2 Strategies For Rare Disease Clinical Research Patient Centricity
By Eugene Sullivan, M.D., chief product strategy officer, Insmed
The last decade has brought a wave of progress for rare disease research and development, with scientific interest at what feels like an all-time high. With life-transforming innovation more attainable than ever before, we are succeeding despite the challenges inherent in the study of rare diseases. Yet despite these advancements, 95 percent of the approximately 7,000 known rare diseases1 still do not have an approved therapy. There are many complex factors at play and no simple solution to usher in the next era of progress, but perhaps the biggest key to future success would be to design holistic research programs that aim to first understand patients and their diverse range of experiences, needs, and priorities. Development programs that build on this foundational understanding are most likely to engender the support of patients and patient advocacy groups and are also most likely to succeed.
In rare disease R&D, we often must start from scratch with each clinical program — forging new regulatory pathways, identifying optimal endpoints, and finding the best ways to recruit an already limited pool of patients. Questions arise that would not come up in a more well-trod disease area — for example, which endpoints best capture the anticipated clinical benefit of the investigational drug? What’s a reasonable duration of study for a rare disease with a slower progression of symptoms? What type of evidence will be necessary to understand the potential benefits and risks of a drug and to achieve regulatory approval? And are there novel approaches to study design that can be applied to most efficiently generate that evidence?
We know it is important, in this process, to seek out the knowledge and experience of clinical and academic experts who can inform study design from the outset. But I would argue that the most critical expert voice is that of the patient. By prioritizing patient involvement throughout the process – listening to their insights and understanding their needs – we can achieve even greater progress in rare disease treatment.
Ensure Patient Advocacy Groups Have Seats At The Table
Throughout my career in both clinical research and advisory roles, I have seen time and again how valuable it is when patients aid the research process by describing, in their own words, how a disease affects their lifestyles; by identifying the most important measures of benefit; and by helping to spread the word about clinical trials and natural history studies. We regularly see the benefits of this inclusive approach in our work at Insmed. For example, when developing our first therapy, we engaged advocacy groups early on, right alongside treating physicians and academic experts, to weigh in on clinical trial design and help ensure patient considerations were pulled through. We maintained that open dialogue across the development process — even inviting patients to speak to our whole organization about their experiences and the impact of living with their disease. These direct patient insights provided a more informed starting point for our scientists and clinicians as they began protocol development, helped inspire employees across the organization in their respective functions, and even supported the packaging design of our approved product.
When considering a patient-centric approach, I recommend dedicating time to understanding the patient advocacy landscape. For example, is there one main patient advocacy group operating in a given disease area, or are there several that serve different roles for patients? Then, see if there are ways to compliantly meet with a few different representatives within those organizations who can help provide diverse perspectives about the patient experience. Also, if there’s an opportunity to get involved with surveys the groups distribute to constituents, this can be another good way to glean insights. Having this comprehensive background on the nature of each organization and its interactions with patients can set the stage for more effective outreach and understanding.
Capture Patient Insights And Patient-Reported Outcomes
Too often when studying rare diseases, it can be challenging to capture objective measures of benefit that are quantifiable, precise, and considered clinically meaningful. Our first line of sight into understanding the patient experience is usually through providers, who themselves may only receive a cross-section of a patient’s experience on a given day rather than a holistic picture of a disease’s impact. Patients — who frequently have a difficult path to diagnosis to begin with and then find themselves left with underwhelming treatment options — are generally self-motivated to help researchers investigate better treatments. Their input can help inform what potential benefits would be most meaningful in a new therapy and what incidence and severity of potential adverse events they would be willing to manage to achieve those benefits. Together with the critical perspectives of healthcare provider teams, we can use these invaluable patient insights to understand and work from the full picture of a disease and its impact.
As one example, at Insmed, we are developing a patient-reported outcomes (PRO) tool to better understand and measure the clinical manifestations of Mycobacterium avium complex (MAC) lung disease and its impact on patients. We are currently validating this tool based on both quantitative and qualitative research, including concept-elicitation patient interviews where patients were invited to share the impact of symptoms on their daily lives and the quality-of-life components that are most important to them. Using this input, we were able to design our study around how best to measure what matters most to patients.
PRO tools are certainly one way companies can ensure their research efforts keep patients at the center. And while developing a new tool is ideal, it is a resource- and time-intensive undertaking, and the logistics may not be feasible in every case. The FDA also offers guidance for repurposing existing PRO tools, which may be a reasonable path for companies looking to use a patient-reported primary endpoint without the complexity of creating and validating an entirely new tool. At times it may be appropriate to include existing related patient-reported outcome instruments as secondary or exploratory endpoints. There is a spectrum of options, all of which serve to enhance our understanding of the patient experience and expand the breadth of patient-reported data in any given disease. Each step forward in this regard is important.
The pursuit of better outcomes for patients with rare diseases serves as our North Star at Insmed. This was a big part of what led me to join the company, and it helps me feel connected to my earlier career as a treating physician. There is no substitute for hearing about a rare disease’s impact directly from patients themselves. Our ability to innovate and be successful in transforming patients’ lives will come from working hand in hand with patients and the advocacy community to elevate the patient voice and define clinical success from their perspective. By centering the development process around the patient experience, we can design stronger clinical trials while simultaneously inspiring our teams — whether in the labs, in the field, or in support functions — with authentic reminders of the seriousness of this work and the potential to bring hope to people with full lives and pursuits of their own outside of their disease.
Reference
1. National Organization for Rare Disorders. Rare Disease Day: Frequently Asked Questions. https://rarediseases.org/wp-content/uploads/2019/01/RDD-FAQ-2019.pdf. Accessed August 9, 2022.
About The Author:
Eugene Sullivan, M.D., is chief product strategy officer at Insmed. A medical doctor trained in internal medicine, pulmonary medicine, and critical care medicine, Sullivan has more than 20 years of experience with a focus on pulmonary and orphan diseases. Previously, he held positions at the FDA, United Therapeutics, and AstraZeneca related to clinical drug development and regulatory matters. He earned his medical degree from the University of Maryland, School of Medicine, and conducted his internship and residency in internal medicine at the Medical College of Virginia. Sullivan completed his fellowship training in pulmonary and critical care medicine at the University of Colorado Health Sciences Center and received a Master of Pulmonary Vascular Disease from the University of Bologna in Italy.