Leadless Pacemakers

December 14, 2016

Tamara Syrek Jensen, JD
Director, Coverage & Analysis Group
Office of Clinical Standards and Quality
Centers for Medicare & Medicaid Services
Mailstop C1-09-06
7500 Security Blvd
Baltimore MD 21244

RE: Medicare Proposed National Coverage Determination for Leadless Pacemakers

Dear Ms. Syrek Jensen:

On behalf of Boston Scientific, we appreciate the opportunity to provide input on the proposed National Coverage Determination (NCD) pertaining to Leadless Pacemakers.

Boston Scientific supports the use of Coverage with Evidence Development (CED) to cover leadless pacemakers. We urge CMS to make several changes to ensure that the final coverage policy strengthens patient protection while also facilitating coverage for leadless pacemakers as the technology evolves and indications expand. In particular, we urge CMS to:

1. Utilize a prospective national registry as a condition for coverage under CED for leadless pacemakers
2. Broaden the description of leadless pacemaker to accommodate future FDA-approved indications
3. Include evidence-based shared decision-making as a condition for coverage

Technology Overview:

Leadless Pacemakers are cardiac pacemakers wherein the entire implantable portion of the system can reside in any chamber of the heart. These devices are “self-contained enclosed capsules that include the pacemaker electronics and battery”. Leadless pacemakers are intended to provide therapy in patients with pacing indications.

Although contemporary VVI pacemakers have been shown to be safe and effective, avoiding the need for an intravascular lead may help mitigate certain risks, including infection, venous occlusion, tricuspid regurgitation, and remedial actions that require lead extraction.

Prospective National Registry as a Condition for Coverage under CED:

Boston Scientific appreciates that CMS is proposing to use a flexible approach to CED to cover leadless pacemakers, and has not dictated specific trial design parameters. While CMS proposes coverage for procedures conducted within the context of a study that address three research questions (and meet other criteria), CMS is not requiring that the study must answer all three questions. We appreciate that CMS recognizes the challenges and compromises associated with designing a single study that conclusively answers all three research questions. For example, IDE studies typically would not be able to answer questions on “the long-term outcomes of leadless pacemakers”.

We appreciate and support flexibility on trial design for pre-market studies. Flexibility for pre-market studies is critical because of the wide variation in trial designs based on the target patient populations, specific indications being studied and other factors.

Boston Scientific agrees with CMS that there are gaps in evidence on leadless pacemakers and we support the use of CED to address these gaps while providing patient access to this valuable technology. CMS has stated in the Proposed Decision Memo for Leadless Pacemakers (CAG-00448N) that “these devices have not been tested in broader, long term studies that include real world practice settings and are currently being followed in FDA-required post market studies.” Prospective, national registries are ideal for collection of broader long term real world evidence. CMS has recognized this approach in previous National Coverage Determinations.

Using a prospective, national registry for post-market data collection for leadless pacemakers would be consistent with other recent National Coverage Determinations on innovative technologies, i.e. National Coverage Determination (NCD) for Transcatheter Aortic Valve Replacement (TAVR) (20.32), National Coverage Determination (NCD) for Transcatheter Mitral Valve Repair (TMVR) (20.33), National Coverage Determination (NCD) for Percutaneous Left Atrial Appendage Closure (LAAC) (20.34).

Boston Scientific supports the use of a prospective, national registry for post-market data collection on leadless pacemakers for the following reasons:

• Comparison of data from a registry with interventional/controlled trials would allow CMS to better assess the impact of hospital and operator experience on health outcomes.


• A prospective, national registry would enroll all patients with FDA approved implants, accommodate a larger sample size and enable CMS to meaningfully capture the incidence of device related long term adverse events. As CMS states in the Proposed Decision Memo for Leadless Pacemakers (CAG-00448N): “Confidence in the current estimates of adverse events remains unclear and many questions remain unanswered.” and, “More information is needed regarding infection rates and remedies; the prevalence of device dislodgement (as a dislodged device will fail to function); the possibility for device extraction; long-term hemodynamic effects and thrombus formation issues; handling of end of battery life; safety of multiple leadless pacemakers; safety of shocks administered to patients with a leadless pacemaker; and variability in outcomes given periprocedural events observed (superior or inferior) based on operators and/or facilities.” Data from a registry would address the evidentiary gaps with respect to adverse events. A comprehensive national registry would provide appropriate patient access to this important new technology in conjunction with a robust mechanism of data collection to answer outstanding questions.


• Individual manufacturer post-market studies can be very different in terms of study design, endpoints, and follow up period. A prospective, national registry would allow better comparison of results across different manufacturers.


• The large sample size and heterogeneity of a prospective, national registry would allow CMS to study a wider range of patient characteristics, conduct appropriate sub group analyses to develop appropriate guidance on target patient characteristics for leadless pacemaker implants. Ultimately, the heterogeneous study population in a prospective, national registry will allow greater generalizability of results to the broader Medicare population and ensure broader patient access under CED.

Modify the Description of Leadless Pacemaker:

Boston Scientific recommends modification of the definition of leadless pacemaker technology. Modification of the definition would minimize the need to repeatedly reconsider the national coverage determination as the technology evolves.

The proposed Decision Memo for Leadless Pacemakers (CAG-00448N) describes leadless pacemakers as follows:

“Leadless pacemakers have the potential to significantly reduce serious adverse events related to pacemaker implantation by eliminating transvenous leads and the need for a surgical pocket. These devices are self-contained enclosed capsules that include the pacemaker electronics and battery, and currently range from around 26 mm to 42 mm in length, and have a maximum diameter between six mm and seven mm (Reddy et al., 2014;Ritter et al., 2015). Leadless pacemakers are delivered via catheter to the right ventricle of the heart, and function similarly to other transvenous single-chamber ventricular pacemakers.”

Leadless pacemakers may not be limited to placement in the right ventricle. Additionally, indications other than bradycardia are being considered for leadless pacemakers. Therefore, we recommend revision to the description of leadless pacemakers as follows (please see the last two sentences of the paragraph below):

“Leadless pacemakers have the potential to significantly reduce serious adverse events related to pacemaker implantation by eliminating transvenous leads and the need for a surgical pocket. These devices are self-contained enclosed capsules that include the pacemaker electronics and battery, and currently range from around 26 mm to 42 mm in length, and have a maximum diameter between six mm and seven mm (Reddy et al., 2014; Ritter et al., 2015). Leadless pacemakers can be delivered via catheter to any chamber of the heart. It is intended to provide therapy in patients with pacing indications and function similarly to other transvenous single-chamber ventricular pacemakers.”

Shared Decision Making:

Boston Scientific supports evidence-based shared decision-making as a condition of coverage for leadless pacemakers, in accordance with ACC/AHA/HRS pacing guidelines which state: “In addition, patients should be informed of the risks, benefits, and alternatives to a particular treatment and should be involved in shared decision making whenever feasible, particularly for COR IIa and IIb, for which the benefit-to-risk ratio may be lower.”

Leadless pacemakers carry a different set of risks and benefits than traditional transvenous pacemakers. Patients may be eligible for both types of devices; therefore the risks and benefits of each type of device should be thoroughly discussed with the patient before a decision to implant is made.

The shared decision-making process is distinct from informed consent, therefore patient enrollment in a clinical trial does not eliminate the need for engagement in a shared decision-making process.

Conclusion:

Boston Scientific supports the use of Coverage with Evidence Development (CED) to cover leadless pacemakers. We urge CMS to consider suggested changes to ensure that the final coverage policy facilitates ongoing access to leadless pacemaker therapy as the technology and patient indications evolve over time. In particular, we urge CMS to utilize a prospective national registry as a condition for coverage under CED for leadless pacemakers, to broaden the description of leadless pacemaker to accommodate future FDA-approved indications and include evidence-based shared decision-making as a condition for coverage.

We appreciate your consideration of our comments.

Kind Regards,
Karen Nordahl

Director, Health Economics & Market Access
Boston Scientific Corporation

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Thank you for the opportunity to comment on the NCD proposal re leadless pacemakers. I have read the entirety of the proposal. I am a cardiologist involved in pacemaker implantation and follow-up (for 36+years)and am involved in the clinical leadership of the Micra Transcatheter Pacemaker Global Clinical Trial since its earliest development.

My specific comments follow:

1)It is important to reiterate that the 2 leadless pacemakers that have been studied in pivotal clinical trials are restricted to use, by design and experience, to the right ventricle. Only one of these has been approved for use by the FDA (Micra: April 6 2016). Broader coverage than for use in the right ventricle would clearly be inappropriate.

2)Regarding periprocedural and post procedural complications as well as the effects of patient characteristics in a general and relatively unrestricted typical pacemaker population, the Micra IDE trial (noted above) was designed to be a "real world" trial and indeed included 725 patients from 19 countries, 56 centers, involving implantation by 94 different implanters. Remarkably positive results in implantation rates (99.2%), major complication rates (4%) and efficacy rates at implant through 6mos (98.3%) are detailed. The FDA-influenced and approved Micra post-market study (PAS), currently enrolling, has been designed specifically to augment information on complications, both short and medium-long term, and patient characteristics. This PAS study is a rigorous scientific endeavor that will be substantially labor intensive and expensive but should provide the information needed to satisfactorily answer these 2 stated issues.

3) The 3rd primary question raised about long-term outcomes will partially be addressed in the Micra PAS but this issue is complex and won't be answered completely for almost a decade. A limited volume of end of service experiences will accrue and be studied in depth in the Micra PAS, and presumably similar pre and post market studies for other leadless devices, but a broader tracking of device experiences in a much larger population, perhaps as a result of information that could accrue in a Medicare database analysis would satisfy better, and much less expensively, end of service questions.

4)It seems to me very inadvisable to restrict use of this newer and very promising leadless technology to the small fraction of potential patients that can be enrolled in a cost effective intensive post market study or studies. Medicare patients deserve, I believe, broad-based access to this technology unfettered by undue restriction to patients enrolled in studies that could always be criticized as not real-worldly.

5)The proposal to require a CED as part of the NCD for this technology seems unnecessary to the extent that FDA mandated post market trials are otherwise both rigorous and required. This point (with or without CED), however, is less important than broad-based access not limited to patients enrolled in FDA approved post-market trials.

Thank you for your consideration.

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December 14, 2016

Ms. Tamara Syrek Jensen, J.D.
Director, Coverage & Analysis Group
Center for Clinical Standards and Quality
Centers for Medicare & Medicaid Services
7500 Security Boulevard, C1-14-15
Baltimore, Maryland 21244

RE: Comments on Proposed National Coverage Determination (NCD) for Leadless Pacemakers (CAG-00448N)

Dear Ms. Syrek Jensen:

Medtronic is the world's leading medical technology company, specializing in implantable and interventional therapies that alleviate pain, restore health, and extend life. We are committed to the continual research and development necessary to produce high-quality products and to support innovative therapies that improve patients' lives. As the manufacturer of the Micra™ Transcatheter Pacing System (TPS), the first and only U.S. Food and Drug Administration (FDA) approved device of its class, we thank CMS for the opportunity to comment on the Proposed Decision Memo for Leadless Pacemakers (CAG-00448N).

In the proposed NCD, CMS proposes to cover FDA-approved studies of leadless pacemakers through Coverage with Evidence Development (CED). Medtronic appreciates that CMS has proposed positive coverage for the use of leadless pacemakers, but we are concerned that the proposed NCD is unduly limiting and does not reach an appropriate balance to ensure patient access to leadless pacemakers while requiring ongoing evidence collection on the effects of the technology. Specifically, without the development of additional FDA-approved studies, the proposed NCD would only cover Medicare beneficiaries enrolled in the FDA-approved post-approval study (PAS) for Micra. This subset of patients represents only a small proportion of Medicare beneficiaries who could benefit from the device under the FDA-approved labeling for the therapy.

To improve coverage of leadless pacemakers in the final NCD, Medtronic recommends the following:

• On the strength of the Micra clinical trial results and the rigor of the existing Micra post-approval study to address questions identified by both FDA and CMS, we believe the evidence is sufficient for CMS to find leadless pacemaker devices reasonable and necessary under sec. 1862(a)(1)(A) of the Social Security Act. We recommend that CMS grant coverage in the final NCD consistent with the labeling for the device and the covered indications for pacemakers in the existing Medicare NCD for single- and dual-chamber pacemakers.


• If CMS decides that additional evidence is necessary and proceeds with CED in the final NCD, we believe any CED requirement must ensure that all indicated Medicare patients have timely and appropriate access to Micra leadless pacing therapy consistent with its labeling. Furthermore, CED should be as least burdensome and non-duplicative as possible, and be subject to CMS review only.


• Towards these goals, CMS should recognize the important information that can be gained from longitudinal analysis employing administrative claims data to address the research questions identified by CMS in the proposed decision memorandum for leadless pacemakers. Such an analysis can augment evidence that will be generated by the existing post-approval study for Micra. Any CED requirements should come with assurances of timely access for all appropriately indicated Medicare beneficiaries, or transitional provisions that assure immediate patient access to leadless pacemakers while CED is implemented.

Detailed technical comments that reflect these recommendations and other important aspects of the NCD are included in the attachment to this letter.

We thank CMS for the opportunity to engage in constructive discussions during the comment period on the leadless pacemaker NCD and appreciate your consideration of Medtronic’s recommendations. If you have questions or need further information, please feel free to contact me.

Medtronic Comments on Proposed Decision Memo for Leadless Pacemakers (CAG-00448N)

Medtronic appreciates that the Centers for Medicare and Medicaid Services (CMS) has proposed positive coverage for the use of leadless pacemakers, but we are concerned that the decision is unduly restrictive. In the proposed NCD, CMS proposes to cover FDA-approved studies of leadless pacemakers through Coverage with Evidence Development (CED). We are concerned that the proposed NCD does not reach an appropriate balance to ensure patient access to leadless pacemakers while requiring ongoing evidence collection on the effects of the technology.

As the manufacturer of the Micra™ Transcatheter Pacing System (TPS), the first and only U.S. Food and Drug Administration (FDA) approved device of its class, Medtronic strongly supports coverage of leadless pacemakers and believes that appropriately-indicated Medicare patients and their physicians should have access to leadless pacing therapy consistent with its approved FDA labeling. Beyond clinical trials, however, the proposed NCD would only cover Medicare beneficiaries enrolled in the FDA-approved post-approval study (PAS) for Micra – representing only a small proportion of patients who could benefit from the device under the FDA-approved labeling for the therapy.

As described in the comment letter and supporting documentation we submitted to CMS on June 16, 2016, Medtronic believes the evidence is sufficient to support coverage for leadless pacemakers as reasonable and necessary under section 1862(a)(1)(A) of the Social Security Act.

Bradycardia is a debilitating disease that disproportionately affects the Medicare population. Cardiac pacemakers are the standard of care for the treatment of symptomatic bradycardia. In a previous NCD for pacemakers, CMS determined that the evidence is sufficient to conclude that implanted permanent transvenous cardiac pacemaker therapy is reasonable and necessary for coverage. Key shortcomings of conventional pacemaker therapy result from the creation of a subcutaneous pocket to house the generator device and the implantation of transvenous leads to deliver pacing therapy.

Leadless pacemakers leverage recent advances in the miniaturization of technology to eliminate the main complications of transvenous pacemakers associated with the need for a subcutaneous pocket and leads. Furthermore, leadless pacemakers were developed to expand access to patients precluded from standard therapy and to improve patient satisfaction with the therapy by eliminating chest scarring and bulging that may occur with traditional pacemaker systems.

Despite the differences in size and shape between transvenous and leadless pacemaker systems, the pacing therapy delivered by available leadless pacemakers is analogous to cardiac pacing delivered by conventional transvenous single-chamber VVIR pacemakers. As such, there is no need to demonstrate the fundamental benefit of pacemaker therapy for leadless pacemakers – only to demonstrate that leadless pacemakers provide such pacing therapy in a safe and effective manner, thereby improving net health outcomes for indicated patients in the Medicare population.

The Micra Transcatheter Pacing System study was an FDA approved, prospective, multi-site, single-arm, worldwide clinical study designed to evaluate the safety and efficacy of the Micra system. Micra patients in the clinical study were typically Medicare-aged (mean age 76 years) with common comorbidities including diabetes, atrial fibrillation, and hypertension.

Through six months of follow-up, 98.3% of those included in the primary efficacy analysis (95% CI, 96.1 to 99.5) had an adequate 6-month pacing threshold (i.e., low and stable pacing thresholds through 6-months versus a pre-specified performance goal of 80%). Study patients had fewer major complications than patients in the historical control cohort comprised of transvenous pacemaker patients (4.0% vs. 7.4%), resulting in a 51% lower risk of complications with Micra than historical controls (P = 0.001).

There were only few Micra system revisions observed in the clinical study, none of which resulted from device dislodgements or systemic infections. Only five of the 725 patients in the Micra clinical study required system revisions, occurring 17 days to 259 days after implant. Micra was successfully extracted percutaneously in one patient, turned to Device OFF mode with a traditional pacemaker implant in three patients, and reprogrammed and a traditional pacemaker implanted in one patient. No adverse events associated with concomitant device placement were reported.

On the basis of the clinical trial findings, FDA approved the Micra single chamber ventricular system for the following conditions:

• symptomatic paroxysmal or permanent high-grade AV block in the presence of atrial fibrillation (AF)
• symptomatic paroxysmal or permanent high-grade AV block in the absence of AF, as an alternative to dual chamber pacing, when atrial lead placement is considered difficult, high risk, or not deemed necessary for effective therapy
• symptomatic bradycardia-tachycardia syndrome or sinus node dysfunction (sinus bradycardia or sinus pauses), as an alternative to atrial or dual chamber pacing, when atrial lead placement is considered difficult, high risk, or not deemed necessary for effective therapy.

The FDA required a post-approval study (PAS) for Micra as a condition of approval, to further confirm safety and effectiveness of the system when used as intended, in “real world” clinical practice, following commercial release. The Micra PAS has a rigorous design that will generate evidence to address open questions raised by both the FDA and CMS. Since the indicated population is predominantly over the age of 65, the PAS will include the Medicare population and produce evidence directly relevant to CMS and Medicare.

The primary study objectives of the Micra PAS are to estimate acute and long-term complications, which will allow for continued significant evidence generation. The Micra PAS is an FDA approved, global, prospective, observational, multi-center study. The PAS includes two primary objectives:

• To estimate acute complication rate related to the Micra system and/or procedure.
• To estimate the 9-year Micra-related complication-free survival probability.

The PAS study is a prospective 9-year follow-up study that will enroll 2,450 patients at 300 sites that will follow patients for acute complication and long-term complications. Within the US, the PAS will enroll approximately 1,000 patients in 150 centers. Given the average age of patients in the Micra IDE study was 76 years, with approximately 85% of patients age 65 or older, it is anticipated that the PAS will enroll a significant number of Medicare beneficiaries.

The two primary objectives will provide sufficient data to demonstrate acute and long-term performance of the Micra system. The PAS includes a secondary objective to characterize treatment and/or procedure related to Micra TPS End of Device Service (EDS), including:

• Explant of Micra system with new leadless pacemaker system implant
• Explant of Micra system with new transvenous pacemaker system implant
• Implant of new leadless pacemaker without explant of Micra system (set to OFF)
• Implant of new transvenous pacemaker system without explant of Micra system (set to OFF).

Other ancillary analyses will further characterize performance of the Micra system, including but not limited to:

• Procedures (implant and explant)
• Implant Type (e.g. de novo, previous pacemaker)
• Electrical Stability Over Time
• MRI Safety

All patients enrolled in the Micra PAS will be prospectively followed for a minimum of nine years post implant or until study closure. The total estimated PAS duration is 11 years. The FDA PAS has selected a patient population size in order to properly power the study to capture both acute complications and long-term performance.

On the basis of the clinical trial findings for Micra and the information that will be produced through the Micra PAS, Medtronic believes the evidence is sufficient to conclude that pacemaker therapy delivered through leadless devices is reasonable and necessary for the treatment of bradycardia when such devices are used within their device-specific FDA-labeled indications.

Furthermore, in a joint statement, the American College of Cardiology (ACC), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography and Interventions (SCAI) supported the creation of a coverage policy that provides patients access to this new and important therapy. Specifically, “The societies support CMS coverage of FDA-approved devices for FDA-approved indications in this NCA.”

Medtronic recommends that leadless pacemakers be covered consistent with FDA labeling and in a patient population that has documented, non-reversible symptomatic bradycardia due to sinus node dysfunction, or documented, non-reversible symptomatic bradycardia due to second degree and/or third degree atrioventricular block.

If CMS concludes that additional evidence collection is necessary and proceeds with CED in the final NCD, we believe any CED requirement must ensure that all indicated Medicare patients have timely and appropriate access to Micra leadless pacing therapy consistent with its labeling. Furthermore, CED should be as least burdensome and non-duplicative as possible.

Medtronic believes that, as part of any potential CED requirement, CMS should recognize the important information that can be gained from a longitudinal study utilizing administrative claims data to address the research questions identified in the proposed decision memorandum. (CMS recently finalized a similar approach in the final NCD for Percutaneous Image-guided Lumbar Decompression for Lumbar Spinal Stenosis (CAG-00433R).) Such a study can augment evidence that will be generated by the existing post-approval study for Micra. It would be critical to ensure that any CED requirement provide timely access for indicated Medicare beneficiaries or include a necessary transition process to allow for uninterrupted and immediate patient access to leadless pacemakers while CED is implemented.

Use of Medicare Claims Data to Address CED Questions

A longitudinal claims data study provides information to address concerns raised by CMS related to the sample sizes and generalizability of the pre-market clinical trials and the post-approval study of Micra leadless pacing therapy to the Medicare population. Such a study would develop evidence aimed at answering the evidence gaps outlined in the proposed decision memorandum for leadless pacemakers. In addition, Medtronic believes that in order to adequately address some of the evidence gaps identified by CMS, a comparison group of patients receiving single chamber transvenous pacemakers could be beneficial. In order for a longitudinal claims study to fulfill the CED requirements, a pre-determined study protocol that incorporates a research design and statistical methodologies that aim to minimize biases associated with observational claims data research is recommended.

Through a combination of procedure codes specific to leadless pacemaker implant procedures and other mechanisms to enable the identification of Medtronic Micra patients (either via direct linkage using manufacturer device registration information or utilizing the clinical trial numbers associated with CED included on claims), a cohort of all Medicare beneficiaries receiving Medtronic Micra leadless pacemaker therapy can be constructed from Medicare claims data. Similarly, a contemporaneous comparison cohort of Medicare beneficiaries receiving single chamber transvenous pacemakers can be developed using procedure codes specific to the type of implant. This type of cohort study enables the longitudinal analysis comparing relevant outcomes, complications, and patient characteristics of Micra leadless pacemaker therapy patients to single chamber transvenous pacemaker patients.

A protocol that explicitly outlines the study design, statistical analysis plan, and proposed methodologies to address issues associated with observational studies should be submitted and approved by CMS. CMS should recognize, however, that a longitudinal cohort study using Medicare claims data introduces potential areas for bias (e.g., such as patient selection, unmeasurable differences between groups, omission bias), and there should be, in coordination with CMS, flexibility in the study design and the methodological approaches throughout the study period. Further, the study duration, frequency of analysis, and the consideration of additional evidence generated under the study proposal should be determined prior to the commencement of the study. CMS assistance may be necessary in accessing the appropriate data for such a study on Micra leadless pacemaker therapy.

The majority of outcomes, complications, and patient characteristics most relevant to leadless pacing therapy are reliably identified in the administrative claims data.

Research Questions and Evidence Gaps Identified by CMS in Proposed Decision Memo

In the NCD, CMS identified six questions with evidence gaps that need to be addressed through CED. The questions, as well as commentary on how they can be addressed using longitudinal analysis of Medicare claims data, are outlined below:

1. What are the peri-procedural, and post-procedural complications, and long term outcomes of leadless pacemakers?

ICD-10 diagnosis codes and procedure codes included in Medicare claims data provide enough detail to identify leadless pacemaker and procedure-related complications in claims data. Similarly, long term outcomes such as mortality, development of heart failure, or hospitalizations are reliably measured in Medicare claims data. While many clinically relevant complications can be measured in claims data through the use of procedure and diagnosis codes, in certain cases, there are limitations surrounding the ability to distinguish to determine between peri- and post-procedural complications in ICD-10 code descriptions.

2. Are leadless pacemakers equivalent or superior to conventional pacemakers in real world use?

As noted above, Medtronic believes that a comparator group consisting of patients implanted with single chamber transvenous pacemakers is beneficial to adequately address the effect of leadless pacemaker therapy for Medicare beneficiaries. A comparator group would contextualize results of the leadless pacemaker group, minimize biases associated with observational data, and address potential temporal trends associated with the treatment effect. Recognizing that a longitudinal claims study is observational research and lacking design elements often included in traditional clinical trials such as randomization and outcome validation, it is essential that a longitudinal claims-based study’s protocol employing claims data be evaluated for the design, biases, and methods proposed to address issues associated with observational data.

In the final NCD issued by CMS, clarifying language related to the definition of “equivalent or superior” may be beneficial for developing a robust research protocol that leverages claims data.

3. What are the infection rates, the long-term hemodynamic effects, and the rates of formation of thrombi?

Medtronic recommends omitting “long-term hemodynamic effects” from Question 3, as it is not measurable using claims data (i.e., left ventricular ejection fraction, or LVEF). In addition, hemodynamics and ventricular function are considered to be surrogate measures for true health outcomes, such as heart failure and mortality. Such surrogate measures are not directly representative of true outcomes. Rather than focus on surrogate measures, any evidence development should instead seek to collect and assess data on true outcomes as available.

Additionally, there is not a meaningful difference between transvenous and leadless pacing systems with regard to hemodynamics and ventricular function. With both forms of pacing therapies, the electrical impulse is delivered via an electrode to the heart in an identical manner – delivered at a single spot on the myocardium. The inclusion of hemodynamics data is not necessary in the context of CMS’ evidentiary goals for CED.

Acute, mid-, and long-term infection rates can be measured in Medicare claims data. Further, diagnosis coding that specifically identifies cardiovascular implantable electronic device (CIED) infections is available, which makes infection rates a highly reliable and clinically relevant adverse event to include in a claims-based data study. However, there are limitations related to the ability to identify the source of the infection and whether it is secondary to another illness.

The rate and formation of thrombi should be more appropriately defined as clinically specific outcomes, such as deep vein thrombi (DVT), stroke, or pulmonary thromboembolism.

Medtronic would consider the inclusion of additional adverse event measures to the extent they are clinically relevant and reliably identified in the procedural and diagnosis coding included in claims data.

4. What are the patient demographics and effects of patient characteristics (age, gender, comorbidities) on the use and health effects of leadless pacemakers?

There are a substantial number of demographics (e.g., age, gender, race, region) and patient characteristics (e.g., comorbidities) included in both the denominator and utilization files of Medicare claims data, which enables subgroup analyses and/or the ability to control for their effects on outcomes. However, certain characteristics, such as LVEF and New York Heart Failure Association (NYHA) class, are not available in claims. There may also be demographics factors influencing the use of and/or outcomes of leadless technology which are not available in claims data (e.g., socioeconomic status).

5. What are the device-related issues (handling of end of battery life; effects of having multiple leadless pacemakers implanted; rate of device dislodgement; and the possibility of device extractions)?

Medtronic is supportive of measuring device-related issues using administrative claims data to the extent they are clinically relevant and reliably identifiable. Pacemaker (leadless and single chamber transvenous) implant, replacement, programming and monitoring are all measurable in claims data. However, there are significant challenges in measuring device-related issues using claims data, such as the required timeframe to observe relevant outcomes and the specificity of the variables included in the analysis. For example, an explant of a device may not reflect battery longevity, but rather the need for a different type of device based on the changes in a patient’s health. Similarly, a timeframe of twelve or more years would be necessary to understand the effects of multiple leadless pacemakers.

Note that Medtronic believes the Micra PAS is more appropriate than claims data to more accurately measure device-related issues. Unlike a longitudinal claims data study, the PAS is better positioned to measure long term and device-specific outcomes given its ability to adjudicate events.

6. How are operators and facility characteristics related to peri-procedural and, post-procedural complications, and long term outcomes of leadless pacemakers?

Given leadless pacemakers are a new technology requiring a new procedure, it is reasonable to expect an implanter learning curve. A longitudinal claims data study will allow for the examination of the number of leadless implants by implanter or facility as a potential predictor of complications and/or long-term outcomes.

Agency Approval of CED Studies

The proposed decision memo links the coverage of leadless pacemakers to FDA-approved studies. If CMS proceeds with CED in the final NCD, Medtronic recommends that CMS retain sole discretion for approval of additional studies to be covered under the NCD. This ensures that studies specifically intended to address evidence gaps and inform coverage determinations are designed with input and approval of the appropriate agency with statutory authority over coverage decisions. CED approaches based on longitudinal studies using administrative claims data as described above may not otherwise be subject to FDA review and approval, and adding such a requirement would be unnecessary and burdensome.

Linking coverage decisions to only FDA-approved studies creates the need to re-evaluate already-approved study methodologies and endpoints that have been determined to satisfactorily meet the FDA’s needs, in order to meet coverage requirements that are not within the FDA’s statutory purview. As such, a linkage causes undue burden on manufacturers and study participants to revisit approved studies, and it may ultimately confuse the distinction between the agencies, placing significant responsibility for coverage elements at the discretion of the FDA. For studies and evidence development to support coverage decisions, we believe CMS should provide final oversight and approval.

Implementation and Transition Provisions to Expedite Patient Access under CED

If CMS proceeds with CED, there may be a lag between the issuance date of the final NCD and the true start of coverage while the details of the CED are implemented. Specifically, manufacturers will require a period of time after the release of the final decision to gain approval for and implement a study. This would especially be the case for longitudinal studies based on claims data, given the novel nature of this approach. Some implementation efforts may necessarily take time, including but not limited to: registering a study on ClinicalTrials.gov; instructing sites on accurate claims processing; and developing claims edits to ensure appropriate capture of claims data.

It is therefore critical to ensure that the time necessary to implement a study does not delay appropriate patient access to leadless pacemakers. If CMS adopts CED for leadless pacemakers, we request that CMS engage with manufacturers to expedite protocol approval (within 30 days of submission) and build in measures allowing for immediate patient access to leadless pacemakers under the approved protocol as the necessary processes to implement the study take place.

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Leadless pacing is now suppord by scientific data. This has led the US FDA to approve the technology. We have many patients who are eagerly awaiting this technology - avoids a surgical incision, no upoper vascular access issues, very low risk of dislodgment, and importantly seemingly no risk of infection.

We were very diasspointed by what CMS proposed as the basis for coverage of payment. If payment is restricted to just a few sites who have already been selected to participate in a post-approval study, this will adversely impact many patients who will be subject to standard transvenous PPMs and their inherent complications.

We ask that CMS reconsider its coverage proposal to make it more feasible for eligible patients to receive this device in the US.

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To CMS,

I am Christopher R. Ellis, MD, FACC, FHRS, Associate Professor and Director of the Vanderbilt University Cardiac Electrophysiology Laboratory. I have followed and implanted 45 patients with transcatheter pacing systems (MICRA) and believe this is both the future of pacing therapy, and a critical, cost reducing and risk reducing invasive therapy.

Using the catheter delivered MICRA rather thank traditional pacemaker, we have (at Vanderbilt) dramatically shortened hospital stays, reduced total cost, and lowered procedural risk in a very high risk cohort patients with multiple co-morbidities; including patients having complete system lead extraction for lead failure or infection.

Additional data we have helped to author support a reduction in pacing thresholds over time, in contrast to traditional systems, where chronic scar at the tip of the pacer lead may gradually deteriorate the function of the pacemaker.

We have used this MICRA for atrial fibrillation patients undergoing AVN ablation, and feel its low thresholds maintain a very reasonable battery longevity even with 100% pacing, despite the device being only 0.8mL in size.

Traditional pacemakers subject patients to risk for pocket hematoma, device infection at the wound, pneumothorax, and lead dislodgment. All of these are almost ZERO risk with MICRA.

I urge CMS to cover transcatheter MICRA pacemaker for clinical use as it has already become a standard of care for our device population at Vanderbilt University.

Sincerely,
Christopher R. Ellis, FACC, FHRS
Director LAA Closure Program
Director Cardiac Electrophysiology Laboratory
Associate Professor of Medicine
Vanderbilt University Medical Center
(615)480-0829 (cell)
christopher.ellis@vanderbilt.edu

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December 14, 2016

Tamara Syrek Jensen, JD
Director, Coverage & Analysis Group
Office of Clinical Standards and Quality
Centers for Medicare & Medicaid Services
Mailstop C1-09-06
7500 Security Blvd
Baltimore MD 21244

RE: Proposed Medicare Coverage Decision Memorandum for Leadless Pacemakers (CAG-00448N)

Dear Ms. Syrek Jensen:

St. Jude Medical (SJM) is writing to provide comments related to the Proposed Medicare Coverage Decision Memorandum for Leadless Pacemakers (CAG-00448N).

St. Jude Medical is driven by our vision and mission to transform the treatment of expensive epidemic diseases including atrial fibrillation, cardiac dysrhythmias, heart failure, stroke, coronary artery disease, congenital heart defects, Parkinson’s disease and chronic pain. We strive to achieve our goal by providing innovative solutions that provide improved care and that reduce the economic burden of costly diseases on health care systems worldwide. We believe that the Nanostim™ leadless pacemaker is an excellent reflection of the kind of innovation that our company is committed to achieving, as we work to transform the treatment options available to patients and providers, alike.

The proposed intended use of the Nanostim leadless pacemaker is consistent with the clinical indications in the IDE trial and the covered indications listed in the current NCD 20.8.3 for Cardiac Pacemakers for transvenous systems. Nanostim achieved CE Mark in October, 2013 with label indications consistent with these as well.

We believe that leadless pacemakers should be considered a reasonable and necessary treatment choice for patients requiring pacing therapy. St. Jude Medical recommends:

• CMS should cover leadless pacemakers for all Medicare beneficiaries for FDA approved indications.
• If CED is mandated for FDA approved leadless pacemakers, CMS should provide coverage for beneficiaries in FDA approved post approval studies and also in other CMS approved registries, and other reasonable data collection modalities.

We believe leadless pacemakers are an important treatment option for patients who require bradyarrhythmia management as leadless pacemakers provide effective pacing therapy while eliminating or reducing complications associated with leads and pocket creation of traditional pacemakers. Principle investigators for the LEADLESS II trial have concluded that the Nanostim leadless pacemaker should be considered as a clinical alternative by physicians who wish to provide their patients a leadless pacing option without the known complications of traditional transvenous pacemakers.

The Food and Drug Administration (FDA) has indicated that no additional guidelines are necessary for leadless pacemakers. In the posted summary of the physician panel on leadless pacemakers that was held on Feb 18, 2016, it was recommended that any patient indicated for a traditional pacemaker system should be eligible to receive a leadless pacemaker, with no restrictions on clinical indications. The panel concluded that indications for traditional systems apply to this device, and that guidance for specific populations is already in place under the current AHA/ACC/HRS guidelines¹. Post approval study design elements identified by the panel have been fully incorporated into these planned trials.

Evidence Statement and Coverage Request
Substantial clinical evidence on the safety and efficacy of leadless pacing is available from multiple IDE studies. As of April 25, 2016, a total of 1,197 patients were enrolled within 3 multicenter trials testing the Nanostim leadless pacemaker (i.e. Leadless II IDE, Japan Leadless Study and Post Market Clinical Follow-up in Europe). In addition, robust data collection is ongoing to demonstrate the long-term outcomes and benefits of leadless pacing in the real-world patient population. Given the body of evidence that is available and further data collection plans, St. Jude Medical requests that CMS issues an NCD without CED to cover leadless pacemakers in patients with FDA-approved label indications.

By issuing an NCD without CED, we believe that CMS will avoid duplication of existing and planned knowledge regarding leadless pacing. Rigorous data collection approaches for leadless pacing have already been required by the FDA through post approval studies that require mechanisms for monitoring device safety. SJM believes that adding other data collection requirements for coverage is unnecessary, duplicative, and limits Medicare beneficiary access to a pacing technology which reduces or eliminates some risks associated with traditional pacing systems.

In the proposed coverage decision, CMS poses several key concerns that they would like addressed through CED. St. Jude Medical is confident that the current clinical data and data collection plans will address the identified concerns regarding leadless device performance, outcomes, and health disparities. CMS states “due to an observational design without direct comparison to conventional pacemakers, the ability to draw conclusions about the relative performace and outcomes of these devices is limited.” We believe that using existing and planned large observational study data along with the long term data that exists for single-chamber implants is sufficient to draw these conclusions.

Pacing Effectiveness
The pacing of Nanostim is comparable to conventional single therapy effectiveness. While Nanostim is smaller and uses a different implant procedure; its functional characteristics are identical to conventional single chamber pacemakers. The IDE study demonstrated acceptable and comparable pacing capture thresholds with Nanostim, as well as therapeutically acceptable sensing amplitudes². These data demonstrate pacing therapy effectiveness that is comparable to traditional systems. Additional data on the performance of Nanostim is currently being collected through a continued access study (CAP) and will be collected in the post approval study.

Device Retrievability The Nanostim leadless pacemaker is designed for safe, percutaneous retrieval using a specially designed retrieval catheter. A recent multicenter study was published on Nanostim retrieval attempts in 16 patients (acute=5 and chronic=11). The retrievals were performed by 9 different operators at 9 centers. Procedural success, defined as complete retrieval of the leadless pacemaker, was achieved in 100% (n=5/5) of the patients whose device had been implanted for ≥ 6 weeks and 91% (n=10/11) of those implanted for =6 weeks; for the unsuccessful retrieval case, the implant duration had been 103 days. During the unsuccessful retrieval attempt, the operators reported that the docking feature could not be engaged because of its position relative to the subvalvular apparatus (in this patient, the original Nanostim implant was turned off and a new Nanostim was implanted). There were no procedure-related adverse events. ^3,6

When compared with transvenous lead extraction, removal of a leadless pacemaker has the potential to reduce risk associated with the procedure. For example, although cardiac avulsion/tear is an ever present concern with removal of any implantable cardiac device, there should be a reduced risk of vascular injury with removal of a leadless pacemaker as transvenous leads have multiple sites of fibrous binding within the vasculature. Additionally, unlike with the extraction of transvenous leads where traction and countertraction is used to disengage the helix of the lead from the myocardium, the specially designed retrieval system allows for the leadless device helix to be disengaged from the myocardium by rotation. It is the distal docking cap of the Nanostim retrieval catheter that is specifically designed to lock onto the docking button of the leadless pacemaker; this allows for the torque transmission to be delivered directed to the helix for disengagement after rotation of the helix. This was evidenced clinically by the observation that the helix on the Nanostim devices was intact in the vast majority of retrievals.^4,7

In addition to having retrieval as an end of life or revision option, the leadless pacemaker can also be permanently disabled and abandoned. SJM is committed to initiating a large, long-term, post approval study (PAS) following FDA approval of the Nanostim leadless pacemaker. The purpose of this post approval study is to confirm safety and effectiveness of the Nanostim Leadless Pacemaker System when used as intended, in “real-world” clinical practice. The study will enroll 1845 subjects at up to 150 centers and the planned follow-up duration is 9 years post implant. Data collection for scheduled follow-up visits on all subjects includes device performance data such as: device interrogation, end of device service, device retrieval/replacement and device longevity. St. Jude Medical is confident that the data collected during the PAS will have the ability to draw conclusions about the relative performace of leadless pacemakers.

In the proposed coverage decision, CMS expressed the need for real world data to answer questions about the “health outcomes from broad leadless pacemaker use.” The LEADLESS II IDE safety endpoint was successfully met for the primary cohort of 300 patients for 6 months, as 93.3% of the patients were free from serious adverse events. Also, no serious adverse device effects (SADEs) were reported in this cohort more than 30 days post implant. These safety results are similar to historic rates reported for traditional single-chamber pacemakers.

Complications and Adverse Events
Extensive data are available to suggest that leadless pacemakers (LCP) have fewer short and mid-term complications, particularly among infectious, pocket-related, and lead-related events. An analysis was conducted to compare short and mid-term complications of LCPs from the LEADLESS II IDE trial with a propensity-matched single-chamber transvenous pacemaker (TVP) cohort using claims data. TVP data were obtained from Truven Health MarketScan claims databases for patients implanted with single-chamber TVPs between April 2010 and March 2014 and over 1 year of pre-implant enrollment data. ICD-9 and CPT codes were used to extract relevant co-morbidities and complications.

Short-term (≤1 months) and mid-term (> 1 to 18 months) complications were compared between the LCP and a propensity score-matched subset of the TVP cohort. Among 718 LCP (75.6 ± 11.9 years, 62% male) and 2,154 TVP patients (76.0 ± 12.4 years, 64% male), LCP patients experienced fewer complications (adjusted HR 0.30; 95% CI 0.22–0.41; p < 0.001), including short-term (5.8% vs. 16.2%, p < 0.001) and mid-term (0.56% vs. 9.6%, p < 0.001) events. In the short-term, LCP patients had more pericardial effusions (1.53% vs, 0.32%, p=0.001) and vascular events (1.11% vs. 0.46%, p=0.096), with fewer dislodgements (0.97% vs. 1.62%, p=0.28) and no thoracic trauma (3.9%) present in the TVP group. In short and mid-term, TVP events absent from the LCP group included lead-related (1.75% and 10.12%), pocket-related (1.35% and 0.93%), and infectious (2.18% and 2.34%) complications.⁵

Patients implanted with leadless pacemakers have been found to have no significant risk of serious adverse device events (SADEs). An analysis was presented at the February 2016 FDA panel meeting to assess which, if any, variables were predictors of adverse events in the LEADLESS II study. Univariate logistic regression modelling was conducted with the following explanatory variables:

• Age
• BMI
• Sex
• Prior cardiac intervention [coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), stent, atherectomy, or ablation]
• Use of anticoagulants
• Use of antiplatelets
• Whether or not repositioning had been attempted

Results of this analysis are detailed in the table below and demonstrate that, at the 5% significance level, there were no significant predictors of having an SADE. A stepwise multivariate model led to the same results, with no significant predictors of having an SADE.

In conclusion, in the LEADLESS II study there were no subgroups of patients identified as having an increased risk for SADEs, at the 5% significance level. Similar analysis in the real-world population will be conducted on data collected in the post approval study to further confirm these findings.

Health Related Quality of Life
Health-related quality of life (HRQoL) data (EQ-5D) was collected in 468 patients through 3 months in the LEADLESS II IDE study. These data demonstrated improved HRQol with Nanostim immediately after implant, as compared to baseline, and the improvement was sustained over time. Furthermore, QOL data will be collected in the PAS over 2 years in order to document the long term QOL outcomes in patients implanted with Nanostim leadless pacemaker.

Treatment Utilization
In the proposed coverage memo, CMS states that there is “no evidence-based shared decision making tool for risk/benefit compared to tradition pacemaker for patient.” As mentioned previously, the FDA physician panel on leadless pacemaker concluded that indications for traditional systems apply to this device, and that guidance for specific populations is already in place under the current AHA/ACC/HRS guidelines. The FDA mandated PAS for Nanostim will include shared decision making between the patient and physician on choice of pacing therapy. SJM does not recommend that blinded randomized control trials be a requirement for coverage with CED as this component is difficult to evaluate in an RCT.

CMS has indicated a desire for real world evidence generation throughout this proposal, while at the same time avoiding duplicative studies. As mentioned in the above, SJM is committed to initiating a large, long-term, post approval study (PAS) in a minimum of 1845 patients following FDA approval of the Nanostim leadless pacemaker. As instructed by the FDA panel, this PAS provides longest follow-up for any pacemaker or cardiac implantable device study (9 years). The data collected in the PAS will provide additional clinical evidence and corresponding subset analyses addressing the long-term outcomes CMS cites in the proposed coverage memo:

• Long-term outcomes for purported life of device to show reduce symptoms and syncope, improved survival.
• The effects of patient characteristics (age, gender, comorbidities) on the use and health effects of leadless pacemakers.
• Infection rates
• The effectiveness of leadless pacemakers specifically in patients aged 80 and older

Plans for data collection in the 9 year Nanostim PAS include:

• Signs and symptoms of pacing therapy effectives
• Acute Complications
• Chronic Complications
• Quality of Life
• Device Electrical Measurements
• Data about Device Retrievability
• Device to device interactions, if any
• Long Term Survival

In addition to the PAS, a robust training program will support safe use of the Nanostim leadless pacemakers upon commercialization and event rates will continue to be monitored in post-approval studies.

Study Design
Long-term data on traditional pacemakers is well documented, published, and can be leveraged for comparison purposes. St. Jude Medical believes that new blinded, randomized, controlled trials (RCTs) or other multiple armed clinical studies, are unnecessary and unreasonable for leadless pacemakers. The requirement for these studies can also unjustifiably limit access to patients who can benefit. The pacing therapy provided by leadless pacemakers is not novel, this new technology improves on device design and implant technique. Hence, findings from the LEADLESS II study can be put into context by comparing to outcomes of conventional pacemaker studies. Therefore, an RCT is not needed to evaluate leadless pacemakers.

The FOLLOWPACE study provides adequate comparison data for traditional pacemakers. The study was conducted among 1517 patients who received a traditional pacemaker. The mean follow-up duration in the LEADLESS II IDE for the total cohort is 6.9 ± 4.2 months while that in the FOLLOWPACE study is 5.8 ± 1.1 years. The safety data for the FOLLOWPACE study are divided into those events that occurred in first 2 months and those that were detected after 2 months. The cardiac perforation/pericardial effusion rate in the LEADLESS II IDE study is higher than that observed in right ventricular (RV) leads in the FOLLOWPACE study in the first 2 months. On the other hand, dislodgements, vascular complications and pneumothorax/ hemothorax were higher in the FOLLOWPACE study in the first 2 months as compared to those in the LEADLESS II IDE study. Additionally, infections, lead related complications and pocket complications observed in the FOLLOWPACE study in the first 2 months added up to 6.3% and are non-existent in the LEADLESS II IDE study. Finally, there were 3.9% lead and pocket related complications in the FOLLOWPACE study in the chronic phase which are not expected to occur with a leadless pacemaker due to absence of lead and pocket.

Therefore, while some events were reported more frequently in the Leadless II study, a number of significant complications are eliminated (lead complications as well as pocket complications) due to the design of the Nanostim. Overall, the short-term safety profiles demonstrated in the two studies are similar.⁶

We believe the available data fully supports coverage of leadless pacemakers in patients appropriate for cardiac pacing therapy. The breadth and scope of the Nanostim and the other FDA mandated PAS for leadless pacemakers is unprecedented. Long-term data on the Nanostim will continue to be gathered in the post approval study. Taken together with other ongoing post approval studies, sufficient data needed to address CMS’s long-term outcomes concerns will be provided as a total of 3,586 patients will be included with 9 year follow-up. Therefore, this planned evidence generation negates the need for CED.

It is conceivable that leadless pacing will eventually become the standard of care for those who need pacing therapy, and should be considered a reasonable and necessary treatment choice. Therefore, St. Jude Medical recommends:

• CMS should cover leadless pacemakers for all Medicare beneficiaries for FDA approved indications.
• If CED is mandated for FDA approved leadless pacemakers, CMS should provide coverage for beneficiaries in FDA approved post approval studies and also in other CMS approved registries, and other reasonable data collection modalities.

St. Jude Medical is deeply committed to ensuring access to leadless pacemaker therapy for those patients who would derive benefit.

We appreciate the opportunity to provide comments regarding this proposed NCD. Should you have any questions or require additional information, please do not hesitate to contact me at 617-416-6359 or RBostic@sjm.com

Sincerely,

Robin Bostic
Vice President, Global Reimbursement and Health Care Economics & Guidelines
St. Jude Medical, Inc.
617-416-6359
RBostic@sjm.com

References

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To whom it may concern,

On behalf of Allina Health (Allina), I appreciate the opportunity to comment on the National Coverage Analysis for Leadless Pacemakers (CAG-00448N). Allina Health is dedicated to the prevention and treatment of illness and enhancing the greater health of individuals, families and communities throughout Minnesota and western Wisconsin. A not-for-profit health care system, Allina Health cares for patients from beginning to end-of-life through its 90+ clinics, 13 hospitals, 15 pharmacies, specialty care centers and specialty medical services that provide home care, senior transitions, hospice care, home oxygen and medical equipment, and emergency medical transportation services.

I am an electrophysiologist writing on behalf of fifteen other electrophysiologists and approximately one hundred cardiologists in Minnesota’s Allina Health system in support of leadless pacemakers. My colleagues and I perform about 3000 pacemaker or defibrillator procedures annually, and have been active participants in research trials studying leadless pacemaker technology. Our physicians and research teams have participated in twenty-nine leadless pacemaker implants under the egis of Medtronic’s MICRA Trial and are also enrolled in the MICRA-PAS (Post Approval Study). We feel leadless pacemakers have a small but very important role in patient care, and expect it to grow over time with improvements in the devices. At present, they are used in the setting of bradycardia, and primarily in patients with chronic atrial fibrillation. They are particularly helpful when there are vascular access difficulties, in the setting of prior infectious issues and for patients with renal failure whose dialysis requires frequent large bore intravenous access. The absence of a trans-venous lead in the system dramatically attenuates the incidences of lead infection, often a very serious and costly complication requiring pacing system extraction and weeks of antibiotics, plus the need for a new system placed via a new vascular access. In addition, the hope is that the technology can advance to where two devices can communicate with each other, allowing for use in dual chamber settings and with subcutaneous implantable defibrillators.

As things stand now, we understand that CMS does not feel the data at hand supports a full National Coverage Decision (NCD) for leadless pacemaker technology, and that it is considering Coverage with Evidence Development (CED). We at Allina encourage the careful study of new technology and devices, and support your analysis. We do, however, feel that leadless pacemakers offer significant advantages over existing pacemakers in some circumstances, and that broad coverage should be granted for those products and indications that have been approved by the FDA. We feel that the studies to date have been thoughtfully designed and carefully executed, and as mentioned above, do plan on fully participating the ongoing MICRA-Post Approval Study. MICRA-PAS is well powered to answer the questions posed about peri-procedural and post-procedural complications, the long term outcomes of leadless pacemakers and the effects of patient characteristics on the use and health effects therefrom. It is our hope that if CED is deemed necessary, that it allows for a broad dissemination of the tool (rather than limiting it to research settings and thus introducing bias to the analysis), and that the data collection would be conducted in a way that would be minimally burdensome for the patients, hospitals and physicians. We further suggest that your important questions might well be answered by the already approved PAS, plus a claims analysis from a wide variety of qualified implanters, rather than a traditional and very expensive registry.

We thank CMS for the opportunity to share our comments on this National Coverage Analysis. We hope CMS will take our comments into account while evaluating the need for a National Coverage Determination.

If you have any questions regarding these remarks, please feel free to contact me at 612-262-4908.

Sincerely,

Stephen Remole, MD, FACC
Metropolitan Heart & Vascular Institute
stephen.remole@mhvi.com

Allyson Hammer
Manager, Organization Integrity & Regulatory Affairs
Allina Health
Allyson.Hammer@allina.com

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At the Regional Heart Center of the UW Medicine, we think leadless pacing is a breakthrough treatment for bradyarrhythmias. We have implanted the Micra Leadless Pacemaker at our institution in patients who meet FDA labelling for this device. One of our initial patients who lacked appropriate vascular access would have needed an epicardial pacemaker system if this device were not available. Another patient had a history of a pacemaker infection and underwent a lead extraction, but then received a leadless pacemaker instead of a transvenous device afterward, eliminating his risk of future pocket infection.

We are concerned about the requirement that patients must be enrolled in an FDA-approved research study to receive this device. We think leadless pacing should be an option for all patients who need single chamber ventricular-only pacing. We agree that post-approval studies of leadless pacing should be performed, as is being done for the Medtronic Micra, but do not think these should be tied into reimbursement. Our concern is that only limited patients at select centers will be offered this therapy until research studies have been completed and published, which may take years. We hope this will be an option to all patients and respectfully ask CMS remove the requirement that patients be enrolled in a post-approval study.

Sincerely,
Jordan Prutkin, MD, MHS

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The Micra leadless pacemaker represents a transformation in care for patients requiring single chamber pacing. The trial leading to its FDA approval was robust and showed outstanding performance, excellent implantation success and a dramatic reduction in overall complications relative to a control derived from similarly rigorous trials of traditional transvenous pacemakers.

While I strongly appreciate the decision by CMS to consider National Coverage for Leadless Pacing, I do not feel that CED is warranted in this case. As a Co-Chair of the Micra Post Approval Study (PAS), I know that the PAS incorporates all of the requirements outlined by the FDA to produce a rigorous, well-powered study designed to ensure the acute safety and long term performance of the device, as well as capture enough end-of-service events to understand how this leadless pacemaker will be managed at the time of expected battery depletion.

The Leadless Pacemaker NCD should allow for broad application of this technology contemporaneously with the enrollment and completion of the PAS. However, to require that all patients be enrolled in the PAS as part of CED would dramatically limit access to this transformational technology and, in fact, relegate Medtronic to performing the equivalent of a second, and larger, IDE trial.

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Approval of this technology needs to account for a few special considerations:

1. It should be available not just sites that were part of the initial study. This is especially true at sites like the University of Colorado which service a large area of the U.S., none of which were part of the initial study. Patients who often need this technology are older and frail. So approving this technology at sites that were only part of the study would basically exclude many patients who would benefit from this technology in a large area of the United States.
2. This is not a difficult technology to use for the properly trained physician. I perform lead extractions and deal with more difficult device implantations. So while our center was not part of the initial study, both myself and my colleagues are definitely qualified to use this technology.
3. This technology is the future of implantable devices. Leads are obviously the weak link of pacemakers and defibrillators so not allowing general use of this technology for qualified device implanters will significantly impede technology advancement.

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December 13, 2016

Tamara Syrek Jensen, JD
Director, Coverage & Analysis Group
Office of Clinical Standards and Quality
Centers for Medicare & Medicaid Services
Mailstop C1-09-06
7500 Security Blvd
Baltimore MD 21244

Dear Ms. Syrek Jensen:

The Advanced Medical Technology Association (AdvaMed) offers the following comments on the Centers for Medicare & Medicaid Services’ (CMS) Proposed Coverage Decision Memorandum for Leadless Pacemakers. In the proposed decision memorandum, CMS proposes to cover FDA-approved studies for leadless pacemakers through Coverage with Evidence Development (CED), and specifically seeks comments on the use of CED in this proposed decision.

AdvaMed’s member companies produce the life-saving and life-enhancing medical devices, diagnostic products and health information systems that are transforming health care through earlier disease detection, less invasive procedures and more effective treatments. AdvaMed members range from the largest to the smallest medical technology innovators and companies.

Our comments relate to the use of CED in the proposed coverage determination for leadless cardiac pacemakers.

AdvaMed has long-supported the use of sound evidence to inform medical practice. In general, we agree that CED can be a useful tool for generating additional evidence in cases where the available evidence regarding a promising medical technology or procedure is not sufficient to support broad, national coverage. Where appropriate, coverage contingent on the development of additional evidence can provide beneficiaries access to innovative medical treatments, particularly when the alternative is non-coverage.

AdvaMed has previously submitted comments to CMS regarding CED generally and regarding specific NCDs incorporating CED. Many of the concerns we have raised are relevant with respect to this proposal with respect to the CED requirement. AdvaMed strongly believes that Medicare’s coverage policies should encourage innovation, and that CED should expand, not restrict, patient access to new technologies and treatments. We are concerned that the proposed NCD for leadless pacemakers does not meet these goals.

As proposed, the NCD for leadless pacemakers would limit coverage of leadless cardiac pacemakers to participants in Food and Drug Administration (FDA) post-approval studies, which by definition will limit coverage to the size and scope of the study. The post-approval studies are designed to study long-term outcomes and confirm safety and effectiveness of these devices in the “real world.” However, the existing post-approval studies for leadless pacemakers will include only a finite number of subjects. The proposed NCD has the potential to exclude patients from coverage for whom the treatment is indicated and who would benefit from leadless pacing therapy, who are not participating in the FDA-approved study.

Furthermore, the currently approved post-approval studies for leadless pacemakers are among the longest, most comprehensive, and costly post-approval studies for cardiac rhythm management devices, and are designed to answer questions about the short-term and long-term effects of use of the devices, including the research questions identified by CMS in the proposed NCD. Given the depth of the existing FDA-approved post-approval studies for leadless pacemakers, AdvaMed is concerned that proposed CED may offer little value beyond the current FDA post-approval studies and may in fact be duplicative of the FDA’s requirements.

AdvaMed supports coverage of leadless pacemakers that have been approved by the FDA within their specific FDA-labeled indications. This is consistent with the recommendations of the American College of Cardiology, the Heart Rhythm Society, and the Society for Cardiovascular Angiography and Interventions, who jointly commented to CMS during the initial 30-day comment period on leadless pacemakers:

AdvaMed urges the agency to broaden its proposal to ensure that the NCD provides coverage for appropriately-indicated Medicare patients who may benefit from leadless pacemaker therapy, consistent with the FDA-labeling for the devices. If CMS does proceed with CED in its final determination, any such CED requirements should be as least burdensome and non-duplicative as possible.

When Medicare coverage is contingent on the collection of additional clinical or scientific evidence (beyond FDA requirements for safety and efficacy), we believe CMS should:

1. collaborate with stakeholders to clearly identify the data collection objectives;
2. consider the minimum data necessary to achieve those objectives;
3. clearly identify, with input from interested stakeholders, scientifically supported study endpoints and the duration of data collection in advance (including clear stopping rules for data collection under CED); and
4. identify an appropriate mechanism to ensure continuous coverage of an item or service after a study ends, to avoid disruption in coverage and continue to allow Medicare beneficiaries to benefit from important FDA-approved technologies and services until a new or revised coverage determination is issued.

As CED generates evidence supporting the use of a new innovation or services, Medicare’s coverage policies should reflect these outcomes and minimize additional requirements.

If you have questions regarding these comments or if you require additional information, please contact me or Chandra Branham, JD, Vice President, Payment and Health Care Delivery Policy, at (202) 434-7219 or cbranham@AdvaMed.org.

Sincerely,

/s/

Donald May
Executive Vice President
Payment and Health Care Delivery Policy

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I feel very strongly that coverage for leadless pacemaker should be approved . This an extremely valuable addition allowing physicians involved in cardiac care to provide much needed therapy for a select group of patients . Patient access should not be limited to those involved in research studies nor should there be any restrictions placed on the patient population meeting the needs for this type of device when other alternatives are less favorable.

Patients who meet the indications for pacemaker implantation and have conditions placing them at increased risk for traditional implants ( venous access limits, infection or erosion risks etc) should have access based on the discretion of the specialists caring for them . Those physicians who have undergone special training for this procedure should have unrestricted access to the leadless pacing system and discretion for implant appropriateness. There does not need to continued research as this therapy has shown itself to be of high value in selected populations who would otherwise be deprived of appropriate therapy that may be lifesaving.

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December 13, 2016

Ms. Tamara Syrek-Jensen
Director, Coverage & Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244

RE: Draft National Coverage Decision (NCD) for Leadless Pacemakers (CAG-00448N) Dear Ms. Syrek-Jenson:

The American College of Cardiology (ACC), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography and Interventions (SCAI) are the non-profit professional associations representing the majority of practicing electrophysiologists and interventional cardiologists in the United States. These members have expertise in the diagnosis and treatment of patients with heart rhythm disorders and structural heart disease. ACC, HRS and SCAI appreciate the opportunity to submit joint comments on the NCA for leadless pacemakers. This letter represents the consensus of the three societies.

The Centers for Medicare & Medicaid Services (CMS) proposes to cover FDA-approved studies for leadless pacemakers through Coverage with Evidence Development (CED). The Societies interpret this proposal to mean that no allowance will be made for coverage of patients who meet FDA approved indications but do not have access to participate in an FDA approved clinical trial (or FDA approved post-market approval study). This restriction will present a significant obstacle to patients’ access to this unique and important new therapy. The Societies strongly encourage CMS to modify its proposal and, instead, cover FDA-approved leadless pacemaker devices for Medicare beneficiaries who meet FDA- approved indications. The Societies recognize that significant questions regarding leadless pacemaker technology remain and strongly support collection of the necessary data to address critical clinical questions. The final coverage policy should provide appropriate patients access to this important new technology in conjunction with a robust mechanism of data collection to answer outstanding questions.

As outlined in our June 16, 2016 comment letter (attached), leadless pacing offers important advantages over transvenous pacemaker technology by eliminating the components most prone to short and long- term complications: the pacemaker leads and pocket. Lead failure and pocket infections are two of the most common and serious causes of morbidity amongst the Medicare patient population with traditional pacemaker systems. Among patients with vascular access limitations, epicardial pacing (a surgical approach associated with significant morbidity and poor long-term pacing outcomes often requiring repeat surgical procedures) would be the only alternative. Prospective evaluation of leadless pacing has demonstrated the technology to be safe and effective compared with transvenous historical controls, with 99.2% of the enrolled 725 patients receiving a successful implant and 96% reaching the primary safety endpoint.ⁱ

As with other new technologies, knowledge gaps remain. Specifically, how will the technology perform in the long term, how will patients be managed once the battery is depleted, will there be low- frequency, late complications, and how will the acute safety and effectiveness of the device compare with transvenous pacing outside of the clinical trials? Answering these questions will improve patient care as more is learned about leadless pacemaker technology in the long term. However, in the short term, a technology exists that the FDA has deemed to be safe and effective to treat patients with (1) symptomatic paroxysmal or permanent high-grade AV block in the presence of AF, (2) symptomatic paroxysmal or permanent high-grade AV block in the absence of AF, as an alternative to dual chamber pacing, when atrial lead placement is considered difficult, high risk, or not deemed necessary for effective therapy, or (3) symptomatic bradycardia-tachycardia syndrome or sinus node  dysfunction (sinus bradycardia or sinus pauses), as an alternative to atrial or dual chamber pacing, when atrial lead placement in considered difficult, high risk, or not deemed necessary for effective therapy.

Physicians and patients should be able to thoroughly consider all available therapies that are appropriate, discuss the known risks and benefits at the current life cycle of the technology, and then make a documented decision on how to proceed. We encourage CMS and the vendor community to work together with societies to develop a robust and minimally burdensome mechanism to capture data needed to answer these questions without restricting access to this important new technology.

Thank you for your consideration. The Societies are committed to accelerating access to safe, effective, reasonable, necessary and innovative technology. If you have questions or need additional information regarding any of these comments, please contact James Vavricek at jvavricek@acc.org, Kim Moore at kmoore@hrsonline.org, or Dawn Gray at dhopkins@scai.org.

Sincerely,

Richard A. Chazal, MD, FACC
ACC President

Michael R. Gold, MD, FHRS
HRS President

Kenneth Rosenfield, MD, MSCAI
SCAI President

i Reynolds D, et. al. New Eng J Med 2016;374:533-41.

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December 14, 2016

Mr. Andrew Slavitt
Acting Administrator
Centers for Medicare and Medicaid Services
200 Independence Ave SW
Washington, DC 20201

RE: CAG-00448N

Dear Acting Administrator Slavitt:

On behalf of the American Heart Association (AHA), including its American Stroke Association (ASA) division and over 30 million volunteers, we appreciate this opportunity to submit comments on the Centers for Medicare and Medicaid Services’ (CMS) proposed decision memo for leadless pacemakers.

As the nation’s oldest and largest voluntary health organization devoted to fighting cardiovascular disease and stroke, AHA continuously seeks ways to improve patient outcomes. We believe leadless pacemakers may provide patients with an important new option for treating or preventing abnormal heart rhythms. The benefits of using a leadless pacemaker in comparison to a traditional pacemaker include the avoidance of risks associated with intravascular leads and no pocket requirement for device placement.

We believe that leadless pacemakers should be available for patients meeting the FDA-approved indications:

• symptomatic paroxysmal or permanent high-grade AV block in the presence of Atrial Fibrillation (AF);
• symptomatic paroxysmal or permanent high-grade AV block in the absence of AF, as an alternative to dual chamber pacing, when atrial lead placement is considered difficult, high risk, or not deemed necessary for effective therapy; and/or
• symptomatic bradycardia-tachycardia syndrome or sinus node dysfunction (sinus bradycardia or sinus pauses), as an alternative to atrial or dual chamber pacing, when atrial lead placement is considered difficult, high risk, or not deemed necessary for effective therapy

Thus, we urge CMS to reconsider this restrictive decision, which limits coverage to Medicare beneficiaries participating in FDA-approved studies. Rather, CMS should extend coverage to eligible patients, while continuing to monitor the safety and effectiveness of leadless pacemakers. Restricting coverage through CED to those enrolled in a FDA-approved study will result in a substantial limitation of access to a novel and useful therapy for patients.

AHA recognizes that leadless makers are a new technology in the United States with accompanying risks that necessitate the collection of additional clinical data relating to long term effectiveness, risk of complications, and extraction. We believe that these evidence gaps are addressed in the product sponsor’s post-approval study required by the FDA. The study will evaluate complication rates related to cardiac perforation, pericardial effusion, dislodgement, embolization, serious groin complications and infections. The study will also evaluate the treatment and procedures related to the explant of leadless pacemakers, as well as the implant of new leadless pacemakers without explant. Since the study will provide a mechanism to collect data on leadless pacemakers in the post-market environment, restricting access through the CED process solely to collect data appears unnecessary.

However, we agree with CMS that provider training should be required for clinicians to become familiar with the device and implantation processes. Leadless cardiac pacemakers represent a new form of pacing technology. The indications for use, patient selection criteria, adverse event profiles, and implant and extraction procedures may differ from the conventional pacemakers providers are familiar with. As such, adequate provider training will be critical to maximizing patient outcomes. Therefore, we support including a physician training requirement as a condition for Medicare coverage.

AHA commends CMS for seeking to provide coverage for a device that can play a significant role in improving the health of patients. We urge CMS to avoid placing unnecessary restrictions on coverage and provide coverage to eligible patients, irrespective of study participation.

Thank you again for the opportunity to share our comments on these issues related to the coverage of leadless pacemakers. If you have any questions, please feel free to contact Stephanie Curtis at stephanie.curtis@heart.org or 202-785-7931.

Sincerely,
Steven R. Houser

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Than you for the opportunity to provide comments to CMS regarding the NCD for Leadless pacemakers.
I would like first to disclose that i am one of the principal investigator of the Micra Post approval study.
I am a cardiac Electrophysiologist in Atlanta, GA. I would like to report my positive experience with the Micra pacemaker. I have had the opportunity to implant Micra in more than 30 patients during clinical trials. This device as proven by the IDE trial and data from the post approval study is implanted safely and successfully in the majority of patients. it has the potential to eliminate lead and pocket related complications of traditional devices. The post approval study (PAS) has the potential to enroll 2000 patients from the US and Europe and provide long-term follow-up on these patients (9 year follow-up). As such i believe the PAS really satisfy CMS requirements in terms of providing close follow-up and reporting of short and long-term complications associated with this device. However, it is very important in my opinion to have this technology available to patients who will potentially benefit from this technology. Limiting its availability to patients enrolled in PAS would deny thousands of patients this important technology. I am hopeful that CMS will find a solution to have this technology available to patients who will potentially benefit from it without limiting it to patients enrolled in the PAS study and without the need for a cumbersome data collection tool that might be redundant in the presence of a comprehensive post approval study,
Sincerely,
Mikhael El-Chami

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Thank you for the opportunity to provide feedback regarding the proposed Medicare coverage decision for Leadless pacemakers (CAG-00448N).
Under protocol, I have implanted approximately 25 St. Jude Nanostim leadless pacemakers and colleagues at Scripps have implanted a similar number of Medtronic Micra devices. Scripps Health is one of the top 20 cardiac EP programs in the country in both volume and reputational score.
Leadless pacemakers are a revolutionary advance in pacing technology. They provide an important opportunity to avoid the complications associated with pacemaker leads and generator pocket issues including infection. While implantation of a leadless pacemaker requires a new skill set, the clinical trials have confirmed my own observation that these are safer than traditional single chamber pacemakers.
Nearly all of my patients implanted love this advance. For example, one plays rugby and is not concerned with potential injury to an implanted chest wall device. In the not to distant future, we will all look back upon implanted devices with leads as an outdated and unnecessarily risky technology.
While reimbursement for leadless pacing needs to exceed that for a single chamber pacemaker, due to the complexity of the technology, I believe that in the long run, it will also be shown to be cost-effective as batteries last longer plus the subsequent cost of lead and pocket complications and replacement will be avoided.
I strongly recommend that CMS issue a NCD without restriction for leadless pacing. I see no reason for a CED here as unneeded burdensome regulation already permeates our field. Currently ongoing and in planning, "real-world" clinical trials are underway to demonstrate the long-term risk and benefits of leadless pacing.
Please approve this needed technology promptly.
Sincerely,
Steven L. Higgins, MD

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I would like to provide a comment re access to leadless pacemakers. The have been 2 US trials. The Medtronic trial was a well designed trial with appropriate data collection and follow up confirming excellent outcomes, at least comparable to current pacemaker technology that utilizes leads. The fact that the second device (ST jude) has had some problems should bot be a consideration since the devices have differing technology and hence the results are different.

Considering the very encouraging results and the well documented multiple complications of systems that utilize leads, there should be broad access to leadless Medtronic pacemakers, based upon similar indications for single chamber ventricular pacemakers.

Coverage with Evidence Development (CED) is not necessary since the data and current Post-Approval Study is comprehensive and compelling.

If CMS mandates CED then data collection should be straightforward and similar follow up for a single lead pacemaker completed at 4-6 weeks after implant and access should be readily available through a wide spectrum of health systems in the US for appropriately-indicated patients. Finally there should not be any additional waiting period to initiate coverage. This is enormously valuable and incremental technology that offers huge benefits to patient care and will ultimate reduce cost due to reduction of lead-related complications.

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