Clinical trials are only as credible as their endpoints

In the 1980s, there was considerable variation in the way clinical measures were used to make judgments about the effectiveness of treatment.¹ It is because of this notion that OMERACT, or ‘Outcome measures in Rheumatology’ – an international initiative established in 1992 – began to redefine outcome measures in rheumatology research. Spun out of a need to develop consensus between clinicians on the appropriate endpoints to include in rheumatoid arthritis (RA) trials, the OMERACT process is widely accepted and has been applied to many other musculoskeletal conditions.^2,3

OMERACT is committed to developing data-driven, interactive, consensual, health outcome measures. These are not only aligned across clinicians and researchers, but other relevant stakeholders – which includes patients. The result is the development of ‘core outcome measurement sets’ that all clinical trials in a given health condition should report on. To become an accepted measure endorsed by OMERACT, it must pass the OMERACT Filter – that is ‘Truth, Discrimination and Feasibility’ in each of its intended settings.²

To understand the process from the inside out, and discuss how rheumatologists are leading the way with PROs, the limbic spoke with OMERACT veteran and Melbourne rheumatologist Professor Peter Brooks, Honorary Professor at the Centre for Health Policy, University of Melbourne.

PROs: Speaking the same language in order to meet common goals

In most clinical situations there are two narratives – the patient’s experience living with their disease on a daily basis and the clinician who sees the patient twice a year, says Prof. Brooks.

“What is important is that both are speaking the same language so common goals of management can be met,” he explains.

Early on OMERACT pioneers recognised the limitations of some existing clinical trial outcomes. If descriptions of outcomes are framed in a way that patients either do not understand or find them irrelevant, their practicality comes into question.

In true shared-decision making, patients must understand and align to the management goal. “If not, clinicians may be setting themselves up for failure if measuring treatment success in this way,”⁴ explains Prof. Brooks.

This is why OMERACT explored the addition of patient reported outcomes (PROs). PROs are reports of how a patient is feeling or functioning in relation to their health condition and its therapy without interpretation by healthcare professionals or anyone else.⁵ They can relate to symptoms, signs, functional status, perceptions or other aspects such as treatment convenience and tolerability.⁵

The purpose of OMERACT was to develop a process that defined a set of outcome criteria that were evidence based and internationally recognised as the gold standard, explains Prof. Brooks. Initially the OMERACT team thought this would be relatively easy to achieve, but this turned out not to be the case.

“Because the European bodies worked in one way and the US in another, it was challenging to find compromise – but eventually we got there. Over the years, we’ve developed criteria for multiple conditions, numerous reports and as an organisation we’ve really led in terms of developing epidemiological criteria. In the end four outcomes emerged as key, that is death, life impact, resource use and pathophysiological manifestations.”

Indeed, OMERACT has been leading the way with patient involvement in their proceedings since 2002.⁴ Now, every aspect of its activities automatically requires patient participation.⁴ Thanks to PRO measures such as fatigue –initially disregarded as a credible outcome – this is now considered to be central to the understanding of the effects of inflammatory arthritis.⁴

“Having patient involvement has made an enormous difference in the way we look at things. We now have data that shows that if you involve patients in these decisions that the measures are much more robust.⁶ It’s really added another dimension to the way we look at trials and endpoints,” says Prof. Brooks.

He adds, “you see similar effects in terms of patient engagement with treatment when patients are encouraged to participate in the treatment decisions. Whether it’s sharing patient notes or involvement in organisations like OMERACT, patients need to be engaged and we need to be talking the same language to really communicate effectively. In its purest form, that’s what PROs are all about – finding ways to measure the impact of disease and management that’s relevant to the patient’s experience.”

How well do PROs correlate with clinical measures of disease and are they useful in predicting long-term patient outcomes?

Prof. Brooks explained, “generally, when managing patients with rheumatological disease we have two objectives. First is symptom resolution – which PROs can be very useful for. They are generally reproducible and sensitive to change. For example, if joint pain is present, the resolution of pain as soon as possible is a logical outcome measure.”⁵

“The second objective is the prevention of subsequent structural deterioration. There has been debate over the years as to the predictive value of PROs as they currently stand for later outcomes. Some, like fatigue, which are very useful for our first objective, are not yet clearly defined in the disease process, and so their predictive value remains unresolved.”⁵

So, are there barriers to the uptake of PROs in clinical practice? “Sometimes there may be a reticence on the part of healthcare professionals to engage patients in clinical decision-making, perhaps due to time constraints during consults,” Prof. Brooks notes. “But some clinical practice shows that if you take the time to understand your patient’s goals of disease management it may lead to better outcomes.”⁶

Is rheumatology ready for technology to start supporting PROs in practice?

Patients are becoming smarter and more technologically savvy and the onus is on the clinician to keep up, says Prof. Brooks . “The opportunities through mobile health for patients to learn about their disease using various apps, using telemedicine consultations etc. is fantastic. We as healthcare professionals really need to engage with that because otherwise patients are going to disengage.”

 According to Prof. Brooks when it comes to specific technologies for monitoring health and treatment outcomes clinicians are often on the backfoot compared to their patients.

“As we’ve already seen in other areas like diabetes, patients are becoming increasingly capable of recording and monitoring their health data (such as blood glucose or HbA1c) and sharing them with their clinicians. These sorts of things are happening right now.”⁷

Prof. Brooks encourages other clinicians to embrace emerging technologies “as they can help widen our view of the patient situation, which can only help to align those two narratives into one.”

This article was sponsored by AbbVie (Mascot, NSW), which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of AbbVie. Treatment decisions based on these data are the full responsibility of the prescribing physician.

References:

1. Boers M et al. The OMERACT Handbook, OMERACT June 2017.
2. Tugwell P et al. Trials 2007;8:38.
3. Tugwell P, Boers M. J Rheumatol 1993, 20:528–530.
4. Kirwan JR et al. Arthritis Rheum 2016;68(6):1334–1336.
5. Gossec L et al. RMD Open 2015;1:e0010019.
6. Slade M. World Psychiatr 2017;16:146–153.
7. Wu Y et al. JMIR Mhealth Uhealth 2017;5(3):e35.