Cost-effectiveness of RefluxStop compared to proton pump inhibitors and Nissen fundoplication for management of persistent gastroesophageal reflux disease in Norway

Cost-effectiveness of RefluxStop compared to proton pump inhibitors and Nissen fundoplication for management of persistent gastroesophageal reflux disease in Norway | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost-effectiveness of RefluxStop compared to proton pump inhibitors and Nissen fundoplication for management of persistent gastroesophageal reflux disease in Norway Sam Harper, Muralikrishnan Kartha, Stuart Mealing, Lars Eftang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4643281/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Oct, 2025 Read the published version in Cost Effectiveness and Resource Allocation → Version 1 posted 11 You are reading this latest preprint version Abstract Background Heartburn, chest pain, and regurgitation are characteristics of gastroesophageal reflux disease. The standard treatment in Norway is proton pump inhibitors (PPIs), but surgical alternatives such as Nissen fundoplication are pursued when medical management proves ineffective. RefluxStop is an implantable device presenting a new approach to restoration of the antireflux barrier. The aim of this study is to evaluate the cost-effectiveness of RefluxStop, Nissen fundoplication, and PPI-based medical management (MM) in Norway. Methods A Markov model was adapted from a published cost-effectiveness analysis developed for the UK NHS assessing the cost-effectiveness of RefluxStop in comparison with PPI-based MM and Nissen fundoplication. The perspective of the Norwegian healthcare payer, lifetime horizon, one-month cycle length, and a 4% annual discount rate for costs and health-benefits were used. Health states included in the model were initial MM, MM relapse, follow-on surgery, reoperations, MM with a higher dose, Barrett’s esophagus, esophageal cancer, and death. Adverse events related to MM and surgeries were included with benefits measured in quality-adjusted life-years (QALYs). Norwegian diagnostic-related group tariffs and literature were used as sources for unit costs. Clinical efficacy data for RefluxStop was based on an ongoing clinical study and comparator treatments were informed by published studies. Deterministic and probabilistic sensitivity analyses were used to address uncertainty of the parameter estimates. Results Compared to PPI-based MM and Nissen fundoplication, the base case incremental cost-effectiveness ratios (ICERs) of RefluxStop were NOK 68,262 and NOK 79,543 per QALY gained, respectively. The results of the model were robust to variation in individual inputs with exception of monthly failure rate of RefluxStop relative to Nissen fundoplication. RefluxStop demonstrated a significantly high probability of cost-effectiveness at the cost-effectiveness threshold of NOK 275,000 per QALY gained, with probabilities of 100% and 92% against PPI-based MM and Nissen fundoplication, respectively. Conclusion The RefluxStop device is highly likely to be cost-effective compared to PPI-based MM and Nissen fundoplication in Norway. Further study is required to assess the real-world long-term safety and efficacy of this novel device. Cost-effectiveness analysis antireflux surgery gastroesophageal reflux disease proton pump inhibitors cost utility Markov model Figures Figure 1 Figure 2 BACKGROUND In Western countries, one of the most common gastrointestinal conditions is gastroesophageal reflux disease (GERD), defined by reflux of gastric contents into the esophagus with troublesome symptoms at least once a week [ 1 , 2 ]. Characteristic symptoms include heartburn and regurgitation, which may considerably impair quality of life and reduce both work and leisure-time productivity [ 1 , 3 , 4 ]. GERD is associated with an increased risk of Barrett’s esophagus and progression to esophageal adenocarcinoma, particularly if left untreated [ 5 , 6 ]. In Norway, the prevalence of weekly GERD symptoms is estimated between 7.8% and 17.1% [ 5 – 7 ]. More specifically, between 2006 and 2009, the prevalence of any reflux symptoms less frequently than once a week was as high as 40.9%, of which 6.7% were severe [ 6 ]. Moderate or severe regurgitation occurs in 24.2% of the population [ 1 ]. The mean annual incidence of severe symptoms has been reported to be 0.23% with a corresponding spontaneous loss of symptoms occurring at 1.22% [ 6 ]. The relatively high prevalence in Norway makes GERD an important target for minimization of healthcare resource consumption. The primary treatment of GERD in Europe is medical therapy, with proton pump inhibitors (PPIs) most often representing the mainstay intervention [ 8 ]. Antireflux surgery is an alternative approach that should be considered in patients with severe symptoms or refractory disease despite optimally dosed medical therapy, particularly in young, healthy adults that would require long-term medical therapy [ 9 , 10 ]. The usage of PPIs in Norway is lower in comparison to other European countries but has increased at a rate of 10% annually between 2003 and 2008 [ 11 ]. The reason for less frequent use in comparison to the rest of Europe may be attributable to the prescription rules in Norway. Interestingly, a small proportion of Norwegian patients with GERD undergo antireflux surgery (0.7%), indicating that such procedures are not often employed in management [ 10 ]. However, the overall number of surgeries has increased dramatically in recent decades [ 12 ]. RefluxStop is a novel implantable device that aims to manage persistent GERD by restoring the normal anatomy of the lower esophageal sphincter, gastroesophageal flap valve, and angle of His [ 13 ]. The approach employs a mechanism of action that expands on the rationale of traditional antireflux procedures with the added benefit of not compressing the food passageway. In a small prospective study, RefluxStop demonstrated 86% improvement in GERD Health-Related Quality of Life score at 1 year postoperatively with 98% of patients having normal pH values on 24-hour pH monitoring [ 13 ]. Furthermore, as a frequent complication of traditional antireflux procedures, new-onset dysphagia was not observed in patients managed with RefluxStop [ 13 ]. This report presents the relative cost-effectiveness of RefluxStop, PPI-based medical management, and laparoscopic Nissen fundoplication for GERD management in Norway. Treating physicians should consider the results of this study to guide decision-making that optimize health benefits with healthcare resource consumption. METHODS To compare RefluxStop with PPI-based medical management and Nissen fundoplication in adults with GERD, a cost-effectiveness analysis was performed. Endoscopic techniques and MSA are not available in Norway; thus, they were not included in the analysis. Clinical outcomes and costs assessed over a lifetime horizon were assessed from a Norwegian healthcare system perspective. Only direct medical costs were included without accounting for indirect societal costs (e.g., lost productivity). Quality-adjusted life-years (QALYs) were used to quantify clinical outcomes for the patient experience. All costs and QALYs were discounted at 4% per year, consistent with recent economic evaluations based on Norwegian perspective [ 14 ]. The analysis assumed a cycle length of 1 month with a half cycle correction applied. Any events in the model were presumed to occur in the middle of each month. Model Structure A Markov model was used in evaluation of the cost-effectiveness of RefluxStop. Model subjects went through a series of health states that were mutually exclusive representing possible outcomes of reflux disease management options. This cost-effectiveness analysis is an adaptation of a recently published study by Harper et al for the cost-effectiveness of RefluxStop from the United Kingdom National Health Service perspective [ 15 ], but has been applied to Norwegian settings. The variability in treatment mechanisms and pathways was reflected in the model framework for medical (Fig. 1 A) and surgical (Fig. 1 B) options. The structure of the model considered variable dosing (i.e., standard and double) of PPI therapy, medication irresponsiveness, primary surgery, secondary surgery (i.e., reoperation), progression to Barrett’s esophagus and cancer of the esophagus, and death. The model structure also included adverse events (AEs) related to all treatment arms. Standard-dose PPIs were presumed in all patients included in the medical management arm as first-line therapy (i.e., ‘Medical management well’ state) with a potential of GERD relapse applicable every month. In the case of relapse, patients would be provided double-dose PPI therapy (i.e., ‘Medical management relapse’ state) and if medication-based therapy works again then the patient could resume standard-dose PPI therapy (i.e., ‘Medical management well’) or if that doesn’t work patient may undergo antireflux surgery. As per the NICE-UK NHS recommendations, Nissen fundoplication was the intervention used in the surgical procedure arm of our model for comparison with RefluxStop [ 16 ]. As MSA is currently not available in Norway, it was not included in the model. Primary (i.e., initial) surgery was the point of model entrance for all patients in the surgical treatment arms (i.e., RefluxStop and Nissen fundoplication). Postoperative states of the model included successful (i.e., ‘Surgery well’) and unsuccessful (i.e., ‘Surgery fail’). Unsuccessful surgery would lead to reoperation (i.e., ‘Surgery re-op’) or patients receiving double-dose PPI therapy (i.e., ‘Medical management high dose’), presumed persistent for the remainder of a patient’s life. The same procedure type as initial surgery was presumed for reoperation. In cases where reoperation also failed, patients would take higher-dose (i.e., double) PPI therapy for the remainder of their lives. All patients in the model (i.e., all treatment arms) were subject to Barrett’s esophagus development at a rate of 0.083% per month, and only patients with established Barrett’s esophagus carried an additional risk of progression to esophageal carcinoma at a rate of 0.06% per month. Norwegian general population mortality and mortality-associated health states were included in the model as outlined below. Model Inputs Clinical and Quality of Life Inputs A simulated group of 1,000 patients aged 52 years and older, of which 56% were male, were followed in the model, consistent with the CE mark trial of RefluxStop [ 13 ]. Such demographics are similar to trials for GERD treatments with large sample sizes, including the UK REFLUX trial [ 17 ] and a US trial of treatments (i.e., medical and surgical) for refractory GERD [ 18 ]. Thus, these hypothetical patients accurately represent real-world patients that are likely candidates to undergo antireflux surgery. Table 1 presents clinical and quality of life parameters. Table 1 Clinical and quality of life inputs used in the model. Parameter Input Source Relapse of GERD symptoms with medical management 2.65% Bojke 2007 [ 31 ] Reoperation following unsuccessful surgery 10.3% Surgery following a relapse of medical management 10.3% Assumed to be the same as the probability in a case of reoperation Probability of surgical failure up to 1-year post-surgery Nissen fundoplication 1.8% Karolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished] [ 20 ] RefluxStop 0.3% Implantica data on file. RefluxStop CE mark study 3-year outcomes [ 19 ] Probability of surgical failure ≥ 1-year post-surgery Nissen fundoplication 1.8% Karolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished] [ 20 ] RefluxStop 0.1% Implantica data on file. RefluxStop CE mark study 3-year outcomes [ 19 ] Probability of surgical failure for reoperation or second-line treatment Nissen fundoplication 0.31% Calculated based on treatment failure rates up to 1 year and post 1 year provided above. RefluxStop 0.17% Calculated based on treatment failure rates up to 1 year and post 1 year provided above. Monthly probability of Barrett’s esophagus All treatment arms 0.083% NICE model developed to support clinical guidance development in dyspepsia and GERD [ 28 ] Risk of adverse effects of PPIs CV events (MI or stroke) 0.01% Calculated based on WHO CVD risk chart working group [ 38 ] and Shiraev 2018 [ 30 ] CKD 0.01% Calculated based on Collins 2012 [ 39 ] and Hussain 2019 [ 40 ] Fracture 0.02% Calculated based on Kanis 2008 [ 41 ] and Zhou 2016 [ 42 ] Pneumonia 0.08% Calculated based on Sun 2019 [ 43 ] and Lambert 2015 [ 44 ] Clostridium difficile 0.001% Calculated based on Clostridium difficile infection: mandatory surveillance 2017/18 report [ 45 ] and Janarthanan 2012 [ 46 ] Stomach cancer 0.002% Brusselaers 2017 [ 47 ] Intraoperative adverse events related to surgery Conversion to open surgery RefluxStop: 2.1% Nissen fundoplication: 1.7% Implantica data on file Karolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished] [ 20 ] Splenic injury RefluxStop: 0.0% Nissen fundoplication: 0.9% Gastro-esophageal injury RefluxStop: 0.0% Nissen fundoplication: 1.0% Liver injury RefluxStop: 0.0% Nissen fundoplication: 1.4% Post-operative adverse events related to surgery Endoscopic esophageal dilation RefluxStop: 0.0% Nissen fundoplication: 0.3% Implantica data on file Skubleny et al [ 48 ] Major complications requiring additional surgery RefluxStop: 0.0% Nissen fundoplication: 1.4% Bjelovic et al [ 13 ] Endoscopic device removal RefluxStop: 0.0% Nissen fundoplication: N/A Implantica data on file Utility decrement: Stable medical management 0.12 Based on Bojke 2007 [ 31 ] Norwegian (Sweden) population norms [ 32 ] Utility decrement: Medical management of GERD relapse 0.28 Bojke 2007 [ 31 ] Utility decrement: Medical management high dose 0.12 Assumed equal to stable medical management Post-surgery utility decrements (applied for 1 month) RefluxStop 0.24 Based on Bojke et al [ 31 ] and originally sourced from Ainslie et al 2003 [ 49 ] Nissen fundoplication 0.24 Utility decrements applied ≥ 1 month following successful surgery in the ‘Surgery well’ state RefluxStop 0.00 Calculated based on utility decrement for dysphagia from Bouvy 2013 [ 50 ] and the proportion reporting dysphagia at 3 years from the RefluxStop CE mark study (Implantica data on file) [ 19 ] Nissen fundoplication 0.01 Calculated based on utility decrement for dysphagia from Bouvy 2013 [ 50 ] and the proportion reporting dysphagia at 5 years from Karolinska Institute review [ 20 ] Unsuccessful surgery utility decrements RefluxStop 0.16 Assumed equal to Nissen fundoplication Nissen fundoplication 0.16 Based on Grant 2008 [ 17 ] and Norwegian (Sweden) population norms [ 32 ] Utility decrements associated with Barrett’s esophagus and esophageal cancer Barrett’s esophagus 0.10 Pollit 2019 [ 35 ] Esophageal cancer 0.44 NICE model developed to support clinical guidance development in dyspepsia and GERD [ 26 ] Abbreviations: C. Diff, Clostridium difficile ; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; GERD, gastro-esophageal reflux disease; MI, myocardial infarction; NICE, National Institute for Health and Care Excellence; PPI, proton pump inhibitor; SSED, Summary of Safety and Effectiveness Data; WHO, World Health Organization The clinical data for RefluxStop was obtained from the CE mark trial [ 13 ] with addition of 3-year follow-up data on file [ 19 ]. The efficacy of medical therapy and Nissen fundoplication were obtained from published literature. Surgical failure was defined in two different periods (i.e., up to 1 year postoperatively and > 1 year postoperatively) for surgical interventions, meant to represent the reporting structures found in investigations for each option. Intraoperative events and postoperative AEs were attributed to Nissen fundoplication and RefluxStop, regardless of whether an initial procedure or reoperation. The events considered for the model were obtained from a global literature review on Nissen fundoplication outcomes recently published [ 20 ]. All those in the medical therapy arm were assumed to receive PPI therapy and a relevant proportion of patients in surgical arms (i.e., Nissen fundoplication and RefluxStop) were assumed to receive PPI therapy in the case of surgical failure. Patients were subject to long-term PPI-related AEs in all comparator arms of the model (i.e., PPI-based medical management, Nissen fundoplication, and RefluxStop), including Clostridium difficile (C.Diff) infection [ 21 ], community-acquired pneumonia [ 22 ], osteoporotic fractures [ 23 ], gastric cancer [ 24 ], chronic kidney disease (CKD) [ 25 ], and cardiovascular (CV) events [ 26 ]. One-off events included osteoporotic fractures, gastric cancer, pneumonia, and C.Diff infection. Events like CKD and CV events were modelled using the proportion-in-state method. Thus, the rate of mortality from CKD and CV events was identical to the rate of complication development in PPI users. Potential long-term complications of GERD include Barrett’s esophagus and esophageal carcinoma [ 27 ]. Barrett’s esophagus developed at a monthly rate of 0.083%, based on a model developed to produce NICE recommendations on GERD [ 28 ]. Patients in all treatment arms were subject to this risk. Furthermore, esophageal carcinoma occurred at a monthly rate of 0.06% in all those with Barrett’s esophagus, as per a systematic review and meta-analysis [ 29 ]. Excess mortality with surgery, esophageal cancer, and long-term PPI-related AEs were considered in addition to general population mortality, determining mortality in different treatment arms of the model. A small risk of intraoperative mortality (0.05%) was attributed to all primary surgeries across relevant model arms. Patients with esophageal carcinoma were assumed to have a monthly risk of death of 3.4% [ 15 ]. All patients in medical therapy states regardless of model arm were subject to a relative mortality risk of 1.57, representing an increased risk of mortality from long-term PPI-related AEs [ 30 ]. With these considerations, mortality estimation did not favor any of the model arms since risk estimates were uniformly applied for all arms. Utility decrements were used to describe Health-Related Quality of Life (HRQoL). For those with successful surgery, utility decrements were based on the proportion of patients with persistent dysphagia as a possible AE after surgery. As such, a utility decrement value of 0.24 was applied for 1 month postoperatively for primary procedures and reoperations (i.e., Nissen fundoplication and RefluxStop). This was sourced from the impact on quality of life from laparoscopic cholecystectomy and the assumption of similarity between the procedures (i.e., both are elective laparoscopic procedures for benign conditions) [ 31 ]. Cost-effectiveness analysis of PPI therapy and laparoscopic Nissen fundoplication for GERD, from the REFLUX trial, informed utility decrements in those taking PPIs [ 17 , 31 ]. Similarly, this analysis informed our model of the utility decrement related to Nissen fundoplication failure, which was presumed to similarly apply to RefluxStop [ 17 ]. Utility decrements were also applied to patients with Barrett’s esophagus and cancer of the esophagus. Since population norms for Norway were not available, the norms of Sweden were used based on the literature [ 32 ] assuming that the population norms will be at least similar due to the geographic, socioeconomic and cultural similarity. Table 1 delineates the HRQoL inputs in the model. Cost Inputs The Norwegian DRG [ 33 ] and published literature were sourced for cost information whenever possible. Values from older literature sources were inflated using a web-based cost conversion tool [ 34 ]. Key cost inputs are summarized in Table 2 . Table 2 Key cost inputs applied in the model. Parameter Input Source Medical and surgical treatment costs Monthly cost of PPI medication (standard dose) NOK 153.81 NoMA medicine database [ 51 ] Monthly cost of PPI medication (high dose) NOK 187.71 NoMA medicine database [ 51 ] Procedure cost – all surgical treatments NOK 104,077.56 Base rate NOK 47,742 multiplied by cost weight 2.18 (155B) from Norwegian DRG [ 33 ] Device – RefluxStop NOK 59,000 Implantica data on file [ 19 ] Training – RefluxStop NOK 225.63 Calculated based on Augestad et al 2013 [ 52 ] and Palser 2018 [ 53 ] Barrett’s esophagus Diagnostic endoscopy NOK 3,341.94 Base rate NOK 4,7742 multiplied by cost weight 0.07 (711O) from Norwegian DRG [ 33 ] Treatment (endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA)) NOK 11,812.17 Calculated based on Pollit 2019 [ 35 ] and Base rate NOK 4,7742 multiplied by cost weight 0.12 (EMR 706O)* and 0.31(RFA 703O) from Norwegian DRG [ 33 ] Monthly monitoring cost NOK 320.91 Calculated based on the NICE model developed to support clinical guidance development in dyspepsia and GERD [ 28 ] and Base rate NOK 47,742 multiplied by cost weight 0.12 (706O) from Norwegian DRG [ 33 ] Esophageal cancer Initial diagnostic and treatment NOK 185,034.70 Calculated based on the NICE model developed to support clinical guidance development in dyspepsia and GERD [ 28 ]. Base rate NOK 47,742 multiplied by cost weight 3.7 (155A) from Norwegian DRG [ 33 ] and Pike et al 2013 [ 54 ] Palliative care NOK 134,288.60 Bugge et al 2021 [ 55 ] Adverse events associated with PPIs CKD monthly cost (including costs of treatment, hospitalization, and end-stage renal disease) NOK 8,160.21 Calculated based on Kerr 2012 [ 56 ], Pike et al 2013 [ 54 ], Eriksson et al 2017 [ 57 ], Kim et al 2022 [ 58 ], and Kidneyfailurerisk.com [ 59 ] Monthly cost of CV events (MI or stroke) NOK 4,099.79 Kim et al 2022 [ 58 ] Fracture (event cost) NOK 89,317.27 Akehurst et al 2011 [ 60 ] Pneumonia (event cost) NOK 21,539.61 Calculated based on Nymark et al 2022 [ 14 ], Lambert 2015 [ 44 ], NICE quality standard for pneumonia in adults [ 61 ] C.Diff. infection (event cost) NOK 24,649.85 Calculated based on Nordling et al 2014 [ 62 ], the Clostridium difficile infection: mandatory surveillance 2017/18 report [ 45 ], and costs of antibiotics as provided in NoMA medicine database [ 51 ] Stomach cancer (lifetime cost) NOK 111,091.93 NICE technology appraisal of ramucirumab (TA378) [ 63 ] Adverse events associated with surgery Conversion to open surgery NOK 30,676.09 Laudicella 2016 [ 64 ] Esophageal dilation NOK 5,729.04 Base rate NOK 47,742 multiplied by cost weight 0.12 (706O)* from Norwegian DRG [ 33 ] Additional surgery for major complications NOK 104,077.56 Assumed to be the same cost as the initial procedure. Device removal NOK 104,077.56 Assumed to be the same cost as the initial procedure. Abbreviations: C. Diff, Clostridium difficile ; CKD, chronic kidney disease; CV, cardiovascular; GERD, gastro-esophageal reflux disease; MI, myocardial infarction; NICE, National Institute for Health and Care Excellence; PPI, proton pump inhibitor *DRG cost weight for EMR and Esophageal dilation assumed similar to Therapeutic Endoscopy PPI (i.e., omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole) and surgery costs were considered in our model. Surgical costs included: 1) device cost, procedure costs, and training costs for RefluxStop; and 2) only procedure costs for Nissen fundoplication as this technique does not require a device or additional training costs. The cost of performing the Nissen fundoplication procedure was identically applied to RefluxStop insertion procedures as it follows the similar standard approach for laparoscopy. Diagnostic, treatment, and monthly management costs were incurred by patients with Barrett’s esophagus [ 35 ]. All patients with Barrett’s esophagus underwent diagnostic endoscopy and were treated with endoscopic mucosal ablation and radiofrequency ablation in cases of dysplasia (16.6%), subsequently followed by endoscopic follow-up over two years with PPI therapy [ 35 ]. Those without dysplasia were assumed to have costs attributable to PPI therapy and endoscopic monitoring only [ 35 ]. Patients demonstrating progression to esophageal carcinoma followed the patient journey outlined by NICE clinical guidance in UK [ 28 ]. Initial diagnostic testing and treatment costs, (such as endoscopy, general practitioner visit, esophagectomy, and chemotherapy), monthly PPI costs, and terminal care costs (in those succumbing to illness) were applied to patients with esophageal carcinoma. A monthly cost of management was presumed in patients with CKD or CV events related to PPI therapy. One-off events incurring costs included osteoporotic fractures, pneumonia, and C.Diff infection. A recurring cost was applied to patients with gastric cancer attributable to supportive care and chemotherapy. Costs associated with surgery-related AEs included conversion to laparotomy, esophageal dilation, major surgical complications, and device removal. Injuries to the spleen, liver, or gastroesophageal anatomy during the intraoperative period were included in the costs of the operation itself. Economic Analysis Estimates for QALYs per patient, life-years (LYs), life expectancy, and total costs were produced for each arm of the study. Incremental differences in these values between model arms were also generated. Incremental measures comparing treatment arms included: 1) incremental cost-effectiveness ratio (ICER), representing the cost per QALY gained; 2) incremental net health benefit (NHB); and 3) incremental net monetary benefit (NMB). In Norway, there is no exact cost-effectiveness threshold, and thus the maximum amount a decision-maker is willing to pay for a unit of health outcome is uncertain [ 36 ]. In the available literature, the range of Norwegian cost-effectiveness thresholds spans from NOK 275,000 to NOK 825,000 per QALY gained [ 14 , 36 ]. To be conservative, our analysis utilized the lower cost-effectiveness threshold of NOK 275,000. NMB and NHB were calculating using a Norwegian cost-effectiveness threshold of NOK 275,000 per QALY gained. Positive incremental values for NMB or NHB are indicators that the management option benefits the healthcare system at the cost-effectiveness threshold. Furthermore, the magnitude of values demonstrates a positive correlation with benefit. Deterministic sensitivity analyses were also performed to determine the uncertainty present in model results. Individual model inputs were varied in isolation with documentation of results to identify inputs with the most influence. The ranges in which model inputs varied were informed by reported confidence intervals (CIs), and in cases where relevant information was not available, assumptions were made. Model inputs which demonstrated uncertainty were sampled from plausible distributions in probabilistic sensitivity analyses. One-thousand iterations using varying input sets were performed. Available reported CIs were used to derive standard errors for generation of probabilistic values. Standard error was assumed to be 10% of the mean value when information was not available. RESULTS Base Case Results Using the cost-effectiveness threshold of NOK 275,000 per QALY gained, RefluxStop demonstrated cost-effectiveness against PPI-based medical management and laparoscopic Nissen fundoplication (Table 3 ). Patients in the RefluxStop arm of the model accrued 0.57 to 1.48 more QALYs than those in other model arms (Table 4 ). Specific to the surgical arm, RefluxStop compared favorably against Nissen fundoplication regarding surgical outcomes (Table 4 ).These included the total number of surgeries, surgical failures, and necessity for postoperative endoscopic dilation. Due to less severe AEs, avoidance of disease progression related to sequelae, and the lower reoperation rate associated with RefluxStop, our model estimated a higher life expectancy in the RefluxStop arm versus all comparators, with differences of 0.45 to 0.73 years in favor of RefluxStop compared to PPI therapy and laparoscopic Nissen fundoplication, respectively (Table 4 ). Table 3 Cost-effectiveness outcomes estimated in the base case analysis, per patient. Summary results RefluxStop Medical management Incremental Nissen fundoplication Incremental vs Nissen fundoplication Cost per patient NOK 188,223 NOK 86,999 NOK 101,224 NOK 142,568 NOK 45,654 QALYs per patient 14.71 13.23 1.48 14.14 0.57 Life years per patient (undiscounted) 37.01 36.14 0.87 36.55 0.47 Life years per patient (discounted) 19.17 18.92 0.25 19.05 0.12 Incremental cost-effectiveness ratio (ICER) NOK 68,262 NOK 79,543 Net monetary benefit (NMB) NOK 306,569 NOK 112,185 Net health benefit (NHB) 1.11 0.41 Table 4 Clinical outcome estimates in the base-case analysis (per 1,000 patients unless otherwise stated) Clinical outcomes (per patient) RefluxStop Medical management Incremental vs Medical management Nissen fundoplication Incremental vs Nissen fundoplication Number of people developing Barrett’s esophagus 0.31 0.30 0.01 0.30 0.00 Number of people developing esophageal cancer 0.04 0.04 0.00 0.04 0.00 Number of surgeries 1.03 0.61 0.42 1.05 -0.02 Number of surgical failures 0.30 0.31 -0.01 0.55 -0.26 Number of endoscopic dilations 0.00 0.40 -0.40 1.01 -1.01 Number of device removals 0.00 0.00 0.00 0.00 0.00 Average life expectancy, years (per patient) 42.55 41.82 0.73 42.09 0.45 Abbreviations: C. Diff, Clostridium difficile ; CKD, chronic kidney disease; PPIs, proton pump inhibitors; reop, reoperation Abbreviations: QALY, quality-adjusted life year. The ICERs of RefluxStop compared to PPI-based medical management and Nissen fundoplication were significantly below the lower Norwegian cost-effectiveness threshold (i.e., NOK 275,000 per QALY gained). The ICERs of RefluxStop were NOK 68,262 and NOK 79,543 per QALY gained against PPI-based medical management and laparoscopic Nissen fundoplication, respectively. The NHB and NMB of RefluxStop against all assessed comparators were positive values. That is, RefluxStop provided net health and monetary benefits, respectively. More specifically, RefluxStop had NHB values of 1.11 against PPI-based medical management and 0.41 against laparoscopic Nissen fundoplication, and NMB values of NOK 306,569 against PPI-based medical management and NOK 112,185 against laparoscopic Nissen fundoplication. The costs of RefluxStop were balanced by the lower costs of PPI therapy (i.e., savings of NOK 19,693.43 and NOK 6,541.27 vs. PPI-based medical management and Nissen fundoplication, respectively) and the costs of managing PPI-related AEs (i.e., savings of NOK 4,785.03 and NOK 1,345.77 vs. PPI-based medical management and Nissen fundoplication, respectively) to an extent. Pertaining to surgical outcomes and complications, RefluxStop provided per-patient lifetime savings compared with laparoscopic Nissen fundoplication (i.e., savings of NOK 1,458.51 for intraoperative events and sequelae necessitating operation, and NOK 3,146.95 for endoscopic dilation). Deterministic Sensitivity Analysis The most influential inputs in deterministic sensitivity analyses were the probabilities of surgical failure with RefluxStop and surgery after medical relapse (Supplementary Fig. 1). Variation of individual input parameters did not alter the orientation of results in the model with exception for the monthly failure rate of RefluxStop in juxtaposition with laparoscopic Nissen fundoplication. Thus, the results of our analysis were robust to variation of parameters overall. Finally, exploration of various cost estimates and risks of AEs did not significantly affect the long-term cost-effectiveness results of our study. Probabilistic Sensitivity Analysis RefluxStop exhibited a high probability of being cost-effective at a Norwegian cost-effectiveness threshold of NOK 275,000. Probabilities of being cost-effective compared with PPI-based therapy and laparoscopic Nissen fundoplication were 100% and 92%, respectively. From probabilistic analyses in 1,000 iterations, the average ICERs obtained were like the base case ICERs against each of the comparators (i.e., NOK 72,271.86 per QALY when compared with PPI-based medical management and NOK 87,459.37 per QALY when compared with Nissen fundoplication). Most of the probabilistic iterations were significantly below the lower cost-effectiveness threshold of NOK 275,000 available from sources specific for Norway (Fig. 2 B). DISCUSSION As one of the most common gastrointestinal disorders in Western societies, GERD poses a significant burden on public health as prevalence continues to increase [ 1 , 2 , 37 ]. Despite a lack of clinical guidance specific to Norway, in line with the paradigms in the rest of Europe, medical management with PPI therapy is pursued [ 8 ]. Compared with other European countries, the use of PPIs in Norway is lower but has steadily increased at an approximate annual rate of 10% [ 11 ], likely increasing the overall cost of GERD treatment in the population. As an alternative to medical therapy, antireflux surgical procedures seem not to be used for management despite recent small increases in utilization [ 10 , 12 ]. With the increasing prevalence of GERD, cost-effective management strategies, including emerging technologies, should be explored to minimize the impact on the healthcare system. Our cost-effectiveness analysis shows that RefluxStop is highly likely to be a cost-effective management strategy for GERD patients in Norway. This novel device was predicted to have a beneficial effect on patient longevity particularly with the consideration of quality of life. This was demonstrated by the incremental gains in QALYs and LYs as compared with available treatment options in Norway (i.e., PPI-based medical management and laparoscopic Nissen fundoplication). More specifically, the base case ICER estimates were significantly below the Norwegian cost-effectiveness threshold of NOK 275,000 per QALY gained with additional sensitivity and scenario analyses indicating that these estimates were less likely to demonstrate large variation with the reasonable change in model inputs. Since the available sources present Norwegian cost-effectiveness thresholds ranging from NOK 275,000 to NOK 825,000 per QALY gained, and the ICER and probabilistic sensitivity analysis showed that RefluxStop was substantially below the lower threshold of NOK 275,000, this novel device can be considered as a highly cost-effective technology. Ultimately, the health benefits of RefluxStop balanced the additional costs from the Norwegian healthcare system perspective. Furthermore, the positive NHB and NMB values indicate that RefluxStop provides both health and monetary benefits relative to the available treatment options in Norway. With narrow focus on surgical options, RefluxStop was also estimated to have a lower rate of surgical complications as compared to laparoscopic Nissen fundoplication. Strengths and Limitations Cost-effectiveness analysis inherently includes a series of assumptions since it is generally not possible to measure all necessary parameters required for comprehensive analysis. In addition, even when measurements are available, they may not adequately represent values appropriate for the analysis at hand. The standard practice to address uncertainties surrounding assumption is the use of sensitivity analysis, which we have done. Much of the clinical data for RefluxStop in this analysis was obtained from a previously published CE mark trial [ 13 ] and unpublished data on file [ 19 ]. For comparator treatments, clinical data was obtained from available literature. However, these publications outlined incongruous population demographics and outcome measures compared with the RefluxStop CE mark trial (e.g., the definition of surgical failure was not uniform between studies). Thus, this analysis represents a naïve comparison. As with any health economic model, the results of this model represent the average patient care scenarios without incorporating exorbitant circumstances. Furthermore, presumptions are often required to facilitate health economic modeling when there is a paucity of informing data. As such, these factors contribute to the uncertainty associated with model results. Despite this, the uncertainties in our analysis were predominantly balanced by the robust results demonstrated by sensitivity analyses. Conclusions Given the substantial economic burden of GERD, optimization of resource allocation in the healthcare system requires innovation and subsequent validation through clinical and health economic studies. In Norway, emerging technologies such as MSA are not available, and patients are managed with long-established conventional modalities of treatment. When compared to treatment options available in Norway, RefluxStop is highly likely to be a cost-effective treatment alternative for those with GERD as evidenced by both health and monetary benefits. Abbreviations AE, adverse event; CKD, chronic kidney disease; CV, cardiovascular; DRG, diagnosis-related group; GERD, gastroesophageal reflux disease; HRQoL, health-related quality of life; ICER, incremental cost-effectiveness ratio; LY, life-year; MM, medical management; MSA, magnetic sphincter augmentation; NHB, net health benefit; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; NMB, net monetary benefit; NOK, Norwegian kroner; PPI, proton pump inhibitor; QALY, quality-adjusted life-year; RCT, randomized controlled trial; UK, United Kingdom. Declarations Ethics approval and consent for participation Ethics approval and consent for participation were not required for this study. Availability of data and materials All relevant data and sources are provided in the manuscript. Additional data used in the model is available upon request from the corresponding author. Competing interests SH and SM are employed by a consultancy company that was commissioned by Implantica to develop the model. MK is an employee of Implantica. None have personal conflicts to declare. LE and RG have no personal conflicts to declare. Funding There was no funding for this study. Author contributions SH, MK, and SM designed and developed the model. LE and RG contributed to the design of the model and validated the results from a clinical perspective. All authors contributed to the manuscript. Acknowledgements There are no relevant acknowledgements to declare for this manuscript. References Gisbert JP, Cooper A, Karagiannis D, Hatlebakk J, Agréus L, Jablonowski H, et al. Consultation rates and characteristics of gastro-oesophageal reflux disease in primary care: a European observational study. Eur J Gen Pract. 2009;15(3):154-60. Richter JE, Rubenstein JH. Presentation and Epidemiology of Gastroesophageal Reflux Disease. Gastroenterology. 2018;154(2):267-76. 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Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27(1):339-47. Sun X, Douiri A, Gulliford M. Pneumonia incidence trends in UK primary care from 2002 to 2017: population-based cohort study. Epidemiol Infect. 2019;147:e263. Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS One. 2015;10(6):e0128004. Public Health England. Clostridium difficile infection: mandatory surveillance 2017/18 2018 [Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/724368/CDI_summary_2018.pdf. Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107(7):1001-10. Brusselaers N, Wahlin K, Engstrand L, Lagergren J. Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden. BMJ Open. 2017;7(10):e017739. Skubleny D, Switzer NJ, Dang J, Gill RS, Shi X, de Gara C, et al. LINX(®) magnetic esophageal sphincter augmentation versus Nissen fundoplication for gastroesophageal reflux disease: a systematic review and meta-analysis. Surg Endosc. 2017;31(8):3078-84. Ainslie WG, Catton JA, Davides D, Dexter S, Gibson J, Larvin M, et al. Micropuncture cholecystectomy vs conventional laparoscopic cholecystectomy: a randomized controlled trial. Surg Endosc. 2003;17(5):766-72. Bouvy JC, Ebbers HC, Schellekens H, Koopmanschap MA. The cost-effectiveness of periodic safety update reports for biologicals in Europe. Clin Pharmacol Ther. 2013;93(5):433-42. Norwegian Medicines Agency Medicine Database. Norway [Internet] [Available from: https://www.legemiddelsok.no/. Augestad KM, Norum J, Dehof S, Aspevik R, Ringberg U, Nestvold T, et al. 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Cite Share Download PDF Status: Published Journal Publication published 29 Oct, 2025 Read the published version in Cost Effectiveness and Resource Allocation → Version 1 posted Editorial decision: Revision requested 06 Jul, 2025 Reviews received at journal 06 Jul, 2025 Reviewers agreed at journal 18 Jun, 2025 Reviews received at journal 15 Sep, 2024 Reviewers agreed at journal 30 Aug, 2024 Reviewers agreed at journal 29 Aug, 2024 Reviewers agreed at journal 25 Aug, 2024 Reviewers invited by journal 27 Jun, 2024 Editor assigned by journal 27 Jun, 2024 Submission checks completed at journal 27 Jun, 2024 First submitted to journal 26 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4643281","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":322093831,"identity":"35208365-101a-46b9-baff-7b66188c42cf","order_by":0,"name":"Sam Harper","email":"","orcid":"","institution":"York Health Economics Consortium","correspondingAuthor":false,"prefix":"","firstName":"Sam","middleName":"","lastName":"Harper","suffix":""},{"id":322093833,"identity":"5a1c7256-69e3-4fc1-9404-b8027c9baa07","order_by":1,"name":"Muralikrishnan Kartha","email":"data:image/png;base64,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","orcid":"","institution":"Implantica","correspondingAuthor":true,"prefix":"","firstName":"Muralikrishnan","middleName":"","lastName":"Kartha","suffix":""},{"id":322093835,"identity":"924cc137-baf5-4afd-8661-006d124a478c","order_by":2,"name":"Stuart Mealing","email":"","orcid":"","institution":"York Health Economics Consortium","correspondingAuthor":false,"prefix":"","firstName":"Stuart","middleName":"","lastName":"Mealing","suffix":""},{"id":322093836,"identity":"2c2b0fcd-efc5-4242-906d-af15ce6c3478","order_by":3,"name":"Lars Eftang","email":"","orcid":"","institution":"Akershus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lars","middleName":"","lastName":"Eftang","suffix":""},{"id":322093839,"identity":"cd5e7ac5-20d7-408d-8fc9-55e699864e84","order_by":4,"name":"Robin Gaupset","email":"","orcid":"","institution":"Akershus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Robin","middleName":"","lastName":"Gaupset","suffix":""}],"badges":[],"createdAt":"2024-06-26 14:05:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4643281/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4643281/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12962-025-00665-1","type":"published","date":"2025-10-29T15:57:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60711412,"identity":"f89b7b1e-3cf2-43b7-850d-959cf6e9b78d","added_by":"auto","created_at":"2024-07-19 20:18:31","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":79967,"visible":true,"origin":"","legend":"\u003cp\u003eModel structure applied to PPI-based medical management (panel A) and surgical treatment options (panel B)\u003c/p\u003e\n\u003cp\u003eAbbreviations: C. Diff, \u003cem\u003eClostridium difficile\u003c/em\u003e; CKD, chronic kidney disease; PPIs, proton pump inhibitors; reop, reoperation\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4643281/v1/040fe2bf9fb651fb1fe66b02.jpg"},{"id":60711413,"identity":"fbcf3131-c875-49a5-9c71-e454f7a9eb73","added_by":"auto","created_at":"2024-07-19 20:18:31","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":85873,"visible":true,"origin":"","legend":"\u003cp\u003eResults of the probabilistic sensitivity analyses against all three comparators presented as cost-effectiveness acceptability curves (panel A) and as a cost-effectiveness plane showing the spread of the individual iterations (panel B).\u003c/p\u003e\n\u003cp\u003eThe black line in panel B indicates the lower Norwegian cost-effectiveness threshold of NOK 275,000 per QALY. The points lying to the right of this line indicate iterations in which RefluxStop was cost-effective vs the assessed comparator (marked by the color of the individual points) and the points lying to the left of the black line indicate those iterations in which RefluxStop was not cost-effective.\u003c/p\u003e\n\u003cp\u003eAbbreviations: QALY, quality-adjusted life year.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4643281/v1/c99b0b78521e9b34f9c3a583.jpg"},{"id":95039848,"identity":"f6b3e799-79f4-4cda-b923-237e90468ac0","added_by":"auto","created_at":"2025-11-03 16:04:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1091478,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4643281/v1/e7b2663d-8879-4a71-acb3-d2169c2f5425.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost-effectiveness of RefluxStop compared to proton pump inhibitors and Nissen fundoplication for management of persistent gastroesophageal reflux disease in Norway","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eIn Western countries, one of the most common gastrointestinal conditions is gastroesophageal reflux disease (GERD), defined by reflux of gastric contents into the esophagus with troublesome symptoms at least once a week [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Characteristic symptoms include heartburn and regurgitation, which may considerably impair quality of life and reduce both work and leisure-time productivity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. GERD is associated with an increased risk of Barrett\u0026rsquo;s esophagus and progression to esophageal adenocarcinoma, particularly if left untreated [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn Norway, the prevalence of weekly GERD symptoms is estimated between 7.8% and 17.1% [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. More specifically, between 2006 and 2009, the prevalence of any reflux symptoms less frequently than once a week was as high as 40.9%, of which 6.7% were severe [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Moderate or severe regurgitation occurs in 24.2% of the population [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The mean annual incidence of severe symptoms has been reported to be 0.23% with a corresponding spontaneous loss of symptoms occurring at 1.22% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The relatively high prevalence in Norway makes GERD an important target for minimization of healthcare resource consumption.\u003c/p\u003e \u003cp\u003eThe primary treatment of GERD in Europe is medical therapy, with proton pump inhibitors (PPIs) most often representing the mainstay intervention [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Antireflux surgery is an alternative approach that should be considered in patients with severe symptoms or refractory disease despite optimally dosed medical therapy, particularly in young, healthy adults that would require long-term medical therapy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe usage of PPIs in Norway is lower in comparison to other European countries but has increased at a rate of 10% annually between 2003 and 2008 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The reason for less frequent use in comparison to the rest of Europe may be attributable to the prescription rules in Norway. Interestingly, a small proportion of Norwegian patients with GERD undergo antireflux surgery (0.7%), indicating that such procedures are not often employed in management [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, the overall number of surgeries has increased dramatically in recent decades [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRefluxStop is a novel implantable device that aims to manage persistent GERD by restoring the normal anatomy of the lower esophageal sphincter, gastroesophageal flap valve, and angle of His [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The approach employs a mechanism of action that expands on the rationale of traditional antireflux procedures with the added benefit of not compressing the food passageway. In a small prospective study, RefluxStop demonstrated 86% improvement in GERD Health-Related Quality of Life score at 1 year postoperatively with 98% of patients having normal pH values on 24-hour pH monitoring [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Furthermore, as a frequent complication of traditional antireflux procedures, new-onset dysphagia was not observed in patients managed with RefluxStop [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e This report presents the relative cost-effectiveness of RefluxStop, PPI-based medical management, and laparoscopic Nissen fundoplication for GERD management in Norway. Treating physicians should consider the results of this study to guide decision-making that optimize health benefits with healthcare resource consumption.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eTo compare RefluxStop with PPI-based medical management and Nissen fundoplication in adults with GERD, a cost-effectiveness analysis was performed. Endoscopic techniques and MSA are not available in Norway; thus, they were not included in the analysis. Clinical outcomes and costs assessed over a lifetime horizon were assessed from a Norwegian healthcare system perspective. Only direct medical costs were included without accounting for indirect societal costs (e.g., lost productivity). Quality-adjusted life-years (QALYs) were used to quantify clinical outcomes for the patient experience. All costs and QALYs were discounted at 4% per year, consistent with recent economic evaluations based on Norwegian perspective [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The analysis assumed a cycle length of 1 month with a half cycle correction applied. Any events in the model were presumed to occur in the middle of each month.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eModel Structure\u003c/h2\u003e \u003cp\u003eA Markov model was used in evaluation of the cost-effectiveness of RefluxStop. Model subjects went through a series of health states that were mutually exclusive representing possible outcomes of reflux disease management options. This cost-effectiveness analysis is an adaptation of a recently published study by Harper et al for the cost-effectiveness of RefluxStop from the United Kingdom National Health Service perspective [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], but has been applied to Norwegian settings. The variability in treatment mechanisms and pathways was reflected in the model framework for medical (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA) and surgical (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB) options. The structure of the model considered variable dosing (i.e., standard and double) of PPI therapy, medication irresponsiveness, primary surgery, secondary surgery (i.e., reoperation), progression to Barrett\u0026rsquo;s esophagus and cancer of the esophagus, and death. The model structure also included adverse events (AEs) related to all treatment arms.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eStandard-dose PPIs were presumed in all patients included in the medical management arm as first-line therapy (i.e., \u0026lsquo;Medical management well\u0026rsquo; state) with a potential of GERD relapse applicable every month. In the case of relapse, patients would be provided double-dose PPI therapy (i.e., \u0026lsquo;Medical management relapse\u0026rsquo; state) and if medication-based therapy works again then the patient could resume standard-dose PPI therapy (i.e., \u0026lsquo;Medical management well\u0026rsquo;) or if that doesn\u0026rsquo;t work patient may undergo antireflux surgery. As per the NICE-UK NHS recommendations, Nissen fundoplication was the intervention used in the surgical procedure arm of our model for comparison with RefluxStop [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. As MSA is currently not available in Norway, it was not included in the model. Primary (i.e., initial) surgery was the point of model entrance for all patients in the surgical treatment arms (i.e., RefluxStop and Nissen fundoplication). Postoperative states of the model included successful (i.e., \u0026lsquo;Surgery well\u0026rsquo;) and unsuccessful (i.e., \u0026lsquo;Surgery fail\u0026rsquo;). Unsuccessful surgery would lead to reoperation (i.e., \u0026lsquo;Surgery re-op\u0026rsquo;) or patients receiving double-dose PPI therapy (i.e., \u0026lsquo;Medical management high dose\u0026rsquo;), presumed persistent for the remainder of a patient\u0026rsquo;s life. The same procedure type as initial surgery was presumed for reoperation. In cases where reoperation also failed, patients would take higher-dose (i.e., double) PPI therapy for the remainder of their lives.\u003c/p\u003e \u003cp\u003eAll patients in the model (i.e., all treatment arms) were subject to Barrett\u0026rsquo;s esophagus development at a rate of 0.083% per month, and only patients with established Barrett\u0026rsquo;s esophagus carried an additional risk of progression to esophageal carcinoma at a rate of 0.06% per month. Norwegian general population mortality and mortality-associated health states were included in the model as outlined below.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eModel Inputs\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eClinical and Quality of Life Inputs\u003c/h2\u003e \u003cp\u003eA simulated group of 1,000 patients aged 52 years and older, of which 56% were male, were followed in the model, consistent with the CE mark trial of RefluxStop [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Such demographics are similar to trials for GERD treatments with large sample sizes, including the UK REFLUX trial [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and a US trial of treatments (i.e., medical and surgical) for refractory GERD [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Thus, these hypothetical patients accurately represent real-world patients that are likely candidates to undergo antireflux surgery. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents clinical and quality of life parameters.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and quality of life inputs used in the model.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInput\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRelapse of GERD symptoms with medical management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.65%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBojke 2007 [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eReoperation following unsuccessful surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSurgery following a relapse of medical management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAssumed to be the same as the probability in a case of reoperation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eProbability of surgical failure up to 1-year post-surgery\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKarolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished] [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImplantica data on file. RefluxStop CE mark study 3-year outcomes [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eProbability of surgical failure\u0026thinsp;\u0026ge;\u0026thinsp;1-year post-surgery\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKarolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished] [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImplantica data on file. RefluxStop CE mark study 3-year outcomes [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eProbability of surgical failure for reoperation or second-line treatment\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on treatment failure rates up to 1 year and post 1 year provided above.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on treatment failure rates up to 1 year and post 1 year provided above.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMonthly probability of Barrett\u0026rsquo;s esophagus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll treatment arms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.083%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNICE model developed to support clinical guidance development in dyspepsia and GERD [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRisk of adverse effects of PPIs\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCV events (MI or stroke)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on WHO CVD risk chart working group [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] and Shiraev 2018 [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on Collins 2012 [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] and Hussain 2019 [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on Kanis 2008 [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] and Zhou 2016 [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.08%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on Sun 2019 [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] and Lambert 2015 [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eClostridium difficile\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.001%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on \u003cem\u003eClostridium difficile\u003c/em\u003e infection: mandatory surveillance 2017/18 report [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e] and Janarthanan 2012 [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStomach cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.002%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBrusselaers 2017 [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIntraoperative adverse events related to surgery\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eConversion to open surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRefluxStop: 2.1%\u003c/p\u003e \u003cp\u003eNissen fundoplication: 1.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eImplantica data on file\u003c/p\u003e \u003cp\u003eKarolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished] [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSplenic injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRefluxStop: 0.0%\u003c/p\u003e \u003cp\u003eNissen fundoplication: 0.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGastro-esophageal injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRefluxStop: 0.0%\u003c/p\u003e \u003cp\u003eNissen fundoplication: 1.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLiver injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRefluxStop: 0.0%\u003c/p\u003e \u003cp\u003eNissen fundoplication: 1.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePost-operative adverse events related to surgery\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEndoscopic esophageal dilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRefluxStop: 0.0%\u003c/p\u003e \u003cp\u003eNissen fundoplication: 0.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImplantica data on file\u003c/p\u003e \u003cp\u003eSkubleny et al [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMajor complications requiring additional surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRefluxStop: 0.0%\u003c/p\u003e \u003cp\u003eNissen fundoplication: 1.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBjelovic et al [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEndoscopic device removal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRefluxStop: 0.0%\u003c/p\u003e \u003cp\u003eNissen fundoplication: N/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImplantica data on file\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eUtility decrement: Stable medical management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBased on Bojke 2007 [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] Norwegian (Sweden) population norms [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eUtility decrement: Medical management of GERD relapse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBojke 2007 [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eUtility decrement: Medical management high dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAssumed equal to stable medical management\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePost-surgery utility decrements (applied for 1 month)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBased on Bojke et al [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and originally sourced from Ainslie et al 2003 [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUtility decrements applied\u0026thinsp;\u0026ge;\u0026thinsp;1 month following successful surgery in the \u0026lsquo;Surgery well\u0026rsquo; state\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on utility decrement for dysphagia from Bouvy 2013 [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e] and the proportion reporting dysphagia at 3 years from the RefluxStop CE mark study (Implantica data on file) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalculated based on utility decrement for dysphagia from Bouvy 2013 [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e] and the proportion reporting dysphagia at 5 years from Karolinska Institute review [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUnsuccessful surgery utility decrements\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAssumed equal to Nissen fundoplication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBased on Grant 2008 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and Norwegian (Sweden) population norms [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUtility decrements associated with Barrett\u0026rsquo;s esophagus and esophageal cancer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBarrett\u0026rsquo;s esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePollit 2019 [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEsophageal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNICE model developed to support clinical guidance development in dyspepsia and GERD [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: C. Diff, \u003cem\u003eClostridium difficile\u003c/em\u003e; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; GERD, gastro-esophageal reflux disease; MI, myocardial infarction; NICE, National Institute for Health and Care Excellence; PPI, proton pump inhibitor; SSED, Summary of Safety and Effectiveness Data; WHO, World Health Organization\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe clinical data for RefluxStop was obtained from the CE mark trial [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] with addition of 3-year follow-up data on file [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The efficacy of medical therapy and Nissen fundoplication were obtained from published literature. Surgical failure was defined in two different periods (i.e., up to 1 year postoperatively and \u0026gt;\u0026thinsp;1 year postoperatively) for surgical interventions, meant to represent the reporting structures found in investigations for each option.\u003c/p\u003e \u003cp\u003eIntraoperative events and postoperative AEs were attributed to Nissen fundoplication and RefluxStop, regardless of whether an initial procedure or reoperation. The events considered for the model were obtained from a global literature review on Nissen fundoplication outcomes recently published [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. All those in the medical therapy arm were assumed to receive PPI therapy and a relevant proportion of patients in surgical arms (i.e., Nissen fundoplication and RefluxStop) were assumed to receive PPI therapy in the case of surgical failure. Patients were subject to long-term PPI-related AEs in all comparator arms of the model (i.e., PPI-based medical management, Nissen fundoplication, and RefluxStop), including \u003cem\u003eClostridium difficile\u003c/em\u003e (C.Diff) infection [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], community-acquired pneumonia [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], osteoporotic fractures [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], gastric cancer [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], chronic kidney disease (CKD) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and cardiovascular (CV) events [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. One-off events included osteoporotic fractures, gastric cancer, pneumonia, and C.Diff infection. Events like CKD and CV events were modelled using the proportion-in-state method. Thus, the rate of mortality from CKD and CV events was identical to the rate of complication development in PPI users.\u003c/p\u003e \u003cp\u003ePotential long-term complications of GERD include Barrett\u0026rsquo;s esophagus and esophageal carcinoma [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Barrett\u0026rsquo;s esophagus developed at a monthly rate of 0.083%, based on a model developed to produce NICE recommendations on GERD [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Patients in all treatment arms were subject to this risk. Furthermore, esophageal carcinoma occurred at a monthly rate of 0.06% in all those with Barrett\u0026rsquo;s esophagus, as per a systematic review and meta-analysis [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExcess mortality with surgery, esophageal cancer, and long-term PPI-related AEs were considered in addition to general population mortality, determining mortality in different treatment arms of the model. A small risk of intraoperative mortality (0.05%) was attributed to all primary surgeries across relevant model arms. Patients with esophageal carcinoma were assumed to have a monthly risk of death of 3.4% [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. All patients in medical therapy states regardless of model arm were subject to a relative mortality risk of 1.57, representing an increased risk of mortality from long-term PPI-related AEs [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. With these considerations, mortality estimation did not favor any of the model arms since risk estimates were uniformly applied for all arms.\u003c/p\u003e \u003cp\u003eUtility decrements were used to describe Health-Related Quality of Life (HRQoL). For those with successful surgery, utility decrements were based on the proportion of patients with persistent dysphagia as a possible AE after surgery. As such, a utility decrement value of 0.24 was applied for 1 month postoperatively for primary procedures and reoperations (i.e., Nissen fundoplication and RefluxStop). This was sourced from the impact on quality of life from laparoscopic cholecystectomy and the assumption of similarity between the procedures (i.e., both are elective laparoscopic procedures for benign conditions) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Cost-effectiveness analysis of PPI therapy and laparoscopic Nissen fundoplication for GERD, from the REFLUX trial, informed utility decrements in those taking PPIs [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Similarly, this analysis informed our model of the utility decrement related to Nissen fundoplication failure, which was presumed to similarly apply to RefluxStop [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Utility decrements were also applied to patients with Barrett\u0026rsquo;s esophagus and cancer of the esophagus. Since population norms for Norway were not available, the norms of Sweden were used based on the literature [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] assuming that the population norms will be at least similar due to the geographic, socioeconomic and cultural similarity. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e delineates the HRQoL inputs in the model.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eCost Inputs\u003c/h2\u003e \u003cp\u003eThe Norwegian DRG [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and published literature were sourced for cost information whenever possible. Values from older literature sources were inflated using a web-based cost conversion tool [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Key cost inputs are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eKey cost inputs applied in the model.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInput\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMedical and surgical treatment costs\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonthly cost of PPI medication (standard dose)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 153.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNoMA medicine database [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonthly cost of PPI medication (high dose)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 187.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNoMA medicine database [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcedure cost \u0026ndash; all surgical treatments\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 104,077.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase rate NOK 47,742 multiplied by cost weight 2.18 (155B) from Norwegian DRG [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDevice \u0026ndash; RefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 59,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eImplantica data on file [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTraining \u0026ndash; RefluxStop\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 225.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalculated based on Augestad et al 2013 [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e] and Palser 2018 [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBarrett\u0026rsquo;s esophagus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnostic endoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 3,341.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase rate NOK 4,7742 multiplied by cost weight 0.07 (711O) from Norwegian DRG [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment (endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 11,812.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalculated based on Pollit 2019 [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] and Base rate NOK 4,7742 multiplied by cost weight 0.12 (EMR 706O)* and 0.31(RFA 703O) from Norwegian DRG [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonthly monitoring cost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 320.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalculated based on the NICE model developed to support clinical guidance development in dyspepsia and GERD [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and Base rate NOK 47,742 multiplied by cost weight 0.12 (706O) from Norwegian DRG [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEsophageal cancer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial diagnostic and treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 185,034.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalculated based on the NICE model developed to support clinical guidance development in dyspepsia and GERD [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Base rate NOK 47,742 multiplied by cost weight 3.7 (155A) from Norwegian DRG [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and Pike et al 2013 [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePalliative care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 134,288.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBugge et al 2021 [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAdverse events associated with PPIs\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD monthly cost (including costs of treatment, hospitalization, and end-stage renal disease)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 8,160.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalculated based on Kerr 2012 [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e], Pike et al 2013 [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], Eriksson et al 2017 [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e], Kim et al 2022 [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e], and Kidneyfailurerisk.com [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonthly cost of CV events (MI or stroke)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 4,099.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eKim et al 2022 [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFracture (event cost)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 89,317.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAkehurst et al 2011 [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia (event cost)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 21,539.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalculated based on Nymark et al 2022 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], Lambert 2015 [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], NICE quality standard for pneumonia in adults [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC.Diff. infection (event cost)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 24,649.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCalculated based on Nordling et al 2014 [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e], the \u003cem\u003eClostridium difficile\u003c/em\u003e infection: mandatory surveillance 2017/18 report [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e], and costs of antibiotics as provided in NoMA medicine database [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStomach cancer (lifetime cost)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 111,091.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNICE technology appraisal of ramucirumab (TA378) [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAdverse events associated with surgery\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConversion to open surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 30,676.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLaudicella 2016 [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEsophageal dilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 5,729.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBase rate NOK 47,742 multiplied by cost weight 0.12 (706O)* from Norwegian DRG [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdditional surgery for major complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 104,077.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAssumed to be the same cost as the initial procedure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDevice removal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 104,077.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAssumed to be the same cost as the initial procedure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: C. Diff, \u003cem\u003eClostridium difficile\u003c/em\u003e; CKD, chronic kidney disease; CV, cardiovascular; GERD, gastro-esophageal reflux disease; MI, myocardial infarction; NICE, National Institute for Health and Care Excellence; PPI, proton pump inhibitor\u003c/p\u003e \u003cp\u003e*DRG cost weight for EMR and Esophageal dilation assumed similar to Therapeutic Endoscopy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePPI (i.e., omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole) and surgery costs were considered in our model. Surgical costs included: 1) device cost, procedure costs, and training costs for RefluxStop; and 2) only procedure costs for Nissen fundoplication as this technique does not require a device or additional training costs. The cost of performing the Nissen fundoplication procedure was identically applied to RefluxStop insertion procedures as it follows the similar standard approach for laparoscopy.\u003c/p\u003e \u003cp\u003eDiagnostic, treatment, and monthly management costs were incurred by patients with Barrett\u0026rsquo;s esophagus [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. All patients with Barrett\u0026rsquo;s esophagus underwent diagnostic endoscopy and were treated with endoscopic mucosal ablation and radiofrequency ablation in cases of dysplasia (16.6%), subsequently followed by endoscopic follow-up over two years with PPI therapy [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Those without dysplasia were assumed to have costs attributable to PPI therapy and endoscopic monitoring only [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Patients demonstrating progression to esophageal carcinoma followed the patient journey outlined by NICE clinical guidance in UK [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Initial diagnostic testing and treatment costs, (such as endoscopy, general practitioner visit, esophagectomy, and chemotherapy), monthly PPI costs, and terminal care costs (in those succumbing to illness) were applied to patients with esophageal carcinoma.\u003c/p\u003e \u003cp\u003eA monthly cost of management was presumed in patients with CKD or CV events related to PPI therapy. One-off events incurring costs included osteoporotic fractures, pneumonia, and C.Diff infection. A recurring cost was applied to patients with gastric cancer attributable to supportive care and chemotherapy.\u003c/p\u003e \u003cp\u003eCosts associated with surgery-related AEs included conversion to laparotomy, esophageal dilation, major surgical complications, and device removal. Injuries to the spleen, liver, or gastroesophageal anatomy during the intraoperative period were included in the costs of the operation itself.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eEconomic Analysis\u003c/h2\u003e \u003cp\u003eEstimates for QALYs per patient, life-years (LYs), life expectancy, and total costs were produced for each arm of the study. Incremental differences in these values between model arms were also generated. Incremental measures comparing treatment arms included: 1) incremental cost-effectiveness ratio (ICER), representing the cost per QALY gained; 2) incremental net health benefit (NHB); and 3) incremental net monetary benefit (NMB). In Norway, there is no exact cost-effectiveness threshold, and thus the maximum amount a decision-maker is willing to pay for a unit of health outcome is uncertain [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In the available literature, the range of Norwegian cost-effectiveness thresholds spans from NOK 275,000 to NOK 825,000 per QALY gained [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. To be conservative, our analysis utilized the lower cost-effectiveness threshold of NOK 275,000. NMB and NHB were calculating using a Norwegian cost-effectiveness threshold of NOK 275,000 per QALY gained. Positive incremental values for NMB or NHB are indicators that the management option benefits the healthcare system at the cost-effectiveness threshold. Furthermore, the magnitude of values demonstrates a positive correlation with benefit.\u003c/p\u003e \u003cp\u003eDeterministic sensitivity analyses were also performed to determine the uncertainty present in model results. Individual model inputs were varied in isolation with documentation of results to identify inputs with the most influence. The ranges in which model inputs varied were informed by reported confidence intervals (CIs), and in cases where relevant information was not available, assumptions were made. Model inputs which demonstrated uncertainty were sampled from plausible distributions in probabilistic sensitivity analyses. One-thousand iterations using varying input sets were performed. Available reported CIs were used to derive standard errors for generation of probabilistic values. Standard error was assumed to be 10% of the mean value when information was not available.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eBase Case Results\u003c/h2\u003e \u003cp\u003eUsing the cost-effectiveness threshold of NOK 275,000 per QALY gained, RefluxStop demonstrated cost-effectiveness against PPI-based medical management and laparoscopic Nissen fundoplication (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Patients in the RefluxStop arm of the model accrued 0.57 to 1.48 more QALYs than those in other model arms (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Specific to the surgical arm, RefluxStop compared favorably against Nissen fundoplication regarding surgical outcomes (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).These included the total number of surgeries, surgical failures, and necessity for postoperative endoscopic dilation. Due to less severe AEs, avoidance of disease progression related to sequelae, and the lower reoperation rate associated with RefluxStop, our model estimated a higher life expectancy in the RefluxStop arm versus all comparators, with differences of 0.45 to 0.73 years in favor of RefluxStop compared to PPI therapy and laparoscopic Nissen fundoplication, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCost-effectiveness outcomes estimated in the base case analysis, per patient.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSummary results\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedical management\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncremental\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncremental vs Nissen fundoplication\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCost per patient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNOK 188,223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNOK 86,999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNOK 101,224\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNOK 142,568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNOK 45,654\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQALYs per patient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife years per patient (undiscounted)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife years per patient (discounted)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIncremental cost-effectiveness ratio (ICER)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNOK 68,262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eNOK 79,543\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNet monetary benefit (NMB)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNOK 306,569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eNOK 112,185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNet health benefit (NHB)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical outcome estimates in the base-case analysis (per 1,000 patients unless otherwise stated)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical outcomes (per patient)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRefluxStop\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedical management\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIncremental vs Medical management\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNissen fundoplication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncremental vs Nissen fundoplication\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of people developing Barrett\u0026rsquo;s esophagus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of people developing esophageal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of surgeries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of surgical failures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of endoscopic dilations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of device removals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage life expectancy, years (per patient)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: C. Diff, \u003cem\u003eClostridium difficile\u003c/em\u003e; CKD, chronic kidney disease; PPIs, proton pump inhibitors; reop, reoperation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: QALY, quality-adjusted life year.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe ICERs of RefluxStop compared to PPI-based medical management and Nissen fundoplication were significantly below the lower Norwegian cost-effectiveness threshold (i.e., NOK 275,000 per QALY gained). The ICERs of RefluxStop were NOK 68,262 and NOK 79,543 per QALY gained against PPI-based medical management and laparoscopic Nissen fundoplication, respectively.\u003c/p\u003e \u003cp\u003eThe NHB and NMB of RefluxStop against all assessed comparators were positive values. That is, RefluxStop provided net health and monetary benefits, respectively. More specifically, RefluxStop had NHB values of 1.11 against PPI-based medical management and 0.41 against laparoscopic Nissen fundoplication, and NMB values of NOK 306,569 against PPI-based medical management and NOK 112,185 against laparoscopic Nissen fundoplication.\u003c/p\u003e \u003cp\u003eThe costs of RefluxStop were balanced by the lower costs of PPI therapy (i.e., savings of NOK 19,693.43 and NOK 6,541.27 vs. PPI-based medical management and Nissen fundoplication, respectively) and the costs of managing PPI-related AEs (i.e., savings of NOK 4,785.03 and NOK 1,345.77 vs. PPI-based medical management and Nissen fundoplication, respectively) to an extent. Pertaining to surgical outcomes and complications, RefluxStop provided per-patient lifetime savings compared with laparoscopic Nissen fundoplication (i.e., savings of NOK 1,458.51 for intraoperative events and sequelae necessitating operation, and NOK 3,146.95 for endoscopic dilation).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDeterministic Sensitivity Analysis\u003c/h2\u003e \u003cp\u003eThe most influential inputs in deterministic sensitivity analyses were the probabilities of surgical failure with RefluxStop and surgery after medical relapse (Supplementary Fig.\u0026nbsp;1). Variation of individual input parameters did not alter the orientation of results in the model with exception for the monthly failure rate of RefluxStop in juxtaposition with laparoscopic Nissen fundoplication. Thus, the results of our analysis were robust to variation of parameters overall. Finally, exploration of various cost estimates and risks of AEs did not significantly affect the long-term cost-effectiveness results of our study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eProbabilistic Sensitivity Analysis\u003c/h2\u003e \u003cp\u003eRefluxStop exhibited a high probability of being cost-effective at a Norwegian cost-effectiveness threshold of NOK 275,000. Probabilities of being cost-effective compared with PPI-based therapy and laparoscopic Nissen fundoplication were 100% and 92%, respectively. From probabilistic analyses in 1,000 iterations, the average ICERs obtained were like the base case ICERs against each of the comparators (i.e., NOK 72,271.86 per QALY when compared with PPI-based medical management and NOK 87,459.37 per QALY when compared with Nissen fundoplication). Most of the probabilistic iterations were significantly below the lower cost-effectiveness threshold of NOK 275,000 available from sources specific for Norway (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAs one of the most common gastrointestinal disorders in Western societies, GERD poses a significant burden on public health as prevalence continues to increase [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Despite a lack of clinical guidance specific to Norway, in line with the paradigms in the rest of Europe, medical management with PPI therapy is pursued [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Compared with other European countries, the use of PPIs in Norway is lower but has steadily increased at an approximate annual rate of 10% [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], likely increasing the overall cost of GERD treatment in the population. As an alternative to medical therapy, antireflux surgical procedures seem not to be used for management despite recent small increases in utilization [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. With the increasing prevalence of GERD, cost-effective management strategies, including emerging technologies, should be explored to minimize the impact on the healthcare system.\u003c/p\u003e \u003cp\u003eOur cost-effectiveness analysis shows that RefluxStop is highly likely to be a cost-effective management strategy for GERD patients in Norway. This novel device was predicted to have a beneficial effect on patient longevity particularly with the consideration of quality of life. This was demonstrated by the incremental gains in QALYs and LYs as compared with available treatment options in Norway (i.e., PPI-based medical management and laparoscopic Nissen fundoplication).\u003c/p\u003e \u003cp\u003eMore specifically, the base case ICER estimates were significantly below the Norwegian cost-effectiveness threshold of NOK 275,000 per QALY gained with additional sensitivity and scenario analyses indicating that these estimates were less likely to demonstrate large variation with the reasonable change in model inputs. Since the available sources present Norwegian cost-effectiveness thresholds ranging from NOK 275,000 to NOK 825,000 per QALY gained, and the ICER and probabilistic sensitivity analysis showed that RefluxStop was substantially below the lower threshold of NOK 275,000, this novel device can be considered as a highly cost-effective technology. Ultimately, the health benefits of RefluxStop balanced the additional costs from the Norwegian healthcare system perspective. Furthermore, the positive NHB and NMB values indicate that RefluxStop provides both health and monetary benefits relative to the available treatment options in Norway. With narrow focus on surgical options, RefluxStop was also estimated to have a lower rate of surgical complications as compared to laparoscopic Nissen fundoplication.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eCost-effectiveness analysis inherently includes a series of assumptions since it is generally not possible to measure all necessary parameters required for comprehensive analysis. In addition, even when measurements are available, they may not adequately represent values appropriate for the analysis at hand. The standard practice to address uncertainties surrounding assumption is the use of sensitivity analysis, which we have done. Much of the clinical data for RefluxStop in this analysis was obtained from a previously published CE mark trial [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and unpublished data on file [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. For comparator treatments, clinical data was obtained from available literature. However, these publications outlined incongruous population demographics and outcome measures compared with the RefluxStop CE mark trial (e.g., the definition of surgical failure was not uniform between studies). Thus, this analysis represents a na\u0026iuml;ve comparison. As with any health economic model, the results of this model represent the average patient care scenarios without incorporating exorbitant circumstances. Furthermore, presumptions are often required to facilitate health economic modeling when there is a paucity of informing data. As such, these factors contribute to the uncertainty associated with model results. Despite this, the uncertainties in our analysis were predominantly balanced by the robust results demonstrated by sensitivity analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eGiven the substantial economic burden of GERD, optimization of resource allocation in the healthcare system requires innovation and subsequent validation through clinical and health economic studies. In Norway, emerging technologies such as MSA are not available, and patients are managed with long-established conventional modalities of treatment. When compared to treatment options available in Norway, RefluxStop is highly likely to be a cost-effective treatment alternative for those with GERD as evidenced by both health and monetary benefits.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAE, adverse event; CKD, chronic kidney disease; CV, cardiovascular; DRG, diagnosis-related group; GERD, gastroesophageal reflux disease; HRQoL, health-related quality of life; ICER, incremental cost-effectiveness ratio; LY, life-year; MM, medical management; MSA, magnetic sphincter augmentation; NHB, net health benefit; NHS, National Health Service; NICE, National Institute for Health and Care Excellence; NMB, net monetary benefit; NOK, Norwegian kroner; PPI, proton pump inhibitor; QALY, quality-adjusted life-year; RCT, randomized controlled trial; UK, United Kingdom.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent for participation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval and consent for participation were not required for this study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll relevant data and sources are provided in the manuscript. Additional data used in the model is available upon request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSH and SM are employed by a consultancy company that was commissioned by Implantica to develop the model. MK is an employee of Implantica. None have personal conflicts to declare. LE and RG have no personal conflicts to declare.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding for this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSH, MK, and SM designed and developed the model. LE and RG contributed to the design of the model and validated the results from a clinical perspective. All authors contributed to the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere are no relevant acknowledgements to declare for this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGisbert JP, Cooper A, Karagiannis D, Hatlebakk J, Agr\u0026eacute;us L, Jablonowski H, et al. Consultation rates and characteristics of gastro-oesophageal reflux disease in primary care: a European observational study. Eur J Gen Pract. 2009;15(3):154-60.\u003c/li\u003e\n\u003cli\u003eRichter JE, Rubenstein JH. Presentation and Epidemiology of Gastroesophageal Reflux Disease. Gastroenterology. 2018;154(2):267-76.\u003c/li\u003e\n\u003cli\u003eVakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900-20; quiz 43.\u003c/li\u003e\n\u003cli\u003eWiklund I. 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BMJ Open. 2016;6(11):e012977.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cost-effectiveness-and-resource-allocation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cera","sideBox":"Learn more about [Cost Effectiveness and Resource Allocation](http://resource-allocation.biomedcentral.com)","snPcode":"12962","submissionUrl":"https://submission.nature.com/new-submission/12962/3","title":"Cost Effectiveness and Resource Allocation","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cost-effectiveness analysis, antireflux surgery, gastroesophageal reflux disease, proton pump inhibitors, cost utility, Markov model","lastPublishedDoi":"10.21203/rs.3.rs-4643281/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4643281/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eHeartburn, chest pain, and regurgitation are characteristics of gastroesophageal reflux disease. The standard treatment in Norway is proton pump inhibitors (PPIs), but surgical alternatives such as Nissen fundoplication are pursued when medical management proves ineffective. RefluxStop is an implantable device presenting a new approach to restoration of the antireflux barrier. The aim of this study is to evaluate the cost-effectiveness of RefluxStop, Nissen fundoplication, and PPI-based medical management (MM) in Norway.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA Markov model was adapted from a published cost-effectiveness analysis developed for the UK NHS assessing the cost-effectiveness of RefluxStop in comparison with PPI-based MM and Nissen fundoplication. The perspective of the Norwegian healthcare payer, lifetime horizon, one-month cycle length, and a 4% annual discount rate for costs and health-benefits were used. Health states included in the model were initial MM, MM relapse, follow-on surgery, reoperations, MM with a higher dose, Barrett\u0026rsquo;s esophagus, esophageal cancer, and death. Adverse events related to MM and surgeries were included with benefits measured in quality-adjusted life-years (QALYs). Norwegian diagnostic-related group tariffs and literature were used as sources for unit costs. Clinical efficacy data for RefluxStop was based on an ongoing clinical study and comparator treatments were informed by published studies. Deterministic and probabilistic sensitivity analyses were used to address uncertainty of the parameter estimates.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eCompared to PPI-based MM and Nissen fundoplication, the base case incremental cost-effectiveness ratios (ICERs) of RefluxStop were NOK 68,262 and NOK 79,543 per QALY gained, respectively. The results of the model were robust to variation in individual inputs with exception of monthly failure rate of RefluxStop relative to Nissen fundoplication. RefluxStop demonstrated a significantly high probability of cost-effectiveness at the cost-effectiveness threshold of NOK 275,000 per QALY gained, with probabilities of 100% and 92% against PPI-based MM and Nissen fundoplication, respectively.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe RefluxStop device is highly likely to be cost-effective compared to PPI-based MM and Nissen fundoplication in Norway. Further study is required to assess the real-world long-term safety and efficacy of this novel device.\u003c/p\u003e","manuscriptTitle":"Cost-effectiveness of RefluxStop compared to proton pump inhibitors and Nissen fundoplication for management of persistent gastroesophageal reflux disease in Norway","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 20:18:26","doi":"10.21203/rs.3.rs-4643281/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-06T14:46:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-06T05:05:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"91065241435261193695524006562808916462","date":"2025-06-18T21:08:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-16T01:15:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100713566904832495697345556235430981867","date":"2024-08-30T06:00:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"320074979919430526212265879506232373660","date":"2024-08-29T16:15:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"168557736527805961756760292038164453404","date":"2024-08-25T19:42:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-27T21:14:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-27T14:24:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-27T14:23:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cost Effectiveness and Resource Allocation","date":"2024-06-26T14:04:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cost-effectiveness-and-resource-allocation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cera","sideBox":"Learn more about [Cost Effectiveness and Resource Allocation](http://resource-allocation.biomedcentral.com)","snPcode":"12962","submissionUrl":"https://submission.nature.com/new-submission/12962/3","title":"Cost Effectiveness and Resource Allocation","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5db6c3bf-5751-489c-b6de-e1a90f3237bc","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T15:59:43+00:00","versionOfRecord":{"articleIdentity":"rs-4643281","link":"https://doi.org/10.1186/s12962-025-00665-1","journal":{"identity":"cost-effectiveness-and-resource-allocation","isVorOnly":false,"title":"Cost Effectiveness and Resource Allocation"},"publishedOn":"2025-10-29 15:57:03","publishedOnDateReadable":"October 29th, 2025"},"versionCreatedAt":"2024-07-19 20:18:26","video":"","vorDoi":"10.1186/s12962-025-00665-1","vorDoiUrl":"https://doi.org/10.1186/s12962-025-00665-1","workflowStages":[]},"version":"v1","identity":"rs-4643281","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4643281","identity":"rs-4643281","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}