Robust analyses for radiographic progression in rheumatoid arthritis
Demonstrating inhibition of the structural damage to joints as a statistically significant difference in radiographic progression as measured by the van der Heijde modified Total Sharp Score (mTSS) is a common objective in trials for rheumatoid arthritis treatments. The frequently used analysis of t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-04-01
|
| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/9/2/e002543.full |
| _version_ | 1797852463219343360 |
|---|---|
| author | Robert Landewé Désirée van der Heijde Yun-fei Chen Luna Sun Mo Daojun |
| author_facet | Robert Landewé Désirée van der Heijde Yun-fei Chen Luna Sun Mo Daojun |
| author_sort | Robert Landewé |
| collection | DOAJ |
| description | Demonstrating inhibition of the structural damage to joints as a statistically significant difference in radiographic progression as measured by the van der Heijde modified Total Sharp Score (mTSS) is a common objective in trials for rheumatoid arthritis treatments. The frequently used analysis of the covariance model with missing data imputed using linear extrapolation (analyses of covariance, ANCOVA+LE) may not be ideal for long-term extension studies or for paediatric studies. The random coefficient (RC) model may represent a better alternative.A two-arm (active treatment and placebo) setting with a week 44 study period was considered. RC model, ANCOVA+LE and ANCOVA with last observation carried forward imputation were compared under different scenarios in bias, root mean square error (RMSE), power and type I error rate.The RC model outperformed ANCOVA+LE in metrics measuring bias, RMSE, power and type I error rate under the evaluated scenarios. ANCOVA and RC provide similar performance when there are no missing data. With missing data, RC+observed (OBS) provides similar or better results than ANCOVA+LE in power and bias.Our simulations support that RC is both a more sensitive and a more precise alternative to the commonly used ANCOVA+LE as a primary method for analysing mTSS in long-term extension and paediatric studies with a higher likelihood of missing data. The RC model can provide a reference at time points with missing data by estimating a slope; mTSS change by one unit change in time. ANCOVA+LE is recommended as a sensitivity analysis. |
| first_indexed | 2024-04-09T19:34:43Z |
| format | Article |
| id | doaj.art-967531ef92844edea1c4c622d0eedf28 |
| institution | Directory Open Access Journal |
| issn | 2056-5933 |
| language | English |
| last_indexed | 2024-04-09T19:34:43Z |
| publishDate | 2023-04-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj.art-967531ef92844edea1c4c622d0eedf282023-04-04T17:00:06ZengBMJ Publishing GroupRMD Open2056-59332023-04-019210.1136/rmdopen-2022-002543Robust analyses for radiographic progression in rheumatoid arthritisRobert Landewé0Désirée van der Heijde1Yun-fei Chen2Luna Sun3Mo Daojun4Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands1 Department of Rheumatology, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaBiomedicines, Eli Lilly and Company, Indianapolis, Indiana, USABiomedicines, Eli Lilly and Company, Indianapolis, Indiana, USADemonstrating inhibition of the structural damage to joints as a statistically significant difference in radiographic progression as measured by the van der Heijde modified Total Sharp Score (mTSS) is a common objective in trials for rheumatoid arthritis treatments. The frequently used analysis of the covariance model with missing data imputed using linear extrapolation (analyses of covariance, ANCOVA+LE) may not be ideal for long-term extension studies or for paediatric studies. The random coefficient (RC) model may represent a better alternative.A two-arm (active treatment and placebo) setting with a week 44 study period was considered. RC model, ANCOVA+LE and ANCOVA with last observation carried forward imputation were compared under different scenarios in bias, root mean square error (RMSE), power and type I error rate.The RC model outperformed ANCOVA+LE in metrics measuring bias, RMSE, power and type I error rate under the evaluated scenarios. ANCOVA and RC provide similar performance when there are no missing data. With missing data, RC+observed (OBS) provides similar or better results than ANCOVA+LE in power and bias.Our simulations support that RC is both a more sensitive and a more precise alternative to the commonly used ANCOVA+LE as a primary method for analysing mTSS in long-term extension and paediatric studies with a higher likelihood of missing data. The RC model can provide a reference at time points with missing data by estimating a slope; mTSS change by one unit change in time. ANCOVA+LE is recommended as a sensitivity analysis.https://rmdopen.bmj.com/content/9/2/e002543.full |
| spellingShingle | Robert Landewé Désirée van der Heijde Yun-fei Chen Luna Sun Mo Daojun Robust analyses for radiographic progression in rheumatoid arthritis RMD Open |
| title | Robust analyses for radiographic progression in rheumatoid arthritis |
| title_full | Robust analyses for radiographic progression in rheumatoid arthritis |
| title_fullStr | Robust analyses for radiographic progression in rheumatoid arthritis |
| title_full_unstemmed | Robust analyses for radiographic progression in rheumatoid arthritis |
| title_short | Robust analyses for radiographic progression in rheumatoid arthritis |
| title_sort | robust analyses for radiographic progression in rheumatoid arthritis |
| url | https://rmdopen.bmj.com/content/9/2/e002543.full |
| work_keys_str_mv | AT robertlandewe robustanalysesforradiographicprogressioninrheumatoidarthritis AT desireevanderheijde robustanalysesforradiographicprogressioninrheumatoidarthritis AT yunfeichen robustanalysesforradiographicprogressioninrheumatoidarthritis AT lunasun robustanalysesforradiographicprogressioninrheumatoidarthritis AT modaojun robustanalysesforradiographicprogressioninrheumatoidarthritis |