Meeting report: the ALPHA project: a stakeholder meeting on lupus clinical trial outcome measures and the patient perspective.

Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome measures to accelerate development of lupus therapeutics.

The ALPHA Project: Establishing consensus and prioritisation of global community recommendations to address major challenges in lupus diagnosis, care, treatment and research.

The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus effort to identify, prioritise and address top barriers in lupus impacting diagnosis, care, treatment and research. To conduct this process, the ALPHA Project convened a multistakeholder Global Advisory Committee (GAC) of lupus experts and collected input from global audiences, including patients. In phase I, the ALPHA Project used expert interviews and a global survey of lupus experts to identify and categorise barriers into three overarching pillars: drug development, clinical care and access to care. In phase II, reported here, the GAC developed recommended actionable solutions to address these previously identified barriers through an in-person stakeholder meeting, followed by a two-round scoring process. Recommendations were assessed for feasibility, impact and timeline for implementation (FIT), where potential FIT component values were between 1 and 3 and total scores were between 3 and 9. Higher scores represented higher achievability based on the composite of the three criteria. Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.

Unique Burdens of Pediatric Clinical Trials in Duchenne Muscular Dystrophy, April 20-21, 2017, Bethesda, Maryland, USA.

Recent increases in the number and breadth of clinical trials for patients with Duchenne muscular dystrophy (DMD) have engendered hope for a better future. Despite the overall enthusiasm by the DMD community for these trials, however, the burdens and pressures that they place on children with Duchenne muscular dystrophy and their families have become painfully apparent. In order to identify, and mediate, these challenges, Parent Project Muscular Dystrophy (PPMD) sponsored a meeting to examine some of these issues more closely in Bethesda, Maryland, on April 20-21, 2017. The meeting focused on key burdens for patients participating in clinical trials including technical (protocol complexity), financial, psychosocial and emotional issues, and informed consent. Participants recommended mitigation strategies falling into clinical, operations, regulatory, and ethical domains. The development of consensus action plans for short- and long-term enhancements in trials should facilitate discovery and development research for DMD patients.

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

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.

The practicing clinician and regulatory safety concerns.

Pharmaceutical agents are prescribed to produce a therapeutic effect, but safety concerns require constant attention to the benefit:risk relationship inherent in their use and the needs of the individual patient. Such calculations involve assumptions about the likely tolerability of harm, in that greater safety risks may be acceptable for use of a lifesaving drug, compared with those acceptable for an agent providing only improved "quality of life." Making such assumptions is an activity integral to the bedside clinician's role, is done during many (perhaps most) patient encounters, and is often undertaken with inadequate information. The historical mandates for regulatory agencies, such as the Food and Drug Administration (FDA) in the United States, have evolved over the past decades to include an intense focus on drug safety. Communicating information about medicinal risk remains a major responsibility for the FDA and similar bodies, but the initiatives undertaken have had variable, and often limited, effectiveness in penetrating the physician-patient interaction. Barriers to the successful communication of safety-related issues include the myriad of influences on and within the FDA, the time constraints on physicians involved in clinical practice, and the methodologies used to share information about both established and new drugs. Current efforts to assess the effectiveness of regulatory efforts at risk communications should lead to changes in the approaches used and, ultimately, improvement in the safe use of both new and established drugs.