OBJECTIVES:  Complete qualitative concept elicitation (CE) and cognitive interviews leading to preliminary development of a patient-reported outcome (PRO) measure to assess treatment benefit in major depressive disorder (MDD) clinical trials. METHODS: Qualitative interviews were conducted with adult MDD patients in the US who recently experienced a major depressive event.  All participants had a Hamilton Depression Rating Scale (HAM-D) total score >18 at screening.  Experienced interviewers conducted CE and cognitive interview sessions using semi-structured interview guides.  The CE interview guide was used to elicit spontaneous reports of symptom experiences along with probing to further explore and confirm concepts.  The cognitive interview guide was developed to evaluate concept relevance, understandability, and structure of the draft items, and to facilitate further instrument refinement.  All interview sessions were audio recorded and transcribed.  The CE interviews were coded for qualitative content analysis using Atlas.ti, and the cognitive interview transcripts were summarized in cognitive report tables. RESULTS: Forty patients [mean age: 46.2; 67.5% female; 45.0% white (non-Hispanic)] participated in the CE interviews.  Mean (SD) HAM-D total score of the participants was 24.4 (4.3).  A total of 3,022 symptom codes, representing 91 different concepts were derived from the transcripts.  Data from the CE interviews was considered alongside existing literature and clinical expert opinion during an item-generation meeting, leading to development of a 36-item measure with a 5-point response scale.  Subsequently, fifteen patients participated in three waves of cognitive interviews, during which, one item was removed and four others were modified.  CONCLUSIONS: The S-MDD is a 35-item PRO measure intended for use as an endpoint in MDD clinical trials to support medical product labeling.  It was developed in accordance with the FDAs PRO Guidance and best practices.  Qualitative interviews have provided evidence for content validity.  Future quantitative studies will confirm the S-MDD’s measurement properties and support FDA qualification.