Opmaak

Evaluation of the GERD Impact Scale, an international, validated patient
questionnaire, in daily practice. Results of the ALEGRIA study

E. Louis1, J. Tack2, G. Vandenhoven3, C. Taeter3 (1) Department of Gastroenterology, CHU of Liege Belgium ; (2) Department of Pathophysiology, KU Leuven, Belgium ; (3) AstraZeneca, Belgium.
Abstract
up to half of all cases, GERD is associated with erosive,or reflux according to the Montreal definition, esophagi- Background and study aims : Gastroesophageal reflux disease
tis (11). However, individuals with GERD suffer signifi- (GERD) is a common chronic disease that is primarily diagnosed
based on symptom severity and frequency. This study gathered

cant pain and discomfort whether or not esophagitis is epidemiological data in a population of GERD patients and
present, and the resulting impairment in QoL is not evaluated the added-value of the GERD Impact Scale (GIS), a
dependent on endoscopic findings (7,12). Thus, interna- novel, validated patient questionnaire, as a tool for initial and long-
term patient management.

tional guidelines recommend that GERD should be diag- Patients and methods : This observational study recruited
nosed and managed on the basis of symptom frequency patients (296 study centers) with symptomatic GERD and a
and severity (3,13-15). Although the symptoms of history of erosive, or reflux, esophagitis. Symptoms were assessed
by GIS and physician-subject interview and recorded at baseline

GERD are experienced by the patient, assessments of (visit 1), at 4–6 weeks (visit 2) and 8–14 weeks (visit 3) ; also
symptom severity have traditionally been carried out by recorded at each visit was the physician’s assessment of GERD
the physician. However, the agreement between patients severity and treatment changes. Analyses were performed on an
intent-to-treat basis.

and physicians in their assessments of severity of reflux Results : Subjects (n=1919 ; mean age, 55 years) were 54%
symptoms seems poor, particularly before treatment and female. Lifestyle characteristics included stress (~70% of subjects),
mean daily consumption of five cups of caffeine-containing bever-
ages (~70%), alcohol consumption of approximately nine units per

The lack of physician-patient agreement in the assess- week (~50%) and smoking/ex-smoker (41%). Proton pump
ment of symptoms has far-reaching implications. In day- inhibitors were prescribed in 99% of cases : mainly esomeprazole
to-day clinical practice, both the decision to offer the (82%), with a median dose of 40 mg. Prescribed therapy was
changed (mainly dosage levels) between visits in ~60% of subjects.

patient treatment and the type of treatment offered are The severity of GERD symptoms and GIS scores decreased sub-
determined by the physician’s initial assessment of stantially throughout the study. Mean GIS scores correlated posi-
symptoms. Poor physician-patient agreement prior to tively with increasing GERD severity and clinical judgment at all
visits. Physicians reported that the GIS helped them define the

therapy may be an obstacle to the appropriate manage- appropriate treatment for the patient and to evaluate the patient’s
ment of GERD and this may contribute to widespread response to treatment in 81% of cases.
treatment dissatisfaction experienced by patients (17).
Conclusions : This study demonstrates the added-value and
usefulness of the patient self-assessment GIS as a management tool
Conversely, studies have shown that the benefits of good for GERD. (Acta gastro enterol. belg., 2009, 72, 3-8).
physician-patient communication are likely to extendbeyond more accurate symptom assessment to improvedpatient health outcomes, satisfaction, well-being and 1. Introduction
When supported by appropriate instruments, patients Gastroesophageal reflux disease (GERD) is estimated may be the most faithful reporters of their own symp- to affect 10–20% of the general population in the toms and this could allow a move towards giving greater Western world, and is a common cause of health care weighting to patients’ own reports (3). In this regard, a seeking in the primary care setting (1,2). GERD occurs novel patient questionnaire, the GERD Impact Scale when movement of gastric contents into the esophagus (GIS), may be of use. This validated questionnaire was causes troublesome symptoms (such as heartburn and designed to aid physicians in the identification of an regurgitation) and/or complications (3). Such symptoms appropriate treatment and to evaluate the patient’s may lead to sleep disturbance (4) and a decrease in the response to treatment. The GIS was developed from an patient’s quality of life (QoL) including a lack of vitality initial systematic literature review, followed by patient and limitations in food and drink intake. Night-timeheartburn and sleep complaints are associated withexcessive gastroesophageal reflux (5). Feelings of poorphysical and mental health interfere with the patient’sability to function normally on a daily basis (6,7) and are likely to impair their performance at work (6,8-10).
Correspondence to : Christine Taeter, M.D., Rue Egide Van Ophemstraat 110,1180 Brussel-Bruxelles, Belgium. E-mail : [email protected] In many patients, GERD is a chronic, relapsing dis- ease that required a long-term management strategy. In Acta Gastro-Enterologica Belgica, Vol. LXXII, January-March 2009 focus groups and primary care physician and patient cog- Three visits were planned in this study. At the first nitive interviews (23). The GIS has demonstrated good visit (day 1), demographic and baseline data (age, gen- psychometric properties in newly diagnosed GERD der, GERD history, current GERD symptoms, clinical patients and those already receiving treatment, and has judgment and prescribed treatment) were recorded after been shown to be a valid and reliable tool for use in clin- obtaining the subjects’ informed consent. At the next two ical practice to identify instances of need for more effec- visits (week 4-6 [Visit 2] and week 8-14 [Visit 3], respec- tive therapy in subjects with a confirmed diagnosis of tively), GERD symptoms, clinical judgment and changes in treatment were recorded. At each visit, the patient was As part of the ALEGRIA (A real Life Evaluation also asked to complete the GIS, as outlined below. All procedures were in accordance with routine clinical Belgium) study (Study ID : NIS-GBE-NEX-2006/1 ; practice and not study-related except for the completion ClinicalTrials.gov Identifier : NCT00545883), which was designed to gather epidemiological data in a primary The study was performed in accordance with the care population of GERD patients with a history of ero- Declaration of Helsinki, all applicable legislation and sive esophagitis, we therefore evaluated symptom con- received all necessary ethical approval.
trol and impact on daily life, from a patient’s perspective,using the GIS. A secondary objective was to evaluate the added value of the GIS in terms of aiding the physician’sdetermination of the appropriate treatment and evalua- In this study, both the Dutch and French versions tion of treatment response. The study was non-interven- of the GIS were used. The GIS is composed of nine tional, being designed and conducted to ensure that the questions (Table 1) and uses a four-graded Likert scale physician’s decision regarding assigning patients to a for answers : i.e. daily, often, sometimes, and never.
particular therapeutic strategy was followed according to The recall period for the questions was the seven days preceding study visits. The nine questions cover threedimensions : upper GI symptoms (questions 1a, 1b and 2. Patients & Methods
1d), other acid-related GI symptoms (questions 1c and1e) and the impact of the symptoms on the patient’s daily A mean score was calculated for each dimension, A total of 2001 patients were included in this study generating a number between 1 and 4. In addition, the from 296 study centers in Belgium. The study was con- pre–post changes from Visit 1 to Visit 2 and Visit 2 to ducted between 5 May 2006 and 5 June 2007.
Visit 3 were also calculated within each severity level.
The patient population included in the study fulfilled the following inclusion criteria : willing and able to signthe informed consent form and comply with the require- 2.3. Demographics, lifestyle factors, and clinical ments of this study, at the discretion of the primary care physician or gastroenterologist ; male or female, agedՆ 18 years ; undergoing treatment for GERD according Demographics, lifestyle factors, duration of GERD, to current practice (24) and according to the summary of history of GERD treatment, and results of endoscopy product characteristics of the prescribed treatment ; suf- (performed prior to study entry) were documented at fering from Los Angeles grade A-D erosive esophagi- Visit 1. The following lifestyle factors were assessed tis (25) and not currently treated with a proton pump using a simple checklist : alcohol use (units per week) ; inhibitor (PPI), for whom the physician has decided to smoking ; ex-smoker ; caffeine intake (units per week) ; initiate or change the treatment for GERD. Excluded stress ; other (description specified).
were females of childbearing potential who were not Type and extent of esophageal tissue damage was using a reliable form of contraception, and pregnant or classified according to the Los Angeles classification Table 1. — Questions of the GERD Impact Scale (GIS)
1. How often have you had the following symptoms : a. Pain in your chest or behind the breastbone ?b. Burning sensation in your chest or behind the breastbone ?c. Regurgitation or acid taste in your mouth ?d. Pain or burning in your upper stomach ?e. Sore throat or hoarseness that is related to your heartburn or acid reflux ? 2. How often have you had difficulty getting a good night’s sleep because of your symptoms ?3. How often have your symptoms prevented you from eating or drinking any of the foods you like ?4. How frequently have your symptoms kept you from being fully productive in your job or daily activities ?5. How often do you take additional medication other than what the physician told you to take (Maalox, Gaviscon, Rennies etc.) ? Acta Gastro-Enterologica Belgica, Vol. LXXII, January-March 2009 Evaluation of the GERD Impact Scale 2.4. GERD symptoms and clinical judgment Table 2. — Demographic and lifestyle characteristics
(intent-to-treat population, n = 1919)
At each visit, the following GERD symptoms were assessed by the physician : heartburn ; acid regurgita- tion ; dysphagia ; and epigastric pain. The severity of symptoms was graded on a four-point scale (none, mild, moderate, or severe). The physician was also asked to give an overall judgment of the patient’s GERD-related symptoms at each visit. This was done in response to the question, “Based on your routine clinical judgment, how would you rate the patient’s severity of GERD-relatedsymptoms ?” using a three-point scale (mild, moderate, aUnit of alcohol equivalent to 300 mL beer, 125 mL wine or 25 mL 2.5. Physician’s judgment of the usefulness of the GIS Table 3. — Clinical characteristics (intent-to-treat
At the end of the study, the physician was asked to population, n = 1919)
make a judgment on the usefulness of the GIS in Los Angeles classification of erosive esophagitis, n (%) response to the question, “Does the GIS facilitate the choice of appropriate treatment for your GERD patient and to evaluate the response to this treatment ?” Two response options were provided : yes and no.
All data obtained in this study were generally summa- rized with descriptive statistics for the intent-to-treat population (i.e. all patients for whom Visit 2 occurred).
Analysis of the added value of the GIS was achieved by aMultiple responses possible.
GERD, gastroesophageal reflux disease.
correlating the mean GIS scores with the GERD symp-tom scores assessed by the physician, the physician’sclinical judgment, endoscopic findings (Los Angelesclassification), and the physician’s judgment of the use- fulness of the GIS using Spearman’s correlation coeffi- Most patients had previously received treatment for their GERD symptoms, most commonly with a PPI (15%had received empiric PPI therapy and 30% received PPI 3. Results
At study entry (Visit 1), PPIs were prescribed in 99% 3.1. Patient demographics, lifestyle factors and clinical of patients ; the main PPI was esomeprazole (82%) with a median daily dose of 40 mg. Prescribed therapy wassubsequently revised in approximately 60% of subjects A total of 2001 subjects were enrolled in the study, of between Visit 1 and 2 and 15% of subjects between Visit whom 1919 were included in the intent-to-treat popula- 2 and 3. In the vast majority of cases, only the dose was tion (Table 2). Patients were typically female (54%) with altered. The nature of therapy changed in most patients a mean age of 55 years (range, 18–95 years) and mean from “acute treatment (full dose)” (79% of patients) at bodyweight of 75 kg (range, 40–152 kg). Lifestyle fac- visit 1 to “maintenance treatment (half dose)” (96% of tors included : stress (approximately 70% of patients) ; consumption of a daily average of five cups of caffeine-containing beverages for approximately 70% of patients 3.3. GERD symptoms recorded by interview and the ; 50% recorded mean weekly consumption of approxi- clinician’s judgment of their severity mately nine units of alcohol ; and 41% of patients weresmokers or ex-smokers. Other relevant factors recorded Heartburn, acid regurgitation and epigastric pain were for 5% of patients included use of non-steroidal inflam- each reported for approximately 90% of patients at Visit matory drugs (NSAIDs), intake of spicy or unhealthy 1, while approximately 70% of patients had dysphagia (Fig. 1). At Visit 1, 46% of patients complained of In terms of clinical characteristics (Table 3), the mean moderate heartburn ; at Visit 2, 45% complained of mild duration of GERD symptoms was 3.5 years (range, 0–66 heartburn and at Visit 3, 59% had no heartburn. Acid years) and the majority of patients had Los Angeles regurgitation decreased from 44% with moderate symptoms at Visit 1 to mild (46.2%) and no symptoms at Acta Gastro-Enterologica Belgica, Vol. LXXII, January-March 2009 Fig. 1. — Severity of GERD symptoms, as assessed by physician interview.
Visit 1, n = 1919 ; Visit 2, n = 1916 ; Visit 3, n = 1879. Adjusted relative frequencies are shown.
Fig. 2. — Mean scores for the three dimensions of the GERD Impact Scale, by visit Visits 2 and 3, respectively. Moderate epigastric pain was 3.4. GERD symptoms and their impact on the patient’s reported in around half of patients (43%) at Visit 1, but daily activities, as recorded by the GIS by Visits 2 and 3 the majority of patients reported no pain(57% and 74%, respectively). Approximately 30% of The mean scores of the three dimensions covered by patients reported having no, mild or moderate dysphagia, the GIS improved substantially during the course of the respectively, at Visit 1, but by Visits 2 and 3, absence of study (Fig. 2). This was also the case when the mean dysphagia was reported by 73% and 84%, respectively.
scores were baseline adjusted. Mean (± SD) scores for The physician’s assessment of GERD severity was the impact of symptoms on daily activities domain were associated with the patient’s answers during the inter- 2.2 ± 0.7, 1.4 ± 0.5 and 1.2 ± 0.4 at Visits 1, 2 and 3, view. During the observation period, the percentage of respectively. Other acid-related GI symptoms domain patients with moderate or severe GERD decreased sub- mean scores were 2.4 ± 0.8, 1.5 ± 0.5 and 1.3 ± 0.4 at stantially : at Visit 1, approximately 90% of patients suf- these time points. Upper GI symptoms domain mean fered from moderate or severe GERD ; this decreased to scores were 2.5 ± 0.8, 1.6 ± 0.5 and 1.3 ± 0.4 at Visits 1, 30% and 15% at Visits 2 and 3, respectively.
Acta Gastro-Enterologica Belgica, Vol. LXXII, January-March 2009 Evaluation of the GERD Impact Scale Table 4. — Correlation (Spearman’s correlation coefficients) of GERD Impact Scale (GIS) mean-scores with clinical
judgments, endoscopy and usefulness of GIS (intent-to-treat population)
aBefore study entry.
bAt study end (Visit 3).
GI, gastrointestinal.
3.5. Physician’s evaluation of the usefulness of the GIS scopic grade of esophagitis. Symptoms improved and correlations with clinical judgment and endoscopy markedly over one or two months of treatment. Our studyreports these data for the first time in Belgium and con- At study end, the majority of physicians reported that firms previous reports from other countries. The particu- the GIS had facilitated treatment decisions and helped to lar weakness of the correlation between GIS and endo- evaluate the patient’s response to treatment in 81% of scopic score in the present study may also be linked to the cases. The Mean GIS mean-scores obtained at Visit 1 fact that the majority of the patients had a same grade of increased slightly with increasing degree of esophagitis endoscopic score (grade A and B), meaning that the pop- on prior endoscopy. There was also a trend for higher ulation was rather homogenous from this point of view.
GIS mean-scores and increasing severity of GERD, The secondary objective of this study was to evaluate according to clinical judgment. Correlation analyses the added value of the GIS, a novel, validated, self- revealed that the GIS mean-scores significantly correlat- administered patient questionnaire for the initial and ed with the physician’s clinical judgment at all visits long-term management of GERD patients. Whether it is (Table 4). The correlation with endoscopy findings was by clinician interview or patient self-assessment by ques- also positive but less pronounced, and no correlation was tionnaire, symptom assessment must support the use of found between the GIS mean-scores and the physician’s specific treatment and lead to improved patient outcomes judgment of the usefulness of the GIS, which shows that if it is to be useful (26). The present study shows that the the GIS score appears to be useful, regardless of the patients’ assessment of their symptoms using the GIS severity of the patient’s disease.
correlated with the current method of symptom assess- Further analysis showed that the patients who had a ment, i.e. the physician’s clinical judgment. This signifi- change in GERD treatment at visit 2 (20 patients cant correlation highlights a supplementary element for increased PPI dose, 1037 patients decreased and the validation of the GIS and the fact that this correlation 703 patients had no change) showed a better improve- is low shows that GIS has an added value over clinical ment in GIS mean-scores between visits 1 and 2, com- judgement and endoscopy, suggesting that it should be pared to patients without change in GERD treatment. At visit 3 (4 patients increased dose, 183 patients decreased During the course of the observation period the and 1561 patients had no change), the improvement was patients’ symptoms improved, as assessed by both clini- similar in both groups. However, there was no real cor- cian-interview and GIS scores, and this appeared to par- relation in GIS scores between patients who did not allel the changes in treatment between visits. As a change PPI treatment at visits 2 or 3, those who patient-reported outcome, the GIS gives an “objective” increased and those who decreased the dose.
measurement of symptoms and their impact, thus allow- 4. Discussion
ing a physician to compare scores between two visits andso helping the physician make the appropriate decision The primary objective of this non-interventional study in patient management. This study did not investigate was to gather epidemiological data in a population of whether the GIS was instrumental in identifying the need GERD patients. This was achieved in approximately for therapy change, but for the vast majority of patients 2000 patients from 296 study centers in Belgium. The (81%) the physicians did state that the GIS helped them data gathered revealed that stress, caffeine consumption to assess the patients’ symptoms, identify the appropriate and smoking were present in a high proportion of treatment and to evaluate the patient’s response to treat- patients. The patient’s treatment history was recorded and ment at visit 2 and 3. As such, the GIS proved to be a symptom assessment by interview revealed that the majority of patients suffered from heartburn, acid regur- Symptom assessment is the most important factor for gitation, epigastric pain and dysphagia. Our study shows both the diagnosis and identification of appropriate only weak correlation between symptoms and last endo- therapeutic strategies and also for monitoring the Acta Gastro-Enterologica Belgica, Vol. LXXII, January-March 2009 8. WAHLQVIST P., REILLY M., BARKUN A. Systematic review : the impact patient’s response to the choice of therapy (14,27). This of gastro-oesophageal reflux disease on work productivity. Aliment is particularly the case because in the majority of patients Pharmacol. Ther., 2006, 24 : 259-272.
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A recent systematic review of the literature concluded 10. DUBOIS R.W., AGUILAR D., FASS R., ORR W.C., ELFANT A.B., that there is a need for a new evaluative tool for the DEAN B.B., HARPER A.S., YU H.T., MELMED G.Y., LYNN R.,SINGH A., TEDESCHI M. Consequences of frequent nocturnal gastro- assessment of GERD symptoms and their response to oesophageal reflux disease among employed adults : symptom severity, therapy (29). The benefits of using a standardized ques- quality of life and work productivity. Aliment Pharmacol. Ther., 2007, 25 :
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es (26). Due to the subjective nature of symptoms it has been reported that patient self-reporting is more appro- 12. KULIG M., LEODOLTER A., VIETH M., SCHULTE E., JASPERSEN D., LABENZ J., LIND T., MEYER-SABELLE W., MALFERTHEINER P., priate than assessment by a clinician (3) and although STOLTE M., WILLICH S.N. Quality of life in relation to symptoms in symptom diaries are generally considered to be the ‘gold patients with gastro-oesophageal reflux disease-an analyses based on the standard’, they are not without their weaknesses and ProGERD initiative. Aliment Pharmacol. Ther., 2003, 18 : 767-776.
13. SZARKA L.A., DE VAULT K.R., MURRAY J.A. Diagnosing gastroe- well-designed questionnaires with an appropriate recall sophageal reflux diease. Mayo Clin. Proc., 2001, 76 : 97-101.
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Acta Gastro-Enterologica Belgica, Vol. LXXII, January-March 2009

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