Rare Disease Report

Patient-Centered Outcome Measures

NOVEMBER 08, 2017
James Radke, PhD
Most people agree that Patient-Centered Outcomes Measures (PCOMs) are measures that should be a part of the drug development and regulatory process. The U.S. Food and Drug Administration (FDA) embraces the concept, as do most advocacy groups and pharmaceutical companies.

Unfortunately, PCOMs are still new to the clinical trial space. Primary outcome measures for a clinical trial tend to favor older, quantifiable outcome measures that allow for historical comparisons and conclusively show if a drug is having a physiologic affect.

A classic example of an older outcome measure deemed somewhat irrelevant is the 6-minute walk test (6MWT) for patients with Duchenne muscular dystrophy (DMD). The 6MWT is only of value during a 3- to 4-year period in a young DMD patient’s life when there is a rapid decline in ambulation (around the age of 10-14 years). The test is inappropriate for younger patients since their decline in ambulance is too slow to show a statistically significant effect, and most older patients cannot walk at all.

As a result, only a small portion of an already small population are generally used for many DMD-related clinical trials. That is slowly changing, but the introduction of novel outcomes measures for DMD studies now involve muscle biopsy results or respiratory measures. Neither measure addresses what is truly important to the patient.

To better understand how to integrate PCOMs into clinical trials and the regulatory progress, the International Rare Diseases Research Consortium (IRDiRC) set up a Task Force on PCOM that stated PCOMs for rare diseases are a ‘necessity,’ but one that requires a lot of work, open dialog, and collaboration among all parties involved. Expanding on the Task Forces’ report, a new article in Orphanet Journal of Rare Diseases by Thomas Morel of KU Leuven in Belgium and Stefan J. Cano, PhD, of Modus Outcomes in London, England.

Morel and Cano provide a ‘roadmap’ to improve PCOM use in rare disease clinical trials and listed 5 key components:

1. Collaboration
Developing PCOMs for a rare disease requires collaboration and should be considered as ‘a non-competitive activity where expertise and resources are pooled.’

Morel and Cano noted that many rare diseases already have a good network of patients, patient groups, health professionals, researchers and drug developers working together to promote scientific knowledge. This collaborative spirit should extend to PCOM research.

The authors suggest that clusters of ‘drugable’ targets/pathways emerge and they be identified as those that can guide outcome measure options.

2. Alignment
There should be a more aligned use of PCOMs in clinical trials and registries, stated Morel and Cano. The authors noted that “incorporating fit-for-purpose instruments that focus on outcomes that truly matter to patients would enhance patients’ acceptance of the burden brought by managed entry agreements on their daily life.

The authors suggest that early clinical studies use multiple outcome measures to allow the development of the most appropriate outcomes to emerge as the clinical trial proceed. To that end, patient groups should be involved in early stages of the process to provide their input on outcomes measures that are relevant to the patient population.

3. Integration
The authors note that value assessment tools incorporate ‘fit-for-purpose instruments’ so that PCOMs are a focus in determining the value of a medication.

4. Innovation
When new information emerges that PCOMs, however unconventional, may be more appropriate as a major primary outcome, it should be embraced by the entire community. The authors also noted that “as our knowledge on natural history for every single rare disease keeps increasing, we must be ready to challenge the established order and any ‘clinically validated’ endpoint altogether.”  

5. Communication
There is a lot of research currently being performed showing the value and importance of PCOM. Unfortunately, much of that research, in the authors’s opinion, is often under-published. More effort to publish PCOM information in highly cited scientific journals and conferences should be taken. Similarly, information (i.e., training materials) should be made available to help patients and advocacy groups steer PCOM research moving forward. 

Morel and Cano concluded their recommendations with the comment that therapies for rare diseases should be developed to treat the patient and not just the disease. To do that, we need more collaboration among all interested parties to ensure new PCOMs can emerge as a means to measure and guide clinical trials.

Morel T, Cano SJ. Measuring what matters to rare disease patients – reflections on the work by the IRDiRC taskforce on patient-centered outcome measures. Orphanet JRare Dis. 2017;12:171 https://doi.org/10.1186/s13023-017-0718-x

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