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Abstract
Objectives To analyse the amount, reporting and handling of missing data, approach to intention-to-treat (ITT) principle application and sensitivity analysis utilisation in randomised clinical trials (RCTs) of rheumatoid arthritis (RA). To assess the trend in such reporting 10 years apart (2006 and 2016).
Methods Parallel group drug therapy RA RCTs with a clinical primary endpoint.
Results 176 studies enrolling a median of 160 (IQR 62–339) patients were eligible. In terms of actual analysis: 81 (46%) RCTs conducted ITT, 42 (23.9%) conducted modified ITT while 53 (30.1%) conducted non-ITT analysis. Only 58 of 97 (59.8%) RCTs reporting an ITT analysis actually performed it. The median (IQR) numbers of participants completing the trial and included in analysis for primary outcome were 86% (74%–91%) and 100% (97.1%–100%), respectively. 53 (32.7%) and 65 (40.1%) RCTs had >20% and 10%–20% missing primary outcome data, respectively. Missing data handling was unreported by 58 of 171 (33.9%) RCTs. When reported, vast majority used simple imputation methods. No significant trend towards improved reporting was seen between 2006 and 2016. Sensitivity analysis numerically improved from 2006 to 2016 (14.7% vs 21.4%).
Conclusions There is significant discrepancy in the reported and the actual performed analysis in RA drug therapy RCTs. Nearly one-third of RCTs had >20% missing data. The reporting and methods of missing data handling remain inadequate with high usage of non-preferred simple imputation methods. Sensitivity analysis utilisation was low. No trend towards better missing data reporting and handling was seen.
- rheumatoid arthritis
- outcome and process assessment
- healthcare
- epidemiology
Data availability statement
Data available upon request.
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Data availability statement
Data available upon request.
Supplementary materials
Supplementary Data
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Footnotes
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Presented at This study has been partially presented as a poster at the 2017 American College of Rheumatology annual meeting as a poster and as an oral presentation at the 2018 American College of Rheumatology annual meeting. References are the following: 2017 conference reference: Aslam F, Torralba K, Khan NA. Handling of Missing Data, Protocol Violation and Performance of Intention-to-Treat Analysis in the Randomized Controlled Trials of Drug Therapy of Rheumatoid Arthritis (abstract). Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/handling-of-missing-data-protocol-violation-and-performance-of-intention-to-treat-analysis-in-the-randomized-controlled-trials-of-drug-therapy-of-rheumatoid-arthritis/. Accessed 11 March 2020. 2018 conference reference: Aslam F, Torralba K, Khan NA. Comparison of Missing Data Reporting and Handling in Randomized Controlled Trials of Rheumatoid Arthritis Drug Therapy: A Snapshot Ten Years Apart (abstract). Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/comparison-of-missing-data-reporting-and-handling-in-randomized-controlled-trials-of-rheumatoid-arthritis-drug-therapy-a-snapshot-ten-years-apart/https://acrabstracts.org/abstract/comparison-of-missing-data-reporting-and-handling-in-randomized-controlled-trials-of-rheumatoid-arthritis-drug-therapy-a-snapshot-ten-years-apart/. Accessed 11 March 2020.
Contributors All authors contributed to the drafting, writing, editing and review of the manuscript. NAK and KDT conceived the idea. FA and NAK collected the data. NAK ran the analysis.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.