Background:Sickle Cell Disease (SCD) is a genetic, progressive, vascular disease that affects approximately 100,000 children and adults in the US. Vaso-occlusive crises (VOCs), also referred to as pain crises, are a primary complication of SCD. VOCs are thought to be caused by several factors, including inflamed, damaged vasculature and increased cellular adherence to the endothelium and other cells, resulting in occlusion of the microvascular system. VOCs have been associated with increased morbidity and mortality.Healthcare visit data partially reflect VOC and SCD outcomes and provide an understanding of healthcare resource utilization (HCRU). However, evaluating only HCRU data misses the breadth and depth of the patient experience and burden of SCD as it fails to capture daily variations of pain and other important quality of life (QoL) concepts. Additionally, patients who avoid seeking care outside the home are not represented in HCRU data.The Sickle Cell Pain Diary- Self Report (SCPD-S) was developed as a daily patient-reported outcome (PRO) measure primarily intended to capture the frequency and severity of SCD-related pain during and outside of a VOC and secondarily to examine the impact of the pain on other patient-relevant QoL concepts. The objective of this study was to investigate the content validity of the SCPD-S.Methods:A draft diary was developed from the literature. In line with FDA guidance for PRO development, the content validation of the SCPD-S included four consecutive steps: (1) literature review to identify important concepts to measure and mapping of concepts to draft diary; (2) expert review to improve wording and layout; (3) round 1 (N=13) of qualitative interviews with patients; and (4) round 2 (N=6) of qualitative interviews with patients. Revisions made to the diary after each step were tested in the following step.In total, 18 in-depth, hybrid concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted in English in person (n=13) and by phone (n=5) with SCD patients in the US aged ≥12 years. A semi-structured guide was used to explore concepts relevant to patients' experience with VOCs and to test the draft diary. The CD portion of the interviews required patients to state their thoughts while reading the diary aloud, after which interviewers probed on areas that seemed confusing and asked questions specific to the diary instructions, recall period, items, and response choices. All interviews were recorded, transcribed, coded and analyzed.Results:All four steps of this content validation study resulted in changes to the SCPD-S. The literature review, expert review, and round 1 patient interviews resulted in expansion of the SCPD-S from 8 to 19 items covering concepts highlighted by patients as important. For example, impact of VOCs on school/work, activities of daily living, social and recreational activities, sleep, and emotional wellbeing were added. Five items from the original diary were significantly revised, as were all response choices. Round 2 interviews confirmed the comprehensiveness of the revised diary, comprehensibility of the wording, and appropriateness of the recall period and response choices. Final changes to the diary included adding skip logic to ensure transition to an electronic format. Saturation analyses revealed that no additional interviews were needed.Conclusions:This study provided evidence that supports the content validity of the SCPD-S, a self-report SCD daily diary focused on capturing daily variations of pain in SCD. Evidence gathered during patient interviews indicated that the SCPD-S is a valuable, fit for purpose measure of VOC-related pain frequency and severity as well as the impact of this pain on other QoL concepts including fatigue and emotional health. In addition, the diary captures the QoL of patients who may not seek care outside the home providing a more holistic view of the overall impact of VOCs and SCD. The numerous changes to the SCPD-S as a result of the study findings highlight the importance of the content validation process in establishing a PRO measure. Future work on the SCPD-S includes development of a scoring algorithm and user's manual, and conducting psychometric validation. Use of the SCPD-S is anticipated in future clinical trials enrolling patients who experience VOCs as a way to help capture the QoL impacts of new interventions designed to reduce the frequency and intensity of VOCs. DisclosuresBailey:Novartis: Employment. Stebbins:Optum: Employment; Novartis: Research Funding. D'Alessio:Novartis: Employment. Raymond:Novartis: Research Funding; Optum: Employment. White:Akcea: Research Funding; Optum: Employment.