The following written comments were submitted to the Dockets Management Staff (HFA-305) Food and Drug Administration by IFFGD President, Ceciel T. Rooker, in response to Docket No. FDA-2019-N-0077 on April 30, 2019.
On behalf of the millions of Americans living with a rare gastrointestinal (GI) illness, the International Foundation for Gastrointestinal Disorders (IFFGD) thanks to the U.S. Food and Drug Administration (FDA) for the opportunity to provide comments to Docket No. FDA-2019-N-0077.
Established in 1991, IFFGD is a 501(c)(3) patient-driven nonprofit organization dedicated to assisting adults and children affected by both rare and common GI illnesses by providing education and support for patients, family members, health care providers, and the public. IFFGD also works to advance critical research aimed at broadening our understanding of the basic mechanisms and clinical care of these conditions and providing patients with better treatment options, and perhaps one day, cures.
Today, I am writing to you regarding FDA’s April 29 public meeting on “Patient Perspectives on the Impact of Rare Diseases: Bridging the Commonalities.”
We applaud the FDA’s continued efforts to bring the perspectives of patients and caregivers to medical product development and approval. To help facilitate patient and caregiver involvement in these processes, IFFGD has worked closely with the FDA for many years, including taking an active role in the 2015 FDA Patient-Focused Drug Development public meeting on Functional GI Disorders.
At IFFGD, we hear from thousands of patients and caregivers who struggle with the daily challenges of life with a chronic GI illness. Many of these conditions are listed as rare diseases by the National Institutes of Health Genetic and Rare Diseases Information Center (GARD) and include, for example, Hirschsprung’s disease, chronic intestinal pseudo-obstruction (CIP), achalasia, eosinophilic esophagitis (EoE), congenital sucrase-isomaltase deficiency (CSID), superior mesenteric artery (SMA) syndrome, and short bowel syndrome (SBS), among others. As advocates for patients and caregivers, we have long believed that we, and patient organizations in general, play a leading role in identifying and describing the needs of this patient population and developing real-world solutions together with members of the medical, research, and governmental communities.
Rare GI disorders can be disabling, and those affected often require a lifetime of care to manage the chronic and often unpredictable symptoms. Complicating this, bowel symptoms present unique difficulties for both patients and physicians. Bowel functions are not easily discussed, and stigma often disrupts open and honest conversations about the medical and emotional needs of those affected. For children, these conditions pose additional challenges, affecting physical and emotional growth, and presenting an ongoing struggle for parents and caregivers to understand and meet the needs of their child.
For example, Michele is a single mother with a child with CIP, a rare disorder of GI motility where coordinated contractions (peristalsis) of the intestinal tract become altered and inefficient. Describing her experience, she said:
“I can’t begin to tell you how many specialists my son had seen in the first five years of his life. His doctors took multiple tests over the years. He was actually misdiagnosed for many years. And every time I would take him to these doctors, I felt like I was never taken seriously. Each time we would see a new doctor, they would basically say the same thing: ‘We know there is something wrong, but we just don’t know what it is.”
Michele’s story illustrates some of the difficulties faced by parents of a child with a rare GI disorder. For both children and adults, life with a rare GI condition often means a seemingly endless search for answers. Little public awareness exists for most rare GI conditions, and basic, easy-to-understand information on the symptoms, diagnosis, and treatment of these conditions is largely unavailable. This often leaves patients and caregivers with feelings of uncertainty and frustration, left to piece together the limited information available to them on their own. Moreover, few clinicians have experience recognizing and managing these conditions, and clinical and investigative experience tends to be concentrated to relatively few, dispersed centers (Stoller JK. 2018. http://doi.org/10.1016/j.chest.2017.12.018.).
Taken together, this landscape of limited public awareness, patient information, and clinician expertise means patients often face diagnostic delays, sometimes suffering for years or even decades before receiving the answers and care they need. During this ‘diagnostic odyssey’ patients spend an average of six years before receiving an accurate diagnosis and the legitimization that comes with it, enduring two to three misdiagnoses and the subsequent inappropriate treatment, and undergoing numerous hospital admissions and investigations (Schieppati A, et al. 2008. https://doi.org/10.1016/S0140-6736(08)60872-7; Limb L, et al. 2010. https://www.raredisease.org.uk/media/1594/rduk-family-report.pdf). The cost to patients and families in terms of wasted time, effort, and resources are immense, and the loss of social and economic opportunities places a tremendous burden on those affected.
In view of the many challenges faced by individuals with rare GI illnesses, we are pleased that the FDA is seeking input from patients and caregivers regarding their experiences and perspectives on life with a rare disease. We hope that the insights gained from this meeting will help the FDA and medical product developers better understand the unmet needs of this population and advance the development of treatments and cures.
To aid the FDA in this endeavor, we have obtained responses from members of the rare GI patient community to the discussion questions published in association with the meeting. These responses demonstrate that general health and social function are significantly decreased in people with rare GI conditions and that treatments that target not only symptoms but the quality of life issues are needed. Specific to the discussion questions, we found the following:
Topic 1. Commonalities in symptom management and treatment considerations
1. What are you currently doing to help manage the symptoms of your rare disease or condition? (Examples may include, but are not limited to, prescription medicines, over-the-counter products, devices, non-drug therapies, or support services)
Broadly, we found that patients with rare GI disorders use a combination of treatment approaches to manage symptoms including, but not limited to, prescription medications, dietary modifications, probiotics and dietary supplements, stool softeners, surgeries, endoscopic procedures, meditation and mindfulness approaches, biofeedback and physical therapy, massage therapy, enteral and parenteral nutrition support, ileostomy and colostomy, and social support.
2. What factors do you take into account when making decisions about how to manage your symptoms?
Patients with rare GI illnesses research therapies online and discuss a potential therapy and its common side effects with family and friends, with other patients on online forums and dedicated social media communities, and with their doctors and other care providers. They take into account common side effects and weigh how disruptive these side effects would be to their daily life against possible improvements they would experience in their symptoms. In addition to side effects, patients also assess the cost of the therapy, treatment burden, and the risk that trying a new therapy may worsen their condition.
a. What potential benefits factor most into your decisions?
Significant improvement in symptoms that most diminish the quality of life over current therapy is the primary consideration patients with rare GI illnesses have when making a decision about treatment. These improvements are weighed against time necessary to see significant change, treatment burden, ability to recuperate after a potential setback if the therapy isn’t effective initially, and cost.
b. How do you weigh potential benefits versus potential common side effects?
Patients with rare GI illnesses are generally willing to accept the potential of common, but not life-threatening, side effects with a new therapy. However, if the benefits are minimal (i.e. do not significantly improve symptoms that diminish quality of life), the risk of trying a new therapy, even with relatively few side effects, is weighed against the cost of a failed attempt in terms of financial cost, time, energy expenditure, and the emotional toll treatment failure takes. This decision is often shared with close family.
c. How to you weigh potential benefits versus potential less common but serious risks?
Therapies with less common but more serious risks are attempted only after other avenues have been exhausted. Patients are more likely to accept common, less serious side effects than try a therapy associated with less common, but potentially life-threatening side effects even if the potential gain is greater. However, willingness to consider therapies with greater risks increases with the severity of illness, how long the individual has been suffering, the number of previous unsuccessful therapies, and lack of many options available.
Topic 2: Commonalities in clinical study considerations and registry considerations
3. What factors have you or would you consider when thinking about participating in a clinical study or registry. (Examples include, but are not limited to, side effects, travel, time commitment, or trial design)
Factors considered by patients with rare GI illnesses when thinking about participating in a clinical study or registry include, but are not limited to, possible side effects, distance/travel needed to participate, length of study, time commitment, symptoms/issues potentially improved by the therapy being studied, whether the therapy being studied had been tried previously, family support, type of therapy being studied (surgical, pharmacological, non-drug therapy), the likelihood of receiving the placebo arm, illness severity and lack of effective relief (many patients reported that they are “desperate” enough to try anything), trial sponsor, whether the individual’s doctor would administer the trial, compensation, and the potential for a cure.
Patients are more inclined to join a registry to be contacted for future studies than to enroll in a clinical trial first. However, if the patient’s doctor or other care provider suggested the trial, they were more likely to enroll even without having previous exposure to clinical trials.
We thank you for your consideration of our comments, and we welcome the opportunity to work with the FDA to further capture the perspectives of patients and caregivers living with rare GI disorders. We believe that understanding the burden faced by patients and caregivers will help the FDA and medical product developers address the unmet needs of this population and develop solutions that shorten the ‘diagnostic odyssey,’ expand targeted treatment options, and ultimately, help improve outcomes.