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The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds

BACKGROUND: Patient perspectives on their disease are undoubtedly important in clinical trials and in practice. To date, no patient-reported outcome (PRO) questionnaire assessing symptoms of Clostridium difficile infection (CDI) has been developed following FDA guidance. The CDI-DaySyms™ is a new co...

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Autores principales: Talbot, George H, Kleinman, Leah, Davies, Evan W, Hunsche, Elke, Roberts, Laurie, Nord, Carl Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630859/
http://dx.doi.org/10.1093/ofid/ofx163.980
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author Talbot, George H
Kleinman, Leah
Davies, Evan W
Hunsche, Elke
Roberts, Laurie
Nord, Carl Erik
author_facet Talbot, George H
Kleinman, Leah
Davies, Evan W
Hunsche, Elke
Roberts, Laurie
Nord, Carl Erik
author_sort Talbot, George H
collection PubMed
description BACKGROUND: Patient perspectives on their disease are undoubtedly important in clinical trials and in practice. To date, no patient-reported outcome (PRO) questionnaire assessing symptoms of Clostridium difficile infection (CDI) has been developed following FDA guidance. The CDI-DaySyms™ is a new comprehensive measure of a broad range of local and systemic CDI symptoms (not only diarrhea) that patients report as meaningful. Objectives were to: finalize the CDI-DaySyms™ items (questions); assign them to domains (concepts); evaluate the questionnaire’s measurement properties; and define responder thresholds. METHODS: Blinded data from a sub-study of two Phase III trials (NCT01987895 and NCT01983683) in CDI patients were analyzed following FDA guidance for validating PRO questionnaires. Patients completed the CDI-DaySyms™ daily from Day 1 until end of treatment. Items were selected for inclusion in the final questionnaire based on a range of validation analyses, input from expert clinicians, and findings from prior qualitative patient research. Responder-threshold analyses used Day-3 data to align with the rapid symptom improvement generally seen in response to CDI therapy. RESULTS: Data were analyzed for 168 CDI patients (median age 60 years; 67.9% female; 81.5% mild/moderate, 11.3% severe, 7.1% unknown disease severity; 80.4% first CDI occurrence, 19.6% first recurrence). Three of the 13 items in the draft CDI-DaySyms™ were deleted; the remaining 10 were statistically assigned to three domains measuring different symptom concepts (Figure). Individual items in each domain correlated strongly with one another and their domain. Domain scores demonstrated acceptable consistency over time in stable patients, were sensitive to change, and correlated in expected directions with scores of other relevant symptom and disease-severity measures. Responder thresholds were defined as score changes of -1.00, -0.80, and -0.70 for Diarrhea, Abdominal, and Systemic/Other Symptoms domain scores, respectively. CONCLUSION: The CDI-DaySyms™ is a valid measure of diarrhea and other CDI symptoms useful in assessing response to therapy. It has good measurement properties, and with only 10 items can be easily administered in clinical trials and in practice. DISCLOSURES: G. H. Talbot, Actelion: Board Member, Consultant and Scientific Advisor, Consulting fee; L. Kleinman, Actelion: Consultant, Research support; 
 E. W. Davies, Actelion: Employee, Salary; E. Hunsche, Actelion: Employee and Shareholder, Salary; L. Roberts, Actelion: Consultant, Research support; C. E. Nord, Actelion: Scientific Advisor, Consulting fee
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spelling pubmed-56308592017-11-07 The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds Talbot, George H Kleinman, Leah Davies, Evan W Hunsche, Elke Roberts, Laurie Nord, Carl Erik Open Forum Infect Dis Abstracts BACKGROUND: Patient perspectives on their disease are undoubtedly important in clinical trials and in practice. To date, no patient-reported outcome (PRO) questionnaire assessing symptoms of Clostridium difficile infection (CDI) has been developed following FDA guidance. The CDI-DaySyms™ is a new comprehensive measure of a broad range of local and systemic CDI symptoms (not only diarrhea) that patients report as meaningful. Objectives were to: finalize the CDI-DaySyms™ items (questions); assign them to domains (concepts); evaluate the questionnaire’s measurement properties; and define responder thresholds. METHODS: Blinded data from a sub-study of two Phase III trials (NCT01987895 and NCT01983683) in CDI patients were analyzed following FDA guidance for validating PRO questionnaires. Patients completed the CDI-DaySyms™ daily from Day 1 until end of treatment. Items were selected for inclusion in the final questionnaire based on a range of validation analyses, input from expert clinicians, and findings from prior qualitative patient research. Responder-threshold analyses used Day-3 data to align with the rapid symptom improvement generally seen in response to CDI therapy. RESULTS: Data were analyzed for 168 CDI patients (median age 60 years; 67.9% female; 81.5% mild/moderate, 11.3% severe, 7.1% unknown disease severity; 80.4% first CDI occurrence, 19.6% first recurrence). Three of the 13 items in the draft CDI-DaySyms™ were deleted; the remaining 10 were statistically assigned to three domains measuring different symptom concepts (Figure). Individual items in each domain correlated strongly with one another and their domain. Domain scores demonstrated acceptable consistency over time in stable patients, were sensitive to change, and correlated in expected directions with scores of other relevant symptom and disease-severity measures. Responder thresholds were defined as score changes of -1.00, -0.80, and -0.70 for Diarrhea, Abdominal, and Systemic/Other Symptoms domain scores, respectively. CONCLUSION: The CDI-DaySyms™ is a valid measure of diarrhea and other CDI symptoms useful in assessing response to therapy. It has good measurement properties, and with only 10 items can be easily administered in clinical trials and in practice. DISCLOSURES: G. H. Talbot, Actelion: Board Member, Consultant and Scientific Advisor, Consulting fee; L. Kleinman, Actelion: Consultant, Research support; 
 E. W. Davies, Actelion: Employee, Salary; E. Hunsche, Actelion: Employee and Shareholder, Salary; L. Roberts, Actelion: Consultant, Research support; C. E. Nord, Actelion: Scientific Advisor, Consulting fee Oxford University Press 2017-10-04 /pmc/articles/PMC5630859/ http://dx.doi.org/10.1093/ofid/ofx163.980 Text en © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Talbot, George H
Kleinman, Leah
Davies, Evan W
Hunsche, Elke
Roberts, Laurie
Nord, Carl Erik
The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds
title The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds
title_full The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds
title_fullStr The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds
title_full_unstemmed The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds
title_short The Clostridium difficile Infection – Daily Symptoms (CDI-DaySyms™) Patient-Reported Outcome (PRO) Questionnaire: Final Validation and Responder Thresholds
title_sort clostridium difficile infection – daily symptoms (cdi-daysyms™) patient-reported outcome (pro) questionnaire: final validation and responder thresholds
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630859/
http://dx.doi.org/10.1093/ofid/ofx163.980
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