ABSTRACT
Background. The Symptoms of Infection with Coronavirus-19 (SIC), a patient reported outcome (PRO) measure, was developed to assess COVID-19 signs and symptoms. Qualitative and cross-sectional studies demonstrated its content validity and preliminary psychometric properties. This study provides additional evidence on the reliability, responsiveness, known-group validity, and meaningful change thresholds of the SIC using methods aligned with regulatory guidance and best practices. Methods. Data were from ENSEMBLE-2, a multicenter, randomized, doubleblind, placebo-controlled phase 3 trial to assess the efficacy and safety of Ad26.COV2.S for the prevention of SARS-CoV-2 infections in adults (aged 18+). The SIC was used in the trial to evaluate COVID-19 signs and symptoms and the Patient Global Impression of Severity (PGIS) was used as an anchor for validation. Intra-class correlations (ICCs) and Cronbach's alphas were computed to evaluate the test-retest reliability and internal consistency, and analyses of variance (ANOVAs) were performed to assess the known-group validity of the SIC. Responsiveness was evaluated using PGIS as an anchor variable and a 1- or 2-point improvement in PGIS was used to estimate the meaningful change thresholds of the SIC. Results. 183 participants with polymerase chain reaction (PCR) confirmed moderate to severe/critical COVID-19 were included (mean +/- SD age: 51.5 +/- 14.8 y;female: 44%;White 65%). ICCs showed strong test-retest reliabilities for most SIC domains (.60 and above). The internal consistency reliability of the SIC had a Cronbach's alpha > .70 for all but one domain (Neurological). Statistically significant differences (p values < 0.05) for the different PGIS severity levels were found for all but one domain (Sensory), supporting known-group validity. All domains showed responsiveness based on changes (improvement and worsening) in PGIS, supporting the ability of the SIC to detect changes in COVID-19 signs and symptoms. Based on mean changes in the PGIS, estimated meaningful change thresholds for SIC domains ranged from -.36 to -2.11. Conclusion. These results, based on data from ENSEMBLE-2, build upon prior cross-sectional analyses and provide additional supportive psychometric evidence on the SIC.
ABSTRACT
Background. The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome (PRO) measure developed to assess the presence and severity of COVID-19 signs and symptoms in adults. To further facilitate the evaluation of new vaccines and treatments in development, similar tools are needed for use within pediatric populations. The objectives of this study were to support adolescent selfcompletion and create an adaptation of the measure for caregiver assessment of signs and symptoms in children aged < 12 years (henceforth, the Pediatric SIC [PedSIC]). Methods. After developing draft versions of the PedSIC and reference materials with definitions to facilitate accurate completion of both measures, iterative rounds of cognitive debriefing interviews were conducted from November 2020 through January 2021 to evaluate understanding of the SIC (in adolescents aged 12-17), and inform refinement of the PedSIC for caregivers of children aged < 12. Recruitment quotas were employed to support sample diversity. Results. Nine adolescents (mean [SD, range] age, 14 [1.76, 12-17] years, 56% female, 78% white;round 1, n=6;round 2, n=3) and 17 caregivers (mean [SD, range] age, 34 [6.28, 26-41] years, 59% female, 65% white;round 1, n=9;round 2, n=8) completed interviews. All adolescents understood and completed the adult version of the SIC without instrument modification. Ease and accuracy of self-completion was improved through the use of reference materials. Caregiver feedback resulted in modification of the PedSIC to include two sections: observable signs (ages < 12), and symptoms assessed with input from children (ages >= 5-< 12). Reference materials provided standardization of item intent. Conclusion. Results support using the SIC, PedSIC, and their associated reference materials to assess the presence and severity of COVID-19 signs/symptoms in adolescents and children aged < 12 years, respectively, who participate in vaccine and treatment clinical trials.