Table 4.
Cost-effectiveness of Maintenance PPI Treatment.
| Author | Year | Methodology | Outcome | Conclusion | Limitation |
|---|---|---|---|---|---|
| Goeree et al11 (Canada) | 2002 | • Strategy E: Maintenance PPI. Acute treatment with a PPI (eg, omeprazole 20 mg or lansoprazole 30 mg once daily) for 4 weeks followed by continuous maintenance treatment with a PPI (same dose). | • Maintenance PPI not only has the highest expected cost per patient over 1 year but also has the lowest expected number of recurrences, expected weeks with heartburn symptoms, and highest QALYs. | • Incremental cost per QALY is CDN$98 422 | • For the symptom relief and symptom recurrence meta-analyses, a majority of studies relied on endoscopy results as a primary entry criterion and outcome measure, whereas symptoms were typically a secondary criterion.
• The authors used moderate-to-severe heartburn as primary measure of GERD symptoms. • 1-year time horizon for the study may be too short to capture long-term complications such as Barrett esophagus or esophageal stricture. • This study used inputs (ie, costs), which are specific to the province of Ontario only. |
| • Strategy G: Step-down maintenance PPI. Acute treatment with a PPI (eg, omeprazole 20 mg or lansoprazole 30 mg once daily) for 4 weeks followed by continuous maintenance treatment with a low-dose PPI (eg, omeprazole 10 mg or lansoprazole 15 mg once daily). | • Dominated through extended dominance | • Dominated through extended dominance | |||
| Gerson et al7 (USA) | 2000 | • PPI-Continuous Arm: Empirical treatment with continuous daily maintenance PPI therapy, without the performance of endoscopy unless there is symptomatic failure. | • A study of continuous PPI therapy as an empirical treatment with continuous daily maintenance PPI therapy, without the performance of endoscopy unless there is symptomatic failure.
• The researchers stated that the outcome of continuous PPI therapy is dominated by on-demand PPI. |
• The researchers stated that the outcome of continuous PPI therapy is dominated by on-demand PPI. | • An analysis of lifetime costs—not known how long patient can expect symptomatic relief.
• Only few of the prior studies used QALYs as a utility measurement and obtained their estimates through a modified Delphi process. • Prior models did not allow patients to switch from H2RAs to PPIs without endoscopy, often did not include the option of Nissen fundoplication, or sent patients without response to PPI for a Nissen without consideration of promotility therapy. • None of the models included patients with nonerosive disease. |
| Kaplan-Machlis et al8 (USA, RCT) | 2000 | • In the study, 268 patients who aged more than 18 years with GERD were enrolled and randomly given omeprazole sodium, 20 mg once daily for up to 6 months.
• Recruited study patients also did not receive PPI or H2RA treatment in the previous 30 days. • Then, for the data analysis, the total cost for omeprazole treatment is assessed. This total cost included direct medical costs, direct nonmedical costs, and indirect costs. |
• As a result, it is shown that 5-year direct medical costs per patient when given omeprazole were notably lower in Denmark, Norway, and Sweden (differences were DKK 8703 [US$1475], NOK 32 992 [US$5155], and SEK 13 036 [US$1946], respectively).
• When indirect costs (loss of production due to GERD-related sick leave) were also included, the cost of surgical treatment increased substantially and exceeded the cost of medical treatment in all countries. |
• It is shown that 5-year direct medical costs per patient when given omeprazole were notably lower in Denmark, Norway, and Sweden (differences were DKK 8703 [US$1475], NOK 32 992 [US$5155], and SEK 13 036 [US$1946], respectively). | • A potential problem with this particular study is that the cost estimates may stem primarily from charges rather than estimates of the true costs.
• The patient completed the questionnaire on traveling and sick leave every 6 months. This rather long period may give rise to recall errors. • Furthermore, the response rate decreased somewhat during the course of the study. Due to these limitations, the estimates of direct medical costs were deemed to be more reliable than the estimates of total costs. |
| Szucs et al13 (Switzerland) | 2009 | • Open-label, randomized, multicenter study comparing the 2 long-term management options with esomeprazole 20 mg—continuous daily or on-demand treatment during 26 weeks—in endoscopically uninvestigated patients seeking primary care in Switzerland for symptoms suggestive of GERD who demonstrated complete relief of symptoms after an initial treatment of 4 weeks with esomeprazole 40 mg.
• Patients found to meet all the inclusion criteria and none of the exclusion criteria at the end of the initial treatment course were randomized in equal proportions to continuous treatment with esomeprazole 20 mg every day. or on-demand treatment with esomeprazole 20 mg. For the randomization, a centrally compiled, computer-generated list was used, which was based on a block size of 4. Each site received a kit consisting of a list of randomization numbers and sealed randomization envelopes for 4 patients. • The investigator was instructed to consecutively allocate the lowest available randomization number, but open the randomization envelopes containing the information on the allocated treatment group only at randomization. It had been planned that each site would recruit 4 patients (or an exact multiple of 4). Each patient in the continuous treatment arm was instructed to take 1 tablet once daily. • In the on-demand arm, the patient was instructed to take 1 tablet daily if needed for the relief of heartburn and to stop when the heartburn is adequately controlled. The study drugs were packed in bottles, and every patient received in total 2 bottles of 100 tablets esomeprazole 20 mg free of charge. The distribution schedule of the study drugs from general practitioner to patient was at the discretion of the general practitioner, ie, the treating physician decided when to distribute study drugs and whether to distribute them all at once or at several occasions. Compliance was determined by counting the tablets returned by the patient. |
• At the end of the 6-month maintenance phase, 93% of the patients treated continuously were classified as “satisfied” (score = 1-4) with their treatment, whereas 77% of the patients, were reported to be “very satisfied” (score = 1-2), Wilcoxon rank sum test (score = 1-7): P < .056.
• The mean number of clinic visits to the investigator for any reason required per patient was 0.50 (SD = 0.647) for those in the continuous group. |
• The data clearly demonstrate that on-demand esomeprazole 20 mg therapy is associated with significantly better effectiveness and lower costs than a strategy consisting of intermittent 4-week treatment courses of omeprazole 20 mg once daily. However, the treatment with continuous esomeprazole was more efficient than the on-demand therapy with regard to remission of heartburn. | • The endpoint used in this primary care study (symptoms of any severity on at least 2 days during the previous week), may not correspond to a definition of relapse in clinical practice. |
Note. PPI = proton pump inhibitor; QALYs = quality-adjusted life in years; GERD = gastroesophageal reflux disease; H2RA = histamine 2 receptor antagonists; RCT = randomized controlled trial.