Mindful Measures: Assessing Content Validity of Patient-Reported Outcomes for Major Depressive Disorder in Clinical Trials

OBJECTIVES: New treatments for major depressive disorder (MDD) are largely evaluated using clinician-reported outcome measures. As MDD is primarily a subjective experience, patient-reported outcomes (PROs) are essential for assessing the overall impact of treatment on patients' quality of life and symptom relief from the patient perspective. PROs must demonstrate content validity in a target patient population by measuring what matters most to patients in ways that are understandable to them. This research evaluated the inclusion and content validity of PROs in MDD clinical trials.

METHODS: A clinicaltrials.gov search was conducted to identify Phase 2-3 MDD trials initiated between 2004-2024 which included PROs assessing depression symptoms/symptom dimensions (e.g., severity, frequency) or their impact on daily life in trial endpoints. A gap analysis was performed to evaluate whether each PRO was developed via five research activities which generate content validity evidence: concept-focused literature reviews, clinical expert input, patient concept elicitation interviews, concept saturation, and questionnaire debriefing interviews.

RESULTS: Of the 162 trials included in this review, 83 (51.2%) included PROs. Eleven trials were excluded as they did not focus on MDD. Nine PROs were included in the gap analysis. Literature evidence was found for two PROs (22.2%), expert input for one (11.1%), concept elicitation for three (33.3%), saturation for one (11.1%), and debriefing evidence for five (55.6%). No PRO development included all five content validity activities.

CONCLUSIONS: This review highlights the limited use of PROs in Phase 2-3 MDD trials. Among the nine PROs evaluating symptoms or impacts in these trials, most lacked evidence of patient involvement in their development. No PRO was developed using all five content validity activities, highlighting gaps in patient perspective. Improved patient involvement in PRO development is needed to ensure PRO reliability and effectiveness in MDD clinical trials.