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In the summer of 2015, rare disease research achieved an exciting milestone: for the first time ever the U.S. Food and Drug Administration (FDA) used a proposed draft guidance prepared by a parent advocacy group as the basis for its own draft guidance for industry. The document, “Duchenne Muscular Dystrophy and Related Dystrophinopathies: Developing Drugs for Treatment,” is intended to assist companies in the clinical development of drugs for the treatment of Duchenne muscular dystrophy and related conditions. X-linked Duchenne muscular dystrophy (DMD) is a progressive and fatal muscle-weakening condition that affects approximately 10,000 to 15,000 people in the U.S., mostly men and boys. Specifically, this guidance addresses FDA’s current policy thinking regarding the clinical development program and clinical trial designs for drugs to support an indication for the treatment of one or more of these dystrophinopathies.

The suggested guidance was prepared by Parent Project Muscular Dystrophy (PPMD), an independent advocacy group, which assembled a committee of parents, scientists, drug company executives and clinicians. Their goal: accelerate drug development for Duchenne, and provide perspective on what makes sense in a trial protocol to meet the needs of regulators and patients. The group encouraged FDA to expand use of accelerated approval for therapies, and to expand the scope of acceptable endpoints. For example, a hallmark of these trials is a six minute walking test as a primary measure of a drug’s success. But this tests eliminates most children under the age of seven, and all of the patients who can no longer walk from participation. They argue that using a test that eliminates such a broad swathe of the patient population is counterproductive for sponsors and frustrating for parents who are desperate to find a cure. Instead they suggested other scientifically relevant tests to measure success, including time to rise from the floor, and pulmonary and cardiac measures.

The documents also suggests giving greater weight to the benefit/risk preferences of patients and caregivers in the case of pediatric illness. To highlight the stark reality of this this point, one parent of a 17-year-old with Duchenne’s wrote: “Duchenne has taken so much from him that I would consider treatments that would allow him to keep the function he has now, even if there are some risks. This may not have been true 10 years ago.” She goes on to argue that the concept of risk vs. reward changes over time, and that older boys who need treatments as fast as possible are probably more willing to accept more risk for what may seem a little reward. “We are willing to take a chance,” she said. “It’s better than no chance at all.”

It is this kind of insight that statisticians won’t find in databases of research, or peer reviewed articles, and it underscores the importance of putting the voice of the patient into the trial design.


Patient advocacy groups are a strong voice in the rare disease research community and valuable allies for biopharma companies. The most powerful among them raise money to support research they deem important, collect data in online patient registries, and are willing to offer feedback to regulators and researchers on the ‘patient important outcomes’ that can determine participation in a trial.

When biopharma companies take time to listen to their advice, and factor their feedback into the trial design, they may discover that this helps them craft a protocol that is more acceptable to patients and parents. This results in a more efficient recruitment process and higher levels of retention, which in turn cuts time and costs while improving the odds of success.

However, to harness the value these groups bring to the table, researchers need to embrace a culture change in the way they plan and manage trials. It can be easy to dismiss the voice patients and caregivers in favor of scientists and statisticians, but neither group of experts has all the answers. While a parent may not be aware of all of the intricacies involved in the regulatory approval processes, so too do statisticians often miss or ignore patient important outcomes, like the fact that maintaining hand-eye coordination is important to Duchenne patients even if they can no longer walk, or not putting children through invasive and seemingly unnecessary procedures as a condition of enrollment in a trial.

Change is hard, especially in the biopharma world, but making room for the patient’s voice will benefit these trials down the line. When it comes to rare disease research, any change that can drive effective treatments to market faster should be warmly embraced by everyone involved.