PP05-40: Patient Experience Data in the Treatment Resistant Depression Esketamine NDA: Patient-Reported Outcomes and Patient Preferences
Associate Director, Patient Reported Outcomes
Janssen Research & Development United States
To understand the patient experience (PE) with esketamine for treatment-resistant major depressive disorder, Janssen proactively included several methods for capturing PE data, including patient reported outcomes (PROs) and patient preferences.
PE data collected in the esketamine phase 3 clinical trials included (1) PROs that aligned with concepts of importance to TRD patients and (2) a patient preference survey utilizing a discrete choice experiment to quantify the value TRD patients place on treatment related benefits and risks.
PE data were an integral component of the protocol, study reports and other regulatory documents in the esketamine NDA. PRO data provided information on self-reported symptoms of depression, functioning and associated disability, anxiety and health related QOL. Results from these PRO assessments, including the key secondary endpoints of Sheehan Disability Scale and the 9-item Patient Health Questionnaire, were suggestive of supporting the primary efficacy endpoint, change in the Montgomery-Asberg Depression Rating Scale total score from baseline to day 28, and the benefits of esketamine from the patient’s perspective as to how they feel and function. The patient preference study quantified the importance TRD patients (n=406) place on benefits and harms associated with treatment, and the maximum acceptable risk that patients were willing to accept for a given benefit. Mood improvement and reduced chance of cognitive and memory problems were the most valued treatment attributes. Short-term post-dose adverse events and logistical issues associated with treatment were of low importance, including among patients with esketamine experience. TRD patients were willing to accept 3% to 5% risk of long-term hypothesized bladder or cognitive-impairment, risks previously reported as associated with ketamine abuse, in exchange for improvement in depression symptoms from severe to moderate. Data were included in the registration package and FDA advisory committee meeting presentation, providing quantitative data on patient perspective of efficacy and risk tolerance. The patient preference study was part of an NDA Advisory Committee Meeting Sponsor Presentation and influenced the B-R voting process. Additionally, the FDA’s review of the esketamine NDA documented the use of (1) PRO data to support findings from other clinical trial endpoints and (2) patient preference data to support patient acceptance of the B-R profile. The FDA perspective on the PRO data was published in the NEJM
As part of the FDA’s Patient Focused Drug Development (PFDD) initiative, Patient Experience data is a key focus for drug development programs. The 21st Century Cures Act requires the FDA to publicly report the type of PE data reviewed to inform regulatory decision making for a new drug application (NDA).
The patient experience data collected by Janssen and its integration into the NDA for esketamine in treatment-resistant major depressive disorder, resulted in comprehensive PE data being available for FDA review as part of regulatory evaluation and decision making. Subsequently, the FDA’s publicly available clinical review of esketamine outlined the PE data that were considered (on the Patient Experience Checklist included in the Clinical Review document) and documented the FDA’s use of the data. In particular, the FDA evaluated the PRO data reported in the Janssen clinical studies and provided interpretation on how it supported the findings of the primary efficacy endpoint. In addition, both the FDA and its advisory committee used the Janssen patient preference data as part of their assessment of patient acceptance of the benefit-risk profile of esketamine.
This example demonstrates how planning for and integrating patient experience methods in drug development can confirm that patient-relevant benefits and harms are identified, and that risk tolerance is understood. This approach can support patients and future R&D program design in developing products that provide meaningful advances from the patient perspective.