Lost in Translation

December 8, 2017

If you want to understand the value of patient-centered outcome measures, consider people with the rare progressive muscle disease Duchenne muscular dystrophy. Children with the condition usually develop muscle weakness around the age of four. Muscle loss begins in the upper legs and pelvis and then progresses to the upper arms. Many of these children are unable to walk by the time they turn 12.

In an online article in Orphanet Journal of Rare Disease, Thomas Morel, a research fellow at KU Leuven in Belgium, and Stefan Cano, a co-founder of the consulting firm Modus Outcomes in the United Kingdom, note that until recently, the focus of DMD drug trials has been assessment of patients’ motor function with the use of the six-minute walk test and standardized clinical assessments of patients ability to walk. But they note Duchenne patients on average lose their ability to walk by the time they are a little more than 10-years-old. With a median survival today of 30, most people affected by DMD, don’t walk.

When the Netherlands-based advocacy group Duchenne Parent Project assembled a broad group of stakeholders that identified the need for novel outcome measures for use across the whole spectrum of DMD patients, they found that what mattered to patients was their ability to put their arms on the table, to be able to use a computer keyboard, to brush their teeth, or pour a drink. As a result, they developed a means for evaluating performance of the upper limbs, and developed patient-reported outcome survey to measure those things that wouldn’t be apparent in the clinic.

“Rare disease therapies should be developed to treat patients, not just their disease: our ability to evaluate outcomes that reflect real benefits from the patient perspective is thus of pivotal importance,” write Morel and Cano. “Current clinical research and practice, however, are not quite there yet.”

Clinical studies of experimental therapies for rare disease pose many challenges. The heterogenous nature of these disease, the small patient populations, and the lack of understanding about the natural history of diseases can make the development of meaningful endpoints challenging. While there’s a growing effort to align clinical outcome measures with the issues that patients define as having the greatest benefit to them, too often outcome measures rely on surrogate endpoints that fail to capture the true value of a drug to a patient. A drug may that provides benefits to patients may be rejected by regulators or declined for reimbursement by payers because the outcomes measured in a trial may fail to reflect significance in regards the endpoints used in a trial.

Patient-centered outcome are measures that reflect health outcomes that matter to patients. The authors note these measures should “always be ‘fit-for-purpose.’” They should measure outcomes that resonate with patients’ daily experience of the disease, preferences, expectations, and values.”

The good news is that efforts to use patient-centered outcome measures are gaining ground. The U.S. Food and Drug Administration has promoted the use of patient-centered outcome and they have gotten more traction with the 21st Century Cures Act, and the Prescription Drug User Fee Act VI.

Collaborations will be key to establishing patient-centered outcome measures. The authors advise that the process is time-consuming and resource-intensive. It should be considered “as a non-competitive activity where expertise and resources are pooled.” Most drug developers and small- and medium-sized companies are without the in-house expertise to develop patient centered outcome measures on their own, working collaboratively would boost creativity, share costs, and avoid the inefficiency of developing multiple instruments for the same purpose. It should include a broad set of stakeholders, such as patient groups, researchers, health professionals, drug developers.

This represents a critical issue for patients, particularly as the pace of innovation advances new therapies, and even potential cures into the clinic. The authors note there’s an opportunity for patient groups to play a leadership role in establishing these measures and point to the work of such groups as Parent Project Muscular Dystrophy, Cure SMA, and the Myotonic Dystrophy Foundation as examples. Patient groups should not sit by waiting for an invitation to the table. They should take the initiative to organize, initiate, and convene such collaborations.


This week’s Global Genes’ RARECast features a conversation with Thomas Morel about the Ophanet Journal of Rare Diseases article. You can find it here.

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