A 21st-Century-Cures Compliant LCD (Detailed Rationale)

21st Century Cures Act required LCD to have an evaluation of evidence submitted and a rationale for the decision.

In the LCD clipped below, released on October 13, 2017, the NGS MAC has taken this guidance seriously and released a detailed evidence evaluation in its LCD decision.  This decision compiles two reconsideration requests into one revised LCD.

The LCD mimics the "objective/subjective" sequential format used in modern NCDs, where the "evidence" is listed and described first, and then a summary and executive conclusion that a decision can be made on the evidence, and what it is.

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https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=35080&ContrId=310&ver=30&ContrVer=1&CntrctrSelected=310*1&Cntrctr=310&name=&DocType=Future&s=24&LCntrctr=180*1&bc=AggAAAQAAAAAAA%3d%3d& 

L35080 NGS MAC

Released 10/16/2017, effective 12/1/2017

Coverage Indications, Limitations, and/or Medical Necessity

Indications:

EsophyX™ is a device for performing transoral incisionless fundoplication surgery (TIF) for treating gastroesophageal reflux disease. This procedure reconstructs the valve at the top of the stomach that helps prevents acid reflux.
Benefits are not available for endoluminal treatment for Gastroesophageal Reflux Disease (GERD) using the Stretta® procedure, the Bard EndoCinch™ Suturing System, Plicator™, Enteryx® or similar treatments as these procedures are not considered reasonable and necessary for the diagnosis or treatment of an injury or disease. Benefits are not available for LINX® Reflux Management System, which is not a true endoluminal treatment but is also not considered reasonable and necessary for the diagnosis or treatment of an injury or disease.

Currently, these procedures other than TIF are considered non-covered due to the fact that current peer-reviewed literature does not support the long-term efficacy and long-term safety of the services. Claims will be denied as "not proven effective."

Limitations:

For TIF, Coverage is not extended to:

1. any patient who has recurrent symptoms or other evidence of failure following a prior TIF. These procedures (repeat TIF) would be considered investigational at this time.
2. any patient in which a staged procedure is being done, as described as a laparoscopic esophageal or paraesophageal diaphragmatic hernia / opening closure followed by a TIF endoscopically.
3. any patient who has a preoperative hiatal hernia greater than 2 cm (this is because the FDA label for this device is for GERD associated with hiatal hernia of equal or less than 2 cm. Use in patients who have preoperative larger hiatal hernias is not appropriate without a change in the FDA approval/label.)
4. any GERD patients with BMI > 35, esophagitis LA grade >B, Barrett’s esophagus > 2 cm, and presence of achalasia or esophageal ulcer or has not been on an appropriate trial of proton pump inhibitors.

Summary of Evidence

Summary of evidence for TIF: 

As noted above, transoral incisionless fundoplication surgery is a method for treating gastroesophageal reflux disease. This procedure reconstructs the valve at the top of the stomach that helps prevents acid reflux. 

1. Anti-Reflux Surgery Supplement to Endogastric Solutions TIF ESOPHYX Reconsideration Request NGS MAC, April 2017.  This is not a peer-reviewed publication but a summary of what the procedure is and a summary of selective publications.   Thus this is not a peer-reviewed publication indexed in the U.S. National Library of Medicine of the National Institutes of Health and thus not valid as supportive literature.
2. Hakansson B., Montgomery M., Cadiere G, et al. Randomised clinical trial: transoral incisionless fundoplication vs. sham intervention to control chronic GERD. Alimentary Pharmacology and Therapeutics. 2015 John Wiley & Sons Ltd.  This publication is indexed in the U.S. National Library of Medicine of the National Institutes.   The study was blinded and divided equally into TIF and sham procedures.  While the follow up period was only six (6) months, the time (average days) in remission offered by the TIF procedure (197) was significantly longer compared to those submitted to the sham intervention (107), P < 0.001. After 6 months 13/22 (59%) of the chronic GERD patients remained in clinical remission after the active intervention. Likewise, the secondary outcome measures were all in of the TIF2 procedure. No safety issues were raised. 
3. Stefanidis G, Viazis N, Kotsikoros N, Long-term benefit of transoral incisionless fundoplication using the esophyx device for the management of gastroesophageal reflux disease responsive to medical therapy.  Diseases of the Esophagus (2017) 30, 1–8.  This publication is indexed in the U.S. National Library of Medicine of the National Institutes of Health.  The study initially had 45 patients who had the TIF procedure and were followed for a mean of 59 months (range 36–75). Only one patient had a complication during surgery and thus was excluded.   The 44 patients all had follow-up upper endoscopy at 6 months, 1 year, and 3–5 years postoperatively.  (72.7%) that completed the study follow up reported elimination of their main symptom, without the need for PPI administration (none PPI usage). Six more patients (13.6%), five with heartburn, and one with regurgitation reported half PPI dose taken for <50% of the preceding follow up period (occasional PPI usage), while six more patients (four with heartburn, one with regurgitation, and one with chest pain) reported full or half PPI dose taken for more than 50% of the preceding follow up period (daily PPI usage). This paper supports the procedure.
4. Technology Coverage Statement on Minimally Invasive Surgical Options for Gastroesophageal Reflux Disease April 2016.  This is a position paper from the American Gastrological Association based on its reviews of TIF publications.  It is strongly supportive.
5. Clinical Spotlight Review: Endoluminal Treatments for Gastroesophageal Reflux Disease (GERD)sages.org/publications/guidelines/endoluminal-treatments-for-gastroesophageal-reflux-disease-gerd.  This is a statement from the Board of Governors of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) on Mar 2017.  Its recommendation is: Based on existing evidence, TIF can be performed with an acceptable safety risk in appropriately selected patients. The procedure leads to better control of GERD symptoms compared with PPI treatment in the short term (6 months), but appears to lose effectiveness during longer term follow-up and is associated with moderate patient satisfaction scores. Objective GERD measures improve similarly after TIF 2.0 compared with PPI. No comparative, controlled trials exist between TIF and surgical fundoplication, but preliminary evidence suggests that the latter can be used safely after TIF failure. (Per SAGES, this is level of evidence +++, strong recommendation)
6. Vaezi M, Bril J, Mills M, et al.  An Episode Payment Framework for Gastroesophageal Reflux Disease.  Gastroenterology 2016;150:1019–1025.  This is an economic and coding paper and not a clinical paper.  It is not supportive. 
7. Hunter JG, Kahrilas PJ, Bell RCW, et al. Gastroenterology. 2015 Feb;148(2):324-333.  The largest RCT with the lowest risk of bias is an industry-sponsored double-blind sham controlled multicenter study (RESPECT) that evaluated transoral fundoplication in patients whose symptoms were not well-controlled on proton pump inhibitors (PPIs).10 Out of 696 patients screened, 129 met inclusion and exclusion criteria and were randomized in a 2:1 ratio; 87 patients received transoral fundoplication combined with six months of placebo and 42 patients received sham surgery with six months of daily PPI therapy (sham/PPI).  Control of esophageal pH improved after TF (mean 9.3% before and 6.3% after; P < .001), but not after sham surgery (mean 8.6% before and 8.9% after). This is supportive.
8. Bell RCW, Barnes WE, Carter BJ, et al. Transoral incisionless fundoplication: 2-year results from the prospective multicenter U.S. study. AM Surg. 2014 Nov;80(11);1093-1105.  This 24-month follow-up has been reported from a prospective multicenter registry of patients with chronic GERD who received transoral fundoplication using the EsophyX2 system with SerosaFuse fasteners. For the 100 consecutive patients who were treated in this community-based study, the median GERD symptom duration was nine years (range, one to 35 years), the median duration of PPI use was seven years (range, one to 20 years), and 92 percent of patients had incomplete symptom control despite maximal medical therapy.  This three-year study provides evidence to demonstrate sustainable improvement in health outcomes, symptom relief, decrease in PPI utilization and improvement in esophageal pH with transoral fundoplication.  This is supportive. 

Summary of evidence for Stretta®:

The Stretta® procedure is an endoluminal treatment for GERD in which radiofrequency energy is delivered to smooth muscle of the lower esophageal sphincter (LES). A flexible catheter equipped with special needle electrodes for precise energy delivery is placed by mouth into the esophagus and carefully controlled radiofrequency energy is then delivered to the LES and gastric cardia, creating thermal lesions. The manufacturer maintains that the changes that occur immediately, and over time, result in a "tighter" LES and a less compliant gastric cardia. Additionally, the interruption of nerve pathways in the LES area is believed to reduce the incidence of inappropriate LES "relaxations," leading to an improvement in GERD symptoms. Substantial peer-reviewed evidence to fully support these assumptions needs to be published.

Summary of evidence for EndoCinch™ Suturing System and the Plicator™:

The Bard EndoCinch™ Suturing System and the Plicator™ are intended for use in endoscopic placement of suture(s) in the soft tissue of the esophagus and stomach and for approximation of tissue for treatment of symptomatic gastroesophageal reflux disease. Substantial peer-reviewed evidence to fully support these assumptions needs to be published.

Summary of evidence for Enteryx®:

Enteryx® is an endoscopic, minimally-invasive procedure in which an ethylene vinyl alcohol polymer solution is injected into one's lower esophageal sphincter muscle using a small needle. This product was recalled by the FDA in September 2005 due to adverse patient events. 

Summary of evidence for LINX® Reflux Management System:

LINX® Reflux Management System - a sphincter augmentation device designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES). The system is comprised of a small flexible band of 10 to 18 interlinked titanium beads with magnetic cores. Using standard laparoscopic techniques, the band is placed around the esophagus at the level of the gastroesophageal junction. The magnetic attraction between the beads is intended to augment the lower esophageal sphincter to prevent gastric reflux into the esophagus without compressing the esophageal wall. Unlike the other procedures mentioned, this is extraluminal, not intraluminal.

1. Saino et al. (2015) reported five-year results on the 44 implant procedures of the magnetic sphincter augmentation (MAS) first performed in the world. Safety and efficacy were evaluated in a prospective, multicenter study with patients serving as their own controls. Thirty-three of the 44 patients (75%) were followed-up at five years. Enrolled patients had an abnormal esophageal pH on ambulatory monitoring, typical GERD symptoms, had been taking daily PPIs, and were between 18 and 75 years of age. Patients were excluded if they had a large hiatal hernia (> 3 cm), Grade B or higher esophagitis (Los Angeles scale), a body mass index (BMI) > 35 kg/m2, Barrett’s esophagus, motility disorders, gross esophageal anatomic abnormalities, or an allergy to titanium, stainless steel, nickel, or ferrous materials. Mean total of time the esophageal pH was < 4 was 11.9% at baseline and 4.6% at five years (P<.001), with 85% (28) of patients achieving a normal pH or a 50% reduction. Mean total GERD-HRQL scores improved from 25.7 to 2.9 (P<.001). Complete discontinuation of PPIs was achieved by 87.8% of patients. Most patients (90.9%) were satisfied with their condition at five years versus none at baseline. Side effects such as gas bloat and difficulty swallowing were no worse after the procedure. There were no long-term complications but there were three of the 44 patients (86.8%) that had a serious adverse event which resolved. Three devices were removed. Limitations of the study were noted as lack of a comparison group, loss of patients during the five-year follow-up, and lack of pH monitoring at all sites after the first year.
2. Ganz et al. (2015) (in press) performed a prospective study of MAS safety and efficacy in the 100 adults who had GERD for six months or more, were partially responsive to daily proton pump inhibitors (PPIs), and had evidence of pathologic esophageal acid exposure. Exclusion criteria included a hiatal hernia > 3 cm, grade C or D esophagitis (Los Angeles scale), BMI > 35, Barrett’s esophagus, or motility disorder. Eight-five patients in 14 centers in the United States and The Netherlands were followed for five years serving as their own controls. The GERD-HRQL questionnaire was performed at baseline on and off PPIs and after the placement of the device. A 50% or great reduction occurred in 83% at five years and a 50% or more reduction of PPI use occurred in 89.4%. Daily use of PPIs was 100% at baseline and 15.3% at five years with 75.3% reporting no use. All patients reported the ability to belch and vomit with no change in dysphagia. Symptoms of bloating/gas decreased from 52% to 8.3%. No device erosions occurred; seven percent (7%) were removed. Limitations of the study were stated as lack of esophageal pH testing and manometry beyond one year and no comparison group.
3. Warren et al. (2015) performed a retrospective cohort study of patients with GERD undergoing placement of the MAS or a Nissen fundoplication (NF) at three high-volume esopohageal centers. Inclusion criteria included age of 18 – 85 years, a documented history of GERD at least partially responsive to PPIs, and positive pH testing. Excluded were those with a prior history of gastric or esophageal surgery, a hiatal hernia > 3cm, esophageal dysmotility and/or distal esophageal amplitude of < 35 mm Hg, and the visible presence of Barrett’s or esophageal stricture. There were a total of 415 patients (201 MSA and 214 NF) compared at one year post-procedure. Although the patients were similar in age and gender, the NF patients had higher BMIs (40 vs. 32), dysphagia (39 vs. 27) DeMeester scores (39 vs. 34), microscopic Barrett’s (31% vs 18%) and hiatal hernia (69% vs. 55%). At a one-year follow-up 354 patients (169 MSA and 185 NF) had significant improvement in GERD-HRQL scores. MSA patients had a greater ability to belch and vomit with less gas bloat. Propensity matched cases (144) showed similar GERD-HRQL scores. The differences in ability to belch or vomit and gas bloat persisted in favor of MSA but mild dysphagia was higher for MSA as was resumption of daily PPIs (24 vs. 12, p = 0.02) Satisfaction rates were similar. There were no deaths and no significant differences in postoperative minor and major morbidities. Two patients had the MSA device removed and two had an NF revision. Study limitations included its retrospective nature and being performed in high-volume esophageal centers may limit its application to other centers.
4. Reynolds et al. (2015) retrospectively compared charges, complications, and outcomes at one year for 119 patients undergoing MSA (54) or NF (67). Follow-up data were available for 48/52 (92%) of the MSA patients and 59/67 (88%) of the NF patients. There were no significant differences between charges, mean GERD-HRQL, or freedom from PPIs. MSA patients had a shorter operating room time and length of stay, reported less gas bloat symptoms and inability to belch or vomit. Two 30-day complications occurred in the NF group but were resolved. Noted limitations were that the study was not powered to detect a difference in PPI use and charges versus costs were compared. It was concluded that MSA might be an alternative for “gap” patients who are those having residual symptoms on PPIs but not having complicated GERD or complete lower esophageal sphincter (LES) failure.

Analysis of Evidence

(Rationale for Determination)

Gastroesophageal reflux disease (GERD) is mostly treated by medical management. As outlined in the ACG Practice Guidelines (updated in 2005) many patients are treated by empirical therapy, without the use of endoscopy. However some patients require additional diagnostic studies and interventions. The Practice Guidelines discusses the historical controversy of medical vs. surgical intervention but did establish the following two treatment guidelines: 

• Antireflux surgery, performed by an experienced surgeon, is a maintenance option for the patient with well-documented GERD.
• Endoscopic therapy controls symptoms in selected patients with well-documented GERD. 

These guidelines note anti-reflux surgery, performed by an experienced surgeon, is a maintenance option for the patient with well documented GERD. In these guidelines endoscopic therapy for GERD was discussed, pointing out there are three broad categories of endoscopic therapy: ‘radiofrequency application to the LES area, techniques designed to decrease reflux using endoscopic sewing devices, and techniques using an injection into the LES region.’ The guidelines also raised remaining issues, including: long-term durability, efficacy in atypical presentation of GERD patients, and efficacy of these procedures performed outside of clinical trials.  

Transoral Incisionless Fundoplication (TIF):

Since these guidelines were updated in 2005, a newer endoscopic suturing technique has emerged in the literature. Transoral Incisionless Fundoplication (TIF) is an endoscopic technique.  At present, the only such device currently on the market is the ExophyX^TM. The FDA cleared this device. The FDA clearance is for those patients with chronic GERD, with continued responsiveness to PPIs, and a small hiatal hernia of less or equal to 2 cm. The TIF procedure is described as: 

During transoral fundoplication, a General Surgeon constructs an anterior partial fundoplication of 270-300 degrees by attaching the fundus to the anterior and left lateral wall of the distal esophagus slightly above the esophagogastric junction through full thickness placation using multiple fasteners around the gastroesophageal junction.  The TIF procedure has had different versions (TIF 1.0 vs. 2.0) depending on the circumferential amount of reestablishment of the valve, i.e. 220 degrees vs. 240 degrees.  

As noted above, the evidence supports limited coverage for Transoral Incisionless Fundoplication (TIF). 

Stretta® procedure: 

At this time, open-label studies or patient registries with short term follow-ups are the dominant source of data. The overwhelming preponderance of reviewers remain equivocal in their support and have called for randomized controlled trials with long-term follow-ups. In the absence of evidence from such studies, and in the absence of wide acceptance, endoscopic treatments for GERD are not proven effective. 

Thus the evidence is not sufficient and/or robust to support any change in coverage.

Enteryx® Procedure: 

Based on the evidence and FDA recall of this product, change in coverage is not warranted. 

LINX® Reflux Management system:  

LINX® Reflux Management system and/or similar treatments are promising for treatment of patients in whom proton pump inhibitor therapy fails. Clinical data from various studies are emerging. At this time, open-label studies or patient registries with short term follow-ups are the dominant source of data. The overwhelming preponderance of reviewers remain equivocal in their support and have called for randomized controlled trials with long-term follow-ups. In the absence of evidence from such studies, and in the absence of wide acceptance, endoscopic treatments for GERD are not proven effective. 

NGS finds the MAS literature to have small numbers of patients with only short follow-up periods with the exception of Saino et al. and Ganz with 44 and 100 patients respectively, noting data were available for 33/44 and 85/100. Randomized controlled studies are lacking, including head-to-head comparisons with other modes of treatment. NGS will review future literature as it becomes available and is provided. 

Thus the evidence is not sufficient and/or robust to support any change in coverage.