**Indications:**

EsophyXTM 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 prevent acid
reflux.  
  
Benefits are not available for endoluminal treatment for Gastroesophageal
Reflux Disease (GERD) using the Stretta procedure, the Bard EndoCinchTM
Suturing System, PlicatorTM, Enteryx or similar treatments as these procedures
are not considered reasonable and necessary for the diagnosis or treatment of
an injury or disease. Coverage is 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 with a hiatal hernia greater than 2 cm, except where the hernia has been reduced to 2 cm or less by a successful laparoscopic hernia reduction procedure prior to the TIF procedure. (Based on (FDA) approval).  
  

  3. 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 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 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.  Seventy-two point seven percent 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). 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 TIF (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.

**Evidence reviewed based on reconsideration request received October 17,
2019**

Gregory et al (2016) This is an economic paper, not a clinical paper. Medicare
does not use cost as a reason to cover or deny a treatment. This does not
support changing the LCD.

Funk et al (2015) This is an economic paper, not a clinical paper. Medicare
does not use cost as a reason to cover or deny a treatment. This has been
previously reviewed by this contractor and this does not support changing the
LCD.

Noar et al (2014) has previously been reviewed by this contractor and this
does not support changing the LCD.

Dughera et al (2014) has been previously reviewed by this contractor and thus
not any new support.

Dughera et al (2011) This old study involved 69 patients but only 56 of them
reached a 48 month follow up. It excludes patients with large hiatal hernias,
severe grade C-D erosive esophagitis despite medical treatment, Barrett
esophagus, or primarily extraesophageal manifestations of GERD (e.g., asthma).
There was no control group. The mean age was only 42+/- 14 years. Thus, these
patients were much younger than typical Medicare beneficiaries. The
radiofrequency treatment significantly improved heartburn scores, GERD-
specific quality of life scores, and general quality of life scores at 24
months and **** 48 months in 52 out of 56 patients (92.8%) and substantially
reduced the use of proton pump inhibitors. The authors stated there was no
conflict of interest. This paper reflects a small uncontrolled study and gives
minimal support to Stretta.

Noar et al (2007) This old study reported on 96 (out of 109) consecutive
patients who were followed for four years. The mean age was only 51 which is
much younger than typical Medicare beneficiaries. All patients had the
diagnosis of GERD confirmed by finding erosive esophagitis at upper endoscopy
(Los Angeles grade A or higher) or abnormal acid contact time detected at
ambulatory esophageal pH testing. Patients with erosive esophagitis were
maintained on medical therapy until all erosions had healed. Esophageal
motility was performed in all patients to exclude those patients with
achalasia. Patients with metaplasia were treated and followed according to
standard Barrett's protocol with EGD and 4-quadrant biopsy at each follow-up.
Gastric emptying scans (GES) were performed on all patients and 31 of 109
demonstrated abnormal emptying. The fact that 1/3rd of the patients had this
concurrent problem is a concern. Patients with stenosis, stricture, or
ulceration of the pyloric valve were excluded. Medication usage decreased
significantly from 100% of patients on twice daily PPI therapy at baseline to
75% of patients showing elimination of medications or only as-needed use of
antacids/over-the-counter PPIs at 48 months.

DISCLOSURE: Noar M.D. has served in the capacity as a member of the clinical
advisory board and has received honoraria for speaking and training for Curon
Medical, Inc, and has no other conflicts of interest to disclose. Lotfi-Emran
S. has no conflicts of interest to disclose. This paper suffers from patients
not being the typical age for Medicare beneficiaries and being uncontrolled.
Thus, it gives minimal support for Stretta.

Reymunde et al (2007) This is another old paper with the authors following 83
consecutive patients with persistent GERD symptoms for 48 months. It was a
nonrandomized study, lacked a control arm, and lacked data of 24-hour pH.
These patients experience a partial response to daily PPI or other
antisecretory medications. All patients underwent a careful evaluation to
document the diagnosis of GERD by ambulatory esophageal pH testing,
demonstrating abnormal esophageal acid exposure time or the presence of
erosive esophagitis at endoscopy. Barium radiography or endoscopy were used to
exclude patients with a hiatal hernia larger than 3 cm. Endoscopy was also
used to exclude patients with severe erosive esophagitis (greater than Los
Angeles grade B) or long-segment Barrett's esophagus. Esophageal manometry was
performed in most patients to exclude those patients with very poor lower
esophageal sphincter (LES) function (LES pressure <5 mm Hg) or aperistalsis.
The authors did not mention the ages of the participants. None of the authors
hold any significant financial interest in the product being discussed that
would represent a conflict of interest. This paper suffers from the age of the
patients not being described and being uncontrolled. This gives minimal
support for Stretta.

Torquati et al (2004) This very old uncontrolled paper reported on 82
patients, and 41 of them (50%) had a follow-up period longer than 18 months.
The authors note, "Follow-up surveys were completed by 36 patients (88%)
during a mean follow-up period of 27.1  3.7 months." Thus, there really were
only 36 patients not 82 followed and the period was quite short. The mean age
of the 82 patients was 46.8 +/- 18.3 years. The authors do not explain if the
age of the 36 patients followed were of the same age. Thus, these patients
were much younger than typical Medicare beneficiaries. Only eleven patients
returned for 24-h pH testing at a mean of 27.4  4.1 months. Acknowledgments:
Dr. Alfonso Torquati is the recipient of a Master of Science in Clinical
Investigation grant from Vanderbilt University School of Medicine. Dr. William
Richards is a member of the Curon Medical Scientific Advisory Board and has
received grant support from Curon Medical. Thus, gives very minimal support
for Stretta.

Herman et al (2014) This is not a human study. It does not pertain to the
esophagus. This is not supportive medical literature.

Perry et al (2012) This is a meta analysis English literature, indexed in
PubMed and Medline databases (1966 to 2010). Sixty-eight articles were
originally identified but 48 were rejected. Thus, there were only 20 articles
and only two of them were random sham-controlled trials. The mean age was
47.57.2 years which is not typical of Medicare beneficiaries. The mean
follow-up interval was 17.115.5 months: thus only 1.5 years. The included
studies were published between 2000 and 2010 and contained 1441 patients with
a mean follow up interval of 15 months. Radiofrequency energy delivery to the
LES produced significant improvements in GERD symptoms and both disease-
specific and global QOL. Esophageal acid exposure was improved, but not
normalized after treatment; and the Stretta procedure did not significantly
increase LES pressure. They noted, "The Stretta procedure has demonstrated the
ability to reduce, but not consistently normalize esophageal acid exposure."
They also noted the "definition of the appropriate patient populations for
Stretta therapy remains controversial." The authors noted that their meta-
analysis was limited by differences in methodology and definition of criteria
for some variables between studies, and absence of blindness in most of the
included studies. The authors did not include a formal assessment of
methodologic quality. The beneficial effects of Stretta were based on single-
arm, pre-post design studies, which are prone to regression to the mean,
making the efficacy of Stretta susceptible to a high risk of bias. Regression
to the mean is a statistical phenomenon that affects all pre-experimental
designs that include, or analyze data from, participants selected on the basis
of an extreme, usually low or high, pre-intervention condition. Although there
is well-recognized value to using single-group studies to identify and
quantify the occurrence of adverse events, the role of these studies in
evaluating efficacy and safety is not well developed. Therefore, the nearly
unanimous efficacy of Stretta for the management of GERD observed in single-
arm studies is not appropriate for informed decision making. Another drawback
is that they did not assess the quality of study methodologies, which is key
to any systematic review. The heterogeneity of the study population across
these reports may also have influenced the interpretation of the pooled
results. We agree with their conclusion that "Larger and longer-term studies
are required to establish the durability of the treatment effect, and to
identify the patient populations that gain the greatest benefit from this
treatment." There is no mention of disclaimers.

Fass et al (2017) All potentially relevant articles were examined to determine
their eligibility using the following inclusion criteria: (1) at least 3
months follow-up, (2) study design was controlled trial or cohort study and
(3) sufficient data for at least one of the six selected outcome variables
(defined below). Exclusion criteria included patients from special populations
(e.g. obese, pediatric or gastroparesis patients), (2) patients undergoing
combined treatment modalities, (3) letters, editorials, review articles and
animal studies and (4) non-English publications. Overall, 28 studies met the
selection criteria, and each was crosschecked with studies included in
previous Stretta meta-analyses to ensure that all relevant studies had been
captured. The authors identified three self-reported symptom variables and
three physiological markers that appear with sufficient frequency in the
studies to enable meta-analysis: (1) PPI use, (2) GERD/HRQL (Health Related
Quality of Life), (3) heartburn score, (4) presence of erosive esophagitis,
(5) esophageal acid exposure and (6) LES basal pressure. Data from the HRQL
instrument--a validated scale for GERD symptom relief that ranges from 0
(asymptomatic) to 50 (incapacitating symptoms) [10, 11]--were reported in only
11 studies. Heartburn score was reported in 13 studies but different scales
were used. Erosive esophagitis data were extracted from the 12 studies that
performed upper endoscopy at baseline and follow-up. Eleven studies reported
esophageal acid exposure time. Nine studies reported LES basal pressure
(mmHg). There were four randomized controlled trials. This is a bit confusing
since on Clinicaltrials.gov there currently are only five registered trials
with "Stretta" in their titles. One is from India and its status is "Unknown."
A second was "Terminated" but was for Management of Reflux After Sleeve
[Gastrectomy] Using Stretta. This is not a typical use anyway. The third is
from China and its status is "Recruiting." The fourth is "Completed." It is
from France and entitled "Stretta In Reflux Uncontrolled by IPP (SIRUP)."
There is no mention of the results being published. The fifth (also from
France) is "Completed (in 2007)" and entitled Evaluation of the Efficiency of
Radiofrequency in the Treatment of Gastroesophageal Reflux Disease. There is
no mention of the results being published. The sixth and final registered
clinical trial is from China and entitled "A New System for GERD Diagnosis and
Treatment (EAISMLP)". It is not yet recruiting. Thus, it is difficult to
understand the discovered randomized clinical trials or their significance.
Collectively at baseline, 97.1% (1743) of patients in the Stretta group were
using PPI. After Stretta treatment, 49% (850) of these patients were using
PPI. Thus, this seems to negate some of the advantages of the procedure.
Concerning HRQL effects, the sham procedure had 1/3rd the effect of the true
treatment. Concerning heartburn scores, treatment effect was not found for
either the Stretta subgroup or the control subgroup. However, when pooled, the
Stretta arm of the RCT studies with the cohort subgroup, Stretta treatment
reduced (thus improved) the heartburn standardized score significantly. For
the random effects model, Stretta treatment marginally reduced the pooled
estimate of frequency of erosive esophagitis at follow-up in all Stretta
subgroups. Stretta treatment reduced (thus improved) the pooled estimate of
esophageal acid exposure. In the RCT subgroups, the pooled estimate of Stretta
treatment effect compared to the sham treatment effect was not significantly
different. However, in the cohort subgroup, the treatment effect in the cohort
subgroup, the treatment effect was significant. For the effects on lower
esophageal sphincter basal pressure. In the RCT subgroups, the pooled estimate
of treatment effect for Stretta was not significantly different than sham
group. Comparing Stretta procedures, sham procedures and laparoscopic
fundoplication procedures the reported adverse event rate for the Stretta
procedure was 0.93% and 7.18% for the LF procedure. For Stretta, small
erosions and mucosal lacerations was the most frequent AE at less than 1%,
while for LF procedures, subcutaneous emphysema was the most frequent AE at
approximately 3%. The authors noted as a limitation of their study include the
lack of contemporaneous control groups in most of the studies. The four RCTs
considered alone have limitations: they enrolled a total of 92 Stretta-treated
patients, whereas the cohort trials and registry enrolled 2376 Stretta-treated
patients. Only one of the outcome measures (erosive esophagitis) was measured
in all four RCTs. Three of the outcome measures (HRQL, heartburn, PPI use)
were measured in only two RCTs. Furthermore, the longest follow-up time in the
RCTs was 12 months, whereas cohort studies included data up to 120 months
(average 23 months). They concluded that their meta-analysis demonstrated that
the Stretta procedure reduced the use of PPIs while improving esophageal acid
exposure time, heartburn symptoms, and HRQL. The reduction in erosive
esophagitis incidence was not statistical significance under the random
effects but did reach statistical significance under fixed effects. There was
no significant effect on LES basal pressure. Disclosures: Dennis J. Scotti is
a part-time consultant with Baker Tilly Virchow Krause, LLC. Baker Tilly
Virchow Krause, LLC is a Business Advisor to Mederi Therapeutics, Inc. David
A. Gregory is a principal with Baker Tilly, a business advisor to Mederi
Therapeutics. Frederick Cahn is a principal with BioMedical Strategies, a
business advisor to Baker Tilly. Ronnie Fass is an advisor to Ironwood and
Mederi Therapeutics, Speaker for AstraZeneca, Dr. Reddy, Mederi Therapeutics
and Takeda and receives research grant from Ironwood. This paper gives minimal
support for Stretta.

CareFirst Medical Policy Reference Manual Medical Policy

HIGHMARK Commercial Medical Policy - Delaware - S-145-010

HIGHMARK Commercial Medical Policy - Pennsylvania - S-145-020

HIGHMARK Commercial Medical Policy - West Virginia - S-145-018

Blue Cross Blue Shield of North Dakota

Novitas Solutions, Inc. LCD L35350

PriorityHealth Medical Policy No. 91483-R9

None of these commercial insurance decisions are in anyway relevant to
Medicare coverage. Of note, other companies such as CIGNA do not cover Stretta
("Each of the following endoscopic anti-reflux procedures for gastroesophageal
reflux disease (GERD), or any other indication, is considered experimental,
investigational or unproven:

  * radiofrequency energy to the gastroesophageal junction (e.g., Stretta System)"

Commercial insurance decisions include contract language as part of their
decision process while Medicare uses evidence based methods. The Novitas Local
Coverage Determination (LCD): Upper Gastrointestinal Endoscopy (Diagnostic and
Therapeutic) (L35350) does not seem to mention Stretta. Of note, none of the
other six Medicare contractors cover Stretta.

A review article entitled Stretta Radiofrequency Treatment for GERD: A Safe
and Effective Modality without any date of publication, journal name or any
information appears to be an unpublished draft and does not support Stretta.

_UpToDate._ This mentions Stretta but not does not give any actual support or
recommendation. However, this is not peer-reviewed published literature. This
also erroneously states "The Stretta system was approved by the Food and Drug
Administration (FDA) in the United States in 2000." We find no evidence that
the FDA approved this device, although it was merely cleared. If we are
incorrect, we would appreciate knowing the FDA premarketing number. However we
note that the Mederi Stretta Catheter and Accessory Kit, Sterile (K152317) was
subject to a recall in 2017 but apparently this has been terminated. Thus,
this is not supportive.

Triadafilopoulos (2016) This review paper states for Stretta, "Despite the
aforementioned favorable results with Stretta in open, uncontrolled trials,
the assessment of controlled data has questioned the value of the procedure.
Using the standards of the Cochrane collaboration, a systematic meta-analysis
of trials evaluated the efficacy of Stretta for the management of GERD. They
analyzed normalization of esophageal pH, augmentation of lower esophageal
sphincter pressure (LESP), health-related quality of life (HRQL), and PPI use.
The pooled data from four trials and 153 analyzed patients showed no
differences between Stretta and sham or PPI therapy for the outcomes of mean
esophageal acid exposure LESP, ability to stop PPIs, or HRQL." Conflict of
Interest: George Triadafilopoulos reports that he has an equity position with
Mederi Therapeutics, C2 Therapeutics, and EndoStim. This article does not
support coverage of Stretta.

Nabi and Reddy (2016) The authors note, "recently published systemic review
and meta-analyses, which included four RCTs, showed no difference between
Stretta versus sham or PPIs in patients with GERD for the outcomes of EAET,
LES pressure, ability to stop PPIs, or HRQL.22 However, one of the criteria
for efficacy in this review was normalization of pH (pH <4 exposure time <4%),
which is rather stringent and not achieved even in patients who respond
successfully to PPIs.23 Moreover, the authors agree that the overall quality
of evidence from RCTs on the efficacy of the Stretta procedure was extremely
low." Conflicts of Interest: The authors have no financial conflicts of
interest. This article does not support coverage of Stretta.

Chang (2015) This is not a medical article in a peer reviewed medical journal
indexed in PubMed of the US National Library of Medicine National Institutes
of Health. It is really an OpEd and does not support changing the LCD.

Subramanian and Triadafilopoulos (2015) This is a short review and offers
minimal support for Stretta.

de Souza et al (2018) This really is a case report of three patients who
underwent Stretta in Sept 2017. The follow up period is not apparent, but
since this was published in 2018, the follow up has to be extremely short.
Declared conflict of interest of all authors: none. This three person "series"
without follow up is not supportive of changing the current LCD.

Sandhu and Fass (2019) This is a very limited review of the literature
concerning Stretta. Conflict of Interest: R Fass was a speaker for Mederi
Therapeutics. DS Sandhu has no conflicts of interest to declare. This offers
minimal support for Stretta.

Triadafilopoulos (2014) previously reviewed by this contractor and thus does
not add any new support for changing the Stretta LCD.

Viswanath et al (2018) This paper was not found indexed in PubMed of the US
National Library of Medicine National Institutes of Health. Thus, it is not
supportive.

Subramanian and Triadafilopoulos (2014) previously reviewed by this contractor
and thus does not add any new support for changing the Stretta LCD.

Ayman et al (2010) previously reviewed by this contractor and thus does not
add any new support for changing the Stretta LCD.

Corley et al (2003) previously reviewed by this contractor and thus does not
add any new support for changing the Stretta LCD. The associated editorial on
page 970 was noted.

Coron et al (2008) Forty-three (43) patients (30 men, mean age: 48 years) with
PPI-dependent typical reflux symptoms were randomized to either RF (n = 23) or
maintenance PPI therapy alone (n = 20). After randomization, seven patients
were lost to follow-up or withdrew their consent to participate, leaving 36
patients available for PP analysis at 6 months. Between the 6th and 12th
months, two patients in the control group were excluded from the study,
leaving 34 patients available for the PP analysis at 12 months (fourteen in
the control arm and 20 in the RA treatment arm). The mean age of participants
was only 48 years old. At 12 months, ITT (intention-to-treat) analysis showed
that 13 /23(56%) patients in the RF group were able to stop or decrease their
PPI use vs. seven of 20 (35%) in the control group (P = 0.16). PP analysis
confirmed these results with 13 20 (65%) patients in the RF group being able
to stop or decrease their PPI use vs. six of 16 (38%) in the control group (P
= 0.10). Thus, this is not statistically significant. At 6 months, 16 20
(80%) patients had <3 symptomatic episodes of GERD occurring per week in the
RF group vs. six of 16 (40%) in the control group (P = 0.01) but no
significant difference was noted at 12 months between both groups. Global
REFLUX-QUAL and SF-36 scores were not significantly different between both
groups at 6 and 12 months. However, two items of the REFLUX-QUAL, namely well-
being and fears, were significantly better in the RF group compared with the
PPI group at 6 months (P = 0.05 and P = 0.03), but this statistical difference
remained at 12 months only for fears. Monitoring of PPI needs showed that the
mean daily dose of PPI was significantly lower in the RF group compared with
the control group at 6 and 12 months (12 _ 11 vs. 30 _ 19 mg day; P = 0.01
and 16 _ 14 vs. 37 _ 30 mg day; P = 0.05 respectively). A 24 hour pH study
performed at 6 months (off PPI therapy) showed that OAE was not significantly
different between the RF and control groups. The absolute change in OAE from
baseline to the 6-month assessment was not significantly different between the
RF and the control group. In addition, upper GI endoscopy revealed that an
esophagitis was noted in 10 (four grade A and six grade B) and seven patients
(five grade A, one grade B and one grade C) of the RF and the control groups,
respectively (P = 0.946). Declaration of personal interests: J. P. Galmiche
has served as a speaker, a consultant and an advisory board member for
AstraZeneca, Given Imaging, Pentax, Janssen-Cilag, Sanofi, Nycomed and has
received research funding from AstraZeneca, Given Imaging, Janssen-Cilag
France and Negma-Gild. F. Zerbib has served as a speaker and a consultant for
AstraZeneca, Janssen-Cilag, Sanofi and has received research funding from
AstraZeneca, Janssen-Cilag France, Sandhill, Addex and Nycomed. P. Ducrotte 
has served as a speaker for AstraZeneca and Janssen-Cilag and has received
research funding from Beaufour Ipsen Pharma and Sanofi. F. Ducrot has worked
on the development of Janssen Pharmaceutical gastrointestinal drugs up to
1985, and has occasionally served as a speaker for AstraZeneca since. S.
Bruley des Varannes has served as a speaker and a consultant for AstraZeneca,
Janssen-Cilag, Sanofi, and has received research funding from AstraZeneca,
Janssen-Cilag France, Medtronic and Danone. Declaration of funding interests:
This work was supported in part by the Societe Nationale Francaise de Gastro-
Enterologie (SNFGE), INSERM and CHU of Nantes. The study was conducted
independently of Curon Ltd with no interference of this company in the trial
design or analysis of results. This study was old, short and small. The
patients' mean age of 48 is far less than the typical Medicare beneficiary.
The results were not impressive. This does not support the change in the LCD
coverage.

Kalapala et al (2017) The study was registered at ClinicalTrials.gov
(Identifier number: NCT02935881). Twenty (20) patients, followed for three
months. Ten (10) underwent the Stretta procedure and 10 were controls (all
were treated with standard dose of PPIs once daily. The mean age of the
treated patients was 38.89 and the controls were 34.00. The primary outcome
measure was the proportion of patients showing improvement in the quality of
life and improvement in the frequency and severity of GERD symptoms
(heartburn, regurgitation, chest pain, and cough). Secondary outcomes included
LES pressure at esophageal manometry, reduction in medication use, and patient
satisfaction. Data on these measures were collected through a questionnaire
consisting of two questions: (1) Are you completely independent of PPIs? and
(2) Are you satisfied with the treatment? Responses were graded on 6-point
Likert scale. At baseline, only 20% (Stretta 20%; control 20%) of patients
overall reported that they were satisfied with their quality of life. Three
months after Stretta treatment, 80% reported satisfaction compared with only
30% in the control group. This is also reflected in the patient satisfaction
response. Three months after treatment, an increase in lower esophageal
sphincter pressure was observed in both Stretta treated as well as the control
group. However, the difference between the groups was not significant.
Conflict of interest: RK, HS, ZN, SD, RT, and DNR declare that they have no
conflict of interest. This paper has too small of a treated number, too short
of a follow up period, and too young of a populations (mean age of the treated
patients 38.89 and controls 34.00) to support any change in the LCD.

Arts et al (2011) previously reviewed by this contractor and thus does support
any change to the LCD.

SAGES. (2015) This review paper briefly mentions Stretta and notes, "However,
although the esophageal acid exposure, as measured by the DeMeester score, was
significantly reduced after treatment (44.4 vs 28.5, P Z .007), it did not
normalize. In addition, no significant increase in lower esophageal sphincter
pressure was observed. Adverse events were infrequent and typically minor. The
technique appears to durably relieve GERD symptoms for up to 10 years in the
majority of patients." This is a bit premature to state this since literature
does not support this follow up. This paper gives very minimal support for
Stretta.

Stefanidis (2017) Statement from the Board of Governors of the Society of
American Gastrointestinal and Endoscopic Surgeons (SAGES) on Mar 2017. This
paper has been previously reviewed by this contractor and thus does support
any change to the LCD.

Auyang et al (2013) and the SAGES Guidelines Committee. These results were not
based on the findings of a systematic review and have serious methodology
issues in study conduct and analysis. For example, the systematic review did
not perform a meta-analysis despite the availability of data from 2 randomized
controlled trials. In addition, most of the studies were single-arm case
series and did not involve a control or comparator, making it impossible to
deduce the effect of the Stretta procedure. A key purpose of the systematic
review and meta-analysis is to determine whether results are observed because
of the intervention or because of bias, owing to poor study design. Therefore,
assessment of the methodologic quality of included studies is an important
requirement for a systematic review and is recommended by the Cochrane
Collaboration. This paper has been previously reviewed by this contractor and
thus does support any change to the LCD.

McClusky III et al (2007) previously reviewed by this contractor and thus does
support any change to the LCD.

Mattar et al (2006) previously reviewed by this contractor and thus does
support any change to the LCD.

Richards et al (2003) previously reviewed by this contractor and thus does not
support any change to the LCD.

Noar et al (2016) The authors "prospectively assessed and compared patient
reported outcomes in 18 refractory LNF patients and 81 standard refractory
GERD patients that all underwent Stretta during 10-year follow-up. Patient-
reported outcomes measured were GERD-HRQL (health-related quality of life),
patient satisfaction scores, and daily medication requirements." Originally
there were 149 patients who reached the 10 year follow up evaluation cutoff.
However, 36 could not be contacted, 11 were deceased, and three declined. The
mean age was 50 which is not the typical Medicare beneficiary age. This was a
non-randomized open-label prospective comparative trial study which was
conducted at a single center. There was inclusion of long-term pH or motility
data. While the study was to compare the results of laparoscopic Nissen
fundoplication patients who underwent Stretta and standard refractory GERD
patients who underwent Stretta, the number of refractory LNF patients were
only 18. This not a true clinical study of Stretta that was randomized. It is
a comparative of treating poor results of a laparoscopic Nissen
fundoplication. Disclosure: Dr. Mark D. Noar has received honoraria for
speaking and training for Mederi Therapeutics Inc., and has no other conflicts
of interest or financial ties to disclose. Patrick J. Squires and Sulman R.
Khan have no conflicts of interest or financial ties to disclose. This paper
is not supportive to changing the current policy.

Mederi (2018) This is an unpublished (does not appear on PubMed) proprietary
evaluation of Stretta. Unpublished works are not acceptable as support for any
Medicare review.

Lipka et al (2015). The authors searched MEDLINE and the Cochrane Central
Register of Controlled Trials (The Cochrane Library) from inception until
February 28, 2014, along with other databases, for randomized controlled
trials of Stretta in patients with GERD. Primary outcomes were physiologic
parameters of GERD, including normalization of esophageal pH values and
augmentation of lower esophageal sphincter pressure (LESP). Secondary outcomes
were health-related quality of life (HRQOL) and ability to stop the use of
proton pump inhibitors (PPIs). For quality assurance purposes, two
investigators were involved throughout the study. Data were pooled under a
random-effects model. The systematic review was performed as per the standards
of the Cochrane collaboration. They then collected data from 4 trials and a
total of 165 patients (153 patients were analyzed). Three trials compared
Stretta vs sham, and 1 trial compared Stretta with PPI therapy. The overall
quality of evidence was very low. The pooled results showed no difference
between Stretta and sham or management with PPI in patients with GERD for the
outcomes of mean (%) time the pH was less than 4 over a 24-hour time course,
LESP, ability to stop PPIs, or HRQOL. The authors concluded that in a meta-
analysis of trials, Stretta for patients with GERD does not produce
significant changes, compared with sham therapy, in physiologic parameters,
including time spent at a pH less than 4, LESP, ability to stop PPIs, or
HRQOL. The initial electronic search retrieved 136 references that were
screened by title and abstract But after the final screening, 4 published
studies met the predetermined inclusion criteria. The study by Arts et al was
a single-center, randomized, controlled trial comparing Stretta with sham
therapy in 22 patients (11 in each group). The study by Aziz et al was a
multi-arm randomized trial comparing sham treatment vs single - and double
dose Stretta. The randomized, multicenter, national, single-arm, cross-over
study by Corley et al studied 64 patients assigned to Stretta (n = 35) or sham
therapy (n = 29). Coron et al performed a multicenter international randomized
controlled trial, with a parallel design, comparing Stretta and PPI therapy.
Forty-three patients were assigned randomly to sham (n = 20) or Stretta (n =
23). The authors noted that the overall methodologic quality of the included
studies was very low as determined by GRADE methodology and prone to high risk
of bias. None of the included studies provided details on randomization
sequence generation, blinding of patients, or outcome assessors. Only a fourth
of studies provided details on allocation concealment and three fourths of
studies had complete reporting of outcomes data. All included studies were
prone to outcome reporting bias because none reported how many patients
actually had complete alleviation of symptoms, normalization of pH, or LES
pressure. All included studies provided details on random error (ie, sample
size calculations, a and b error, and expected difference). Conflicts of
interest: Joel E. Richter is a consultant for Endostim, Inc and Givens
Imaging. This paper does not support the use of Stretta.

**Summary of evidence for EndoCinch TM Suturing System and the PlicatorTM:**

The Bard EndoCinchTM Suturing System and the PlicatorTM 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. Eighty-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 greater reduction occurred in 83% at five years and a 50% or greater 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.

**Evidence reviewed based on reconsideration request received March 12, 2019
**

On 03/15/2018 the FDA approval for updating the precautions statement to state
that use of the LINX Reflux Management System in patients with a hiatal hernia
larger than 3 cm should include hiatal hernia repair to reduce the hernia to
less than 3 cm and that the LINX Reflux Management System has not been
evaluated in patients with an unrepaired hiatal hernia greater than 3 cm,
added a hiatal hernia clinical data summary in the instructions for use,
updated the instructions for use section to highlight the recommendation to
repair a hiatal hernia, if present, at the time of the LINX Reflux Management
System implantation, and updated the patient information booklet to align with
the instructions for use and include 5 year clinical study results.

  1. Aiolfi et al (2018) reported a systematic review and meta-analysis comparing early outcomes of laparoscopic Nissen and Toupet fundoplication (LF) and Magnetic Sphincter Augmentation (MSA). After identifying all possible studies, seven were determined to be appropriately performed (Louie 2014, Reynold 2015, Sheu 2015, Riegler 2015, Warren 2016, Reynolds 2016, and Asti 2016). There is concern that the two Reynolds papers and the Warren paper had overlapping patients. They concluded that: "Patients with GERD may benefit from both LF and MSA in terms of, safety, risk of dysphagia, postoperative disease-related quality of life, and PPI suspension rate at one-year follow-up. MSA appears to induce less bloating and flatulence, and to facilitate belch and vomiting. Whether MSA should be considered a first-line surgical option in appropriately selected patients remains to be determined." A concern is that the mean age of the patients ranged from 39.3 to 54 years of age (geometric mean 48.8), which is far below the age of the typical Medicare beneficiary. MSA was associated with a significantly lower incidence of gas/bloat symptoms (OR=0.39 [95% CI, 0.25-0.61]; P<0.001) and a greater incidence in the ability to vomit (OR=10.10 [95% CI, 5.33-19.15]; P<0.001) and belch (OR=5.53 [95% CI, 3.73-8.19]; P<0.001). However, dysphagia requiring endoscopic dilation occurred equally in the 2 groups (9.3% versus 6.6%, respectively; OR=1.56 [95% CI, 0.61-3.95]; P=0.119). The incidence of endoscopic dilation and the incidence of reoperation were similar between groups (P>0.1). This does offer support to the LINX. "Funding disclosure: None. Conflicts of interest: None."  
  

  2. Alicuben et al (2018) reported on data obtained from the device manufacturer Torax Medical, Inc., as well as the Manufacturer and User Facility Device Experience (MAUDE) database. The study period was from February 2007 through July 2017 and included all devices placed worldwide. According to the authors, 9453 devices were placed during this study period with only 29 reported cases of erosions. The risk of erosion was 0.05% at one year and 0.3% at four years. The authors noted the 12-bead device, which was responsible for 18/29 (62%) of erosions, is no longer available for implantation. This relies on the self-reporting by physicians which can underestimate the numbers. Grant Support: There was no financial assistance. This does offer support to the LINX but since this only looked at erosion, the support is limited to safety, not to effectiveness.  
  

  3. American Society of General Surgeons. LINX Statement of Support from ASGS. 2014. https://theasgs.org/position-statements/linx-statement-of-support-from-asgs/. This gives an opinion with limited basis of evidence to support this. This does give some support but it must be noted that no matter what categorization or scale is used, testimonials, opinions of respected authorities, and reports of expert committees are the lowest level of evidence. There is no statement related to financial conflict although it is apparent that this organization represents surgeons who perform this procedure.  
  

  4. Ayazi et al (2019) published a "retrospective review of prospectively collected data" on 350 patients who underwent magnetic sphincter augmentation and their hiatal hernia (HH) status (none, small [<cm], large [3cm], paraesophageal). There were 65 patients (18.6%) with no HH, 205 (58.6%) with small HH (< 3 cm), 58 (16.6%) with large HH ( 3 cm) and 22 (6.2%) with paraesophageal HH. Preoperative esophagogastroduodenoscopy (EGD) with biopsy was performed to assess the presence of esophagitis, Barrett's esophagus and the presence and size of a hiatal hernia. The average age was only 53.5 which is not typical for the Medicare population. At a mean follow-up of 13.6 (10.4) months, the rate of outcome satisfaction was high and similar between the four groups (p = 0.72). The authors do not explain 13.6 verses 10.4. A total of 19 patients required readmission within 90 days after surgery. The study suffers from several issues. First, the patients were not typical Medicare age patients. Second, the short follow up period. Third, it was not a randomized controlled study. Fourth, related to #3, there was no comparison to the Laparoscopic Nissen fundoplication. Disclosures: Dr. Blair A. Jobe is on the scientific advisory board of Johnson and Johnson and Medtronic and receives a consulting fee. Drs. Shahin Ayazi, Nobel Chowdhury, Ali H. Zaidi, Kristy Chovanec, Yoshihiro Komatsu, Ashten N. Omstead, Ping Zheng and Toshitaka Hoppo have no conflicts of interest or financial ties to disclose.  
  

  5. Ayazi et al (2019) compared the costs of laparoscopic magnetic sphincter augmentation (MSA) and laparoscopic Nissen fundoplication (LNF) in a large healthcare system. Of note, the article starts off with, "Magnetic sphincter augmentation (MSA) is a promising antireflux surgical treatment." It then notes, "Laparoscopic Nissen fundoplication is a safe, effective, and durable treatment." This is an economic study and costs cannot be used by Medicare as a reason for denying coverage. Disclosure: Dr. Jobe is on the scientific advisory board of Johnson and Johnson and Medtronic and receives a consulting fee. Drs. Ayazi, Zaidi, Zheng, Chovanec, Chowdhury, Salvitti, Newhams, Levy, and Hoppo have no conflicts of interest or financial ties to disclose. This work was completed with assistance of VITAL, Highmark Health.  
  

  6. Bell et al (2019) reported on 152 patients with moderate to severe regurgitation symptoms while they were being treated with once-day proton-pump inhibitors. "Enrolled patients were randomly assigned 2:1 to the following treatment arms: Twice-daily PPI (BID PPI) therapy with omeprazole 20 mg (N Z 102) or laparoscopic MSA (N Z 50). Primary endpoint efficacy and safety assessments were performed at 6 months and are the subject of this report." The range of patients was 21-76 with a mean of only 46; again not in the typical Medicare age. Also, only 134 were analyzed. "Per protocol, 89% (42/47) of MSA patients achieved resolution of moderate-to-severe regurgitation at the 6-month primary endpoint. In stark contrast, only 10% (10/101) of patients in the medical therapy arm reported relief from moderate-to-severe regurgitation at the 6-month endpoint." However, these numbers do not add up to the 134 who were subsequently analyzed. Additional concerns are the short follow up, and the above noted age of the patients. While the authors noted, "This is the first prospective, randomized, controlled study comparing MSA with BID PPI therapy in a population of patients with GERD with moderate-to-severe regurgitation despite once-daily PPI therapy." There are several problems with this study. First, all the improvement is subjective rather than some objective measurements. Second, this was not a blinded study. Of course it is difficult to perform a sham abdominal procedure. The short follow up period and the atypical ages of the patients compared to the typical Medicare age are additional concerns. This gives minimal support. "DISCLOSURE: All authors are grant recipients from Torax Medical; A. Park, research grant support from Stryker Endoscopy."  
  

  7. Buckley et al (2018) reported on 200 patients in a multicenter prospective study treated with magnetic sphincter augmentation (MSA) and a concurrent hiatal hernia repair of greater than 3 centimeters. In fact, 78% of patients had axial hiatal hernias greater or equal to 5 cm or large paraesophageal component. Twenty-nine percent presented with an intrathoracic stomach. Seventeen had undergone a prior hiatal hernia repair with fundoplication. The mean age was 59.5. Non-permanent mesh reinforcement of the hiatal repair was performed in 85% of the patients. One hundred and fifty-six were followed at a median of 8.6 months. While twenty percent of patients had Barrett's metaplasia, and 40% had esophagitis, there was no mention of these conditions on follow up. The amount of various antacid medication was not quantified. Again, the improvements were subjective. The fact that all the patients had large hiatal hernia repairs concurrently makes it difficult to interpret what improvement was from the MSA and what was from the hiatal hernia repair. Funding: This study received no funding. Compliance with ethical standards. Disclosures: Dr. F.P. ''Tripp'' Buckley III is on the speakers' bureau for Torax Medical. Dr. Reginald C.W. Bell is on the speakers' bureau for Torax Medical. Stephanie Doggett PA-C is on the speakers' bureau for Torax Medical. Katherine Freeman N.P. and Rachel Heidrick R.N have no conflicts of interest or financial ties to disclose. This paper gives very minimal support to LINX.  
  

  8. Chen M et al (2017) performed a meta-analysis of four clinical trials which involve 624 patients. Three of the publications (Louise, Reynolds, and Warren) have been previously reviewed by this contractor. The Sheu article had not. If trials were included in the meta-analysis, the criteria had to be fulfilled as follows: (1) Compare the original outcomes of MSA (Magnetic Sphincter Augmentation) and NF (Nissen fundoplication) for the treatment of GERD; (2) report on at least incidence of adverse events, complications, and proton-pump inhibitor use. There were similar outcomes in the number of adverse events and complication between two groups were shown. The authors noted, "There are still many unanswered questions whether MSA is still appropriate for hiatal hernias which are more than 3 cm, whether the long-term outcomes of MSA are the same as the short-time outcomes, whether the incidence of LINX device removed and erosion will increase as time goes on, and so on. Therefore, it is very important and necessary to perform randomized controlled trials to describe the efficacy of MSA compared to NF in short term and long term." The authors "have no conflicts of interest or financial ties to disclose." This gives minimal support to LINX.  
  

  9. Skubleny D et al (2016) performed a meta-analysis of laparoscopic Nissen fundoplications with magnetic sphincter augmentation. However, the three primary studies were Riegler et al, Warren et al, and Sheu et al. Thus, it is incorrect to accept this as new evidence since the original articles and meta-analysis have already been evaluated. Disclosures: Daniel Skubleny, Noah J. Switzer, Jerry Dang, Richdeep S. Gill, Xinzhe Shi, Christopher de Gara, Daniel W. Birch, Clarence Wong, Matthew M. Hutter and Shahzeer Karmali have no conflicts of interest or financial ties to disclose.  
  

  10. Smith C et al (2014) reported on the post-operative course of 66 patients who received the magnetic sphincter augmentation. The average follow-up was only 5.8 months (range 1 to 18.6 months). Forty-four of the 66 patients had hiatal hernia. The average age was 53.7 which is below the typical Medicare age. There was no control group. They concluded,... "This is a promising new offering for patients with GERD." They did specifically comment on the learning curve for surgeons performing this surgery. Disclosure Information: "Drs. Smith and DeVault received pay as consultants to Torax Medical during the final review of the results of their Pivotal Trial. Dr. Smith presented outcomes data to the FDA advisory panel and continues to advise the company on how to deploy Linx in clinical practice. Mauricia Buchanan has nothing to declare."  
  

  11. Smith C et al (2017) reported on data obtained from the device manufacturer Torax Medical, Inc., as well as the Manufacturer and User Facility Device Experience (MAUDE) database. The study period was from March 22, 2012 (FDA approval) through May 31, 2016, and unlike the Alicuben paper, included only events occurring in the United States. An estimated 3283 patients underwent magnetic sphincter augmentation (165 surgeons at 191 institutions). The median implant duration was 1.4 years, with 1016 patients implanted for at least 2 years. No deaths, life-threatening events, or device malfunctions were reported. The overall rate of device removal was 2.7% (89/3283). Disclosure Statement: Drs. C.D.S., J.C.L., and R.C.B. received consulting and research funding from Torax Medical. This does offer support to the LINX as being not dangerous, but no support for it being effective.  
  

  12. Telem D et al (2017) authored a SAGES Committee Paper on SAGES technology and value assessment committee (TAVAC) safety and effectiveness analysis: LINX_ reflux management system. This is a SAGES Committee Paper. Except for Asti et al who reported the results of a retrospective review of prospectively collected data examining the outcomes of 164 patients undergoing LINX implantation with median follow-up of 48 months, all the papers reviewed by SAGES have been evaluated by this contractor. As this SAGES paper notes about the articles reviewed: Limitations of currently published data. 
    * Patients used repeatedly in some publications.
    * There may be a publication bias in favor of LINX, as several studies were either funded by the manufacturer or were performed by investigators affiliated with the manufacturer.
    * Most studies were performed in high volume centers in highly selected patients and may not reflect broader clinical practice, which may lead to underreporting of complications.
    * Current studies lack randomization and blinding.

Expert panel recommendation

This expert panel convened by the SAGES Technology and Value Assessment
Committee finds that:

With regards to safety:

  * Safety analyses suggest the LINX procedure was associated with few serious adverse events and no reported mortality.
  * The most common anticipated side effect was acute dysphagia.
  * The reported rate of erosion is in the range of 0.1-0.2%. The published literature on erosions suggests that the device can be safely removed endoscopically or laparoscopically without serious adverse outcomes.
  * Some devices require removal, most often for recurrent GERD or persistent and/or severe dysphagia.
  * No new patterns of failure or complications have been reported in long-term follow-up.
  * Longer-term follow-up supports the FDA conclusion that the device is safe.

With regards to efficacy, the panel concludes:

  * LINX implant results in pH normalization, improved quality of life, and complete cessation of regular PPI use on a consistent basis. The ability to belch and vomit is maintained following implantation of LINX, and de novo moderate-severe gas bloat is uncommon.
  * When compared to laparoscopic fundoplication, rates of success in alleviating GERD symptoms and dysphagia are similar following LINX. Bloating side effects may be lower.
  * Longer-term follow-up data demonstrates that the LINX Reflux Management System is effective in the management of GERD.

Conclusions

  * Longer-term (3-5 years) experience with the LINX Reflux Management System confirms the initial safety profile that led to FDA approval of the device.
  * The LINX device has been demonstrated to result in long-term GERD control based on symptomatic outcomes, PPI utilization, and pH studies.
  * LINX is a reasonable treatment option for appropriately selected patients with GERD who meet indications for antireflux surgery. The LINX procedure is part of the armamentarium in the treatment of GERD. As such, it should be performed by surgeons familiar with the workup and different management alternatives of GERD and not offered in isolation.
  * Implantation of the LINX device should be covered and reimbursed by insurance for appropriate patients who meet the selection criteria as described above.

Disclosures Dana Telem, MD: Research funding at Cook, Consulting Fees at
Ethicon and Medtronic, Honoraria at Gore. Andrew Wright, MD: Honoraria at
Medtronic. Paresh Shah, MD: Consultant at Stryker, Zmicro, Olympus,
Endoevolution. Matthew Hutter, MD: Reimbursed to attend Masters in MIS Forum
by Olympus. This document underwent prescreening review prior to submission to
SAGES Board of Governors for approval by SD Schwaitzberg, MD and Patricia
Sylla, MD.

Again, as noted above, it must be noted that no matter what categorization or
scale is used, testimonials, opinions of respected authorities, and reports of
expert committees are the lowest level of evidence.

  1. Trad K et al (2018) studied transoral incisionless fundoplication (TIF). Clinical outcomes were evaluated at 5 years post-TIF 2.0. A total of 63 chronic gastroesophageal reflux disease (GERD) sufferers with troublesome symptoms refractory to proton pump inhibitor (PPI) therapy, absent or 2 cm hiatal hernia, and abnormal esophageal acid exposure were randomized to the TIF group or PPI group. This study has nothing to do with magnetic sphincter augmentation and thus does not support LINX. In summary, it does however support TIF.  
  

  2. Yadlapati R (2018) convened an expert panel and gave their evaluations of nine patients with GERD. The treatment options were laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, and radiofrequency energy delivery. Of note, radiofrequency energy delivery such as the Stretta procedure is not covered by National Government Services. Financial support: RY and JEP supported by NIH R01 DK092217 (JEP). Potential competing interests: MFV, MFV, SJS, JR, DK, POK, PJK, CPG, LG, RF, DOC, JC, LH: None. RY: Consultant for Ironwood. CPG: Research: Medtronic; Consultant: Ironwood, Torax, Quintiles; and Teaching: Medtronic, Sandhill. NJS: Research funding: Boston Scientific, CSA Medical, C2 Therapeutics, CDx Medical, Interpace Diagnostics, and Medtronic. Consultant for Shire and Cook Medical. BEL: Scientific advisory board member for Ironwood, Salix. JEP: Consultant for Crospon, Ironwood, Torax, Astra Zeneca, Takeda, Impleo, Medtronic, and Sandhill. Expert panels are the lowest category of medical evidence. Thus, this is very minimal support for LINX.

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 ExophyXTM. The FDA cleared this device. The FDA clearance
is for those patients with chronic GERD, with continued responsiveness to
PPIs, and a hiatal hernia greater than 2 cm, when a laparoscopic hiatal hernia
repair reduces the hernia to 2 cm or less. 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.

**Analysis based on reconsideration request received October 17, 2019**

Forty three (43) papers were submitted with this reconsideration request.

  * Thirteen of them had previously been evaluated by National Government Services and had already been included in the bibliography. These did not add any new support for Stretta.
  * Eight "positive coverage" documents were included. None of these are from Medicare contractors but rather commercial insurance plans which use contract language as part of their decision process rather than evidence based methods that Medicare requires. These did not add any support to Stretta.
  * Many of the remaining twenty-two (22) articles were old.
  * Others were small studies or had short follow up procedures.
  * Many pertained to patients not reflective of typical Medicare beneficiaries.
  * The methodologic quality and design of the study of most were poor.
  * Some were unpublished and/or not found in PubMed of the National Library of Medicine of the National Center for Biotechnology Information.
  * A forty-fourth article (a review one based on the Cochrane Data Base) was mentioned in one of the submitted articles. This was obtained, reviewed and added.

In summary, there was not sufficient, robust evidence submitted to change the
current non-coverage of Stretta. Stretta will remain non-covered.

**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.

**Analysis based on reconsideration _request received March 12, 2019_ **

The number of submitted literature was small and that included one paper that
was not related to the LINX procedure. There were also eight other papers
submitted with the current reconsideration that had previously been reviewed
by this contractor (Bonavina J 2013, Ganz 2016, Lipham 2015, Louie BE 2014,
Reynolds 2016, Riegler 2015, Saino 2015, and Warren 2016) and thus not
reviewed again. In addition, some of the current papers appear to contain
overlapping patients. While the SAGES Technology and Value Assessment
Committee paper was reviewed and noted, expert and/or consensus statements are
the lowest form of recognized levels of evidence. The follow up periods for
the studies were short and most patients were not of the typical Medicare age.
There is concern about conflict of interest but this is difficult to avoid. In
summary, there were concerns about the quality of the evidence including
randomization, the above mentioned likely patient overlap between 3 studies,
and concern of long-term efficacy and safety assessments. The first Ayazi
(2019) gives very limited support for LINX since the mean age of patients were
not in the typical Medicare population, the follow up period was short, it was
not a randomized controlled study, and there was no comparison to the
Laparoscopic Nissen fundoplication. The second Ayazi (2019) gives no support
for LINX. It is an economic study and cost savings are not acceptable for
determining Medicare coverage. In addition, it notes, "Magnetic sphincter
augmentation (MSA) is a promising antireflux surgical treatment" as well as
"Laparoscopic Nissen fundoplication is a safe, effective, and durable
treatment."

Thus, the submitted medical evidence does not reach a level to support the
changing of this contractor's non-coverage policy.