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-2015-D-2479 on October 15, 2019.
Thank you for your leadership at the Office of Policy in the Food and Drug Administration (FDA). The International Foundation for Gastrointestinal Disorders (IFFGD) is grateful for the opportunity to comment on the FDA’s Draft Guidance for industry entitled “Gastroparesis: Clinical Evaluation of Drugs for Treatment.” (Docket No. FDA-2015-D-2479).
IFFGD is a registered nonprofit education and research organization dedicated to informing, assisting, and supporting people affected by gastrointestinal (GI) disorders. IFFGD works with patients, families, physicians, nurses, practitioners, investigators, regulators, employers, and others to broaden understanding about GI disorders, support and encourage research, and improve digestive health in adults and children.
Functional GI and motility disorders are the most common GI disorders in the general population, including gastroparesis. These disorders are classified by symptoms related to any combination of the following: motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system processing.
Below are our specific comments on section of the Draft Guidance for industry entitled “Gastroparesis: Clinical Evaluation of Drugs for Treatment.” (Docket No. FDA-2015-D-2479):
Lines 60-67 of Section II. Background
IFFGD is concerned with the removal of guidance information regarding disease severity and impact of gastroparesis on quality of life. In a survey by Yu, et al. of 1423 patients living with gastroparesis, 67% of these individuals rated their quality of life as fair or poor. 58% of responders reported a worsening of their symptoms over the previous year. Of the total responders, 30% were not working and 15% work limited hours as a result of their gastroparesis. [1]
Lines 76-77 of Section II. Background
We appreciate continued consideration of the urgent need for drugs and therapies to treat patients with gastroparesis. The language in the 2015 guidance, “drugs with a favorable risk-benefit profile,” more accurately describes the patient need as opposed to “safe and effective therapies” in the 2019 draft guidance. Clarification on this change is necessary for both patients and industry as gastroparesis patients express an understanding that to achieve symptom relief, certain risk may be necessary, and many are willing to take these risks.
IFFGD completed an unpublished survey of 200 gastroparesis patients to study their quality of life (QOL), disease severity, and patient risk assessment when considering medications and trials. In a question answered by 175 patients, 75% of responders expressed a 50% or below current state of health on a scale of zero being the worst possible health and 100 a healthy, normal life. Responders were also asked, if they were guaranteed to live until 100 years old with their current state of health, how many years are they willing to take off of their life to live in a perfect state of health. Of the 164 responders, 89% said they were willing to lose ten years or more of their life with 30% of the total responders
answering that they would be willing to lose twenty years to improve their health. These results, along with others from this survey, demonstrate that patients are knowledgeable and understand that a high-risk drug or therapy trial with potential significant benefits may be worth the risk. IFFGD would be happy to share these survey results.
Lines 116-124 and 134-136 of Section III. A. Trial Design
The requirement of a randomized, double-blind, placebo-controlled trial (line 116) and the requirement for twelve-week trial duration (line 124) is an unnecessary burden for this patient community. Due to disease severity, patients who are receiving placebo will have increasing difficulty traveling and completing all treatment requirements throughout the trial. The recommendations for a “randomized, controlled, long-term safety study of twelve months” (134-136), requires further interpretation. If the control of these studies will require a placebo, this creates a severe, unnecessary burden for patients. The extended length will threaten quality of life for patients while creating challenges in their ability to complete the entire study. The presence of comorbidities, disease severity, and unpredictable health of participants must be considered when developing clinical trial and safety study durations.
Lines 223-224 of Section III. D. Trial Endpoints
Relieving even just one symptom in patients suffering from gastroparesis can make a significant difference in an individual’s quality of life. The recommendation that “the primary endpoint should not be limited to a single sign or symptom,” is very concerning and should be evaluated further. Many gastroparesis patients suffer from multiple signs and symptoms, as stated in the document, but some symptoms may cause a more substantial burden on quality of life over others.
Lines 99-109 Section III. Endpoints and Trial Design
IFFGD is especially concerned with the requirement that drugs intended to treat certain signs and symptoms do not worsen others (lines 103 – 105). An overall global improvement of quality of life should be considered, as a slight worsening of one or two symptoms in the presence of significant improvement of the one most bothersome symptom for a patient should be considered success.
IFFGD works on behalf of many patients with gastroparesis and appreciates the FDA’s work to revise the agency’s current thinking on the development of clinical outcome assessment tools and statistical considerations for the use of those tools as efficacy endpoint measures for this debilitating disease. We hope you will consider the Foundation a resource as you work to finalize this rulemaking.
