EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: Focus on ANCA-associated vasculitis

Bernhard Hellmich ¹, Oliver Flossmann ², Wolfgang L Gross ¹, Paul Bacon ³, Jan Willem Cohen-Tervaert ⁴, Loic Guillevin ⁵, David Jayne ², Alfred Mahr ⁶, Peter A Merkel ⁶, Heiner Raspe ¹, David GI Scott ⁷, James Witter ⁸, Hasan Yazici ⁹ and Raashid A Luqmani ^10*

¹ University Hospital of Schleswig-Holstein, Germany
² Addenbrooke’s Hospital, United Kingdom
³ University of Birmingham, United Kingdom
⁴ University Hospital Maastricht, Netherlands
⁵ University of Paris Descartes, France
⁶ Boston University School of Medicine, United States
⁷ University of East Anglia, United Kingdom
⁸ U.S. Food and Drug Administration, United States
⁹ University of Istanbul, Turkey
¹⁰ University of Oxford, United Kingdom

^* To whom correspondence should be addressed. E-mail: raashid.luqmani{at}noc.anglox.nhs.uk.

Accepted 2 December 2006

Abstract

Objectives:To develop EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis.

Methods:An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing 5 European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence-based and expert opinion-based approach in accordance with the standardised EULAR operating procedures, the group identified 9 topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis.

Results:Based on the results of the literature research the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti-neutrophil cytoplasm antibody associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to address vasculitis-specific issues rather than general issues of trial methodology. The recommendations address the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant endpoints, and biomarkers. On the basis of expert opinion, a number of aspects of trial methodology were deemed important for future research.

Conclusions: On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well designed research in non AAV systemic vasculitides.

Keywords: antineutrophil cytoplasm antibody, clinical trial, cytotoxic, vasculitis

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