Understanding Patient Perspective Critical in Benefit-Risk Assessment

Duchenne Muscular Dystrophy Illustrates Potential Utility of Innovative Benefit-Risk Assessments in Regulatory Review

01.06.14 | By Kristin Van Goor

The assessment of the benefit-risk balance of a medicine is a key component of the drug development and regulatory review process. This assessment is also an important determination that each patient and doctor must make when choosing a treatment strategy. Often, the elements considered to be most pivotal to this assessment differ depending on whether you are the patient, physician, regulatory or manufacturer.

As the following guest blogpost by Holly Peay, Vice President of Education and Outreach for Parent Project Muscular Dystrophy, and Timothy Franson, Principal at FaegreBD Consulting, explains, the understanding of the severity of the disease and the patients’ risk tolerance is an important component of the benefit-risk assessment process, particularly when evaluating new medicines to treat rare diseases, such as Duchenne Muscular Dystrophy, for which there are no or few treatment options. Holly and Tim elaborated on these ideas in a white paper they recently co-authored entitled, Benefit-Risk Assessments in Rare Disorders: The Case for Therapeutic Development in Duchenne Muscular Dystrophy as the Prototype for New Approaches.

We are committed to working with the FDA, patient organizations, and all stakeholders on exploring new approaches to understanding and incorporating the patients’ perspectives into the drug development and regulatory review processes to advance the development of medicines to meet currently unmet patient needs.


Benefit-risk (b-r) assessments are the “bottom line” for regulatory product approvals, and an important consideration when prescribers and patients select treatments. Regulators perform b-r assessments to size up that balance from a population perspective.

In contrast, patients, caregivers, and healthcare practitioners approach the same issue through the lens of the affected individual. These stakeholders may use different sources to inform deliberations about b-r tradeoffs, may define and prioritize benefits and risks differently, and may differ on the strength of evidence required to make a decision.

Parent Project Muscular Dystrophy (PPMD) and other rare disease communities hope to see treatment preferences and risk tolerance of patients and families play a much larger role in FDA’s deliberative processes. This is especially important for progressive diseases that currently have limited treatment options. Duchenne Muscular Dystrophy (Duchenne), a rare progressive muscle disease diagnosed in childhood, presents a prototype for new approaches in rare disease treatment advances, in both spirit and concept.

The FDA’s b-r evaluation processes are usually well described for common diseases, but rare disorders require unique considerations. For example, risk assessments for new drugs to treat common diseases can be compared to well-described natural history of the disease, and previous studies in large populations. However, many rare diseases lack extensive natural history studies to profile their disease progression and there may be considerable variations in disease course across patients. These difficulties faced by rare disorder clinical trials must be framed against a backdrop of a progressive, fatal disorder. The challenges of lack of precedents, uncertain natural history, and few potential trial participants confront sponsors and regulators; but most importantly, these challenges frustrate families, who are watching their children decline. In public forums, many parents ask for a faster development and approval process, with more regulatory tolerance for uncertainty and risk.

However, regulators and reviewers should rightly question how well anecdotal reports from patient advocates reflect the perceptions of the broader patient/parent community. To better frame evolving b-r assessments, innovative approaches are required to capture the range of treatment benefits valued by patients, as well as their tolerance for risk factors.

PPMD recently completed a survey of 119 Duchenne caregivers which provides new information about b-r. As one example, stopping or slowing muscle weakness were highly valued treatment attributes, even absent survival benefits, and participants were willing to accept increased risks for such benefit tradeoffs. These findings are relevant to how regulators assess b-r in integrated fashion. The data are consistent with FDA’s patient focused drug development program, and therefore could impact how study design, endpoint factors and other key considerations are assessed.

Duchenne illustrates the potential utility of innovative b-r assessments in amending regulatory frameworks, especially when based on sound data. PPMD’s Duchenne benefit/risk study can be used as a model for rare disorder b-r pursuits, and could also translate into use for individual b-r deliberations in practice settings. In the case of Duchenne, with few options for intervention, caregivers and patients often feel powerless to change the outcome of the disease. Participating in data-gathering activities allows them to contribute to the process and empowers the patient voice.

The voice of the patient took center stage at PPMD’s recent Duchenne Policy Forum. In attendance were patients, caregivers, industry, clinicians and 18 members of the FDA. The Agency was there to listen and address topics such as unmet medical need, natural history, surrogate markers, and benefit risk assessments in Duchenne. The goal of the meeting was to begin the development of draft guidance on Duchenne to reflect the combined experience and wisdom of the Duchenne community. PPMD is committed to leading a community-wide effort to develop guidance by mid-2014 to inform and accelerate the agency's review of Duchenne candidate therapies.

New approaches are required to expedite the development of treatments for diseases like Duchenne, which have no approved treatments and both figuratively and literally threaten “life and limb”. Patient organizations can play a vital role in gathering such information, to assure that patient perspectives are fully integrated in regulator b-r decision-making. Benefit vs. risk translates to life or death in drug development outcomes.

For more information on the treatment preferences study visit this link.

To read family stories about Duchenne priorities visit this link

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