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

      research-article
      1 , * , 2 , 3 , 3 , 3 , 4 , 4 , 5 , 6 , 7 , 6 , 7 , 6 , 7 , 6 , 7 , 8 , 9 , 7 , 10 , 6 , 11 , 6 , 7 , 12 , 13 , 14 , 15 , 15 , 15 , 16 , 17 , 18 , 19 , 20 , 17 , 21 , 17 , 22 , 17 , 23 , 24 , 24 , 24 , 15
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          Abstract

          Background

          The 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.

          Objectives

          This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI).

          Methods

          Data 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).

          Results

          The 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).

          Conclusions

          Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.

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          Most cited references14

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          Coefficient alpha and the internal structure of tests

          Psychometrika, 16(3), 297-334
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            Use of existing patient-reported outcome (PRO) instruments and their modification: the ISPOR Good Research Practices for Evaluating and Documenting Content Validity for the Use of Existing Instruments and Their Modification PRO Task Force Report.

            Patient-reported outcome (PRO) instruments are used to evaluate the effect of medical products on how patients feel or function. This article presents the results of an ISPOR task force convened to address good clinical research practices for the use of existing or modified PRO instruments to support medical product labeling claims. The focus of the article is on content validity, with specific reference to existing or modified PRO instruments, because of the importance of content validity in selecting or modifying an existing PRO instrument and the lack of consensus in the research community regarding best practices for establishing and documenting this measurement property. Topics addressed in the article include: definition and general description of content validity; PRO concept identification as the important first step in establishing content validity; instrument identification and the initial review process; key issues in qualitative methodology; and potential threats to content validity, with three case examples used to illustrate types of threats and how they might be resolved. A table of steps used to identify and evaluate an existing PRO instrument is provided, and figures are used to illustrate the meaning of content validity in relationship to instrument development and evaluation. RESULTS & RECOMMENDATIONS: Four important threats to content validity are identified: unclear conceptual match between the PRO instrument and the intended claim, lack of direct patient input into PRO item content from the target population in which the claim is desired, no evidence that the most relevant and important item content is contained in the instrument, and lack of documentation to support modifications to the PRO instrument. In some cases, careful review of the threats to content validity in a specific application may be reduced through additional well documented qualitative studies that specifically address the issue of concern. Published evidence of the content validity of a PRO instrument for an intended application is often limited. Such evidence is, however, important to evaluating the adequacy of a PRO instrument for the intended application. This article provides an overview of key issues involved in assessing and documenting content validity as it relates to using existing instruments in the drug approval process.
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              What is sufficient evidence for the reliability and validity of patient-reported outcome measures?

              This article focuses on the necessary psychometric properties of a patient-reported outcomes (PROs) measure. Topics include the importance of reliability and validity, psychometric approaches used to provide reliability and validity estimates, the kinds of evidence needed to indicate that a PRO has a sufficient level of reliability and validity, contexts that may affect psychometric properties, methods available to evaluate PRO instruments when the context varies, and types of reliability and validity testing that are appropriate during different phases of clinical trials. Points discussed include the perspective that the psychometric properties of reliability and validity are on a continuum in which the more evidence one has, the greater confidence there is in the value of the PRO data. Construct validity is the type of validity most frequently used with PRO instruments as few "gold standards" exist to allow the use of criterion validity and content validity by itself only provides beginning evidence of validity. Several guidelines are recommended for establishing sufficient evidence of reliability and validity. For clinical trials, a minimum reliability threshold of 0.70 is recommended. Sample sizes for testing should include at least 200 cases and results should be replicated in at least one additional sample. At least one full report on the development of the instrument and one on the use of the instrument are deemed necessary to evaluate the PRO psychometric properties. Psychometric testing ideally occurs before the initiation of Phase III trials. When testing does not occur prior to a Phase III trial, considerable risk is posed in relation to the ability to substantiate the use of the PRO data. Various qualitative (e.g., focus groups, behavioral coding, cognitive interviews) and quantitative approaches (e.g., differential item functioning testing) are useful in evaluating the reliability and validity of PRO instruments.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Project administrationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Project administrationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: Writing – original draft
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draft
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draft
                Role: InvestigationRole: ResourcesRole: Writing – original draft
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draft
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: ResourcesRole: Writing – original draft
                Role: InvestigationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 March 2018
                2018
                : 13
                : 3
                : e0194180
                Affiliations
                [1 ] Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, MD, United States of America
                [2 ] Evidera Evidence, Value & Access by PPD, Seattle, WA, United States of America
                [3 ] Evidera Evidence, Value & Access by PPD, Bethesda, MD, United States of America
                [4 ] National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States of America
                [5 ] Madigan Army Medical Center, Fort Lewis, WA, United States of America
                [6 ] Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University, Bethesda, MD, United States of America
                [7 ] Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, United States of America
                [8 ] Naval Medical Center, San Diego, CA, United States of America
                [9 ] Defense Institute for Medical Operations, San Antonio, TX, United States of America
                [10 ] Naval Medical Center, Portsmouth, VA, United States of America
                [11 ] Walter Reed National Military Medical Center, Bethesda, MD, United States of America
                [12 ] Children’s National Medical Center, Washington, DC, United States of America
                [13 ] Instituto Nacional de Enfermedades Infecciosas, Mexico City, Mexico
                [14 ] Hospital General Dr. Manuel Gea González, Mexico City, Mexico
                [15 ] Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
                [16 ] UCL, London, United Kingdom
                [17 ] INSIGHT Influenza Study Groups, Rochester, MN, United States of America
                [18 ] Institute of Clinical Trials and Methodology, University College, London, United Kingdom
                [19 ] Institute for Global Health, University College, London, United Kingdom
                [20 ] Kirby Institute, University of New South Wales, Kensington, Australia
                [21 ] University of North Carolina, Chapel Hill, NC, United States of America
                [22 ] University of Cologne, Cologne, Germany
                [23 ] Hospital General de Agudos JM Ramos Mejia, Buenos Aires, Argentina
                [24 ] Johns Hopkins University School of Medicine, Baltimore, MD, United States of America
                University of Washington, UNITED STATES
                Author notes

                Competing Interests: ED Bacci, NK Leidy, JL Poon, and S Stringer, are salaried employees of Evidera Evidence, Value & Access by PPD (Evidera). JH Powers is an employee of Leidos Biomedical Research. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The view(s) expressed in this article are those of the author(s) and do not reflect the official policy or position of Uniformed Services University of the Health Sciences, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., National Institutes of Health or the Department of Health and Human Services, Brooke Army Medical Center, Walter Reed National Military Medical Center, Landstuhl Regional Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Air Force, the Department of the Navy, the Department of the Army or the Department of Defense or the US Government. Mention of trade names, commercial products, or organizations does not imply endorsement by the US Government.

                Author information
                http://orcid.org/0000-0002-5150-5119
                Article
                PONE-D-17-32171
                10.1371/journal.pone.0194180
                5863969
                29566007
                9c547d17-7a49-45d2-bae3-d5eed1b697a1

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 1 September 2017
                : 26 February 2018
                Page count
                Figures: 1, Tables: 6, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: Contract No. HHSN261200800001E
                Award Recipient :
                This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, NIAID. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This study was supported by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences (USUHS). This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under Inter-Agency Agreement (#64019). ED Bacci, NK Leidy, JL Poon, and S Stringer, are salaried employees of Evidera Evidence, Value & Access by PPD (Evidera). Evidera received funding (in whole or in part with federal funds) from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, to conduct the study and develop this manuscript. JH Powers is an employee of Leidos Biomedical Research under a Federally Funded Research and Development Contract (FFRDC) between Leidos and the National Institutes of Health. Leidos (JHP) and Evidera (EDB, NKL, JLP, SS) provided support in the form of salaries for the above noted authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. S Pett has received funding from the Medical Research Council, UK.
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