In recent years, the US FDA has become more critical of instruments used to measure patient-reported outcomes (PROs) in clinical trials. To facilitate decisions related to the approval of drugs, labels and promotional claims based on PROs, the FDA created the Study Endpoints and Label Development (SEALD) group. SEALD has developed a PRO guidance related to the use of PRO measures used to support drug approvals and label claims, including recommendations for establishing thresholds for meaningful change at the individual level (i.e., defining a responder). This article examines in detail the FDA-recommended methodology for defining a responder and analyzing responder-based PRO measure results. We also present other responder analysis approaches for consideration in furthering the precision and interpretation of this methodology.

Selection of a psychometric approach depends on many factors. Researchers should justify their evaluation method and consider the intended audience. If the instrument is being developed for descriptive purposes and on a restricted budget, a cursory examination of the CTT-based psychometric properties may be all that is possible. In a high-stakes situation, such as the development of a patient-reported outcome instrument for consideration in pharmaceutical labeling, however, a thorough psychometric evaluation including IRT or RMT should be considered, with final item-level decisions made on the basis of both quantitative and qualitative results.

By careful planning of anchor selection, study design, and psychometric methods, COA researchers can establish defensible responder thresholds that ultimately aid patients and clinicians in making informed treatment decisions.

In patients with advanced melanoma in the CheckMate 066 study, baseline health-related quality of life (HRQoL) with nivolumab was maintained over time, with statistically significant and clinically meaningful improvements in some exploratory analyses, and no HRQoL improvements with dacarbazine. Added to the survival benefit of nivolumab, the benefit-to-risk ratio favors nivolumab over dacarbazine.

Interpreting change in scores on patient-reported outcome instruments is a key aspect of instrument development. Without interpretation guidelines, the clinical meaning of significant improvements observed within a treatment group cannot be ascertained. While the field has contemplated this topic for several decades, there remains inconsistency in terminology, methods, and application. Careful selection of methods can result in determining when change is meaningful, but researchers must keep an open mind to the methods that best fit their study and instrument. In many cases, anchor-based methods are appropriate, but the statistical model that evaluates them should be defensible (eg, linear regression, repeated-measures modeling, logistic regression). Sometimes, researchers must entertain the use of novel methods that may be more appropriate for their planned studies and instrument (eg, standard setting, exit interviews, conjoint analysis). The selection of the method is best supported by clear, transparent communication with the regulatory agency to ensure that the method can support its goals.

Release of the US FDA patient-reported outcome (PRO) guidance raised expectations within the pharmaceutical industry for the use of PRO measures in support of labeling claims. The FDA developed the guidance with admirable intent, and the recommendations within this document are based on sound scientific principles. However, implementation of the guidance has been somewhat inconsistent within the Study Endpoints and Label Development (SEALD) and across the various FDA-reviewing divisions. Industry and regulatory bodies need to work toward gaining common ground to best support registration of treatments that could extend patients' lives, reduce symptoms, and/or improve health-related quality of life. PROs are valuable tools in communicating these messages, and realistic implementation of the FDA PRO Guidance may truly facilitate this process.

The PSQ is a valid and reliable measure and may be a valuable tool to assess patient preference and satisfaction with a weekly oral tablet and 6-month subcutaneous injection for postmenopausal bone loss.

Inattention and impulsivity symptoms are common among adults with attention-deficit/hyperactivity disorder (ADHD), which can lead to difficulty concentrating, restlessness, difficulty completing tasks, disorganization, impatience, and impulsiveness. Many adults with ADHD find it difficult to focus and prioritize. Resulting outcomes, such as missed deadlines and forgotten engagements, may ultimately impact the ability to function at work, school, home, or in a social environment. The European Medicines Agency guidelines for evaluating medicinal products for ADHD recommend inclusion of both functional outcomes, such as school, social, or work functioning, and outcomes related to symptoms of ADHD in clinical studies of novel medication primary efficacy endpoints. Due to its performance in other disease areas and the relevance of its items as evidenced by content validity analyses, the Sheehan Disability Scale (SDS) was chosen to assess functional impairment in ADHD. The aim of this study was to investigate the psychometric properties of the SDS, used as a brief measure of functional impairment in a number of psychiatric disorders, in adult patients with ADHD. To the authors’ knowledge, this is the first study to evaluate the reliability of the SDS (based on Cronbach’s coefficient alpha and test-retest reliability), its validity (construct and known-groups validity), and its ability to detect change in this patient population. This study also established a preliminary responder definition for the SDS in this study population to determine when change can be considered clinically beneficial in a clinical trial setting. The psychometric results support the use of the SDS subscales (items 1–3) and total score (sum of items 1–3) in an ADHD population. In addition, the evaluation provides evidence for a three-point preliminary responder definition for the SDS and further evidence of its responsiveness in adults with ADHD. Altogether, the results indicate that the SDS is a simple and easy-to-score scale that would have great utility in future clinical trials for monitoring functional impairment in adults with ADHD.