• Concept elicitation interviews generated a range of symptoms and symptom descriptions used in the development of the items, instructions, recall period, response options.

• Concept elicitation showed a wider range of symptoms experienced by patients than used to evaluate influenza therapies in previous studies.

• Cognitive interviews suggest excellent content symptom coverage in the draft FLU-PRO items.

• Participants completed the FLU-PRO quickly and easily.

• Participants understood the instrument content as intended.

• A quantitative validation study will be performed to evaluate the FLU-PRO in a sample of English and Spanish-speaking adults with influenza and influenza-like conditions, including:

• Item-level analyses and item reduction, factor analysis; Rasch or IRT analyses as appropriate.

• Reliability: internal consistency of scale and any subscale scores and reproducibility (test-retest reliability).

• Construct validity.

• Responsiveness including score interpretation.

Themes

• Symptoms and their severity identified and described by study participants are shown in Figure 1 and Figure 2.

Figure 1: Most frequently reported influenza symptoms by system and country

Figure 2: Most severe influenza symptoms by country

Themes Stage 2: Cognitive Interviews

• Characteristics of second separate group of patients shown in Table 2

Table 2: Demographics and baseline characteristics by country

Participant Reactions to FLU PRO

• Participants had good understanding of the instructions, recall period, response options and the majority of items.

• Participants considered content/items relevant to their recent and previous flu experiences.

• As expected, several items were identified as overlapping or highly related:

• Sore throat, swollen throat and difficulty swallowing (n=5 US; 4 Mexico).

• Felt lightheaded and felt dizzy (n=5 US; 2 Mexico).

• Head congestion, sinus pressure and headache (n=4 US; 11 Mexico).

• Sore or painful eyes and eyes sensitive to light (n=2 US; 0 Mexico).

• Additional overlapping or difficult items, raised only by the Mexico participants were:

• Sinus pressure, nasal congestion, runny or drippy nose (n=10).

• Trouble breathing and nasal congestion (n=6).

• Chest tightness, pain with breathing or coughing, muscular/general pain (n=5).

• Body aches or pains with other symptoms (n=4).

• Difficulty describing loose cough (n=6).

• Correlations between these items and systematic item reduction are planned for the next stage of instrument development.

Figure 3: Draft FLU PRO questionnaire format sample question:

• Following quantitative validation, the FLU-PRO will be available as a standardized method for evaluating symptoms of influenza.

• Research is underway examining suitability of the instrument for children/adolescents and to perform further evaluations in inpatients.

• Centers for Disease Control and Prevention. Seasonal Influenza (Flu). 2012; Available from: http://www.cdc.gov/flu/about/disease/index.htm. Accessed September 5, 2013.

• Food and Drug Administration. Guidance for industry on patient-reported outcome measures: use in medical product development to support labeling claims. Fed Regis. 2009;74(235):65132-65133.

• Leidy NK, Vernon M. Perspectives on patient-reported outcomes : content validity and qualitative research in a changing clinical trial environment. Pharmacoeconomics. 2008;26(5):363-370.

• Patrick DL, Burke LB, Gwaltney CJ, Leidy NK, Martin ML, Molsen E, Ring L. Content validity--establishing and reporting the evidence in newly developed patient-reported outcomes (PRO) instruments for medical product evaluation: ISPOR PRO good research practices task force report: part 1--eliciting concepts for a new PRO instrument. Value Health 2011a;14:967-977.

• Wild D, Grove A, Martin M, Eremenco S, McElroy S, Verjee-Lorenz A, et al. Principles of good practice for the translation and cultural adaptation process for patient-reported outcomes (PRO) measures: report of the ISPOR task force for translation and cultural adaptation. Value Health. 2005;8(2):94-104.

The authors would like to thank the site clinical coordinators for facilitating data collection and Evidera research assistants for data entry, cleaning, and assistance with the analyses. We would also like to thank the patients who volunteered to participate in this study.

This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. 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 research was supported in part by the National Institute of Allergy and Infectious Diseases.

Discussion

Conclusion

References

Acknowledgments

Development of the Patient Reported Outcome Instrument FLU-PRO to Standardize and Quantify Symptoms of Influenza

John H. Powers MD1; Sonja M. Stringer MPH2; Sarah Clifford PhD2; Katherine Kim MPH2; John Arnold MD3; Christina Schofield MD; Patrick Danaher MD3; Nathaniel Stepp MD3; Bree Brown3; Karl Kronmann MD3; Timothy Burgess MD3; Mary Fairchok MD3; Michelande Ridore3; Eugene Millar PhD3; M. Lourdes Guerrero MD MS4;

Guillermo M. Ruiz-Palacios MD4; Andrés Hernández MD MS4; Ana Patricia Rodríguez-Zulueta4; Arturo Galindo-Fraga4;Alice Rosenberg RN1; Nancy Kline Leidy, PhD2 1Clinical Research Directorate / Clinical Monitoring Research Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA,

2Evidera, Bethesda, MD, USA 3 Infectious Disease Clinical Research Program, Bethesda, MD,USA, 4 Mexico Emerging Infectious Diseases Clinical Research Network (LaRed), Mexico City, Mexico

• To develop a patient-reported outcome (PRO) measure to

standardize the assessment of influenza (FLU) symptoms in clinical studies: The FLU-PRO.

• Using well-documented methods of instrument development (FDA 2009, Patrick et al. 2011).

• Influenza is a contagious respiratory illness caused by influenza

viruses.

• Influenza causes mild to severe illness, and may lead to death (CDC 2012) with an estimated 226,000 hospitalizations and 3,000 to 49,000 deaths in the US annually.

• Patients who survive influenza experience morbidity and disability related to bothersome symptoms.

• Currently, there is no standardized, validated measurement scale for quantifying the profile and severity of influenza symptoms.

• A comprehensive, standardized, precise measure of influenza symptoms will facilitate understanding of the natural history of influenza, variability within and across populations, and the effects of treatments on patient centered outcomes.

Introduction

Purpose

Overview

• 2-stage instrument development method involving adults (> 18 years) with documented influenza recruited through clinical sites in the US and Mexico.

• Written informed consent obtained during the clinic visit.

• In each stage, cross-sectional qualitative 1:1 telephone interviews were performed.

• Trained interviewers used a semi-structured interview guide.

• Interviews were audio-recorded and transcribed for analyses.

• The software program ATLAS.ti (version 5.0), was used to facilitate the systematic analysis of data.

• Transcripts were coded and reviewed by a second analyst with any discrepancies resolved through discussion with the primary or senior analyst.

Stage 1: Concept Elicitation

• To gather information regarding patient experience of influenza symptoms, including type, magnitude, expression, pattern of onset and recovery.

• Saturation, the point at which additional sampling offers no new information, was documented in a saturation grid (Leidy and Vernon 2008).

Methods

Stage 1: Concept Elicitation (cont.)

• The multi-disciplinary FLU-PRO development team (researchers & clinicians) met via webinar to review results and decide on content and structure (item phrasing, length, response options, recall).

• Translatability Assessment: The draft instrument was reviewed by an expert in PRO instrument translation and e-PRO formatting to assure translatability of words and phrases and simple conversion to an electronic format.

• The draft FLU-PRO instrument was translated into Spanish for cognitive interviews in Mexico using methods that ensured conceptual equivalence with the source document (Wild et al. 2005).

Stage 2: Cognitive Interviews

• To assess comprehension and interpretability of the draft FLU-PRO instrument from the respondent’s perspective.

• Data were used to document content validity and make final adjustments before subjecting the instrument to quantitative evaluation.

Stage 1 Concept Elicitation Interviews

Table 1: Demographics and baseline characteristics (N=46)

Methods

Results

Results Results