Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI)

Abstract

BackgroundThe inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza.ObjectivesThis study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI).MethodsData from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach’s alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1–7).ResultsThe analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72–0.86 for domain scores. Reproducibility (Day 1–2) was 0.64 for Total, ranging from 0.46–0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9–62.2; p<0.01). Mean score improvements Day 1–7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes).ConclusionsResults suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.

Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study

“…Clinical symptoms were assessed using the FLU-PRO Symptom Severity Assessment Tool, a participant-directed questionnaire designed to assess influenza disease severity that has been validated in both natural infection and influenza challenge studies [39][40][41] . In addition, a physician assessment was also performed daily for 10 days to determine the presence or absence of influenza signs/symptoms.…”

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation

“…Prior analyses of the FLU-PRO in patients with and without influenza have shown that changes in item scores of ,0.5 are not clinically meaningful. 10,28 The "ability to detect change" assessment evaluates the sensitivity of a PRO instrument in detecting clinically important changes in patients' health conditions. In this study, the ability of the FLU-PRO to detect change was assessed by summarizing the RSV participant's average change from baseline in daily symptom scores at illness weeks 1 to 3 and comparing it with minimal clinically significant changes.…”

“…The large sample size (N = 1268) resulted in statistical significance for small differences that were not clinically meaningful (ie, smaller than the minimal clinically significant change determined by both distribution-based and anchoredbased methods). 10,28 The FLU-PRO's ability to detect change was demonstrated: all symptom score changes, except for earache and gastrointestinal symptoms, were clinically meaningful in week 1 of illness (Fig. 1).…”

“…Therefore, we used the results of other FLU-PRO studies, in which changes in item scores of .0.5 were defined as clinically meaningful. 10,28 The importance of including patient-centered outcomes in clinical trials is being increasingly recognized. Standardization of methods for capturing symptoms improves the accuracy and efficiency of clinical trials.…”

“…7 Symptom data were recorded using the inFLUenza Patient-Reported Outcome (PRO) instrument (FLU-PRO), which has been evaluated in patients with influenza-like illness with and without confirmed influenza. [8][9][10] In addition to assessing vaccine efficacy, we evaluated the validity and reliability of the FLU-PRO for use in RSV prevention studies, as specified in Food and Drug Administration (FDA) guidance on the development of PROs, 11 and evaluated the validity of the composite primary endpoint based on PRO-captured symptom data plus virologic confirmation. We also analyzed the results of selfswabbing compared with site-collected swabs for virologic confirmation.…”