Development and content validation of the Long COVID/ post-acute sequelae of COVID-19 (PASC) patient-reported outcome (PRO) instrument.

Abstract

Background: Post-acute sequelae of COVID-19 (PASC) or Long COVID is a post-viral complication of SARS-CoV-2 infection, causing ongoing symptoms and impaired function over a prolonged period of time. There is limited understanding of how the signs and symptoms of Long COVID/PASC affect patients' lives and how to measure them, which is essential when developing care strategies. This study aimed to develop and evaluate the content validity for a novel patient-reported outcome (PRO) instrument in Long COVID/PASC through qualitative research, which was informed by the patient experience of Long COVID/PASC and both patient and clinician input.

Methods: A review of literature and PRO instruments developed for Long COVID/PASC identified measurement gaps for the context of use (i.e., weekly assessment of signs/symptoms in clinical trial research). This informed the development of the preliminary Long COVID/PASC PRO instrument, which was tested via patient interviews (combined concept elicitation and cognitive debriefing) to align with regulatory standards, and discussions with clinical experts were conducted to provide clinical insights. The final instrument was modified based on this input to further promote its content validity.

Results: Thirty participants were interviewed about their Long COVID/PASC experiences. Participants most frequently reported experiencing tiredness after physical activity (n = 29/30; 97%), general tiredness (n = 28/30; 93%), shortness of breath (n = 25/30; 83%), cough (n = 23/30; 77%) and muscle/body aches (n = 23/30; 77%). All participants reported that Long COVID/PASC had an impact on their health-related quality of life. Almost all (n = 27/28; 96%) sign/symptom concepts were reported in the first three sets of interviews suggesting conceptual saturation was achieved. Items, response options and the recall period of the preliminary Long COVID/PASC PRO instrument were understood as intended (≥ 90%) and relevant to most participants across both rounds (≥ 47%). Modifications were made to the instrument following patient input, resulting in the 18-item Long COVID/PASC instrument. Clinician input (n = 3) corroborated participant interview results, supporting the content validity of the Long COVID/PASC PRO instrument.

Conclusion: The Long COVID/PASC PRO instrument has been developed in line with regulatory standards and the qualitative evidence demonstrated strong content validity in a Long COVID/PASC population. Research to evaluate psychometric properties will provide further evidence of the instrument's measurement properties.