How a patient advocacy group developed the first proposed draft guidance document for industry for submission to the U.S. Food and Drug Administration

Furlong et al. Orphanet Journal of Rare Diseases (2015) 10:82 DOI 10.1186/s13023-015-0281-2 REVIEW Open Access How a patient advocacy group developed the first proposed draft guidance document for industry for submission to the U.S. Food and Drug Administration Pat Furlong1*, John F. P. Bridges2, Lawrence Charnas3, Justin R. Fallon4, Ryan Fischer1, Kevin M. Flanigan5, Timothy R. Franson6, Neera Gulati7, Craig McDonald8, Holly Peay1 and H. Lee Sweeney9 Abstract Among the challenges confronting patients with rare diseases is a dearth of treatment options. The development of safe and effective new therapies is hampered by challenges associated with conducting clinical trials in small populations. In this article, we describe how the Duchenne muscular dystrophy community–led by Parent Project Muscular Dystrophy–created a proposed draft guidance document for industry for submission to the U.S. Food and Drug Administration. This unprecedented undertaking involved a broad coalition of more than 80 stakeholders collaborating across nine time zones to produce a document in only 6 months. We hope that other rare disease communities and advocacy organizations can use our experience as a model for developing their own draft guidance documents. Keywords: FDA, Industry guidance, Duchenne muscular dystrophy, Public policy, Advocacy, Rare disease, Clinical trial, Patient engagement, Drug development Introduction Duchenne muscular dystrophy (Duchenne) is a genetic disorder characterized by progressive muscle weakness and degeneration [1–4]. It is caused by a mutation in the gene that encodes dystrophin, a protein critical to muscle integrity [1, 2, 4]. Boys are affected almost exclusively, with an estimated incidence of approximately 1 in every 4000 live male births [2, 4, 5]. Duchenne is typically diagnosed between 3 and 5 years of age, following the onset of symptoms such as delayed walking, difficulty climbing stairs, frequent falls, and difficulty running and jumping [1, 2, 4]. More than 90 % of patients require the use of a wheelchair by their midteens [5]. Weakened heart and lung muscles lead to various cardiac and pulmonary complications (e.g., cardiomyopathy, difficulty breathing, respiratory infections) [2, 4]. * Correspondence: 1 Parent Project Muscular Dystrophy, 401 Hackensack Avenue, 9th Floor, Hackensack NJ 07601, New Jersey Full list of author information is available at the end of the article Affected individuals may also have varying degrees of cognitive, behavioral, or language impairment [4]. Within the last 15 years, individuals with Duchenne did not survive much beyond their teen years [1, 2, 4]. With improvements in care, the mean lifespan has increased to more than 25 years, with some patients living into their 30s, 40s, or even 50s [1, 2, 4]. Corticosteroids are prescribed off-label to slow the decline in muscle strength and function; current treatment guidelines recommend their use in all qualified individuals [4]. No drug currently has an FDA-approved indication for Duchenne [6]. To help accelerate the development and review of potential therapies for Duchenne, the Parent Project Muscular Dystrophy (PPMD) spearheaded an effort to develop the first patient advocacy-initiated draft guidance for a rare disease. This report details the process used to write the guidance, which included a broad coalition of more than 80 stakeholders collaborating across nine time zones. It is our hope that other rare disease © 2015 Furlong et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Furlong et al. Orphanet Journal of Rare Diseases (2015) 10:82 communities and advocacy organizations can use this model for developing their own draft guidances. Deciding to develop draft industry guidance The decision to develop a draft industry guidance came after PPMD had been working for more than a decade to educate the FDA and other regulatory agencies about Duchenne and its catastrophic effects on both patients and families. Several events were pivotal in making this decision. In March 2013, the European Medicines Agency (EMA) issued a draft guideline for public comment on the clinical investigation of medicinal products for the treatment of Duchenne and Becker muscular dystrophy [7]. The community stakeholders believed this draft guideline did not adequately address the needs of the Duchenne community. In response, PPMD convened an expert advisory committee to develop and issue recommendations about how the U.S. Food and Drug Administration (FDA) could most effectively evaluate new therapies for Duchenne. The committee included leading voices in academia, industry, and patient advocacy. The resulting white paper, “Putting Patients First,” was released in April 2013 [8]. PPMD also held several meetings with the FDA about developing a guidance for Duchenne. In July 2013, PPMD met with FDA staff that included Center for Drug Evaluation and Research director Janet Woodcock. The meeting was a continuation of ongoing efforts to provide the agency with relevant information and data that might encourage greater flexibility in the drug review process. One of the topics discussed was the possibility of a guidance for industry addressing drug development for Duchenne. The purpose of such a document would be to assist sponsors in the clinical development of drugs and address the FDA’s current thinking about various issues that arise at all stages of product development, including the types of clinical trials that could be used to demonstrate efficacy and safety. Guidance documents traditionally have been authored by FDA staff. During the discussion, the FDA staff acknowledged that the agency had neither the time nor resources to develop industry guidances for many of the rare diseases that might benefit, including Duchenne. As an alternative, FDA staff invited PPMD to submit a proposed draft guidance document, pursuant to language in the 2011 Good Guidance Practice (GGP) provisions [9]. A wellwritten proposed draft guidance could serve as the basis for–and hasten the development of–FDA’s own version of an industry guidance for Duchenne. PPMD knew this invitation could not be declined. But given that no one outside FDA had ever developed a guidance document for industry, accepting the invitation meant entering uncharted territory. To begin navigating that terrain, PPMD organized a daylong policy forum Page 2 of 9 modeled on a recently concluded scientific meeting in London. The policy forum, titled “Optimizing Clinical Trials in Duchenne Muscular Dystrophy in the New Era of Impr (...truncated)