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Drug Safety

pp 1–8 | Cite as

Rheumatology Common Toxicity Criteria (RCTC): An Update Reflecting Real-World Use

  • Christian M. Stach
  • Victor S. Sloan
  • Thasia G. WoodworthEmail author
  • Brian Kilgallen
  • Daniel E. Furst
Original Research Article
  • 10 Downloads

Abstract

Introduction

The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatology Common Toxicity Criteria (RCTC) version 2.0 was published in 2007 by the OMERACT Drug Safety Working Group, building on limited experience with RCTC version 1.0, to facilitate standardization of assessment (grading) and reporting of adverse events (AEs) commonly seen in rheumatic disease clinical trials (Woodworth et al. in J Rheumatol 34:1401–1414, 2007).

Objectives

The objectives of this study were to (1) report the real-world performance of RCTC 2.0; (2) report immediately correctable errors in RCTC 2.0, and provide a revised RCTC 2.1; and (3) begin to identify the need for a comprehensive revision of RCTC 2.0.

Methods

Safety data outputs for several large rheumatic/autoimmune disease clinical trials in which RCTC 2.0 was used were evaluated for accuracy of reporting and the ability to assess differences among treatments. We examined RCTC 2.0 tables for errors, as well as for omission of terms for AEs that commonly occur in more recent rheumatology clinical trials. We also considered recommendations from recent US Food and Drug Administration (FDA) and international initiatives such CDISC (Clinical Data Interchange Standards Consortium) to improve the consistency of safety data collection and interpretability of safety data analyses.

Results

RCTC 2.0 enabled comparisons of safety data across treatment groups, including grading. However, we discovered inaccuracies in laboratory results grading and omission of AE terms now recognized to occur in rheumatic disease clinical trials.

Conclusion

The RCTC 2.0 performed as intended, although some inaccuracies and omissions were found. We provide a corrected version, RCTC 2.1, and also recommend further revision of the RCTC within OMERACT guidances to include AEs that have been reported in rheumatology clinical trials since RCTC 2.0 was published. Ideally, a revised RCTC 3.0 would not only facilitate standardized assessment and reporting of AEs, but would also expand and encourage accurate comparison of the safety profiles of treatments for rheumatic/autoimmune diseases.

Notes

Acknowledgements

We wish to thank Ms. Mischa Mangum and Ms. Claudia Real for their diligent administrative support.

Compliance with Ethical Standards

Funding

We received no specific funding for this study.

Conflict of interest

The authors declare the following conflicts of interest: Christian M. Stach, employee and stockholder of UCB; Victor S. Sloan, employee and stockholder of UCB; Thasia G. Woodworth, past chair, OMERACT Drug Safety Working Group; Brian Kilgallen, former employee and stockholder of UCB; Daniel E. Furst, Grant/Research Support: BMS, Pfizer, Roche/Genentech; Consultant: Novartis, Pfizer, Roche/Genentech, Sanofi; Speakers Bureau (CME or non-promotional only): none; no stocks, royalties, direct financial holding, expert testimony, or board of directors.

Ethical approval and patient consent

Ethical approval and patient consent were not required.

Supplementary material

40264_2019_864_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 43 kb)
40264_2019_864_MOESM2_ESM.docx (26 kb)
Supplementary material 2 (DOCX 26 kb)

References

  1. 1.
    Woodworth T, Furst DE, Alten R, Bingham CO 3rd, Yocum D, Sloan V, et al. Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology Common Toxicity Criteria v.2.0. J Rheumatol. 2007;34:1401–14.PubMedGoogle Scholar
  2. 2.
    Ioannidis JP, Evans SJ, Gotzsche PC, O’Neill RT, Altman DG, Schulz K, et al. Better reporting of harms in randomized trials: an extension of the consort statement. Ann Intern Med. 2004;141:781–8.CrossRefGoogle Scholar
  3. 3.
    PhUSE. Analysis and displays associated with adverse events. 2017. https://www.phuse.eu/documents//workinggroups/deliverables/adverse-events-white-paper-version-10-03-feb-17-11796-19835.pdf. Accessed Sept 2019.
  4. 4.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Post-approval safety data management: definitions and standards for expedited reporting. 2003. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2D/Step4/E2D_Guideline.pdf. Accessed Sept 2019.
  5. 5.
    US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 2017. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf. Accessed Sept 2019.
  6. 6.
    Woodworth TG, Furst DE, Strand V, Kempeni J, Fenner H, Lau CS, et al. Standardizing assessment of adverse effects in rheumatology clinical trials. Status of omeract toxicity working group march 2000: towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies. J Rheumatol. 2000;28:1163–9.Google Scholar
  7. 7.
    TransCelerate Biopharma Inc. http://www.transceleratebiopharmainc.com. Accessed Sept 2019.
  8. 8.
    Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8:18.CrossRefGoogle Scholar
  9. 9.
    Charles-Schoeman C, Gonzalez-Gay MA, Kaplan I, Boy M, Geier J, Luo Z, et al. Effects of tofacitinib and other dmards on lipid profiles in rheumatoid arthritis: implications for the rheumatologist. Semin Arthritis Rheum. 2016;46:71–80.CrossRefGoogle Scholar
  10. 10.
    Souto A, Salgado E, Maneiro JR, Mera A, Carmona L, Gomez-Reino JJ. Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta-analysis. Arthritis Rheumatol. 2015;67:117–27.CrossRefGoogle Scholar
  11. 11.
    FDA. Determining the extent of safety data collection needed in late stage premarket and postapproval clinical investigations. 2016. https://www.fda.gov/downloads/drugs/guidances/ucm291158.pdf. Accessed Sept 2019.
  12. 12.
    OMERACT. The OMERACT glossary. https://omeracthandbook.org/workbooks-%26-glossary. Accessed Sept 2019.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.UCB Biosciences GmbHMonheimGermany
  2. 2.UCB Biosciences IncResearch Triangle ParkUSA
  3. 3.Rutgers-Robert Wood Johnson Medical SchoolNew BrunswickUSA
  4. 4.Division of Rheumatology, David Geffen School of MedicineUniversity of California, Los AngelesLos AngelesUSA
  5. 5.SDCTempeUSA
  6. 6.University of WashingtonSeattleUSA
  7. 7.University of FlorenceFlorenceItaly

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