Response to Comments: Category III Codes (L35490)

I am writing this email in support of CCE (Colon Capsule Endoscopy) obtaining its own distinct CPT code. I have performed 10 studies in my community GI practice. The technical results and accuracy are excellent. There is clearly a group of patients who need CRC screening and do not want to undergo standard colonoscopy. These include patients who are afraid of colonoscopy, fearful of anesthesia and those who simply will not take a day off of work for the procedure. Having CCE would increase our screening rate much higher than it currently is in GI private practice and thus diagnose colon polyps and CRC in earlier curable stages.
Dr. Mark Molos CEO WestGlen Gastrointestinal Consultants, Kansas

WPS appreciates the comments from a practicing clinician. The coverage decision must be made based on the medical evidence in the reconsideration request. The shortcomings of the submitted are outlined in the “Summary of Evidence” section of the LCD.

PillCam™COLON 2 System Clinical Presentation

• Medtronic respectfully requests WPS reconsider its Category III Codes LCD and provide coverage for the approved indications for the PillCam™ COLON 2 system (CPT® code 0355T)
• PillCam™ COLON 2 qualifies for Medicare coverage as a diagnostic test, as it is safe and effective, as well as reasonable and necessary for a defined patient population based upon FDA approved indications
  • For patients after an incomplete colonoscopy
  • In patients with symptoms of GI bleeding that are at a high risk for colonoscopy or anesthesia complications
• Medtronic is not requesting coverage of PillCam™ COLON 2 as a screening test for colorectal cancer
• WPS recognizes the medical necessity of alternative testing to optical colonoscopy
  • WPS’ coverage of diagnostic CTC is well-established
  • CTC coverage is for similar indications as the approved PillCam™ COLON 2 indications
  • PillCam™ COLON 2 has shown comparable, and in some cases superior, diagnostic yield to CTC in patients at risk for sedation or after incomplete colonoscopy.

Evidence Summary – PillCam™ COLON 2 Capsule
Summary
PillCam™ Colon system effectively visualizes the colon with a strong sensitivity and specificity for identifying clinically relevant colon polyps when compared to the gold-standard, optical colonoscopy and CTC. In addition, CCE improves diagnostic yield after incomplete colonoscopy and has shown superiority over CTC in this population. Finally, it should be noted that CTC is generally reimbursed as an alternative to OC in patients with increased risk factors for colonoscopy and sedation. CCE has demonstrated good performance in patients at elevated risk of colonoscopy, has shown equivalent and in some cases, superior diagnostic yield compared to CTC in variety of patient cohorts, and avoids the radiation exposure that patients obtain during CTC.
Dr. G Panagakos of Medtronic

This material would have been more appropriate for an informal meeting to initiate the reconsideration process. The material presented included articles not included in the reconsideration request, so they cannot be considered. The speaker did not address the shortcomings of the literature in the reconsideration request.

I am a gastroenterologist at Indiana University Hospital and the first author of the pivotal trial entitled, “Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening population1,” which led to FDA approval of capsule colonoscopy in persons with an incomplete colonoscopy and, later, in patients with gastrointestinal bleeding who are not candidates to undergo conventional colonoscopy. I have read the proposed LCD regarding capsule colonoscopy and am commenting on that LCD.

First, colonoscopy clearly remains the best imaging test for colorectal polyps. It should be remembered, however, that the proposed LCD is to allow coverage for the FDA determined indications of incomplete colonoscopy and for patients with rectal bleeding who are not candidates for sedation and colonoscopy. By definition, these patients either have segments of their colon or their entire colon that cannot be evaluated by colonoscopy. Therefore, it is most important to consider the performance of capsule colonoscopy relative to CT colonography, which is the alternative to colonoscopy in these situations. CT colonography has superior performance to barium enema, which is still used in some centers. However, trials comparing CT colonography to capsule colonoscopy have found capsule colonoscopy is superior with regard to polyp detection2. This includes a randomized controlled trial of capsule colonoscopy vs. CT colonography in screening patients3, which was presented at DDW 2019 (the TOPAZ trial) and which also found that capsule colonoscopy outperformed CT colonography. It is reasonable for clinicians to want the best imaging test for polyps available when conventional colonoscopy is not feasible. The evidence clearly indicates that this test is capsule colonoscopy and not CT colonography.

In my practice, I operate one of the largest referral centers for complex colonoscopy in the world. I have performed more than 800 colonoscopies in patients with previous incomplete colonoscopies, with a 98% success rate in completing colonoscopy in these persons4. In this setting we very commonly see patients who have had an incomplete colonoscopy followed by a CT colonography, and are then referred because the study is technically inadequate or because a lesion was detected. We are currently preparing our experience with CT colonography in this setting for publication, and I can report that there are very high rates of inadequate examinations, very poor sensitivity, and very poor specificity also. In short, we need a better test for imaging when conventional colonoscopy is not feasible, and capsule colonoscopy has already been proven to be better than CT colonography.

I hope you will consider these issues and approve coverage for capsule colonoscopy for its FDA approved indications.
Douglas K. Rex, M.D., MACP, MACG, FASGE, AGAF, Distinguished Professor Emeritus of Medicine,
Indiana University School of Medicine
References:
1. Rex DK, Adler SN, Aisenberg J, et al. Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening population. Gastroenterology 2015;148:948-57 e2.
2. Spada C, Hassan C, Barbaro B, et al. Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial. Gut 2015;64:272-81.
3. Cash BD, Fleisher MR, Fern S, et al. 479 a Multicenter, Prospective, Randomized Study Comparing the Diagnostic Yield of Colon Capsule Endoscopy Versus Computed Tomographic Colonography in a Screening Population. Results of the Topaz Study. Gastrointestinal endoscopy 2019;89:AB87-AB8.
4. Bick BL, Vemulapalli KC, Rex DK. Regional center for complex colonoscopy: yield of neoplasia in patients with prior incomplete colonoscopy. Gastrointestinal endoscopy 2016;83:1239-44.

WPS appreciates the comments of practicing clinicians. Two of the cited articles were in the reconsideration request, and they are discussed in the summary of the evidence section of the LCD.
A reference list was provided without the required attached documents. The additional two articles were not in the reconsideration request, so they will not be addressed in the comment period.

On behalf of Medtronic, I am pleased to submit comments to WPS GHA on the Proposed Local Coverage Determination Category III Codes (DL35940). Medtronic is the world's leading medical technology company, specializing in minimally invasive therapies that provide innovative solutions that improve patient outcomes and expand access to care for gastrointestinal disease and cancers. We are committed to the continual research and development necessary to produce high-quality products and to support innovative solutions that improve patients' lives.

As clinical research has progressed, capsule endoscopy technology has evolved and improved. On February 20, 2014, the FDA cleared the PillCam™ COLON 2 system, a class II medical device technology, and expanded indications were cleared on January 14, 2016. The PillCam™ COLON 2 capsule endoscopy system (CCE) allows for visualization of the colon. Another PillCam™ wireless capsule device, currently covered by WPS, is designed to visualize the small bowel. Capsule endoscopy using the PillCam™ SB 3 system allows for direct visualization of the small bowel when diagnosing or monitoring lesions that may be related to Crohn’s disease, GI bleeding, or iron deficiency anemia. CCE expands the use of capsule endoscopy to detect polyps in symptomatic patients who are at elevated risk for colonoscopy or sedation or in patients with incomplete colonoscopy.
As the manufacturer of CCE, we are concerned that the exclusion of coverage for 0355T in the Proposed LCD Category III Codes withholds a safe and effective diagnostic option for visualizing the colon for a defined set of Medicare beneficiaries. We believe that the available clinical evidence supports coverage for CCE as a reasonable and necessary test. We appreciate the opportunity to submit the following comments and addendum for WPS’ consideration.

WPS’ Coverage of Alternative Diagnostic Tests
WPS’ recognition of the medical necessity for alternative testing to optical colonoscopy (OC) is well-established by its coverage of CT Colonography (CTC) for a defined patient population. The coverage indications, limitation and/or medical necessity guidelines set forth in WPS’ retired LCD for CT Colonography (Virtual Colonoscopy) (L34697) established coverage for CTC for similar indications as the approved indications for CCE.
CCE is not intended to replace colonoscopy, nor is Medtronic requesting coverage of CCE as an initial screening test for colorectal cancer. However, the clinical literature demonstrates that the diagnostic yield of CCE is equal to, if not better than, CTC in certain patient groups. Medtronic believes CCE should receive the same consideration for coverage in a non-CRC screening population as CTC and respectfully requests WPS strongly consider inclusion of CCE (0355T) in the LCD Category III Codes (L35490).

Summary of Evidence
In evaluating literature to support coverage for CCE, WPS highlighted a number of perceived limitations of the data presented including applicability to the Medicare population and sample size. The attached addendum addresses the comments identified in the Draft LCD. In addition to the information in the addendum, we request that WPS consider the following.
CTC is covered as an alternative to diagnostic OC in patients with a history of previous incomplete OC and/or serious complication during OC. In addition, CTC is covered as an alternative to diagnostic OC in patients with previous documented conditions which make OC unsafe.
Likewise, the PillCam™ COLON 2 system is FDA cleared and indicated for detection of colon polyps in patients after incomplete optical colonoscopy with adequate preparation and for detection of colon polyps in patients with evidence of gastrointestinal bleeding of lower GI origin with major risk factors for colonoscopy or moderate sedation. However, WPS does not currently cover CCE for these indications, unlike CTC.
Both CTC and CCE have shown favorable sensitivity and specificity when compared to OC.
When compared to colonoscopy, one study showed that CTC had 90% sensitivity and 86% specificity for adenomas ≥ 10mm and 78% sensitivity and 88% specificity for lesions ≥ 6mm. The per-patient sensitivity for adenomas ≥ 6mm in diameter was 78%. (4) CTC has also demonstrated a sensitivity of 82% to 92% for adenomas >1cm in size. (11)
Likewise, trials of the second-generation colon capsule have shown per-patient sensitivity for polyps ≥ 6mm 84% to 88% and polyps ≥ 10mm 88% to 89% when compared to conventional colonoscopy. (1,2,3,6) A meta-analysis reported sensitivity and specificity of 86% and 88% respectively for detection of polyps ≥ 6mm, and 87% and 95% for detection of polyps ≥ 10mm. The capsule identified all invasive cancers detected by colonoscopy. (20) In addition, a recent study assessed the diagnostic accuracy of the capsule for the detection of colonic advanced neoplasia and reported a sensitivity of 90% for detection of advanced neoplasia ≥ 6 mm. (21)

Limitations with CTC
The reported sensitivity and specificity of CTC to detect all polyps range widely and decrease with decreasing polyp size. (4) CTC is associated with a miss rate and may fail to detect up to 20% of adenomas ≥ 6mm. (5, 7) CTC is operator-dependent, and significant differences in diagnostic yield have been reported among radiologists. (7) In addition, several studies have suggested that the detection of flat and serrated lesions by CTC is variable to poor. (4,10,11)
For example, a multicenter prospective study was designed to evaluate the performance of CCE and CTC for the diagnosis of non-polypoid (flat) lesions ≥ 20mm and all shapes of polyps ≥ 10mm. A total of 30 non-polypoid lesions and 51 lesions of all shapes in 27 patients were assessed. Per-lesion sensitivity of non-polypoid lesions ≥ 20mm by CCE was 87%, compared to that of CTC which was 67% (p=0.0143). Per-lesion sensitivity of lesions of all shapes ≥ 10mm by CCE was 88%, compared to that of CTC which was 69% (p=0.0063). (16)

In addition, both CTC and CCE require colonic preparation prior to utilization. However, CTC also requires colon insufflation and radiation exposure. (4) There is controversy over the long-term potential harms associated with radiation dose effects from CT examinations, especially in obese patients and those undergoing repeated examinations. (4)
Both CTC and CCE have shown effectiveness in patients with incomplete colonoscopy and in patients with risk factors for OC
A prospective, multicenter study examined 96 patients who received CCE after incomplete colonoscopy. 72% of patients achieved full colonic views with CCE alone; with CCE combined with the incomplete OC, 92.7% of patients achieved full colonic views. CCE revealed new lesions in 60.4% of patients, and 44.8% of patients needed management and treatment modification due to new revelations on CCE. It was concluded that CCE was a suitable diagnostic modality to view the colonic mucosa, and more diagnoses of significant colonic lesions were made with CCE. (9)

A prospective trial examined 50 patients who underwent immediate CCE after incomplete OC. 84% of the patients achieved full colonic views. The overall capsule diagnostic rate in unexplored colon was 76%, resulting in an incremental yield of 38%. 26% of the patients required significant changes in management due to CCE findings. The conclusion of this study was that CCE is a viable method to assess unexplored segments of colon after incomplete OC, and that CCE may relieve burden on endoscopy and radiology. (13)
One study showed that CCE allowed examination of the non-visualized part of the colon following incomplete colonoscopy in 86% of cases and the CCE findings facilitated medical decision-making for 58.8% of patients. (7)
Several studies comparing CCE and CTC have shown that CCE is as good as, or better than, CT colonography, including in patients with incomplete colonoscopy. (6)
For example, one study examined 50 patients with positive FOBT who underwent CCE and CTC followed by OC. In the intention to diagnose analysis, CTC identified polyps ≥ 6mm with 88.2% sensitivity and 84.8% specificity, while CCE identified polyps ≥ 6 mm with 88.2% sensitivity and 87.8% specificity. For polyps ≥ 10mm, CTC’s sensitivity was 78.6% with a 91.7% specificity, while CCE had a sensitivity of 92.8% with a specificity of 91.6%. These data showed that CCE detected polyps with a high level of accuracy and was comparable or even superior to CTC for the visualization of polyps. (14)
Another prospective, single-blinded study examined 97 patients with previous incomplete colonoscopy who received CCE and CTC. CCE identified 24 patients (24.5%) with polyps ≥ 6mm, while CTC identified 12 (12.2%), yielding a relative sensitivity of 2.0, indicating that CCE was significantly more sensitive than CTC. For polyps ≥ 10mm, CCE identified 5 patients (5.1%) while CTC identified 3 (3.1%) with a relative sensitivity of 1.67. (15)

Likewise, CCE has shown effectiveness when used in patients with risk factors for OC.
A prospective, multicenter study examined 107 patients with failed colonoscopy (72%) or with risk factors / comorbidities making colonoscopy with sedation contraindicated (28%) who underwent CCE. Complete colorectal examination by the colon capsule was available in 83.2% of cases. The authors noted the usefulness of the colon capsule when colonoscopy has failed or when anesthesia is contraindicated. (17)
A prospective, single center study examined 70 patients at risk of colorectal cancer who were unable to undergo colonoscopy due to anesthetic risk and co-morbidities, or who refused colonoscopy, and who received CCE to assess completion rate, level of bowel preparation and rate of adverse events. Capsule excretion rate in twelve hours was 77%, all patients accepted CCE as an alternative diagnostic tool, and 93% agreed to have another CCE study. No complications were reported during or after CCE examination. The authors concluded that “PillCam™ Colon capsule was effective at detecting significant lesions and might be considered an adequate alternative diagnostic tool in patients unable or unwilling to undergo colonoscopy.” (18)

In an editorial written in response to a study testing the efficacy of CCE in improving screening among first-degree relatives with a history of CRC, the authors note, “The role of CCE as a complementary test is valid also in the context of incomplete colonoscopies, for which CCE was shown to be effective in completing a colon examination and to impact the medical decision process. When compared to perhaps the most directly comparable non-invasive screening option (i.e., computerized tomography colonography), CCE performance for the detection of polyps was equal or exceeded computerized tomography colonography.” (12)

GI societies have commented on both CTC and CCE
The ASGE Technology Status Evaluation Report Update on CT colonography from 2019 indicates that CTC may be used adjunctively in patients who have had incomplete colonoscopy and is preferred over barium enema. (4) The ASGE colorectal cancer screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer in 2017 noted that CT colonography appeals to a niche of patients who are willing to undergo bowel preparation and are concerned about the risks of colonoscopy. (11) The recommendation goes on to note that capsule colonoscopy would be expected to appeal to a niche population concerned about the risks of colonoscopy, in a fashion similar to CT colonography. (11)
However, CTC is considered a tier 2 option while CCE remains a tier 3 option. (11) It is interesting to note that the lack of reimbursement for CCE is listed as one of the reasons CCE remains as a tier 3 option, while the authors also note that performance characteristics alone would place capsule endoscopy in tier 2. (11)
The Canadian Association of Gastroenterology (CAG) has also commented on the usefulness of CCE in patients with incomplete colonoscopy and in patients who are unwilling or unsuitable for colonoscopy. CAG Clinical Practice Guidelines from 2017 note the following: In cases in which a previous colonoscopy was incomplete or for patients who are unable/unwilling to undergo colonoscopy, CCE has been shown to be a reasonable alternative. (6)

Likewise, the European Society of Gastrointestinal Endoscopy (ESGE) guidelines have noted that CCE can be considered an option in patients with contraindications or unwilling to undergo OC and/or with an incomplete OC. (22)

Conclusion
The PillCam™ COLON 2 capsule endoscopy system effectively visualizes the colon with a strong sensitivity and specificity for identifying clinically relevant colon polyps when compared to CTC and to the gold-standard, optical colonoscopy. (1,2,3,4,6,11,20,21) In addition, CCE improves diagnostic yield after incomplete colonoscopy and has shown equivalence (and in some cases superiority) over CTC in this population. (7,9,13) Likewise, CCE has shown effectiveness in patients with risk factors for OC. (12,17,18) GI societies and key opinion leaders have noted that CCE, like CTC, may be an appropriate alternative when used in these niche groups. Although CTC is generally reimbursed for these purposes, CCE remains non-reimbursed. (4,6,11,22) Given the evidence available to date showing similar effectiveness and diagnostic yield when compared to CTC and given the added benefit of CCE in avoiding patient radiation exposure, we respectfully request consideration that CCE be covered for indications that are shared with CTC.
Thank you for the opportunity to comment on WPS’ Proposed Local Coverage Determination Category III Codes (DL35490). Should you have any questions or need further information, please do not hesitate to contact me.

Sincerely,

Willis Scott Mozingo, M.D., Director of Medical Affairs

Thank you for your comments. Please see responses below.

Addendum – Response to WPS Comments
In the Proposed Local Coverage Determination Category III Codes (DL35490), the LCD reviewer read and commented on the 6 publications referenced below. The draft policy cites the literature submitted for review as mostly preliminary studies with an unjustified sample size with limitations well outlined by the respective authors, as well as the associated editorials. The reviewer’s comments are noted below. Our response follows.
1. Eliakim R, Yassin K, Niv Y, Metzger Y, Lacter J, Gal E et al. Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy. Endoscopy 2009.

WPS Comments:
This is a feasibility study. The maximum age of the subjects was 57 years of age, limiting its applicability to the Medicare population. The sample size is not justified. The authors assert further investigation is needed. The study does not support coverage. The journal’s impact factor is 6.4, placing it in the top 5% of journals.

Medtronic Response:
The study by Eliakim et al. from 2009 represents the first report on the performance of the second-generation colon capsule system. At that time, the authors commented that further investigation would be needed. In fact, a number of studies have been published since 2009 which examine performance of the second-generation colon capsule (Hussey et al. (13) Spada et al. (1), Nogales et al. (9), Rondonotti et al. (14), Spada et al.(15), Utano et al. (16), Negreanu et al.(18)). Regarding the maximum age of 57 years old, the report mentions that “the upper age limit of 57 was mandated by the Israeli Ministry of Health review board because of the use of sodium phosphate as a propulsive agent to shorten capsule transit time in the small bowel." Note that alternatives to sodium phosphate with no such age limitation were reported later. For example, Rex et al. 2015 (reference #4 previously submitted), reports the successful usage of oral sulfate solution (SUPREP® Bowel Prep Kit) in 689 subjects with mean age of 57 years. Hussey et al. reports mean age of 57 (22 – 83); Morgan et al. reports mean age of 60.2 (32 – 70); Rondonotti et al. reports mean age of 59.2; and Spada et al. reports median age of 60 (33 – 75).

Response 4(a)
If the study of Eliakim is not as rigorous as other articles, why submit this one in the reconsideration request? One of the articles referred to was in the reconsideration request, and its shortcomings are addressed in the “Summary of Evidence” section of the LCD.

2. Hussey M, Holleran G, Stack R, Moran N, Tersaruolo C, McNamara D. Same-day colon capsule endoscopy is a viable means to assess unexplored colonic segments after incomplete colonoscopy in selected patients. United European Gastroenterology Journal 2018.

WPS Comments:
The subjects in this investigation were invited to participate in this uncontrolled study of colon capsule endoscopy (CCE) after having undergone an incomplete optical colonoscopy. There is no data on those who declined the invitation to participate. The sample size is not justified. It is troubling that subjects older than 50 years of age were five times more likely to have an incomplete CCE. The methodology of this study is weak. The study does not support coverage. The journal’s impact factor is 3.4, placing it in the top 20% of journals.

Medtronic Response:
The study aimed to assess the efficacy of same-day CCE immediately after incomplete optical colonoscopy (OC), and concluded that same-day CCE is a viable alternative means to assess unexplored segments of the colon. The study showed an overall combined completion rate using OC and CCE of 92.7%. Note that, although patients in this study had CCE the same day as incomplete OC, it is not required for CCE studies to be performed on the same day as OC. Patients with incomplete OC are often asked to return for follow-up studies such as CTC, CCE or repeat OC. In this case, all would require a repeat prep procedure. Regarding the comment “It is troubling that subjects older than 50 years of age were five times more likely to have an incomplete CCE,” only 16% (12 patients) experienced incomplete colonic views based on CCE alone. Of those, 66% (8 patients) were >50 years old. However, the authors go on to note that relevant comorbidities such as diabetes and parkinsonism were more prevalent in those patients experiencing incomplete studies. The authors speculate that these comorbidities “could represent potentially significant influences on both gastric motility as well as overall bowel preparation which may influence potential future same-day CCE patient selection.”

Response 4(b)
The Medtronic response does not address the fatal flaw of an unjustified sample size. The reason for the incomplete CCE is speculative; regardless of the reason, the finding of the study is that patients in the Medicare population are more likely to have an inadequate CCE.

3. Morgan DR, Malik PR, Romeo D, Rex DK. Initial US evaluation of second-generation capsule colonoscopy for detecting colon polyps. BMJ Open Gastroenterology 2016.

WPS Comments:
This study was performed using a “population enriched for polyps.” There is no discussion of the validity of extrapolating these results to the general Medicare population. A second purpose of this investigation was to evaluate the “use of the magnesium citrate as a boosting and prep agent.” The authors express a concern that this may have influenced the specificity of capsule colonoscopy. An additional concern of the investigators is that because this was a preliminary investigation, the sample size is too small to properly assess sensitivity. The concerns of the investigators are difficult to ignore. The impact of this journal is 1.6, placing it in the top 70% of journals.

Medtronic Response:
This is a US prospective multicenter study to assess the accuracy of CCE and to evaluate the use of magnesium citrate as a boost in a mixed screening and symptomatic population. CCE sensitivity for the detection of polyps ≥ 10mm and ≥ 6mm was 100% and 93% respectively, and the specificity was 93% and 80%. The sensitivities were similar, although numerically higher, to that reported in Rex et al. 2015 (reference #4 previously submitted). With the use of magnesium citrate as the boost, the overall quality of the preparation was inferior to that reported in Rex et al. which used oral sulfate solution (SUPREP® Bowel Prep Kit) as the boost, accounting for the improved completion rate and superior colon prep. The authors indicated that the use of magnesium citrate could be one of the causes for the lower specificity, and that magnesium citrate was not adequate as a boost agent.
The effectiveness of a specific prep regimen is an important consideration and potential limitation for OC, CTC and CCE. The prep regimen recommended in the PillCam™ Colon System User Manual is the same as the prep and boost regimen validated in Rex et al. 2015 (#4 previously submitted)

Response 4(c)
The Medtronic response does not address the sample size, the ability to extrapolate the findings to a population that was not enriched for polyps, or the fact that the hypothesis under investigation is not germane to coverage.

4. Rex DK, Adler SN, Aisenberg J, Burch Jr. WC, Carretero C, Chowers Y, et al. Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening population. Gastroenterology 2015.

Tierney WM. Colonoscopy versus capsule: sharing the spotlight. Gastroenterology 2015 (This is the editorial associated with Rex et al.)

WPS Comments:
Rex et al. is a nicely done study that is supportive of capsule colonoscopy. However, the authors note that capsule colonoscopy requires a more extensive bowel prep than fiberoptic colonoscopy, has a high technical failure rate, and “the logistics of performing same-day colonoscopy in patients with a positive capsule study are difficult.” The associated editorial (Tierney) reiterates these issues asserting the need to clarify the role of capsule colonoscopy among screening options. The impact factor of Gastroenterology is 21, placing it in the top 2% of journals.

Medtronic Response:
Technical failures, defined in the study as short transit time and poor preparation, occurred in 9% of patients. It is unclear how relevant such “failures” would be in actual clinical practice. For example, if an actionable lesion were found during a capsule study with short transit time, that patient would be sent for OC despite qualifying as a “technical failure” as defined in this study. Regarding the logistical difficulties associated with same-day OC in a patient with a positive capsule study, the same limitations may be present with other non-OC modalities. It is also noted that several studies have reported on the feasibility of same-day CCE after incomplete OC (Hussey et al. (13) and Triantafyllou et al. (19)). It is important to note that the authors’ comments were made in the context of considering the capsule as a colorectal cancer screening test. The authors go on to point out that the capsule “appears to be an appropriate imaging choice for patients who cannot undergo colonoscopy or had incomplete colonoscopy,” the same indications for which coverage is currently requested.
Regarding the comment related to the role of capsule endoscopy among screening options, it is important to note that CCE coverage is not being requested for screening in the general population. Rather, CCE coverage is being requested for the indications cleared by the FDA, which are similar to the indications for which CTC is currently covered:

• It may be used for detection of colon polyps in patients after an incomplete optical colonoscopy with adequate preparation, and a complete evaluation of the colon was not technically possible.
• In addition, it is intended for detection of colon polyps in patients with evidence of gastrointestinal bleeding of lower GI origin. This applies only to patients with major risks for colonoscopy or moderate sedation, but who could tolerate colonoscopy and moderate sedation in the event a clinically significant colon abnormality was identified on capsule endoscopy.

Response 4(d)
As noted in the “Summary of the Evidence” this is the strongest of the articles submitted in the reconsideration request. Medtronic did not address the concerns raised by the investigators and the editorial writer. WPS looks forward to more evidence of similar rigor.

5. Rondonotti E, Borghi C, Mandelli G, Radaelli F, Paggi S, amato A, et al. Accuracy of capsule colonoscopy and computed tomographic colonography in individuals with positive results from the fecal occult blood test. Clinical Gastroenterology and Hepatology 2014.

Johnson DA. Can capsule colonoscopy and computed tomographic colonography accurately evaluate patients with positive results from the fecal immunochemical test, and are these ready for prime time? Clinical gastroenterology and Hepatology 2014; 12: 1311-4. (This is the editorial associated with Rondonotti et al.)

WPS Comments:
The associated editorial (Johnson) provides a nice summary of the flaws of Rondonotti et al.: sample size not justified, a satisfaction assessment tool that had not been validated, and the fact that it is a pilot study. The journal has an impact factor of 7.9, placing it in the top 3.5% of journals.

Medtronic Response:
There are a number of additional reports (listed below) assessing CCE vs CTC in variety of patient cohorts. CTC has inherent disadvantages when compared to CCE such as questionable accuracy for lesions ≤ 6mm and for flat lesions regardless size and radiation exposure. The studies cited below conclude that the diagnostic yield of CCE is equivalent (and in some cases superior) to CTC.

• Utano K et al. Colon capsule endoscopy versus CT colonography in patients with large non-polypoid tumors: a multi-center prospective comparative study. Digestion 2019 [Epub ahead of print]
• Spada C, et al. Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial. Gut 2015; 64(2): 272-81.
• Pioche M et al. Colon capsule versus computed tomography colonography for colorectal cancer screening in patients with positive fecal occult blood test who refuse colonoscopy: a randomized trial. Endoscopy 2018; 50(8):761-769
• Milluzzo et al. Colon capsule endoscopy and its effectiveness in the diagnosis and management of colorectal neoplastic lesions. Expert Review of Anticancer Therapy, 2019;19(1): 71-80
• Gonzalez Suarez B. et al. Colon Capsule Endoscopy versus CT Colonography in Colorectal Cancer Screening patients with Positive Fecal Immunochemical testing: A Prospective and Randomized trial. Preliminary results. Gastrointest Endosc 2016;83(5S): AB360 [Abstract]
• Cash BD et al. A multicenter, prospective, randomized study comparing the diagnostic yield of colon capsule endoscopy versus computed tomographic colonography in a screening population. Results of the TOPAZ study. Gastrointestinal Endoscopy 2019; 89, No. 6S: AB87-AB88 [Abstract]

Response 4(e)
Only one of the articles cited in Medtronic’s response was in the reconsideration request; that article’s shortcomings are addressed in the “Summary of the Evidence” section of the LCD. Medtronic’s response does not address the sample size, the fact that this is a pilot study, or invalidated satisfaction instrument.

6. Spada C, Hassan C, Barbaro B, Iafrate F, Cesaro P, Petruzziello L, et al. Colon capsule versus CT colonography in patients with incomplete colonoscopy: a prospective, comparative trial. Gut 2015.

WPS Comments:
The authors conclude that this study demonstrates the feasibility of capsule colonography. However, they express concerns about false negative and false positive rates being inadequately addressed as well as interobserver and intra-observer variability. The endoscopist who provided the gold standard test knew these patients had a significant finding on a previous test. The authors assert further work is needed. The journal has an impact factor of 17 placing it in the top 2% of journals.

Medtronic Response:
Limitations relative to the potential for false negative findings were present for both CCE and CTC given that patients without clinically relevant lesions on CCE and CTC did not undergo further OC. In addition, CCE showed a two-fold increase in the diagnostic yield of clinically relevant lesions when compared to CTC, without an increase in the proportion of false-positive results. Also, a number of additional studies, including those listed in the comments provided for the study by Rondonotti et al., have assessed the performance of CCE compared to CTC and found the diagnostic yield of CCE to be equivalent (and in some cases superior) to CTC.

Response 4(f)
The Medtronic response does not address the fact that this is a feasibility study; the issues of the false negative rate, the false positive rate, or the inter-rater reliability issues; or the fact that the gold standard endoscopist was not truly blinded.

General comments: The purpose of the response to comments is to help the stakeholder to understand why the request was denied and to prepare a more rigorous request in the future. The stakeholder failed to address the flaws in the submitted literature that WPS identified. The stakeholder seemed to feel that the provision of extra verbiage would overcome that oversight. It did not. The flaws in the submitted literature resulted in a request that was not supportive of coverage.

WPS also encourages a more judicious approach to submitting literature than was evident in the response to comments. Five robust articles would be sufficient to successfully support coverage.

References

1. Spada C, et al. Second-generation colon capsule endoscopy compared with colonoscopy. Gastrointest Endosc 2011;74 581-9. e1.
2. Eliakim R, et al. Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy. Endoscopy 2009; 41:1026-31.
3. Wang A, et al. ASGE Technology Status Evaluation Report Wireless capsule endoscopy. Gastrointestinal Endoscopy 2013; 78(6): 805 – 815
4. Farraye F, et al. ASGE Technology Status Evaluation Report Update on CT colonography Gastrointestinal Endoscopy 2019; 69(3): 393 – 398
5. Atia M, et al. Editorial: The Dilemma of Incomplete Colonoscopy: What is the next best test? Clinical Gastroenterology and Hepatology 2013; 11(5): 541- 542
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Colon cancer continues to affect hundreds of thousands of people annually in the United States. In 2019, approximately 135,000 people will be diagnosed with colon cancer and 40,000 people will die from the disease. Many GI societies including the American Gastroenterologic Association and American College of Gastroenterology, along with the American Cancer Society had put forth the proposition that 80% of eligible people have a colon cancer screening exam by 2018. Here we are in the latter stages of 2019 and that number only reaches 67%. Many of these people who have undergone colonoscopy as a screening too have incomplete exams due to the anatomy of the colon and the inability to visualize the entire colon. A subsequent examination is needed to visualize the entire colon. One alternate exam is a CT colonography that has been shown to be inferior to other alternate examinations, including the Pillcam COLON 2. The PillCam COLON 2 exam is a non-invasive exam that has been shown to visualize the entire colon in over 94% of subjects. It is better tolerated and patient satisfaction is higher than CT colonography. The yield in finding significant polyps, and therefore, the efficacy is higher than CT colonography. In this population, that is, patients undergoing colon cancer screening by colonoscopy, and being found to have an incomplete colonoscopy, a Pillcam COLON 2 exam is the most efficacious and better tolerated than alternative exams.
The literature does show evidence of Pillcam COLON 2 as a viable entity in these diagnoses. The Rex study is the most poignant and in real life patients, that capsule colonoscopy requires a more extensive bowel prep than fiberoptic colonoscopy, has a high technical failure rate, and the logistics of performing same-day colonoscopy in patients with a positive capsule study are difficult, have not been as egregious as once thought. Patients are tolerant of the preparation, the high failure rate is low (6%) and, although, the logistics of performing same day capsule can be challenging, it is certainly possible, and highly probable, in this population.
I am, therefore, requesting that WPS cover PillCam COLON 2 for the FDA approved indications.
I appreciate your attention in this matter. It will go a long way in eliminating colon cancer in our lifetime as well as helping to prevent patients and caregivers from being exposed to this deadly disease.
Steven E. Fern, D.O.

WPS appreciates the comments from a practicing clinician. The coverage decision must be made based on the medical evidence in the reconsideration request. The shortcomings of the submitted are outlined in the “Summary of Evidence” section of the LCD.