Development and validation of a patient-reported outcome instrument in partial responders to proton pump inhibitors

Abstract

Objective. The Reflux Symptom Questionnaire 7-day recall (RESQ-7) was developed, in line with the US Food and Drug Administration (FDA) guidelines, to address the need for a patient-reported outcome (PRO) instrument assessing symptoms specifically in patients with gastroesophageal reflux disease (GERD) who are only partially responsive to proton pump inhibitor (PPI) therapy. Materials and methods. The RESQ-7 was constructed using patient interviews and expert consensus. The instrument was psychometrically validated in a clinical trial setting in patients with persistent GERD symptoms despite PPI therapy. Results. Evaluation of content validity yielded a 13-item structure for the RESQ-7, incorporating symptoms overlooked by existing GERD questionnaires, such as hoarseness, cough, difficulty swallowing and burping. Principal component analysis suggested a four-domain structure. All domains had a high inter-item correlation (Cronbach's α lower 95% confidence limits: 0.77–0.87 for intensity; 0.72–0.82 for frequency). Test–retest reliability was fair-to-good or excellent (intraclass correlation coefficient lower 95% confidence limits: 0.70–0.78 for intensity; 0.65–0.75 for frequency). Convergent and discriminant validity were confirmed by correlation comparisons with the Gastrointestinal Symptom Rating Scale. Discussion. The RESQ-7 demonstrated good content validity and psychometric properties in patients with GERD and a partial response to PPIs. The weekly recall makes the RESQ-7 appropriate for use in routine clinical care. The authors believe that it is the first instrument to be developed specifically for patients with a partial response to PPI therapy in line with FDA guidelines on PROs (ClinicalTrials.gov identifier: NCT00703534).

Key Words::

• gastroesophageal reflux
• proton pump inhibitors
• questionnaires

Acknowledgements

Specific author contributions: A. Rydén: analysis and interpretation of data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. H. Denison: study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content and study supervision. M. Karlsson: study concept and design, analysis and interpretation of data and critical revision of the manuscript for important intellectual content. N. Vakil: study concept and design, acquisition of data, analysis and interpretation of data and critical revision of the manuscript for important intellectual content. A. Rydén, H. Denison and N. Vakil approved the final version of the manuscript. This manuscript was completed shortly after M. Karlsson's death. Financial support: This study was funded by AstraZeneca R&D, Mölndal, Sweden. Writing support was provided by Dr Martin Bell, from Oxford PharmaGenesis^™ Ltd, Oxford, UK, and was funded by AstraZeneca R&D, Mölndal, Sweden.

Declaration of interests: A. Rydén, H. Denison are employed by AstraZeneca R&D, Mölndal, Sweden. M. Karlsson was employed by AstraZeneca R&D, Mölndal, Sweden at the time of her death. N. Vakil has received consultancy fees from Novartis Pharmaceuticals, AstraZeneca, Takeda Pharmaceutical, Meridian Bioscience, XenoPort, Orexo, Axcan Pharma and Ironwood Pharmaceuticals. He has received grant/research support from AstraZeneca and XenoPort, and has ownership interest (e.g. stocks, stock options) in Orexo and Meridian Bioscience.