review

. 2015 May;23(5):677-85.

doi: 10.1016/j.joca.2015.03.011.

OARSI Clinical Trials Recommendations: Key analytic considerations in design, analysis, and reporting of randomized controlled trials in osteoarthritis

E Losina¹, J Ranstam², J E Collins³, T J Schnitzer⁴, J N Katz⁵

Affiliations

¹ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. Electronic address: elosina@partners.org.
² Department of Clinical Sciences, Orthopedics, Lund University, and Skane University Hospital, Lund, Sweden. Electronic address: jonas.ranstam@gmail.com.
³ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: jcollins13@partners.org.
⁴ Northwestern University School of Medicine, USA. Electronic address: tjs@northwestern.edu.
⁵ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: jnkatz@partners.org.

PMID: 25952341
PMCID: PMC4772721
DOI: 10.1016/j.joca.2015.03.011

Review

OARSI Clinical Trials Recommendations: Key analytic considerations in design, analysis, and reporting of randomized controlled trials in osteoarthritis

E Losina et al. Osteoarthritis Cartilage. 2015 May.

. 2015 May;23(5):677-85.

doi: 10.1016/j.joca.2015.03.011.

Authors

E Losina¹, J Ranstam², J E Collins³, T J Schnitzer⁴, J N Katz⁵

Affiliations

¹ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. Electronic address: elosina@partners.org.
² Department of Clinical Sciences, Orthopedics, Lund University, and Skane University Hospital, Lund, Sweden. Electronic address: jonas.ranstam@gmail.com.
³ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: jcollins13@partners.org.
⁴ Northwestern University School of Medicine, USA. Electronic address: tjs@northwestern.edu.
⁵ Orthopedic and Arthritis Center for Outcomes Research, Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: jnkatz@partners.org.

PMID: 25952341
PMCID: PMC4772721
DOI: 10.1016/j.joca.2015.03.011

Abstract

To highlight methodologic challenges pertinent to design, analysis, and reporting of results of randomized clinical trials in OA and offer practical suggestions to overcome these challenges. The topics covered in this paper include subject selection, randomization, approaches to handling missing data, subgroup analysis, sample size, and issues related to changing design mid-way through the study. Special attention is given to standardizing the reporting of results and economic analyses. Key findings include the importance of blinding and concealment, the distinction between superiority and non-inferiority trials, the need to minimize missing data, and appropriate analysis and interpretation of subgroup effects. Investigators may use the findings and recommendations advanced in this paper to guide design and conduct of randomized controlled trials of interventions for osteoarthritis.

Keywords: Design; Economic evaluation; Missing data; Outcomes; Randomized controlled trials; Reporting.

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Conflict of interest statement

Conflict of Interest

Elena Losina –none

Jonas Ranstam –none

Jamie Collins – none

Jeffrey N. Katz –none

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References

1. Beavers KM, Beavers DP, Newman JJ, Anderson AM, Loeser RF, Jr, Nicklas BJ, et al. Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis. Osteoarthritis and cartilage. 2015 Feb;23(2):249–56. - PMC - PubMed
1. FDA Document: Guidelines for industry. Statistical principles for clinical trial E9; International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use; 16 September 1998.
1. Miller F, Bjornsson M, Svensson O, Karlsten R. Experiences with an adaptive design for a dose-finding study in patients with osteoarthritis. Contemporary clinical trials. 2014 Mar;37(2):189–99. - PubMed
1. Bland JM, Altman DG. Some examples of regression towards the mean. BMJ. 1994 Sep 24;309(6957):780. - PMC - PubMed
1. Dobson F, Bennell K, Hinman R, Roos E, Abbott H, Stratford P, et al. OARSI recommended performance-based tests to assess physical function in osteoarthritis of the hip or knee: authors’ reply. Osteoarthritis and cartilage. 2013 Oct;21(10):1625–6. - PubMed

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[1] Beavers KM, Beavers DP, Newman JJ, Anderson AM, Loeser RF, Jr, Nicklas BJ, et al. Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis. Osteoarthritis and cartilage. 2015 Feb;23(2):249–56. - PMC - PubMed

[2] Beavers KM, Beavers DP, Newman JJ, Anderson AM, Loeser RF, Jr, Nicklas BJ, et al. Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis. Osteoarthritis and cartilage. 2015 Feb;23(2):249–56. - PMC - PubMed

[3] FDA Document: Guidelines for industry. Statistical principles for clinical trial E9; International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use; 16 September 1998.

[4] FDA Document: Guidelines for industry. Statistical principles for clinical trial E9; International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use; 16 September 1998.

[5] Miller F, Bjornsson M, Svensson O, Karlsten R. Experiences with an adaptive design for a dose-finding study in patients with osteoarthritis. Contemporary clinical trials. 2014 Mar;37(2):189–99. - PubMed

[6] Miller F, Bjornsson M, Svensson O, Karlsten R. Experiences with an adaptive design for a dose-finding study in patients with osteoarthritis. Contemporary clinical trials. 2014 Mar;37(2):189–99. - PubMed

[7] Bland JM, Altman DG. Some examples of regression towards the mean. BMJ. 1994 Sep 24;309(6957):780. - PMC - PubMed

[8] Bland JM, Altman DG. Some examples of regression towards the mean. BMJ. 1994 Sep 24;309(6957):780. - PMC - PubMed

[9] Dobson F, Bennell K, Hinman R, Roos E, Abbott H, Stratford P, et al. OARSI recommended performance-based tests to assess physical function in osteoarthritis of the hip or knee: authors’ reply. Osteoarthritis and cartilage. 2013 Oct;21(10):1625–6. - PubMed

[10] Dobson F, Bennell K, Hinman R, Roos E, Abbott H, Stratford P, et al. OARSI recommended performance-based tests to assess physical function in osteoarthritis of the hip or knee: authors’ reply. Osteoarthritis and cartilage. 2013 Oct;21(10):1625–6. - PubMed

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OARSI Clinical Trials Recommendations: Key analytic considerations in design, analysis, and reporting of randomized controlled trials in osteoarthritis

Affiliations

OARSI Clinical Trials Recommendations: Key analytic considerations in design, analysis, and reporting of randomized controlled trials in osteoarthritis

Authors

Affiliations

Abstract

Conflict of interest statement

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References

Publication types

MeSH terms

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LinkOut - more resources

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Medical