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Issues in the design of new clinical trials for rheumatoid arthritis therapeutics

Nature Clinical Practice Rheumatology volume 4, pages 641–648 (2008)Cite this article

Abstract

Rheumatoid arthritis (RA) is a chronic, heterogeneous disease, for which there has traditionally been few reliable prognostic indicators or simple clinical outcome measures with which to adequately assess disease status or clinical improvement. These challenges have hindered the assessment of new therapeutic agents. Investigators in rheumatology have, therefore, attempted over the past two decades to develop new approaches and scoring systems to facilitate the study and development of therapies. As a result of these efforts, the efficacy of almost all new agents tested in clinical trials are now assessed with widely accepted scoring systems that measure improvement in three important areas. First, changes in patient signs and symptoms are measured via composite indices of both clinical and laboratory parameters. Second, the progression of structural damage is assessed by radiographic imaging. Finally, long-term improvement in patient function is measured via patient-reported outcomes. These changes to clinical trial design have been adopted by health authorities around the world. Further challenges, however, must be overcome in order for progress to continue.

Key Points

  • Three parameters are critical to the study of new investigational agents for rheumatoid arthritis (RA): clinical outcomes, radiographic outcomes and patient function

  • Two composite clinical outcome scoring systems—the American College of Rheumatology index and the Disease Activity Score—are widely used by rheumatologists in the study of RA

  • Several radiographic outcome measures are used in RA studies, including the Sharp and Larsen scores and their modifications, while patient function is assessed by the Health Assessment Questionnaire and Short Form-36

  • Careful selection of study participants, accurate study of dose effects, use of adequate comparators and long-term safety monitoring are all important features in the study of new investigational agents for RA

  • Challenges for the future include the need for new definitions for clinical and radiographic response, data on acceptable timing and duration of therapy, more-efficient trial designs, more studies of head-to-head comparisons and combination therapies, and increased emphasis on drug safety

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Acknowledgements

I would like to acknowledge Donald J Schwieterman MD for his guidance and generosity, both recently and over the years.

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  1. 3901 Point Road, Mobile, AL 36619, USA wds@tekgenics.org

Authors and Affiliations

  1. WD Schwieterman is an Independent Consultant, Tekgenics, Inc., Mobile, AL, USA.,

    William D Schwieterman

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Schwieterman, W. Issues in the design of new clinical trials for rheumatoid arthritis therapeutics. Nat Rev Rheumatol 4, 641–648 (2008). https://doi.org/10.1038/ncprheum0948

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