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					                               DETAILED PROGRAM- OMERACT 8

Chair: Peter Merkel

         In the past decade there has been a marked increase in the number and quality of clinical trials
in the idiopathic inflammatory vasculitides. This has been fueled by the cooperative efforts of several
groups (European Vasculitis Study Group [EUVAS]; International Network for the Study of Systemic
Vasculitides [INSYSS]; and the Wegener’s Granulomatosis Etanercept Trial Group [WGET]). These
groups have focused on ANCA-positive vasculitis and Giant Cell Arteritis. Sponsorship of these
activities has come from the United States National Institutes of Health (NIH), the European League
Against Rheumatism (EULAR), and industry partners.
         The 2003 funding of the Vasculitis Clinical Research Consortium (VCRC) is another major
step in the field of clinical investigation in the vasculitides. The VCRC group grew out of the highly
successful collaborative research initiatives of INSSYS and WGET. The VCRC is funding through the
NIH and is part of the Rare Diseases Clinical Research Network. Dr. Merkel is the Principal
Investigator of the $6.25 million grant to create and run the VCRC. The VCRC includes 10
international vasculitis centers and room for more to participate. The VCRC will provide intellectual
and logistical infrastructure to help drive clinical and translational investigation in vasculitis in the
coming years. The VCRC grant supports the establishment of serum, plasma, cell, DNA, and tissue
banks; longitudinal investigator effort on projects related to serum biomarkers; patient care costs;
meeting costs for the core Research Group; administrative expenses; website development; patient
support group liaison; and a vasculitis clinical research fellowship. A separately funded Data and
Technology Coordinating Center (DTCC) provides extensive support for the VCRC for data collection
mechanisms, database management, and data analysis. Both longitudinal cohort studies and
therapeutic clinical trials will be conducted through the VCRC. Inherent in the mission of the VCRC
is the need for proper outcome tools for the vasculitides included in the VCRC.
         In 2005, a grant from EULAR was awarded to a) create guidelines for clinical trials in
vasculitis; b) and advance projects in outcomes assessment using EUVAS clinical trial data. The
working group for this EULAR grant includes many of the key members of the OMERACT working
group including Dr. Luqmani (Principal Investigator of grant), Dr. Hellmich (co-facilitator of grant),
Dr. Flossman (fellow), and Dr. Merkel (specifically invited because of OMERACT/VCRC connection
and to be a US representative).
         This increased clinical trial activity in vasculitis has been accompanied by development of new
outcome measures and use and validation of existing measures. However, there are inevitable
improvements required of the current measures; some diseases have no outcome tools. Finally, there
is potential for confusion, due to the development of a number of disease assessment measures. These
issues need to be resolved in order to allow for comparisons among studies and more cooperative
progress in future multi-center studies.
         The already well-established cooperation and good will among the major international
vasculitis clinical investigators, combined with the potential and resources of the VCRC makes this an
excellent time to address the critical challenges in outcome measure assessment in the vasculitides

OMERACT 7 Vasculitis SIG. Meeting achievements and Subsequent Progress:
        The OMERACT 7 Vasculitis SIG was a huge success. Not only was it well attended by both a
variety of international vasculitis investigators, but it also attracted the interest of biometricians,
industry representatives, and many other OMERACT attendees. Through work done pre-OMERACT,
at OMERACT, and post-OMERACT, the VCRC-OMERACT group was highly productive. This
inclusive group has reached a significant level of consensus on the research agenda necessary to make
substantive progress in developing a core set of universally accepted measures for disease activity,
disease state, and damage for the small-vessel, ANCA-associated vasculitides (Wegener's
granulomatosis and microscopic polyangiitis). The domains of disease evaluation which require
attention were agreed upon as were the different types of measures needed.
        The progress of this group is well outlined in our OMERACT 7 report scheduled for
publication in Journal of Rheumatology December 2005. It is important to note that this paper has 14
authors working in 7 countries on 3 continents. This paper not only outlines our research agenda, but
also reviews the state of the science of the measures as they relate to the OMERACT filter.
        Additionally, this same group of international vasculitis investigators has conducted a
Comparative Outcome Measure Exercise (COMEX) of disease activity measures in WG/MPA that
they presented at the 2004 ACR meeting with a manuscript in preparation. These data are inherent in
the OMERACT process and are helping to drive the next set of exercises/studies with the overall goal
of developing a new/revised activity measure.
        A project to defining consensus and data-driven disease state definitions for use in clinical trials
has begun. This work directly stems from OMERACT 7. Several trainees (fellows) are involved in
this project. Operational definitions are under discussion with subsequent validation.
        Two projects have begun to address the assessment of damage in vasculitis. The AVID
(ANCA-Vasculitis Index of Damage) project, and the revision of the VDI are directly related to the
OMERACT process and will involve multiple investigators from many more sites than are currently
involved in the process (thus adding to the interested population for OMERACT 8). AVID will
include on-line data entry and is funded though the VCRC (see above). The EULAR funded project
will use EUVAS data and generate new data in the validation of damage assessment. We propose to
use the OMERACT meeting to ensure that these projects are complementary. That is part of the pre-
Malta OMERACT agenda.
        Our progress is markedly enhanced by our receiving adequate research funding and resources
and our access to multiple high-quality datasets from clinical trials for study. More importantly, we
have ongoing cohorts (VCRC, EUVAS) and new trials (RAVE: rituximab for WG/MPA; NIH funded)
within which to conduct these studies (eg: WGET study for disease states; RAVE will test AVID).
        Finally, funding for the VCRC-OMERACT projects remains extensive, allowing us to conduct
these several studied simultaneously, to transport participants, and increase the number of involved
investigators. The VCRC is the main source of funding, but Drs. Merkel and Stone (co-PIs) have also
received, since OMERACT 7, funding for an RO1 (NIH) grant specifically to conduct the WG/MPA
outcome exercises. Note: Drs. Boers and Felson are named co-investigators on this grant. Similarly,
Dr. Luqmani is the PI on a EULAR grant awarded for complementary work. Dr. Merkel is a named
co-investigator on the EULAR award just as Dr. Luqmani and others in Europe are named in the
Merkel/Stone grant. Additionally, several trainees have or will use these studies as the basis for career
development grants.

       Our group met regarding the OMERACT Vasculitis work at the ANCA-Vasculitis Meeting in
June 2005 (Germany) and will meet again at the ACR meeting in San Diego as well as by
teleconference monthly leading up to the Malta meeting.

        Because of the extensive progress, support, and enthusiasm of our large group of core
investigators and ever widening collaborators, we expected to make more progress over the next 6
months and present a well-planned, well-presented, and productive OMERACT8 workshop.

The Clinical Problems to be Addressed and the Intended Outcome of the Workshop:
       Rigorously validated, widely accepted, outcome measures for ANCA-Associated (small vessel)
Vasculitis (AAV) remain a critical but unmet need in the field of vasculitis research. The work of the
VCRC-OMERACT outcomes initiative is directly aimed at addressing this problem.

       We specifically aim to address the following in the 2-hour workshop:
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       1. Introduction to the field and issue of interest for workshop: Peter Merkel – 10 minutes
       2. Disease Damage. The discussion will be centered on the different approaches by the AVID
          and VDI projects (see above) and how to proceed and prioritize questions/work. We would
          also seek advice from OMERACT participants on the approach to finalize and validate
          revised instruments. Potential discussion leaders: Philip Seo and Raashid Luqmani;
          TOTAL = 45 minutes.
       3. Disease States. Work prior to the meeting should allow for a review, feedback, and
          approval for consensus definitions of “remission”, “low disease”, “moderate disease”, and
          “high disease”, possibly with two tiers for each (“on treatment” and “off treatment”) and a
          time factor. The workshop would open the discussion beyond the vasculitis community to
          help us determine what, if any next steps are needed and help assess the need and place for
          state definitions (controversial). Potential discussion leaders: Alfred Mahr and Peter
          Merkel; TOTAL = 30 minutes.
       4. Disease Activity. Work from the COMEX (see above) and preliminary CANVAS
          exercises as well as data analyses from clinical trials on performance of activity scores will
          form the basis of a focused discussion on how to generate data to create a new instrument.
          Potential discussion leaders: Tuhina Neogi and Oliver Flossmann; TOTAL = 30 minutes.

Since we do not wish to lose focus on the main objectives and have limited time, we will defer use of
break-outs. However, we remain open to advice on this matter. Furthermore, we would think that
voting may have a role but also will take guidance on that and will need to see how the work
progresses. For example, we may seek a vote on next steps for the group to consider where there are
divergent opinions or options. This feedback from non-insiders could be refreshing.

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