Kalaitzakis and Björnsson were also comparable in terms of patient’s global evaluation, with 87.9% of patients on esomeprazole and 96% of patients on rabeprazole reporting that symptoms improved (p > 0.05) (Fock et al 2005). A third study comparing esomeprazole 20 mg with pantoprazole 20 mg od for the treatment of NERD patients (n = 529) reported that the median time to ﬁrst symptom relief was 2.0 days for both PPIs (Monnikes et al 2005). This study was designed to show non-inferiority of the pantoprazole group compared with the esomeprazole group with a signiﬁcance level of 5%. The Hodges-Lehmann estimator and the one-sided 95% CI according to Moses were calculated. Non-inferiority was concluded if the lower boundary of the 95% CI was greater than –2 days, as the difference of 2 days was considered clinically signiﬁcant. For the primary endpoint variable (time to ﬁrst symptom relief), the one-sided 95% CI was zero (0.00). Considering that the non-inferiority margin was set at –2 days, the lower boundary of the 95% CI (0.00) was higher. Thus, the authors concluded that pantoprazole was as effective as esomeprazole for time to ﬁrst symptom relief. Similar results were obtained for time to sustained symptom relief (Monnikes et al 2005). Although no trial comparing continuous esomeprazole with lansoprazole therapy was identified, in a recently published single-blind study esomeprazole 20 mg on demand was compared with lansoprazole 15 mg od (Tsai et al 2004). Seven hundred and seventy-four patients with NERD who achieved complete resolution of heartburn after short term (2–4 weeks) treatment with esomeprazole 20 mg were randomized to receive either esomeprazole 20 mg on demand or lansoprazole 15 mg continuous daily treatment. Signiﬁcantly more patients were willing to continue taking esomeprazole on demand than lansoprazole od after 6 months (93% vs 88%, p = 0.02). The authors concluded that esomeprazole 20 mg on demand was more acceptable to NERD patients compared with lansoprazole 15 mg od (Tsai et al 2004). However, it should be pointed out that this was a single-blind trial (due to its nature) and that it may hardly constitute evidence of superiority of esomeprazole to lansoprazole in NERD, as the two PPIs were administered in different ways. Therefore, results of this study may merely reﬂect patient preference for on-demand therapy. Long-term (6 month) on-demand esomeprazole treatment has been reported to be superior to placebo in the therapy of patients with NERD as assessed in two double-blind, randomized clinical trials in which NERD patients were included after achieving complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (Talley 660 et al 2001, 2002). In one of these, 342 patients with NERD were randomized to receive either esomeprazole 20 mg or placebo on demand for 6 months (Talley et al 2001). The proportion of patients who discontinued treatment due to insufﬁcient control of heartburn was signiﬁcantly higher among placebo compared to esomeprazole recipients (51% vs 14%, p < 0.0001). In the second study, 721 patients were randomized to esomeprazole 20 mg, 40 mg, or placebo on demand for 6 months (Talley et al 2002). During this period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Although a p < 0.0001 was calculated for comparisons between either esomeprazole group and placebo, no signiﬁcant difference was observed between the esomeprazole treatment groups (p = 0.15). Thus the authors concluded that esomeprazole 20 mg is superior to placebo for on-demand treatment of NERD and that a higher esomeprazole dose does not confer additional clinical beneﬁt. However, it should be pointed out that almost 60% (58%) of patients who were randomized to placebo were willing to continue treatment (Talley et al 2002). These results clearly indicate that not all patients who have had resolution of symptoms after 4 weeks of PPI therapy will need continuous treatment in the future. Esomeprazole in the treatment of GERD and health-related quality of life There has been increasing interest in evaluating patient- reported outcomes such as health-related QoL. It is widely accepted that patients with GERD experience decrements in health-related QoL compared with the general population (Revicki et al 1998; Prasad et al 2003; Pace et al 2005), similar to those seen in patients with other chronic diseases (Kulig et al 2003). Patients with non-erosive GERD, erosive GERD, and Barrett’s esophagus have been reported to have similar impairment in health-related QoL (Kulig et al 2003). Successful treatment of GERD with symptom resolution results in improvements in health-related QoL (Revicki et al 1998; Prasad et al 2003). In a recent large uncontrolled study assessing the impact of GERD on QoL as well as the effect of acute esomeprazole treatment on QoL, indices were evaluated (Kulig et al 2003). A total of 6215 patients prospectively diagnosed with GERD underwent endoscopy and received treatment with esomepra- zole 20 mg od (patients with NERD) or 40 mg od (erosive GERD). Symptoms and health-related QoL were evaluated at baseline and after 2 weeks of treatment by means of validated Therapeutics and Clinical Risk Management 2007:3(4)