ReQuest-- the challenge of quantifying both esophageal and extra-esophageal manifestations of GERD.

Gastroesophageal reflux disease (GERD) is highly prevalent in Western countries. It is characterized by esophageal and extra-esophageal symptoms (both typical and atypical) as well as by a number of potential complications. As the majority of patients have normal gross endoscopic findings, the assessments of symptom severity and quality of life, as well as the patients' response to treatment have become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. An ideal GERD symptom questionnaire, suitable as a primary end-point for clinical trials, should: (1) be sensitive in patients with GERD, (2) cover frequency and intensity of typical and atypical GERD symptoms, (3) be multidimensional (cover all symptom dimensions), (4) have proven psychometric properties (validity, reliability and responsiveness), (5) be practical and economical, (6) be self-assessed, (7) use 'word pictures' which are easy to understand for patients, (8) respond rapidly to changes (responsiveness in short-time intervals), (9) be used daily to assess changes during and after therapy, and (10) be valid in different languages for international use. A literature review revealed five evaluative scales that met some of the above characteristics, but none fulfilled all of them. Therefore, a new evaluative tool for the assessment of GERD symptoms and their response to therapy is needed. The Reflux Questionnaire (ReQuest) is a self-assessed questionnaire developed and validated to assess the effect of treatment on the spectrum of GERD-related symptoms. Initially, GERD symptoms were identified on the basis of available literature, knowledge from previous clinical trials, experienced physicians, and patient interviews. An overall of 67 typical and atypical symptom descriptions were grouped into six different dimensions of GERD (acid complaints, upper abdominal/stomach complaints, lower abdominal/digestive complaints, nausea, sleep disturbances, other complaints). To these six dimensions a seventh, general well-being was added. Each dimension was tested by questions for frequency and intensity (except general well-being, for which only the intensity was determined). Thereafter, ReQuest was translated into different languages and tested in mother tongue patient focus groups. ReQuest psychometric properties (test-retest reliability, internal consistency, construct validity, responsiveness) were validated in two clinical trials of erosive GERD and endoscopic negative (en) GERD. In the first open, multicenter study, ReQuest was assessed in 430 patients with erosive GERD grade A-D. Patients with GERD grade A were treated with pantoprazole 20 mg od whereas those with GERD grade B-D received 40 mg od. The second open, multicenter, multinational trial with pantoprazole 20mg od assessed the ReQuest in over 800 patients with endoscopic negative GERD. Furthermore, ReQuest was used to determine the 'normal' ranges of GERD symptoms in individuals without GERD evidence. Over 300 healthy volunteers took part in a 4-day evaluation by completing ReQuest on each of the four study-days, as well as GSRS and PGWB on day 1. Based on the 90% percentiles determined in this study, a 'normal' range was calculated for ReQuest and relative subscales. The study showed that even individuals without GERD evidence can experience mild GERD symptoms. The derived 'normal' ranges within the population can be used for classification of symptom relief. In conclusion, ReQuest proved to be a valid, reliable, and responsive tool for measuring both typical and atypical GERD symptoms, and to be particularly suitable for measuring daily symptom changes and identifying normalization of the clinical picture in therapeutic trials.