Writing in the May edition of DIA’s Global Forum magazine, Erica Lyons, Sarrit Kovacs, Matthew Kowalik, and Jessica Lee from the Division of Gastroenterology, Office of New Drugs, CDER at the US FDA look at how patient input is increasingly being utilised in new drug development, its importance in assessing a drug’s benefit, and the challenges to wider implementation.
Assessment of the patient voice has become recognized as a vital component in the evaluation of new candidate therapies. To address this, FDA has partnered with stakeholders on multiple patient-focused drug development (PFDD) initiatives to facilitate incorporation of patient and caregiver input into drug review and evaluation. These include the FDA Patient-Focused Drug Development Guidance Series for Enhancing the Incorporation of the Patient’s Voice in Medical Product Development and Regulatory Decision Making.
Here, we present an example of how evaluating the patient experience is essential to assessing the benefit for drugs under investigation for the treatment of eosinophilic esophagitis (EoE). We also present a recommended approach to implementing and analyzing clinical outcome assessment (COA) data to determine clinical benefit to patients in these development programs.
EoE is a Clinicopathologic Disorder
EoE is a chronic immune-mediated disease triggered by allergen exposure and characterized by eosinophil-predominant inflammation and clinical symptoms of esophageal dysfunction. It is part of a larger group of disorders known as eosinophilic gastrointestinal disorders (EGIDs). Untreated, EoE leads to esophageal stricture, dysphagia, and risk of food impaction. Clinical signs and symptoms vary with the patient’s age: Infants and toddlers present with feeding difficulties; school-aged children are likely to have vomiting or pain; and adolescents and adults report dysphagia and food impaction.
EoE has an estimated incidence of five to ten cases per 100,000 persons per year, and a prevalence of 50 to 100 cases per 100,000 persons in North America and Europe. Clinical features and histologic activity can vary independently in patients with EoE; the resolution of symptoms may accompany ongoing histologic activity, and clinical symptoms can persist during histologic remission (defined by decrease in eosinophil count). Thus, treatment of EoE has two goals: eliminate or decrease symptoms of active disease and normalize esophageal histology.
Assessment of Benefit
To address the need to provide evidence of improvement on clinical symptoms, FDA’s Guidance for Industry: Eosinophilic Esophagitis: Developing Drugs for Treatment has recommended that (1) significant improvement from baseline in signs and symptoms (using a well-defined and reliable COA instrument) and (2) histologic response be evaluated as co-primary endpoints in drug development programs for EoE. As a co-primary endpoint, inclusion of a patient-focused COA in these clinical trials is necessary to demonstrate clinical benefit and support both potential drug approvals and labeling claims. Although EoE can present with heterogeneous symptoms, adolescents and adults predominantly present with dysphagia; therefore, this symptom has been the most widely-characterized and identified for inclusion in a COA co-primary endpoint for EoE.
Although the importance of evaluating the patient voice in these development programs is widely accepted and FDA guidance exists on a recommended approach to increase the interpretability of these COA endpoints, challenges during their development, implementation, and analysis remain.