Typically characterized by frequent or troublesome heartburn REVIEW

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2009;7: REVIEW What Makes Individuals With Gastroesophageal Reflux Disease Dissatisfied With Their Treatment? PETER BYTZER Department of Medical Gastroenterology, Køge University Hospital, University of Copenhagen, Copenhagen, Denmark BACKGROUND & AIMS: Despite the efficacy of proton pump inhibitors (PPIs) as therapeutics for patients with gastroesophageal reflux disease (GERD) in randomized controlled trials, a number of studies have shown that a proportion of patients with GERD are not satisfied with their treatment. This article reviews the possible reasons why patients are dissatisfied with the way their disease is managed. METHODS: Studies published between 1970 and 2007 were identified from PubMed, EMBASE, and the author s existing database. The 2708 publications were reviewed, and irrelevant ones were excluded. Eleven studies were found to be appropriate for use in this review. RE- SULTS: Patients who are given prescriptions for PPIs tend to be more satisfied than those given H 2 -receptor antagonists. Partial responders are likely to be more dissatisfied than patients whose symptoms are fully resolved. A decrease in health-related quality of life is associated with greater dissatisfaction. Patients are more likely to be satisfied if they are taken seriously by their physician and if their symptoms are investigated. They are also more likely to be satisfied if the patient-physician consultation is interactive. CONCLUSIONS: Patient satisfaction is a complex issue that depends on many factors. Patient satisfaction can be influenced by treatment regimen, general level of well-being, the bedside manner of the physician, and the quality of patient-physician communication. Improvements in recognition of GERD can improve management of the disease as well as patient satisfaction with their care and treatment. Typically characterized by frequent or troublesome heartburn and/or acid regurgitation, gastroesophageal reflux disease (GERD) is a chronic, painful condition that impairs health-related quality of life (HRQoL). 1 GERD might result in disturbed sleep, reduced productivity at work, and impaired daily activities. 2,3 Proton pump inhibitors (PPIs) offer effective treatment for GERD, with clinical trials showing high rates of symptom resolution and healing of reflux esophagitis. 4 6 Studies have shown that treatment with PPIs is associated with increased HRQoL in patients with GERD. 7,8 PPIs appear to be more effective in patients with reflux esophagitis than in patients with reflux disease without esophagitis. A review of studies examining the efficacy of PPIs found the 4-week symptom response rate to be significantly higher in patients with reflux esophagitis than in patients with nonerosive reflux disease (56% vs 37%; P.0001). 9 Despite the efficacy of treatment for GERD in clinical trials, there is the perception that in clinical practice a proportion of patients are not satisfied with their treatment. For example, at the Marrakech workshop on symptom evaluation in reflux disease, 95% of the 28 attending gastroenterologists agreed that more than one third of patients with GERD are somewhat dissatisfied with their current prescription therapy. 10 This finding is supported by the results of population-based studies that have reported the overall level of satisfaction with treatment among individuals with GERD. A U.S. study of 11,600 individuals with chronic heartburn found that 54% of patients who took prescription medication were not totally satisfied with their treatment. 11 Similarly, in a population-based survey of 1681 individuals with reflux symptoms (22% of whom took PPIs and 27% of whom took antacids or alginates), 33% said that they were not totally satisfied with their treatment. 12 This study systematically reviews the possible reasons why these individuals with GERD are dissatisfied with their treatment. Methods Studies to be included in this review were identified from PubMed and EMBASE (Figure 1). Studies were restricted to those published between 1970 and 2007 in English. Reviews of patient dissatisfaction and the author s existing database were also examined for appropriate publications. These searches identified 2708 unique publications. These were reviewed by title, abstract, and then full manuscript; studies that reported irrelevant information were excluded at each stage. These searches identified 11 studies appropriate for use in this review. Four studies used a questionnaire to assess satisfaction levels, 11,13 15 five studies measured satisfaction by using a Likert scale, and two studies did not report how satisfaction was assessed. 12,21 Results Factors Influencing the Satisfaction of Patients With Gastroesophageal Reflux Disease: Health Status Degl Innocenti et al 16 surveyed 217 individuals who had been diagnosed with GERD and who rated their symptoms as moderate or severe. 22 All individuals had been treated with esome- Abbreviations used in this paper: GERD, gastroesophageal reflux disease; H 2 RA, H 2 -receptor antagonist; HRQoL, health-related quality of life; PPI, proton pump inhibitor; QOLRAD, Quality of Life in Reflux and Dyspepsia by the AGA Institute /09/$36.00 doi: /j.cgh

2 August 2009 PATIENT DISSATISFACTION IN GERD 817 prazole 40 mg for 4 weeks. The study questionnaire included a single item that asked how satisfied are you with the study treatment you received? Responses to this question were measured on a 7-point Likert scale with the options completely satisfied, very satisfied, quite satisfied, no change, dissatisfied, very dissatisfied, and completely dissatisfied. This study found that patients who reported their heartburn to be more severe before treatment, and who are likely to have had more severe GERD, were significantly more likely to be satisfied after 4 weeks treatment with a PPI than those with less severe symptoms at baseline (P.001). However, a French postal survey of the general population (n 5395) found individuals with more frequent symptoms to be less satisfied with their treatment. 12 This study identified 1681 individuals with GERD (heartburn and/or regurgitation), 419 of whom had frequent symptoms (at least weekly) and 1252 who had less frequent symptoms. Significantly fewer subjects with at least weekly heartburn symptoms were completely satisfied with their treatment when compared with those with less frequent symptoms (67% vs 80%; P.01). This study did not report how satisfaction was assessed. However, this effect was not consistent across all treatments. Complete satisfaction with treatment with antacids/alginates was significantly lower in subjects with frequent symptoms than in those with occasional symptoms (63% vs 83%; P.01), whereas the level of satisfaction with PPI treatment was unaffected by symptom frequency (68% vs 75%; P.05). 12 Type of Medication A number of studies also suggested that the type of medication used can affect satisfaction. A telephone survey in the United States identified individuals who had experienced heartburn within the previous 7 days or who were taking medication to eliminate heartburn (n 1000). 21 All respondents were asked whether they experienced nighttime heartburn. Of the 791 individuals who did experience nighttime heartburn, 71% (399/562) of those taking over-the-counter medications and 51% (165/324) of those taking prescription medications were not completely satisfied with their treatment (significance not reported). This study did not report how satisfaction was assessed. In a second U.S. survey of 11,604 individuals who were using prescription medication to treat chronic heartburn, the type of medication taken also appeared to influence patient satisfaction. 11 This study measured satisfaction by using a 10-point scale ranging from 1 (totally unsatisfied) to 10 (totally satisfied). For analysis, the scale was reduced to 5 points: totally satisfied (9 10 points), somewhat satisfied (7 8), neither satisfied nor unsatisfied (5 6), somewhat unsatisfied (3 4), and totally unsatisfied (1 2). When stratified by type of medication, 59% of those taking PPIs were totally satisfied (2424/4109), and 24% were somewhat satisfied (974/4109). Of those patients taking H 2 -receptor antagonists (H 2 RAs), 46% were totally satisfied (1744/3782), and 31% were somewhat satisfied (1176/3782), and of those taking prokinetics, 43% were totally satisfied, and 30% were somewhat satisfied (sample size not reported) (Figure 2). PPI treatment was associated with significantly higher levels of satisfaction than H 2 RA treatment ( ; P.001). Figure 1. Flow of prospective studies through the search and selection process. Figure 2. Satisfaction is higher in patients taking PPIs than in those taking H 2 RAs or prokinetics. 11

3 818 PETER BYTZER CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 7, No. 8 A prospective, randomized, open, parallel-group study carried out in Norway assessed satisfaction in 1797 individuals with symptoms suggestive of GERD (heartburn as the predominant symptom, with or without acid regurgitation). 17 Satisfaction was assessed by using a 7-point Likert scale with the options completely satisfied, very satisfied, quite satisfied, satisfied, dissatisfied, very dissatisfied, and completely dissatisfied. This study found that after 6 months, significantly more patients were completely satisfied or very satisfied with continuous (82.2%) or on-demand (75.4%) PPI therapy than with continuous H 2 RA therapy (33.5%; P.0001). Pooled data from 2 phase III randomized, double-blind, parallel-group trials of individuals with endoscopy-negative reflux symptoms (n 849) showed that after 4 weeks of treatment, individuals prescribed lansoprazole 30 mg (n 286) were significantly more likely to be satisfied with their treatment than those taking ranitidine 150 mg (n 281) (83.0% vs 74.9%; P.001). 14 However, no significant differences were seen between those taking lansoprazole 15 mg (n 282) and those taking ranitidine 150 mg (78.7% vs 74.9%; P.13). Satisfaction was measured by using a validated questionnaire. Treatment Regimen A regular treatment regimen appears to be related to satisfaction in patients with GERD. For example, 2 randomized prospective studies found that continuous once-daily esomeprazole tended to be associated with greater patient satisfaction than on-demand esomeprazole, 17,19 although the difference in satisfaction was relatively small in both studies ( %) and only reached significance in the study by Hansen et al 17 (82.2% completely/very satisfied with continuous treatment vs 75.4% completely/very satisfied with on-demand treatment; P.01). Both these studies assessed satisfaction by using a 7-point Likert scale. The duration of the treatment regimen might also influence patient satisfaction. In a study by Meineche-Schmidt et al, 18 patients with symptoms suggestive of GERD (heartburn as the predominant symptom with or without acid regurgitation) who were symptom-free after 4 weeks of treatment with esomeprazole 40 mg daily were randomized to 3 different strategies in case of relapse during the subsequent 6 months: esomeprazole 20 mg on demand (453 patients) or esomeprazole 40 mg daily for either 2 weeks (449 patients) or 4 weeks (455 patients). Satisfaction was assessed by using a 7-point Likert scale with the options completely satisfied, very satisfied, quite satisfied, satisfied, dissatisfied, very dissatisfied, and completely dissatisfied. There were no significant differences between the 3 treatment arms in terms of patients being satisfied. However, significantly more patients in the 4-week group than in the 2-week group were very satisfied with their treatment (84% vs 74%; P.05). Several studies have shown that treatment change can have an effect on patient satisfaction. In a study of 105 patients in the United States who were converted from omeprazole to lansoprazole, Nelson et al 15 found that satisfaction scores were significantly lower after conversion than they were before conversion (mean score standard deviation, and , respectively; P.001). This was supported by the results of a second survey of 158 patients who underwent a formulary change from omeprazole to lansoprazole. 13 This study found that significantly more patients preferred the medication they were taking before conversion (64% vs 36%; P.005). Dissatisfaction Is Predicted by Lack of Response to Treatment The presence of residual symptoms is associated with dissatisfaction with PPI treatment. A survey of 400 individuals who took a prescribed PPI at least once during the week before the study (treated conditions included heartburn, acid indigestion, reflux, ulcer, and hiatus hernia) assessed satisfaction with this treatment by using a 10-point Likert scale in which 10 indicated extreme satisfaction, and 0 indicated complete lack of satisfaction. 20 This study found that 49% of respondents were extremely satisfied with their treatment when the group was considered as a whole, whereas only 34% of those with breakthrough symptoms were completely satisfied (significance not reported). Well-Being and Quality of Life In the study by Degl Innocenti et al, 16 the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD) was used to assess patients level of emotional distress, sleep disturbance, problems with food and drink, limitations in physical and social functioning, and vitality. This questionnaire uses a 7-point scale on which a higher score indicates a better HRQoL, and the minimal important difference is approximately 0.5. This study found that the greater the improvement in vitality with treatment, the more likely it was that patients would be satisfied with their treatment (P.001). Discussion This review identified a number of factors that are associated with dissatisfaction with treatment in patients with GERD. Patients taking PPIs tend to be more satisfied than those receiving less effective treatment. However, a proportion of patients taking PPIs are dissatisfied with their treatment. It is possible that this is linked to the finding that dissatisfaction is also related to the presence of residual symptoms. Approximately 40% of individuals who are taking prescription medication for reflux symptoms still have residual symptoms. 23 An international survey of 1908 individuals with symptoms of GERD found that of the 727 who had a formal diagnosis of GERD and who were taking prescribed medication, 68% reported some unresolved symptoms. 24 A number of mechanisms have been proposed to explain these residual symptoms. The most widely discussed are weakly acidic reflux and visceral hypersensitivity. 25 It is possible that these 2 potential causes are actually related, and that visceral hypersensitivity leads to greater awareness of weakly acidic reflux, rather than the reflux itself being the cause. Lack of response to PPI treatment could also be influenced by the presence of other gastrointestinal disorders. Patients with GERD typically have a range of symptoms simultaneously, which reflects the prevalence of concomitant diseases such as functional dyspepsia and irritable bowel syndrome. 26,27 These disorders are less likely to respond to PPI therapy and might therefore result in unresolved symptoms. Other potential explanations for lack of response to PPI treatment include duodenogastroesophageal reflux, delayed gastric emptying, or eosinophilic esophagitis, although evidence for these mechanisms

4 August 2009 PATIENT DISSATISFACTION IN GERD 819 is lacking. Finally, it has been shown that nonadherence to PPI therapy is common 28,29 and is also likely to result in residual symptoms. Dissatisfaction is also associated with lower HRQoL. Decreasing HRQoL is correlated with decreasing satisfaction with medical care in general. 14,30,31 Patients tend to be more satisfied if they are taken seriously and if their symptoms are investigated. For example, some studies have shown that satisfaction among patients with dyspepsia is greater if they undergo endoscopy, regardless of the result of the procedure. 32,33 Studies in other therapy areas have also found that, in general, when patients report that their expectations are met, they also report greater satisfaction Results of a study of 750 patients who visited a clinic because of physical symptoms showed that patients with no unmet expectations had less worry about serious illness (54% vs 27%; P.001) and greater satisfaction (59% vs 19%; P.001) than those with unmet expectations. 40 In a study of a related group of 500 patients, the presence of unmet expectations markedly decreased patients satisfaction immediately after the visit and also 2 weeks and 3 months later. 41 There is also evidence that making the consultation process more interactive between patient and physician improves the level of satisfaction in patients with peptic ulcer disease. 42 Ways to Improve Patient Satisfaction With Treatment for Gastroesophageal Reflux Disease Figure 3 summarizes strategies to improve patient satisfaction with treatment for GERD, each of which is discussed in detail below. Secure the correct diagnosis. To ensure patient satisfaction, it is vital that patients receive the correct diagnosis. Some patients with less troublesome heartburn or reflux might have functional upper gastrointestinal disorders (eg, functional dyspepsia) rather than GERD and might not receive benefit from PPIs or other antisecretory medications. 43 They are therefore likely to remain dissatisfied with their treatment. Diagnostic questionnaires can assist physicians in making the correct Figure 3. Potential strategies to improve patient satisfaction. diagnosis and can therefore help to improve patient satisfaction Treatment algorithms that predict patient response to PPIs have also been proposed. 47,48 These tools could help to ensure that each patient receives the most appropriate treatment. Diagnostic testing such as endoscopy, ph studies, and motility testing might also be useful, but GERD can be diagnosed in primary care on the basis of symptoms alone. 1 Provide effective treatment and promote adherence. Absence of symptoms correlates with satisfaction in patients with GERD. 20 Strategies for improving patient satisfaction must therefore take into consideration which treatments are the most effective and must also ensure high levels of adherence to the treatment. Nonadherent patients are more likely to have residual symptoms and therefore to be dissatisfied with their medication. Conversely, patients who are already dissatisfied with their treatment might be more likely to become nonadherent to their medication. Improve communication between physician and patient. Making the consultation process more interactive can improve patient satisfaction. 42 This can be done by asking simple questions and by using terminology that the patient can understand and relate to easily. This could involve asking about the impact of GERD on daily living (ie, well-being). Communication can also be assisted through the use of patient questionnaires, educational leaflets, 52 or patient agenda forms. 53 Manage patient expectations. It is important that clinicians ensure that patients with GERD are aware that it is a chronic disease, and that therapy will alleviate their symptoms but will not cure their disease. This ought to reduce the number of patients who are surprised or dissatisfied when their symptoms return if they stop taking PPIs, even if they were symptomfree while taking medication. However, not all patients expect complete absence of symptoms in the long-term, and many patients with GERD are willing to continue a treatment strategy that provides substantial, but less than absolute, symptom control. 54 In a study of 91 patients starting PPI therapy, only 4 patients (4.4%) had no real expectations of this medication. 55 The leading expectations were improvement in (61%) or elimination of (33%) perceived symptoms, healing of esophagitis (50%), return to normal daily life (46%), and improvement in quality of life (44%). Thirty-six percent expected no further therapy after this initial treatment, and 34% expected the PPI treatment to have no side effects. Occasional heartburn and/or regurgitation are experienced by a substantial proportion of the population. Patients with troublesome or frequent reflux symptoms might therefore be particularly in need of reassurance from their primary care physician that they have a real disease and not just heartburn. However, patients also need to be reassured that they are at low risk of esophageal cancer, especially if they have normal endoscopy results, and even if they have nondysplastic Barrett s esophagus. Improved physician-patient communication will help physicians to identify patients specific expectations about their treatment and other care. Strengths and Limitations A key strength of this review is the fact that the searches identified a wide range of studies with varying methodologies. However, it should be remembered that different people will interpret the concept of satisfaction in different ways. It is likely

5 820 PETER BYTZER CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 7, No. 8 to be interpreted differently by each patient and is dependent on factors such as the outcome of treatment, the interpersonal skills of health professionals, physician confidence and continuity, the quality of the patient-physician relationship, the level of patient participation and control, the accessibility, availability, and convenience of treatment, and the financial circumstances of the patient. These differing interpretations of satisfaction might impact on the generalizability of the results. Another limitation is the lack of uniformity in the measurement of satisfaction across the various studies. In particular, only 4 studies used validated questionnaires to measure satisfaction. Furthermore, none of the studies examined potential confounding factors for patient satisfaction such as patientphysician relationship and physician confidence. Future Research Future patient satisfaction surveys need to consider carefully the sampling time frame of the study and to adjust for pertinent patient characteristics. 41 There is also a need to increase the emphasis on patient satisfaction as an outcome in clinical trials. 10 Many patients with GERD make changes to their lifestyle to try to alleviate their symptoms. 56,57 It would be interesting to study the impact of this self-care on patient satisfaction. Adherence to medication and dissatisfaction with this medication seem likely to be related. However, to my knowledge, no studies have been performed to examine this link. Research to explore this potential connection would be of great interest. Validated tools such as the GERD Treatment Satisfaction Questionnaire and the Treatment Satisfaction Questionnaire for GERD are available for assessing the true satisfaction of patients with their treatment. 30,58 It would be valuable to use these questionnaires to establish whether the GERD Impact Scale 51 and the Reflux Disease Questionnaire 44,45,59 can improve patient satisfaction in clinical practice. Conclusions Levels of satisfaction reflect the true success of GERD therapy from the patient s perspective. Despite the availability of highly effective treatments for GERD, population-based surveys show that at least one third of individuals taking medication for GERD are not satisfied with their treatment. This is particularly true for those taking over-the-counter medicines to relieve symptoms. This review shows that patient satisfaction can be influenced by a number of factors including treatment regimen, general level of well-being, the patient s expectations, and the quality of patient-physician communication. The last of these is probably the most amenable to improvement through measures such as the use of validated questionnaires to help physicians identify more effectively which symptoms patients have and the impact of these symptoms on the patient s well-being. Leaflets can also be used to encourage patients to volunteer more information. Improving communication will also make physicians more aware of patients specific expectations. Improved recognition of GERD can also improve management of the disease, and, in turn, improve patient satisfaction with care and treatment. Systematic use of treatment satisfaction data could be used to make choices between alternatives in the organization or provision of health care for individuals with GERD. References 1. 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7 822 PETER BYTZER CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 7, No. 8 of individuals with heartburn. Arch Intern Med 1999;159: Shikiar R, Flood E, Siddique R, et al. Development and validation of the gastroesophageal reflux disease treatment satisfaction questionnaire. Dig Dis Sci 2005;50: Halling K, Junghard O, Dent J, et al. Development of an enhanced questionnaire for diagnosis of gastroesophageal reflux disease based on the reflux disease questionnaire, the GERD impact scale and the gastrointestinal symptom rating scale. Gut 2007; 56(Suppl 3):A209. Reprint requests Address requests for reprints to: Dr Peter Bytzer, Department of Medical Gastroenterology, Køge University Hospital, DK-4600 Køge, Denmark. peter.bytzer@dadlnet.dk; fax: (45) Acknowledgments The author would like to acknowledge the help of Drs Catherine Hill and Catherine Henderson (Research Evaluation Unit, Oxford PharmaGenesis Limited, Oxford, UK), supported by AstraZeneca R&D Mölndal, who assisted with literature searches, managed the references, and edited the text of the manuscript for clarity, flow, and consistency. Conflicts of interest The author discloses the following: Peter Bytzer has received research funding from manufacturers of proton pump inhibitors (AstraZeneca, Eisai, Janssen-Cilag) and H 2 -receptor antagonists (Eli Lilly, GlaxoSmithKline) and has served on advisory boards, as a consultant, and on the speakers bureau for manufacturers of antireflux medication (AstraZeneca, Eisai, Janssen-Cilag, Nycomed, Orexo, Reckitt Benckiser, Wyeth).