Cost-effectiveness of the RefluxStop device for management of refractory gastroesophageal reflux disease in Switzerland

Figures & data

Figure 1. Model structure applied to PPI-based medical management (A) and surgical treatment options (B).

Abbreviations: C. Diff, Clostridium difficile; CKD, chronic kidney disease; PPIs, proton pump inhibitors; reop, reoperation.

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 et al. (2007)^17
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 [unpublished]^18
RefluxStop	0.3%	Implantica data on file. RefluxStop CE mark study 3-year outcomes^19
LINX	5.8%	LINX SSED^20
Probability of surgical failure ≥1-year post-surgery
Nissen fundoplication	1.8%	Karolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished]^18
RefluxStop	0.1%	Implantica data on file. RefluxStop CE mark study 3-year outcomes^19
MSA	0.6%	LINX SSED^20
Probability of surgical failure for reoperation or second-line treatment
Nissen fundoplication/MSA	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^21
Risk of adverse effects of PPIs
CV events (MI or stroke)	0.01%	Calculated based on WHO CVD risk chart working group^22 and Shiraev 2018^23
CKD	0.01%	Calculated based on Collins and Altman (2012)^24 and Hussain et al. (2019)^25
Fracture	0.02%	Calculated based on Kanis et al. (2008)^26 and Zhou et al. (2016)^27
Pneumonia	0.08%	Calculated based on Sun et al. (2019)^28 and Lambert et al. (2015)^29
Clostridium difficile	0.001%	Calculated based on Clostridium difficile infection: mandatory surveillance 2017/18 report^30 and Janarthanan et al. (2012)^31
Stomach cancer	0.002%	Brusselaers et al. (2017)^32
Intraoperative adverse events related to surgery
Conversion to open surgery	RefluxStop: 2.1% Nissen fundoplication: 1.7% MSA: 0.0%	Implantica data on file^19 Karolinska Institute. Literature review and analysis: Laparoscopic Nissen Fundoplication. [unpublished]^18
Splenic injury	RefluxStop: 0.0% Nissen fundoplication: 0.9% MSA: 0.0%
Gastroesophageal injury	RefluxStop: 0.0% Nissen fundoplication: 1.0% MSA: 0.0%
Liver injury	RefluxStop: 0.0% Nissen fundoplication: 1.4% MSA: 0.0%
Post-operative adverse events related to surgery
Endoscopic esophageal dilation	RefluxStop: 0.0% Nissen fundoplication: 0.3% MSA: 0.1%	Implantica data on file^19 Skubleny et al.^10 LINX SSED^20
Major complications requiring additional surgery	RefluxStop: 0.0% Nissen fundoplication: 1.4% MSA: 0.5%	Bjelovic et al. (2020)^11 NICE Interventional Procedures Guidance on LINX (IPG585)^33
Endoscopic device removal	RefluxStop: 0.0% Nissen fundoplication: N/A MSA: 0.0%	Implantica data on file^19 Alicuben et al. (2018)^34
Utility decrement: Stable medical management	0.12	Based on Bojke et al. (2007)^17 Swiss population norms^35
Utility decrement: Medical management of GERD relapse	0.28	Bojke et al. (2007)^17
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. (2007)^17 and originally sourced from Ainslie et al. (2003)^36
Nissen fundoplication	0.24
MSA	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 et al. (2013)^37 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 et al. (2013)^37 and the proportion reporting dysphagia at 5 years from Karolinska Institute review^18
MSA	0.02	Calculated based on utility decrement for dysphagia from Bouvy et al. (2013)^37 and the proportion reporting dysphagia using an average from three MSA studies^20^,^38^,^39
Unsuccessful surgery utility decrements
RefluxStop	0.16	Assumed equal to Nissen fundoplication
Nissen fundoplication	0.16	Based on Grant et al. (2008)^15 and Swiss population norms^35
MSA	0.16	Assumed equal to Nissen fundoplication
Utility decrements associated with Barrett’s esophagus and esophageal cancer
Barrett’s esophagus	0.10	Pollit et al. (2019)^40
Esophageal cancer	0.44	NICE model developed to support clinical guidance development in dyspepsia and GERD^21

Abbreviations: C. Diff, Clostridium difficile; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; GERD, gastroesophageal 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.

Table 2. Key cost inputs applied in the model.

Parameter	Input	Source
Medical and surgical treatment costs
Monthly cost of PPI medication (standard dose)	CHF 51.54	SFO Spezialitätenliste^51
Monthly cost of PPI medication (high dose)	CHF 62.35	SFO Spezialitätenliste^51
Procedure cost – all surgical treatments	CHF 13,998	Average base rate CHF 9,694 for Bern canton multiplied by cost weight 1.444 from Swiss DRG^48
Device – RefluxStop	CHF 6,700	Implantica data on file^19
Device – MSA	CHF 5,170	Implantica data on file^18
Training – RefluxStop and MSA	CHF 25.81	Calculated based on Buyukkaramikli et al. (2020)^52 and Palser et al. (2018)^53
Barrett’s esophagus
Diagnostic endoscopy	CHF 6,912	Average base rate CHF 9,694 for Bern canton multiplied by cost weight 0.713 from Swiss DRG^48
Treatment (endoscopic mucosal ablation and radiofrequency ablation)	CHF 11,228	Calculated based on Pollit et al. (2019)^40 and average base rate CHF 9,694 for Bern canton multiplied by cost weight 0.663 from Swiss DRG^48
Monthly monitoring cost	CHF 253.13	Calculated based on the NICE model developed to support clinical guidance development in dyspepsia and GERD^21, and average base rate CHF 9,694 for Bern canton multiplied by cost weight 0.713 from Swiss DRG^48
Esophageal cancer
Initial diagnostic and treatment	CHF 21,920	Calculated based on the NICE model developed to support clinical guidance development in dyspepsia and GERD^21, average base rate CHF 9,694 for Bern canton multiplied by cost weight 2.11 from Swiss DRG^48^,^52
Palliative care	CHF 17,904	Panje et al. (2020)^13
Adverse events associated with PPIs
CKD monthly cost (including costs of treatment, hospitalization, and end-stage renal disease)	CHF 676.39	Calculated based on Kerr et al. (2012)^54, Buyukkaramikli et al. (2020)^52, Gandjour et al. (2002)^55, Blach et al. (2019)^56, Fischer et al. (2022)^57, Sandoz et al. (2004)^58, and Kidneyfailurerisk.com^59
Monthly cost of CV events (MI or stroke)	CHF 2,276.50	Wieser et al. (2012)^60
Fracture (event cost)	CHF 21,262.36	Svedbom et al. (2013)^61
Pneumonia (event cost)	CHF 4,068.89	Calculated based on Keitel et al. (2014)^62, Lambert et al. (2015)^29, NICE quality standard for pneumonia in adults^63
C.Diff. infection (event cost)	CHF 3,183.60	Calculated based on Pillai et al. (2019)^64, the Clostridium difficile infection: mandatory surveillance 2017/18 report^30, and costs of antibiotics as provided in SFO Spezialitätenliste^51
Stomach cancer (lifetime cost)	CHF 15087.95	NICE technology appraisal of ramucirumab (TA378)^65
Adverse events associated with surgery
Conversion to open surgery	CHF 4,166.22	Laudicella et al. (2016)^66
Esophageal dilation	CHF 6,427	Average base rate CHF 9,694 for Bern canton multiplied by cost weight 0.663 from Swiss DRG^48
Additional surgery for major complications	CHF 13,998	Assumed to be the same cost as the initial procedure.
Device removal	CHF 13,998	Assumed to be the same cost as the initial procedure.

Abbreviations: C. Diff, Clostridium difficile; CKD, chronic kidney disease; CV, cardiovascular; GERD, gastroesophageal reflux disease; MI, myocardial infarction; NICE, National Institute for Health and Care Excellence; PPI, proton pump inhibitor.

Table 3. Cost-effectiveness outcomes estimated in the base case analysis, per patient.

Summary results	RefluxStop	Medical management	Incremental vs Medical management	Nissen fundoplication	Incremental vs Nissen fundoplication	MSA	Incremental vs MSA
Cost per patient	CHF 33,780	CHF 27,493	CHF 6,286	CHF 33,844	–CHF 65	CHF 42,715	–CHF 8,936
QALYs per patient	17.55	14.58	2.97	16.51	1.04	14.81	2.75
Life years per patient (undiscounted)	33.99	32.85	1.14	33.44	0.55	32.48	1.52
Life years per patient (discounted)	20.96	20.49	0.48	20.75	0.21	20.36	0.60
Incremental cost-effectiveness ratio (ICER)		CHF 2,116		Dominant		Dominant
Net monetary benefit (NMB)		CHF 290,785		CHF 104,433		CHF 283,854
Net health benefit (NHB)		2.91		1.04		2.84

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	MSA	Incremental vs MSA
Number of people developing Barrett’s esophagus	0.29	0.28	0.01	0.28	0.01	0.27	0.01
Number of people developing esophageal cancer	0.04	0.04	0.00	0.04	0.00	0.04	0.00
Number of surgeries	1.03	0.57	0.45	1.05	−0.02	1.09	−0.06
Number of surgical failures	0.28	0.28	0.00	0.53	−0.25	0.95	−0.67
Number of endoscopic dilations	0.00	0.35	−0.35	0.93	−0.93	0.42	−0.42
Number of device removals	0.00	0.00	0.00	0.00	0.00	0.01	−0.01
Average life expectancy, years (per patient)	39.00	37.73	1.27	38.27	0.73	37.27	1.73

Figure 2. Results of the probabilistic sensitivity analyses against all three comparators presented as cost-effectiveness acceptability curves (A) and as a cost-effectiveness plane showing the spread of the individual iterations (B).

The black line in (B) indicates the Swiss cost-effectiveness threshold of CHF 100,000 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.

Abbreviations: QALY, quality-adjusted life year.

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