The inclusion of patients' opinions in the assessment of interventions has gained greater prominence over the last decades. Regulator agencies now call for the inclusion of patient-reported outcomes (PRO) in clinical trials evaluating pharmaceuticals interventions 1234. PRO of interest include health-related quality of life (HRQL), symptom assessment, and more recently, treatment satisfaction, in gastroesophageal reflux disease (GERD).

Whereas HRQL measures the patient's physical, psychological, and social level of function, treatment satisfaction assesses the patient's attitude towards the treatment, or the extent to which the patient is satisfied or not with the results of the treatment. Thus, treatment satisfaction focuses on the interaction of expectations and preferences for treatments and is defined as the individual's rating of important attributes of the process and outcomes of the treatment experience 5. Coyne and co-workers 6 have summarized a number of patient important domains that describe satisfaction with treatment including symptom relief, flexibility with dosing, and treatment expectations. Treatment satisfaction is also associated with prescription regimens that involve less invasive dosing regimens 578910, such as daily versus twice daily use 11.

Evaluating treatment satisfaction may assist healthcare providers in understanding the issues that influence adherence with therapeutic interventions. In addition, treatment satisfaction can be a useful PRO when treatments show similar efficacy because differences in satisfaction could lead to patient preferences for one treatment over another and greater adherence with various treatment regimens.

Demographic variables such as age, ethnicity, and gender may influence satisfaction 12. Older people tend to be more satisfied with medical care than younger people 131415, and Caucasian people on the whole are more satisfied than non-Caucasians 16. In contrast, gender does not appear to influence treatment satisfaction 17.

The objectives of this study were to assess correlates of treatment satisfaction, including demographic factors, symptoms, and HRQL, as well as change scores in PRO instruments in patients with moderate to severe GERD receiving a proton pump inhibitor, esomeprazole.

Table 1 shows the baseline demographic characteristics and frequencies of the included patients. The mean age was 50 years, and approximately 50% of the patients were female. The mean number of months since diagnosis was 86 months. Approximately 70% were full-time or part-time employed, and 88% were Caucasians.

Table 2 depicts the mean baseline scores for the QOLRAD, the four symptoms scale, the FT, the SG, the HUI, and the SF-36. The mean QOLRAD scores at baseline were lowest for the food/drink domain, indicating worse HRQL for this domain, and the mean scores at baseline for the four symptoms show that patients had most problems with heartburn. Furthermore, the mean SF-36 scores at baseline were lowest (worse) for the bodily pain dimension, and highest (best) for the social functioning domain. Figure 2 shows the distribution of the treatment satisfaction scores. Approximately 50% of the patients were completely satisfied, 25% were very satisfied, and approximately 15% were quite satisfied. About 7% reported no change or dissatisfaction of different severity.

Table 3 portrays the results from the multiple linear regression analysis. Ethnicity, baseline QOLRAD vitality, baseline heartburn from the four symptoms scale, and QOLRAD vitality change score remained as independent variable when all variables had entered the model. Caucasian patients were more likely to be satisfied with the treatment than patients of other ethnicity. Higher baseline QOLRAD vitality scores, higher levels of heartburn and larger change on the QOLRAD vitality score were associated with greater treatment satisfaction.

The objective of this study was to assess correlates of treatment satisfaction in patients with moderate to severe GERD receiving esomeprazole. We found that Caucasian ethnicity, greater vitality and more severe heartburn at baseline, correlates with treatment satisfaction. Furthermore, the greater the improvement on vitality change score, the more likely the patient is to be satisfied with the treatment.

The strengths of this study include the detailed assessment of a number of demographic characteristics, HRQL and symptoms. However, this study has two important limitations. First, we did not perform a placebo controlled trial limiting our ability to assess satisfaction as a true treatment result versus other reasons for satisfaction. Second, investigators have not conducted a thorough psychometric assessment of the treatment satisfaction instrument we used in this study.

Nevertheless, the present study yields four important results. First, in this sample of GERD patients without prior endoscopic evaluation of their symptoms, Caucasian ethnicity was positively associated with treatment satisfaction. Ethnic origin is perhaps one of the most complex demographic characteristics 12 and it has previously been reported that Caucasian people on the whole are more satisfied than non-Caucasians 16.

Second, higher vitality scores, as assessed by the QOLRAD, were associated with higher treatment satisfaction. A patient's health status prior to receiving treatment may cause the patient to be either more or less satisfied with treatment. Clearly and McNeil 28 reported positive correlations between health status and satisfaction. However, it is unclear if satisfaction was correlated with health status before intervention or with health status after intervention. A possible interpretation of the positive association between QOLRAD vitality and treatment satisfaction in our study might be that patients with a high vitality score at baseline are less distressed by their disease, and therefore tend to be more satisfied. The association in our study between higher vitality scores, as assessed by the QOLRAD, and higher treatment satisfaction is in line with Revicki and co-workers 29 who found that patients reporting greater severity in heartburn symptoms were more likely to report psychological distress and impaired well-being compared with those who reported no or mild symptoms. However, Revicki et al measured HRQL with a generic instrument while we used a disease-specific instrument.

Third, higher scores for heartburn, assessed with the four symptoms scale, were related to higher treatment satisfaction. Thus, in our study population, patients with high discomfort from heartburn at baseline perceived a high satisfaction with treatment.

Fourth, the higher the improvement on the QOLRAD vitality (change score), the more likely the person is to be satisfied with the treatment.

Patients' age is regarded as the most consistent determinant characteristic of satisfaction 131415. The results from this study did not reveal that treatment satisfaction was related to age. However, Fitzpatrick 3031 and Fox and Storms 32 highlight the lack of consistency of the effect of age in satisfaction studies. Since satisfaction studies focused on a variety of concepts, such as satisfaction with medical care, satisfaction with hospital management, satisfaction with health services, and satisfaction with treatment, it might be that the association between age and satisfaction is dependent on the concept assessed. The lack of an association to age reveals also the possible that our study population was too homogenous with regard to age.

Although some studies have reported that patient gender affects satisfaction values 3334, other studies did not find such association 1735. In line with this, in our study population treatment satisfaction was not associated with gender.

The current results may be unique to the study sample since no placebo control group was included in the study and, therefore, we were unable to evaluate whether the factors related to treatment satisfaction are related to real treatment effects or patients' need to please and placebo effects. The efficacy, tolerability and safety of esomeprazole versus other proton pump inhibitors has been shown in other studies 3637383940. In this study, patients had moderate to severe symptoms of GERD and some patients had received proton pump inhibitors prior to this study. The latter indicates that our study population is selected with regard to symptom severity, and mixed with regard to previous medication, which might limit generalizability of the findings. Treatment satisfaction in patients with mild GERD symptoms and with no previous experience of proton pump inhibitors remains unknown.

Investigators often use several PRO instruments, each with many dimensions and single items that are more or less correlated in clinical studies. This can lead to a large number of statistical tests being carried out and an increased risk of statistically significant findings occurring by chance in the absence of adjustment of P-values. In the present report we did not carry out adjustments for multiple comparisons for two main reasons. Firstly, the analysis of correlations was intended to be exploratory rather than confirmatory. Secondly, there is no consensus on how to adjust in analyses of the nature we conducted in this study. A simple adjustment according to Bonferroni would be too conservative, in part because many of the PRO variables are closely correlated.

Different drug therapies may elicit unwanted side-effects, which could compromise the patients' HRQL, and adherence with the treatment. Thus, a challenge in the management of GERD is to achieve as high adherence as possible. In addition, treatment satisfaction can be of use when different drug therapies show similar efficacy since it can lead to a preference for one drug over another and greater adherence.

Our study also supports the need for validated treatment satisfaction instruments because the available instruments vary widely in clinical trials 41 and the majority of studies rely on single items. There is a need for developing and improving psychometric documentation of instruments measuring treatment satisfaction 42.

We examined correlates of treatment satisfaction, including demographic factors, symptoms, and HRQL, as well as change scores in HRQL, in patients with moderate to severe GERD who were not investigated by endoscopy. We observed that Caucasian ethnicity was positively related to treatment satisfaction. Furthermore, higher vitality and more severe heartburn were associated with treatment satisfaction. Finally, the higher the improvement on the QOLRAD vitality (change score), the more likely the patient is to be satisfied with the treatment.

Alessio Degl' Innocenti was the project leader for this manuscript, edited the clinical protocol of the study, interpreted the data, and wrote the final manuscript as well as early versions. Gordon H Guyatt and Holger Schünemann were the principal investigators of the study, wrote the clinical protocol and grant application, are responsible for the study protocol, interpreted data and participated in writing the final as well as early versions of this manuscript. Ingela Wiklund contributed to the study protocol, interpreted the data and edited the manuscript. Diane Heels-Ansdell was responsible for the statistical analysis and edited the final manuscript as well as early versions. David Armstrong was co-principal investigator of the study, revised the clinical protocol, assessed patients, interpreted data and edited the final manuscript as well as early versions. Carlo A Fallone and Sander Veldhuyzen van Zanten revised the clinical protocol, assessed patients, interpreted data and edited the final manuscript as well as early versions. Samer El-Dika, Alan N Barkun, and Peggy Austin revised the clinical protocol, interpreted data and edited the final manuscript as well as early versions. Peggy Austin also co-ordinated the study. Lisa Tanser contributed to co-ordination of the study. All authors read and approved the final manuscript. The AstraZeneca global publications group approved the manuscript.