Response to Comments: Select Minimally Invasive (GERD) Procedures

A professor of surgery wrote in support of the LINX procedure stating there are at least 20 million Americans dependent on a daily dose of a PPI. About 40% of these patients continue with symptoms despite these high dose medications. 

We appreciate the comments. However, we must base all our decisions on published peer-reviewed medical articles indexed in PubMed from U.S. National Institutes of Health's National Library of Medicine.

A surgeon in support of the LINX device stated: "The LINX device has been an FDA approved device since March of 2012. It is designed for the strengthening of the lower esophageal sphincter in the treatment of GERD. In comparison to currently covered anti-reflux procedures (surgical fundoplication), LINX recovery is at least equally effective, if not superior, in alleviating reflux symptoms. Additionally, LINX carries better safety and side effect profile than fundoplication. Recovery is quicker and easier as well."

Please see above.

A thoracic and esophageal surgeon in support of magnetic sphincter augmentation stated: "There is a significant amount of data already available justifying the procedure, which also is much more reproducible than standard fundoplication. I am hopeful that these decisions can be reconsidered, as they are hampering the progress for treatment of this very common disease.”

We appreciate the comments. We have reviewed all the submitted medical literature. The review of these papers in our opinion does not justify coverage of magnetic sphincter augmentation. The issue here is not fundoplication.

A thoracic surgeon in support of LINX anti-reflux device indicated that it has proven to be safe, effective and long-lasting. The medical literature supports not only the efficacy, but the long term cost-effectiveness and safety.

We appreciate the comments. However, we must base all our decisions on published peer-reviewed medical articles indexed in PubMed from U.S. National Institutes of Health's National Library of Medicine. We do not currently concur that the medical literature supports the efficacy of magnetic sphincter augmentation. Medicare cannot use cost-effectiveness as a reason for coverage.

Another surgeon commented: “LINX is a standard FDA approved treatment for GERD. Surgical treatment options that are considered standard today include laparoscopic Nissen fundoplication and LINX procedure. Both of these treatments have been shown in published studies to be more effective than medical management. LINX is comparable for mid-long-term studies to be as effective and durable as laparoscopic Nissen fundoplication with less risk of mortality and major morbidity. It has been recommended based on the available published literature to be a standard surgical treatment for GERD in newly updated nationally published guidelines from the Society for Gastrointestinal and Endoscopic Surgeons.”

We appreciate the comments. Our review of the submitted medical literature does not currently support the coverage of magnetic sphincter augmentation.

A reflux specialist and board-certified surgeon stated: “The current standard practice remains laparoscopic fundoplication. In my expert opinion, the LINX procedure out-classes fundoplication in many respects while maintaining all of its benefits. Postoperative dysphagia (difficulty swallowing), gas-bloat syndrome, and need for revision are all too common in fundoplication, leading to further expensive procedures / surgical revisions, and most importantly, dissatisfied patients.”

Thank you for the comments. Please see the above related NGS responses.

A surgeon offered the following: "The group conducting the literature review frequently mentioned a lack of data from patients in the Medicare population. Sadly, this will continue to be an issue if LINX is not approved by Medicare."

The surgeon also stated: "There is no physiologic reason why two patients of different ages, with similar esophageal motility and post-op anatomy, would have different response rates to the device. Therefore it is not logical to wait for more data in the target age range to be published before approving the device. The report of the publications does not discuss length of OR time or hospital stay. For most patients the first two main steps of the surgery are the same for fundoplication vs LINX (reduction of any hiatal hernia and closure of the crura). However, the third step of the surgery - completing an anti-reflux procedure takes less time with the LINX device than with fundoplication."

The surgeon also noted that: "It has been reported that the mortality rate for LINX is 0. It is not zero for fundoplication, mainly due to the risk of a leak."

We appreciate the comments. However, we must base all our decisions on published peer-reviewed medical articles indexed in PubMed from U.S. National Institutes of Health's National Library of Medicine.

Another commenter stated: "There are several surgical treatment options for GERD, one of the most common being the Nissen Fundoplication. The Nissen Fundoplication has shown to have a 90% positive patient satisfaction rate, but it has been plagued with several potential complications to include gas bloat, food getting stuck, inability to belch or vomit, and recurrence of symptoms over time due to loosening of the wrap. Currently in my practice, I see many patients who have had prior anti-reflux surgery, most commonly the Nissen Fundoplication, and they are presenting with recurrent symptoms of reflux and often recurrent hiatal hernias. In fact the literature suggests that patients with a hiatal hernia have a 50% chance of recurrence of the hernia over time. Redo surgery is much more challenging with higher complication rates.

The LINX is an FDA approved device, since 2012. It is designed as a surgically implanted device that strengthens the lower esophageal sphincter to prevent GERD. It has been shown to have an extremely safe profile and has been very effective at controlling GERD and symptoms of heartburn. Several key advantages of the LINX is that it doesn’t loosen over time like the Nissen Fundoplication, and patients are able to belch and vomit with the device in place."

The following was also noted:

• the recurrence of hiatal hernias is much lower than what is seen after the Nissen Fundoplication, currently at less than 5% recurrence; 
• recovery tends to be quicker and often can be performed as an outpatient surgery without overnight stay in the hospital; and
• effective, as an alternative to the fundoplication after paraesophageal hernia repairs, currently with a lower long-term recurrence of the hernia.

We appreciate the comments. Please see our responses above.

A surgeon commented that: “In comparison to currently covered anti-reflux procedures (surgical fundoplication), LINX Reflux Management System is at least equally effective, if not superior, in alleviating reflux symptoms. Additionally, LINX carries better safety and side effect profiles than fundoplication, and recovery is faster and easier on the patient as well.”

We appreciate the comments. All submitted medical literature in peer-reviewed medical journals indexed in PubMed from U.S. National Institutes of Health's National Library of Medicine has been reviewed. Please see our responses above.

One commenter wrote in support of the proposed LCD DL35080 in which the Contractor concludes, based on J&J’s March 2019 submitted medical evidence that published LINX data does not reach a level to support the changing of NGS’ non-coverage policy. The commenter also stated that: “In addition, Ganz et al describe a population of 85 patients with 5-year follow up and no device erosions or malfunctions. While this seems favorable, there are a notable number of U.S. explants of the LINX device, according to FDA data. 

Smith et al (Lap & Adv Surg Tech 27:586, 2017) published there were 89 explants between 2012 and 2016, representing 2.7% explants out of a total of 3,283 cases performed. Reasons for removal were dysphagia (52) and reflux (19). The period in Smith et al. was 3/2012 to 5/2016. Smith et al. were an industry funded study (Torax).  

According to the MAUDE database today, there were actually 235 registered explants and device removals, from CY2012 to CY2016 inclusive, representing a 7% explant rate if the same 3283 cases were used as denominator (independent FDA data search by third party; figure below). Possibly, this represents delayed reporting from data available to Smith et al., or different use of keywords, but 7% is a meaningful difference from 2.7%. See: FDA MAUDE database accessed October 22, 2019, via https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/results.cfm

Alicuben et al (J GI Surg 22:1442, 2018) affirm, the MAUDE data base is a voluntary, self-reported database and is not expected to generate a maximum for adverse events rates, due to under-reporting or under-counting. Alicuben et al., which was independently funded, state, MAUDE “cannot be used to calculate adverse event rates.”

We appreciate the comments and support of the draft LCD.

A Board Certified General Surgeon stated: "I am the principal and corresponding author of one of the studies discussed in the review of LINX (item 6, page 8/20). I am also co-author and co-investigator of one of the studies (RESPECT) discussed in the review of TIF (Item 7, page 4/20); please keep that in mind when I mention the RESPECT study in the following discussion, as I am intimately familiar with that study. TIF is now an accepted and covered procedure by Medicare.

First, as primary author of the study, I would like to offer some input on both the study and the review’s comments of Clinical Study 6, page 8/20 on the proposed LCD.

The review of this study (Bell et al 2019) states the following:

"Also, only 134 were analyzed. Per protocol, 89%(42/47) of MSA patients achieved resolution of 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 patients compared to the 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.”

1. It is unclear where the number “134” originates, as it is nowhere in the manuscript. All numbers were triple-checked by the author, submitted twice to all authors, and reviewed by 3 independent reviewers for GIE.
2. The patient age group is typical of the various studies of the various procedures (TIF, Stretta, LINX). The RESPECT study for TIF, which the reviewer found supportive of TIF, had a median patient age of 52 with only 9% of patients aged > 65. The TEMPO TIF study (not mentioned in the review of TIF but also a non-blinded RCT of TIF v PPI) had a median age of 51.5, with 8% of patients > 65 yo. Criticism of, or acceptance of age groups in studies should be consistent across the various procedures analyzed. It is unclear physiologically why a Medicare age group should be any different from a slightly younger age group, and I would ask that this objection be removed.
3. Short follow-up concerns.

1. This study randomized patients to medical or surgical therapy and the time-frame for follow-up was set primarily in terms of the medical therapy arm – patients that did or did not respond by 6 months to bid PPIs were unlikely to change with further follow-up. Other LINX studies support durability of LINX beyond 6 months with little change in outcome of regurgitation or heartburn symptoms. A 1-year follow-up study has been recently published and which I am including.
2. The RESPECT study for TIF, which again the review found supportive of TIF, had only 6 month follow-up. Consistency in standards is appropriate for a government reviewing agency.

4. “All the improvement is subjective rather than some objective measure.” This statement is incorrect.

1. To quote from the online issue of this study, page 5:“Impedance-pH testing measures both pH and the number of reflux events, regardless of acidity, and is considered a valuable technique for evaluating GERD in patients receiving PPI therapy.⁷ The primary criteria for assessing reflux by using impedance-pH testing is the number of re- flux events per 24 hours (Fig. 4).²⁴ By this measure, MSA controlled reflux significantly better than BID PPIs (22.5 IQR: [13.0-40.5] compared with 49.0 IQR:[31.0-76.78]; P < .001). Additionally, 91% (40/44) of patients in the MSA arm had a normal number of reflux episodes at 6 months versus 58% (46/79) in the BID PPI arm. Eighty- nine percent (39/44) of patients in the MSA arm had normal esophageal acid exposure by percentage of time with pH <4 as well as the DeMeester score, compared with 75% (59/79) and 71% (56/79) in the BID PPI arm, respectively. Mean esophageal acid exposure (percentage of time with pH <4) in the MSA group (2%) trended to being lower than in the BID PPI group (5%), but did not reach statistical significance (P = .065). The mean DeMeester score in MSA patients was 8 compared with 18 in the BID PPI arm (P = .059)."
2. Mean esophageal acid exposure in the LINX group decreased from 11.5% to 2% at 6 months. This was not emphasized as other studies have confirmed the improvement in esophageal acid exposure with LINX.
3. To try to clarify the intent of the study with regards to objective outcomes – it is well accepted that PPIs do little to decrease the number of reflux episodes, and that regurgitation is a symptom is related to volume, and number, of reflux events. This study demonstrated that double-dose PPIs did not result in a normal number of reflux events to the same degree that LINX did.
4. Again, with regards to consistent standards: In the RESPECT study – which the review found supportive of TIF, mean esophageal acid exposure improved from 9.3% to 6.3%, less than that of LINX, yet still significant.

5. “This was not a blinded study. Of course it is difficult to perform a sham abdominal procedure.”

1. It is not clear whether this is a valid concern as the review contradicts itself, For this to be a true concern, again applied across the board, then every new surgical procedure should be subjected to a blinded, sham -controlled study.
2. A recent editorial on LINX by Dr Joel Richter, (attached) is worth quoting: “Although a sham study cannot be done, large case series from the US and Europe have been unanimous in showing that the MSA device is highly effective in treating GERD.”

Thank you for the comments. “It is unclear where the number “134” originates, as it is nowhere in the manuscript.” This is from figure one of the article. Under Analysis it states for “MSA arm”, “Analyzed (n=47).” It also states for the “BID PPI arm”, Analyzed (n=87).” Thus we concluded that 134 (47+87) patients were analyzed.

At the time of the reviews, 84% of Medicare patients were 65 years old or older. Thus it is appropriate to want studies that reflect typical Medicare age patients. As people get older, they tend to develop other disease processes and worsening of their original health. This is why life insurance premiums rise as one ages.

Please see the above related NGS responses.

The manufacturer stated: "We respectfully disagree with NGS’s conclusion that the submitted new evidence with regards to the LINX Reflux Management System (RMS) were insufficient to warrant a change in coverage for Medicare beneficiaries, and we offer additional perspectives to support coverage in response to NGS’s concerns in the proposed LCD.

In NGS’s comments, there is specific mention made to the lack of Medicare patients included in several clinical trials. In fact, Medicare-aged beneficiaries have been included in all referenced studies, including the LINX IDE Pivotal Trial study (Ganz 2013). A sub-analysis of that study yields similar outcomes to the broader study population both in terms of ability to vomit and ability to belch at baseline compared to 36-month follow-up.

Long-term Safety

LINX has prioritized capturing a high volume of unique patient data into published studies. Out of ~20,000 total LINX implants worldwide, safety data has been reported on at least 9,400 patients over 4-year follow-up (50% of total patients who underwent the procedure) [1]. In comparison, the number of unique patient data studied from patients who underwent Transoral Incisionless Fundoplication (TIF) is approximately 1,600 patients, which is a maximum of 7% of patients who underwent the procedure [2].

As submitted in the LCD Reconsideration request, LINX has undergone a head-to-head randomized control trial that compared LINX to twice-daily (BID) 20 mg omeprazole PPI. 152 GERD patients (including Medicare-aged beneficiaries) with moderate-to-severe regurgitation were prospectively enrolled in this double-arm, cross-over study and were followed for 6 months. The RCT demonstrated significant relief from regurgitation with LINX therapy compared to patients in whom the PPI dosage was increased from single to double-dose. Specifically, the RCT demonstrated that 89% of patients experienced complete resolution of their moderate-to-severe regurgitation symptoms compared to 10% of the BID PPI arm (p<0.001). (Bell RC, et al, "Laparoscopic magnetic sphincter augmentation vs. double-dose proton pump inhibitors for management of moderate to severe regurgitation in GERD a randomized controlled trial," Gastrointestinal Endoscopy, vol. 89, no. 1, pp. 14-22, 2019).

The completion of one RCT, two FDA trials providing significant long term follow up, as well as multiple studies and peer-reviewed articles support the use of the LINX Reflux Management System. Its long-term safety and efficacy indicate that the LINX procedure has withstood appropriate scrutiny, can no longer be considered experimental/investigational, and therefore should be considered a part of the armamentarium in the proven and effective surgical treatment of GERD in appropriate patients for Medicare beneficiaries."

Thank you for the comments. Please see the NGS responses above.