Patient Outcomes Need to Take Center Stage in Developing Rare Disease Treatments

Magdalena Kegel avatar

by Magdalena Kegel |

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The successful development of meaningful therapies for rare diseases such as Angelman syndrome requires scientists to find out what matters most to patients with these conditions, two European researchers argued in an opinion piece promoting patient-centered outcomes.

In the commentary, published in the Orphanet Journal of Rare Diseases, the duo argued that although patient-centered outcomes is an increasingly hot topic, plenty of work remains before they will be implemented properly in clinical trials.

Researchers first need to determine which factors are important to patients with various rare diseases, and then learn how to measure them in an adequate way, they wrote in the article, Measuring what matters to rare disease patients – reflections on the work by the IRDiRC taskforce on patient-centered outcome measures.

The researchers — Thomas Morel of KU Leuven in Belgium, and Stefan J. Cano of Modus Outcomes in the U.K. — pointed out that currently used outcome measures in clinical trials often fail to measure patient benefits, leading to increasing difficulties in getting new treatments approved by regulatory authorities.

“Core to these failures is the inability to demonstrate statistical significance and meaningful benefit,” they wrote. “Failed therapies or flawed outcome measurement?”

Moreover, therapies that are approved may not be reimbursed by healthcare payers if they consider the evidence supporting a treatment’s effectiveness inadequate.

They are supported in this view by the U.S. Institute for Clinical and Economic Review, which also state that clinical trials often fail to measure issues important to patients.

“Has the rare disease voice been lost in translation?” Morel and Cano asked.

So what can be done about this situation?

In 2011, the European Commission and the U.S. National Institutes of Health started an initiative known as the International Rare Diseases Research Consortium to allow the growth of global collaboration and investment in rare disease research. Four years later, the consortium set up a task force on Patient-Centered Outcome Measures.

The task force acknowledges that patient-centered outcome measures are key to advancing rare disease therapy development. But plenty of obstacles to the implementation of such outcomes exist.

For instance, researchers need to agree on which outcomes to measure. In this respect, patients need to be involved in identifying the issues they care about most. Nevertheless, patient-centered outcomes are not limited to patient-reported outcomes.

In addition, observations by doctors and other observers, or therapy performance ratings, also might be considered patient-centered outcomes. But, to be valid, patients need to confirm that proposed factors are, indeed, important, as the issues identified by doctors may not be what is close at heart to patients.

“Because a rare disease affects every aspect of their daily life, patients and their caregivers become experts of the rare condition and of the important outcomes of diseases that need to be addressed,” Morel and Cano wrote.

But the process of gathering patient opinions, just as any rare disease research, is made difficult by the small numbers of patients affected by a condition, who often are spread around the globe.

Another hurdle lies in the fact that more than half of all rare disease patients are children, in which the reliability of self-reports is not adequate. It also is difficult to assess the relevance of observer reports in children, they argued.

Importantly, learning to understand what is dear to patients requires researchers to step back from the typical “how much?” questions they are used to ask, instead focusing on qualitative aspects by asking “what?” and “how?” questions.

While there are several methods that can be used to obtain such information, the duo argued that patient organizations play a key role in any such work. Working together with researchers, such organizations can “steer, or even lead” the work to identifying key issues in various patient groups, they argued, providing examples from work of successful patient organizations.

Once factors important to patients have been identified, however, researchers need to learn how to correctly measure them. Considering the vast number of rare diseases, each affecting only a small number of patients, it may be more feasible to adapt existing tools rather than develop new ones.

Another way to speed up the work would be to use common measures for similar diseases or conditions sharing certain features, they suggested.

Patients need to be involved in this part of the process, they maintained, because only a patient can provide the feedback needed to allow for correct interpretation of a measure. For instance, a patient can offer the perspective that allows understanding of questions such as “What does a 2-point change on a 0- to 10-point scale mean? Is a 2-point change from 10 to 8 saying the same as a change from 4 to 2?”

Among the important points Morel and Cano made was to underscore that rare disease research in general, and patient-centered outcomes in particular, should be considered a non-competitive activity, in which resources and expertise are pooled to advance outcomes.

“A multi-stakeholder collaboration should emerge, with the rare disease patient community at its center, to promote the development and use of Patient-Centered Outcomes Measures to help achieve Patient-Centered Care across all rare diseases,” they concluded.