Look -: but also listen!: ReQuest™:: An essay on a new validated scale to assess the outcome of GERD treatment

The ReQuest (TM) (Reflux Questionnaire) is a new instrument: a diary developed specifically to allow patients to measure the totality of their gastroesophageal reflux disease (GERD) symptoms and to track changes each day during treatment, an increasingly important need in clinical trials. This paper reviews the background, development, testing, and validation of the instrument and shows how its flexibility allows it to be used in new ways to assess different aspects of GERD. Development: There were four key steps. (1) A full symptom spectrum was gathered from experts, literature and, crucially, from GERD patients, and comprised 67 symptom descriptions. (2) By expert consensus, these symptom descriptions were empirically condensed into six easier-to-handle 'dimensions' (acid complaints, upper abdominal/stomach complaints, lower abdominal/digestive complaints, nausea, sleep disturbances, other complaints), to which the seventh, general well- being, was added, a key feature of the instrument. The symptom burden of each dimension is measured as frequency x intensity (general well-being: intensity only). (3) This prototype instrument was tested in PPI clinical trials involving patients with erosive and non- erosive GERD, while the data generated were used to validate the prototype. (4) Finally, the scale was refined by factor analysis, a statistical process. Outcome: Detailed statistical testing validating the scale and factor analysis confirmed that empirically condensing the symptom descriptions into dimensions did not affect the measurement properties of the instrument. Further Application: The structure of ReQuest (TM) and its product, which is numerical, makes the instrument highly flexible and allows for its use in other GERD areas. (1) Its subscales, ReQuest (TM)-GI and ReQuest (TM)-WSO, measure symptoms traditionally associated with reflux and with general well-being, respectively, and permit these to be quantified and tracked independently. (2) Minor degrees of reflux symptoms are common amongst the healthy. The level was determined in a large population without evidence of disease, and a 'GERD symptom threshold' calculated. Reduction below this threshold to 'background levels' is a more realistic end point in clinical trials than the rarely achieved 'complete absence'. (3) ReQuest (TM)-GI was re-scaled and integrated with the modified Los Angeles scale used to grade esophageal appearances at endoscopy. The new instrument is a matrix, the ReQuest (TM)/LA-classification, which allows both symptoms and endoscopy appearances to be expressed by a single set of numbers in individual patients and in populations. (4) This in turn allows identification of patients who on treatment achieve 'complete remission', i.e. healing and symptom relief. PPI clinical trials confirm that it takes a longer period of treatment to reach this endpoint than healing or symptom relief alone. Thus the conventional 4-8 weeks of PPI therapy may unwittingly result in under-treatment. (5) Studies are in progress to determine the 'minimum clinically important difference' (MCID). This is the minimum change measured on treatment, which is judged as being of clinical benefit, an increasingly important subject. (6) Finally, the ReQuest (TM) used in clinical trials has been simplified for application in day-to-day clinical practice. The results obtained with 'ReQuest in Practice (TM)', the simplified version, are similar to those observed with the full version, as confirmed in a large-scale study in general practice. The clinical practice version has alo been validated. Conclusion: (1) The characteristics of ReQuest (TM) make it suitable for use as the primary endpoint in clinical trials assessing the outcome of GERD. (2) The subscales allows for closer examination on the nature of GERD and response to treatment. (3) A simplified version has proven suitable for use in daily practice. Copyright (c) 2007 S. Karger AG, Basel.