Standardized Assessment of Adverse Events in Rheumatology Clinical Trials: Summary of the OMERACT 7 Drug Safety Module Update

MARISSA N.D. LASSERE, KENT R. JOHNSON, MAARTEN BOERS, KERRI CARLTON, RICHARD O. DAY, MARTEN de WIT, I. RALPH EDWARDS, JAMES F. FRIES, DANIEL E. FURST, JOHN R. KIRWAN, PETER S. TUGWELL, THASIA G. WOODWORTH, and PETER M. BROOKS

ABSTRACT.

A presentation, demonstration, and discussion of recently developed adverse event instruments were the topics for the OMERACT 7 Drug Safety Module. The module began with a plenary introducing the needs and challenges of adverse event ascertainment. It was followed by a review of module work from previous OMERACT meetings on a prototype coding instrument (Rheumatology Common Toxicity Criteria), then a brief description of the process behind the recently developed patient self-report and investigator report adverse event instruments. These current instruments are designed for use in controlled trials although they could be used in other settings. The instruments rely primarily on patient self-reporting using a checklist, which the investigator then folds into a parallel structured but more medically sophisticated instrument. In pilot testing, this innovative dual-use system has shown reliability and acceptability, while preserving validity. A "stakeholder panel" of representatives from 8 sectors followed -- patient, nurse investigator, regulator, clinician scientist, industry, OMERACT, global public health/WHO, and Cochrane Collaboration -- for their perspectives on the needs, challenges, and potential ways forward for adverse event ascertainment and reporting in clinical trials. At the breakout session small focus groups participated in hands-on interactive testing of one of 3 versions of the instruments, which differ in degree of comprehensiveness. Each focus group had a participatory patient with rheumatoid arthritis. At a second plenary there was group feedback by rapporteurs and presentation of results from pilot studies of iterative testing of validity, reliability, and feasibility of the instruments. During plenary discussion a frequent suggestion for improvement was to refine the process so that event ascertainment could be done entirely using the patient instrument with minimal input from the investigator at the visit, if patient-investigator agreement was high. Most found the patient checklist attractive, particularly if the patient instrument was shown to be reliable and valid. Finally, a future research agenda was discussed. (J Rheumatol 2005;32:2037-41)

Key Indexing Terms:

ADVERSE EVENTS MEASUREMENT
RANDOMIZED CLINICAL TRIALS
INSTRUMENT VALIDATION
DRUG TOLERABILITY INDEX

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From the University of New South Wales, Department of Rheumatology, St. George Hospital, Sydney; Department of Clinical Pharmacology, Mater Hospital, University of Newcastle, Newcastle, Australia; Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; World Health Organisation Collaborative Centre for International Drug Monitoring, Uppsala, Sweden; Stanford University School of Medicine, Palo Alto; Geffen School of Medicine at the University of California in Los Angeles (UCLA), Los Angeles, California, USA; University of Bristol Academic Rheumatology Unit, Bristol, United Kingdom; Centre for Global Health, University of Ottawa, Institute of Population Health, Ottawa, Ontario, Canada; ABGH Novartis Pharma, Basel, Switzerland; and Faculty of Health Sciences, University of Queensland, Royal Brisbane Hospital, Herston, Australia.

M.N.D. Lassere, MB, BS, Grad Dip Epi, PhD, FRACP, FAFPHM, Associate Professor in Medicine, Conjoint Appointee, University of New South Wales, Department of Rheumatology, St. George Hospital; K.R. Johnson, MD, Senior Research Officer, Department of Clinical Pharmacology, Mater Hospital, University of Newcastle; M. Boers, MSc, MD, PhD, Professor of Clinical Epidemiology, Department of Clinical Epidemiology and Biostatistics, VU University Medical Center; K. Carlton, BSc, MSc, Research Officer, St. George Hospital; R.O. Day, MD, FRACP, Professor of Clinical Pharmacology, St. Vincent Hospital, University of New South Wales; M. de Wit, Dutch Arthritis Patients' League, The Netherlands; I.R. Edwards, MB, ChB, FRCP; Professor, Director, World Health Organisation Collaborative Centre for International Drug Monitoring; J.F. Fries, Professor of Medicine, Stanford University School of Medicine; D.E. Furst, Carl M. Pearson Professor of Rheumatology, Geffen School of Medicine at UCLA; J.R. Kirwan, BSc, MD, University of Bristol Academic Rheumatology Unit; P.S. Tugwell, MD, MSc, Director, Centre for Global Health, University of Ottawa, Institute of Population Health; T.G. Woodworth, MD, Executive Director, Global Therapeutic Area Profiling Head, ABGH Novartis Pharma; P.M. Brooks, Executive Dean, Faculty of Health Sciences, University of Queensland, Royal Brisbane Hospital.

Address reprint requests to Dr. M.N.D. Lassere, Department of Rheumatology, St. George Hospital, Belgrave Street, Kogarah, NSW 2217, Australia. E-mail: lasserem@sesahs.nsw.gov.au

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