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The Patient-Focused Drug Development initiative of the U.S. Food and Drug Administration (FDA) aims to ensure that the patient experience of disease and treatment is an integral component of the drug development process. The 21st Century Cures Act and Prescription Drug User Fee Act (PDUFA) VI require the FDA to publicly report the type of patient-experience data reviewed in a new drug application (NDA) to inform regulatory decision-making. This report describes a recent approach adopted at Janssen of integrating patient-experience data into the NDA for esketamine (SPRAVATO®) nasal spray with a newly initiated oral antidepressant (esketamine + AD) for treatment-resistant depression. During the development of esketamine + AD, patient-experience data were collected using several patient-reported outcomes, including the Sheehan Disability Scale and 9-item Patient Health Questionnaire (PHQ-9). Additionally, a patient-preference study assessed the relative importance of benefits and harms that patients allocated to different attributes of treatment. Preferences were collected from patients enrolled in phase 3 esketamine trials and from an online panel of primarily ketamine-naive patients. Patient-experience data were integrated into the esketamine NDA, the FDA advisory committee meeting briefing document, and the Sponsor’s presentation. The FDA acknowledged reviewing the patient-experience data and determined that they supported esketamine + AD for treatment-resistant depression. This report highlights the importance of integrating patient-experience methods early in drug development, their impact on assessing patient-relevant benefits and risks, and how they can help improve clinical program design.

Background Given the urgent need for vaccines and treatments for coronavirus disease 2019 (COVID-19), the Symptoms of Infection with Coronavirus-19 (SIC), a comprehensive, patient-reported outcome (PRO) measure of signs and symptoms associated with COVID-19, was developed in full alignment with current US regulatory guidance to support evaluations of vaccines and treatments in development. Methods An initial version of the SIC was developed to address concepts identified through a targeted literature review and consultation with experts in infectious diseases and clinicians routinely managing COVID-19 in a hospital setting. A qualitative study was conducted in sites in the United States among 31 participants aged ≥ 18 years who were English-speaking and willing and able to provide informed consent and a self-reported history by telephone or online method. The measure was refined based on additional feedback from the clinicians and three iterative rounds of combined concept elicitation and cognitive debriefing interviews conducted with patients, caregivers, and healthy volunteers. Results Among 39 scientific articles identified in the literature review, 35 COVID-19 signs and symptoms were reported and confirmed during interviews with clinicians, patients, and caregivers. Patients and healthy participants suggested changes for refining the draft SIC to ensure consistent interpretation and endorsed both the 24-h recall period and use of an 11-point numeric rating scale (NRS) for capturing change in symptom severity. The final version of the SIC captures the daily presence or absence of 30 symptoms and a rating of severity for 25 of the 30 symptoms using an NRS for those symptoms reported as present. Conclusions The SIC comprehensively addresses observations described in the literature, by clinicians, and by patients, and captures patients’ experiences with COVID-19 in a manner that minimizes complexity and facilitates completion for both patients and healthy volunteers. This measure is thus appropriate for use in clinical trials of both therapeutics and vaccines for COVID-19.

Objectives There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge. Methods Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges. Using examples from cardiovascular trials, this article describes a potential path forward with a focus on applications in the United States. Results Think Tank members identified one key challenge: a common understanding of the level of evidence that is necessary to support patient-reported outcome measures (PROMs) in trials. Think Tank participants discussed the possibility of creating general evidentiary standards depending upon contextual factors, but such guidelines could not be feasibly developed because many contextual factors are at play. The attendees posited that a more informative approach to PROM evidentiary standards would be to develop validity arguments akin to courtroom briefs, which would emphasize a compelling rationale (interpretation/use argument) to support a PROM within a specific context. Participants envisioned a future in which validity arguments would be publicly available via a repository, which would be indexed by contextual factors, clinical populations, and types of claims. Conclusions A publicly available repository would help stakeholders better understand what a community believes constitutes compelling support for a specific PROM in a trial. Our proposed strategy is expected to facilitate the incorporation of PROMs into cardiovascular clinical trials and trials in general.

The diabetic foot ulcer scale (DFS) questionnaire is a specific instrument designed to assess the impact of foot ulcers and their treatment on quality of life in people with diabetes. Based on the results of semi-structured interviews and focus-group discussions with foot ulcer patients and caregivers, the DFS consists of 58 items grouped into 11 domains: leisure, physical health, daily activities, emotions, noncompliance, family, friends, positive attitude, treatment, satisfaction, and financial. Two studies have been conducted to develop and validate the DFS. The first of these included 173 patients with diabetes and current foot ulcers (n = 48), healed foot ulcers (n = 54), or no history of foot ulcers (n = 71). A generic measure of health status, the SF-36, was used to test construct validity. The DFS had good internal consistency. Significant differences between patients with current ulcers and those with healed ulcers were observed in the mean scores for the leisure, emotions, and financial domains (p < 0.05). Marked differences were also observed in physical health, daily activities, and friends domains, indicating that the DFS is able to discriminate patients with healed ulcers from those with current ulcers. The DFS was further evaluated in a relevant clinical setting (n = 288); confirmatory factor analysis confirmed the hypothesised factor structure of the DFS, but with slight suggestions for improved scaling. The DFS scales also demonstrated adequate test–retest reliability and sensitivity to change in wound status over time, indicating its appropriateness for use in clinical trials. Copyright © 2002 John Wiley & Sons, Ltd.

Summary: Purpose: In epilepsy, patient-based assessments are increasingly used as outcome measures in clinical trials of novel therapies alongside the traditional clinical measures of efficacy. The objective of this study was to validate psychometrically a quality of life (QOL) measure developed for use with recently diagnosed epilepsy patients. Methods: The NEWQOL (Quality of Life in Newly Diagnosed Epilepsy Instrument) is a 93-item self-administered battery designed to assess QOL in patients with new-onset epilepsy. NEWQOL consists of eight multi-item scales (13 subscales) measuring several health parameters: Anxiety, Depression, Social Activities, Symptoms, Locus of Control/Mastery, Neuropsychological Problems (includes the following subscales: Fatigue, Memory, Concentration, Motor Skills, and Reading), Social Stigma, Worry, Work Limitations, and several single-item measures (General Health, Number of Seizures, Social Limitations, Social Support, Self Concept, Ambition Limitations, Health Transition, and General Limitations). The NEWQOL was collected at baseline and 1 week post-baseline from 108 patients in the U.K. and U.S. Results: All of the multi-item scales had high item discriminant validity, good test-retest reliability, and acceptable levels of internal consistency reliability; all but the Reading and Stigma subscales had negligible floor and ceiling effects. General linear models were used to examine the known groups validity of NEWQOL. Significant differences were observed in the Worry, Symptoms, Summary Neuropsychological Scales, and all Neuropsychological subscales (Memory, Fatigue, Concentration, Motor Skills, and Reading), indicating poorer functioning in the more frequent or severe seizure groups. Conclusions: Results from this study offer supportive evidence that NEWQOL has good validity and reliability and can discriminate between patient groups, particularly in relation to symptoms and psychological problems. We conclude that NEWQOL represents a useful measure for future studies in this patient population.

Researchers developing or using health-related quality of life (HRQOL) instruments can benefit from knowledge of state-of-the-art formatting methods for self-administered questionnaires. Three objectives in formatting design are: (1) to reduce errors in respondent navigation through the questionnaire that lead to item non-response and question misinterpretation; (2) to reduce respondent and administrative burden; and (3) to enhance respondent motivation in question answering and compliance with the request to participate. Based on an extensive literature review to identify techniques that have been shown to meet these objectives, we developed specific guidelines for HRQOL instruments concerning all aspects of questionnaire formatting. These guidelines represent well-motivated recommendations for improving HRQOL instruments, although their overall impact has not been empirically tested. We applied the guidelines to several HRQOL instruments that are widely used internationally, and obtained approval from the developers for all formatting changes to their instruments. Applying cognitive design principles and empirically substantiated formatting techniques produces an HRQOL instrument formatting with six critical attributes: simple, consistent, organized, natural, clear and attractive. The present paper contributes to the emerging research literature on the cognitive processes by which respondents answer HRQOL questions and demonstrates how 'cognitive aspects of survey methodology' research can improve HRQOL data collection efforts.

Cancer-related anaemia is associated with a wide spectrum of symptoms that can negatively affect quality of life. Because epoetin alfa has demonstrated efficacy in correcting cancer-related anaemia, the impact of this treatment on quality of life was evaluated in a multinational, randomised, double-blind, placebo-controlled trial in 375 anaemic cancer patients receiving non-platinum-based chemotherapy. The cancer-specific measures of quality of life included the general scale (FACT-G Total) and fatigue subscale (FACT-An Fatigue subscale) of the Functional Assessment of Cancer Therapy-Anaemia and the Cancer Linear Analogue Scales measuring energy, ability to do daily activities, and overall quality of life. These measures were also used to examine the relationship between haemoglobin levels and quality of life. Both univariate and multiple linear regression analyses of quality of life data were performed. Results of the univariate analysis have been reported previously. The a priori-planned multiple linear regression analysis, which accounted for the effects of disease progression and several other possibly confounding variables on quality of life, showed a significant advantage for epoetin alfa over placebo for the five scales (all, P

Summary: Purpose: The relationship between seizure frequency and both health care costs and quality of life (QOL) was investigated in a retrospective, cross-sectional, multicenter study in France, Germany, and the United Kingdom. Methods: Three hundred outpatients with stable partial epilepsy were approximately evenly distributed among five seizure—frequency groups, ranging from seizure—free in the last 3 months (group 1) to daily seizures (group 5). Economic data, obtained through patient interviews and record abstraction, comprised direct medical costs, direct nonmedical costs, and indirect costs for the preceding 3 months. Total societal costs in the three countries were pooled and converted to United States dollar equivalents. QOL was assessed through a self—administered questionnaire, the Functional Status Questionnaire (FSQ). Results: Mean total costs increased from $780 in group 1 to $2,171 in group 5 (p = 0.0001), with significant increases in each cost category as seizure frequency increased. Greater seizure frequency also significantly (p = 0.0270) correlated with lower employment rates, which ranged from 57% in group 1 to 30% in group 5. QOL declined as seizure frequency increased. Particularly affected were basic and intermediate activities of daily living (ADL), mental health, social activity, and feeling about health. Conclusions: The study results show that higher seizure frequencies are associated with higher direct and indirect costs and with reduced QOL for patients with epilepsy.