Treatment of non-erosive gastroesophageal reflux disease patients with proton pump inhibitors

Nasuh Buyukkaramikli, Katharina Abraham, Hilde Vroling, Eveline Bunge, Edoardo Pennesi, Maiwenn Al, Matthijs Versteegh, Anouk Oordt
Record ID 32018000306
Original Title: Behandlung einer nicht-erosiven gastroösophagealen Refluxerkrankung mit Protonenpumpeninhibitoren
Authors' objectives: Proton-pump inhibitors (PPIs) represent, at the moment, the cornerstone for the treatment of gastroesophageal reflux disease (GERD) patients with symptoms such as heartburn or acid regurgitation. Due to the high safety profile and efficacy of the technology, the current reimbursement policy in Switzerland might favour the administration of PPIs in non-erosive GERD (NERD) patients in a continuous fashion, presumably leading to over-prescription of PPIs. This health technology assessment (HTA) focuses on the long-term continuous versus on-demand PPI therapy, in adult NERD and endoscopically uninvestigated GERD patients. The HTA is conducted in clinical effectiveness (including efficacy, effectiveness, and safety), cost-effectiveness, legal, social, ethical, and organisational domains. The operationalisation of the on-demand PPI therapy reimbursement is assumed to be realised with reimbursement restriction levels, defined as the maximum number of PPI pills to be reimbursed per year (100, 200 and 365 pills per year).
Authors' results and conclusions: Long-term PPI therapy is effective in managing the symptoms of NERD and uninvestigated GERD patients. Based on efficacy and effectiveness outcomes, the overall satisfaction of the patients with both therapy modalities (continuous and on-demand PPI therapy) and the health-related quality of life were in general high and differences between continuous and on-demand PPI therapy were quite small, resulting in a lacking clinically relevant difference between these two therapy modalities. Furthermore, no major safety issues were reported in the included studies. With the evidence found in the clinical-effectiveness review, for most outcomes of interest it was not possible to draw a conclusion in favour of continuous or on-demand PPI therapy, amongst others caused by lacking between-group statistical comparisons and heterogeneity in studies and study outcomes, resulting in mixed results. The efficacy evidence showed that long-term on-demand therapy results in lower PPI pill consumption per day compared with continuous therapy. The observed difference for the outcome heartburn symptom relief was in favour of continuous therapy and may largely be attributed to the specifications of the therapy modality (with on-demand therapy a dose of PPI is taken when clinical symptoms occur, which may explain the higher symptom load). The results of the cost-effectiveness model showed, that on-demand PPI therapy is cost-effective under different reimbursement policies (no pill restriction, restriction to 100 pills, 200 pills [base case] and 365 pills per year) compared to continuous PPI therapy, for uninvestigated GERD and NERD populations. From the model outcomes it can be deducted that there is no significant difference expected in terms of QALYs, between on-demand and continuous PPI therapy. On the other hand, the on-demand PPI therapy is expected to lead to a cost saving of 1’276, 896 and 588 CHF per patient for the health insurer, respectively, over the course of a patient’s life time when the restriction levels of 100, 200 and 365 pills per year are applied. Since the QALY difference between two arms is extremely small, the cost savings due to the on-demand PPI therapy lead to tremendously high ICER values for continuous therapy. Under these reimbursement restriction levels (100, 200 and 365 pills per year), the additional lifetime out-of-pocket payment for PPI medications will be 760, 380 and 72 CHF per patient. From the one-way sensitivity analysis results, one can observe that PPI usage and the per pill PPI price seem to be among the most influential parameters on the incremental costs. The probabilistic HTA Report 4 sensitivity analysis results reveal that the cost-effectiveness is subject to substantial parametric un-certainty, however, the impact of this uncertainty on the decision is rather limited. The continuous PPI therapy is never cost-effective for plausible willingness to pay threshold levels (up to 100,000 CHF per QALY gained). The 5-year estimated budget saving of changing from continuous PPI therapy to on-demand PPI therapy is estimated to be between 50 and 127 million CHF for the uninvestigated GERD and NERD patients in Switzerland. This budget impact depends on the nature of the policy implementation (sudden or gradual implementation) as well as the reimbursement restriction threshold (200 or 365 pills per year) and the scope of the reimbursement restriction (i.e. if patients who fail on-demand PPI therapy but are stable under continuous PPI therapy before endoscopy are included or not). The present study did not find relevant issues or limitations pertaining the implementation of a restriction on PPIs reimbursement system in the legal, social, ethical, or organisational domains.
Authors' methods: Systematic literature searches were performed in PubMed (MEDLINE),, and other complementary databases to identify relevant published evidence for all HTA domains between the years 2000 and 2019. For the clinical and cost-effectiveness domains, data was ex-tracted from the included studies in predefined evidence tables and summary tables were made for different study types (i.e. comparison/non-comparison studies for the clinical-effectiveness and trial/model-based economic evaluations for the cost-effectiveness). For the other domains, the evi-dence was described narratively. The literature search on the cost-effectiveness of long-term con-tinuous versus on-demand PPI therapy in Switzerland did not provide sufficient evidence. Therefore, for the cost-effectiveness and budget impact analysis of on-demand PPI therapy, a de novo Markov cost-effectiveness model and budget-impact model were developed, characterising the natural his-tory of the disease in a patient’s lifetime under the Swiss clinical practice. The cost-effectiveness and budget-impact models simulated the cost implications of implementing on-demand PPI therapy HTA Report 3 reimbursement restriction with a given maximum quota for the number of PPI pills per year from a healthcare insurer perspective. Additionally, the out-of-pocket PPI medication cost estimates, re-sulting from different reimbursement restriction policies were also presented. The uncertainty around these estimates were explored in different sensitivity and scenario analyses.
Project Status: Completed
Year Published: 2020
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Switzerland
MeSH Terms
  • Proton Pump Inhibitors
  • Gastroesophageal Reflux
  • non-erosive gastroesophageal reflux
  • reflux
  • proton pump inihibitor
  • gastroesophageal reflux disease (GERD)
  • PPI
  • PROMs
  • efficacy
  • effectiveness
  • safety
  • costs
  • economics
  • cost-effectiveness
  • budget impact
  • legal
  • social
  • ethical
  • organisational
Organisation Name: Swiss Federal Office of Public Health (FOPH)
Contact Address: Federal Office of Public Health, Schwarzenburgstrasse 157, CH-3003 Berne, Switzerland
Contact Name: Klazien Matter-Walstra
Contact Email:
Copyright: Swiss Federal Office of Public Health
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.