Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis — an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the Continental Divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Tugwell said.
Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
Dr Maarten Boers (left) and Dr Peter Tugwell, founders of OMERACT
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Tugwell and Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
Attendees gathered for a photo at the OMERACT 2018 meeting, the last time that the organization was able to hold its biennial meeting in person.
OMERACT Accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
“Speed Is a Limitation”
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A Consensus on Pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking Ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s Patient Participants Bring Important Perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
Source: Read Full Article