Positron Emission Tomography

January 11, 2013

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
7500 Security Boulevard
Baltimore, Maryland 21244

RE: Comment on National Coverage Determination Decision Memorandum for Positron Emission Tomography (CAG-00065R)

Dear Dr. Jacques:

The Medical Imaging & Technology Alliance (MITA) thanks the Centers for Medicare and Medicaid Services (CMS) for posting its proposed decision memo on our request for reconsideration of the National Coverage Determination (NCD) of Positron Emission Tomography (PET), Section 220.6 of the Medicare National Coverage Determinations Manual. We also are grateful for the opportunity to provide comment on the draft decision memo, as there are several items that we wish to address.

This comment letter will cover the following discussion areas in response to the proposed decision memo:

• CMS’ overall response to the MITA reconsideration request submitted on March 30, 2012
• Use of PET in cardiology
• Use of PET in neurology
• Use of guidelines in CMS coverage decisions
• Other considerations

We are pleased that CMS has responded directly to our request by proposing that local Medicare Administrative Contractors (MACs) may determine coverage within their respective jurisdictions for PET procedures using radiopharmaceuticals for their labeled indications for oncologic imaging that are approved by the US Food and Drug Administration (FDA). We believe this is the correct step forward and will pave the way for innovative technologies to inform medical decision making for cancer patients with Medicare benefits. We have expressed our agreement with CMS previously that this diagnostic modality has matured, and through our request for reconsideration, we reiterated that the evidence base supports the use of PET imaging for Medicare beneficiaries without the restrictive language now in force.

We are very concerned, though, that CMS stopped short of our complete request, which delineated local coverage of all PET tracers that are newly approved by the FDA, not just oncologic tracers. As you are aware, PET procedures inform medical decision making in the specialties of cardiology and neurology as well. We are disappointed that these applications were not included in the decision memorandum. We believe that the consideration of coverage for PET tracers should be no different than for other items and services (for example, if the same compounds were labeled with a SPECT tracer); thus, we continue to be concerned that the requirements in the proposed decision memo differentiate PET tracers from all other radiopharmaceuticals, drugs and items the agency routinely covers. To recap our request, we proposed a revision to the Medicare Coverage Manual as follows:

Use of PET in Cardiology

Cardiac PET tracers have been in use for many years, and there is national coverage for their use. At a minimum, any new FDA approved cardiac PET radiopharmaceutical with an FDA approved indication that is the same as a current CMS covered indication should not be subject to automatic non coverage. The American College of Cardiology Foundation Appropriate Use Criteria Task Force with the American Society of Nuclear Cardiology (ASNC), the American College of Radiology (ACR), the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine and endorsed by the American College of Emergency Physicians published the Appropriate Use Criteria (AUC) for Cardiac Radionuclide Imaging. The use of PET scans is specified in the AUC; thus, there are professional society guidelines in place for the appropriate utilization of these scans. Our request would allow new cardiac PET tracers to receive local coverage to the degree that MACs deem appropriate.

ASNC also has also published ASNC Imaging Guidelines for Nuclear Cardiology Procedures - PET Myocardial Perfusion and Metabolism Clinical Imaging. This document provides the technical information for cardiac PET image acquisition, quality control, display and interpretation.

In the proposed decision memo, CMS expressed concern that guidelines for cardiac PET imaging were fewer than for oncology PET imaging. Oncology is a very diverse disease with many different types of tumors affecting all organ systems whereas cardiac imaging is limited to one organ and the vast majority of the imaging is of one type, perfusion imaging. Thus, it is reasonable that fewer guideline sources exist for cardiac PET imaging than for oncologic PET imaging. Based on the maturity and the long-standing utilization of these guidelines, we therefore urge CMS to include cardiac PET tracers in the decision memo.

Use of PET in Neurology

We acknowledge CMS has opened a national coverage request for beta amyloid PET imaging, and it is now being deliberated. However, we believe the proposed decision memo should have discussed any neurological applications of PET procedures, not just those for beta amyloid imaging. Although a beta amyloid PET tracer is the only available neurologic FDA-approved tracer on the market today, innovative companies are developing other agents that will be critical to medical decision making for other neurologic applications. Again, we strongly urge CMS to include any newly approved tracer (including those with neurologic applications) as eligible to receive local coverage.

Use of Guidelines

MITA appreciates the depth of research that CMS performed in arriving at this decision, but we are concerned with the manner in which guidelines were used in this draft decision memo. In many cases, a newly FDA-approved radiopharmaceutical will not have available guidelines; certainly not to the depth which you seem to deem necessary. This is why our request centered on adherence to covering only the FDA labeled indication, which will have robust clinical data at the time of approval. When guidelines become available, they should be used to inform decisions; however, lack of established guidelines should not preclude a new product from the possibility of coverage. When a new proprietary tracer is approved, the sponsor company/manufacturer will ensure that education is available to help both referring physician and imagers determine when the new product/test is appropriate. Professional societies also will develop criteria for determining when the study is appropriate or inappropriate after FDA approval. In the case where a guidance exists for the same indication of a PET tracer (or even a different radiopharmaceutical), it would be appropriate for that guidance document to be applied to the newly approved tracer.

CMS has expressed concern about the possibility of self-interest in the establishment of guidelines by members of the imaging community; however, as with any clinical guideline, the expertise resides in the professional society issuing such guidance. We trust that the medical professionals who develop guidelines do so with the best interest of patients in mind; we strongly believe that medical decision making (by both attending physicians and by those who develop guidelines) are independent of any self-interest. Thus, we believe that when guidelines exist for a particular item or service (including the use of a PET tracer in the detection of disease), these guidelines should be followed by the professional community and CMS should be confident in their utility to inform coverage decisions.

Other Considerations

We are also troubled by your statement in the “Other Considerations” section encouraging studies as part of future coverage requests on the determination of harms that PET radiotracers may cause. This concept lies outside the scope of our request, and we believe it will create an undue burden on innovators as they make coverage requests. Manufacturers must prove to the FDA that their products are both effective and safe in order to receive approval for marketing in the United States. Additionally, facilities must now achieve accreditation from any number of officiating entities , so CMS’ concern about harms from the variability in Standard Uptake Values (SUVs) should be assuaged. We would encourage CMS to confirm with FDA in determining that a product is safe not just for Medicare patients, but for all patients. We disagree that additional safety or “harm” studies should be part of the coverage determination, as products are required to undergo rigorous safety testing prior to being allowed on the market.

We are hopeful that CMS will further revise the decision memo to reflect the consensus mentioned in our concluding statements set forth in our March 30, 2012 reconsideration request. As such, recent advances in PET imaging and CMS’ past experience with PET coverage no longer support a clinical rationale for a preemptive national non-coverage policy for any new PET radiopharmaceutical agents that undergo rigorous FDA review and approval.

As always, we are eager to work collaboratively with CMS and the MACs to establish appropriate local coverage policies as new agents are approved by the FDA. We also are happy to answer additional questions you may have.

Sincerely,

/s/
Gail M. Rodriguez, PhD
Executive Director, MITA
Vice-President, NEMA

Less

Dear Dr. Jacques-

Cardinal Health is pleased to respond to the Centers for Medicaid and Medicare Services (CMS) request for comments on the reconsideration request of Section 220.6 of the National Coverage Determinations (NCD) Manual, dealing with Positron Emission Tomography or PET imaging. Cardinal Health’s Nuclear Pharmacy Services dispenses over 12 million nuclear medicine and PET radiopharmaceutical doses annually in the United States. We also provide support for more than 20 early phase clinical trials in nuclear medicine and PET.

While we are encouraged by CMS’s proposed decision memo indicating the removal of the exclusionary language for future FDA-approved oncologic radiopharmaceuticals, we are disappointed that the proposed memo stopped there. During the first open comment period, CMS requested comments on the breadth of the reconsideration request. We felt and still feel that the breadth of the reconsideration request was appropriate and we have inserted our original discussion on this topic:

“CMS also requested comment on the breadth of the reconsideration request. We feel the breadth of the request is appropriate given the current evidentiary requirements for FDA approval as noted above. Future PET radiopharmaceuticals which are approved by the FDA, should be treated in the same manner as all other diagnostic radiopharmaceuticals. Specifically, without a change to section 220.6, a newly FDA-approved PET radiopharmaceutical is automatically treated as not reasonable and necessary for its FDA labeled indication. Removing the “exclusionary language” would allow the new radiopharmaceutical to be covered by the local Medicare Administrative Contractors (MACs) upon FDA approval, but would not exclude the possibility of a full National Coverage Analysis. This flexibility is entirely appropriate given the success of this method for all other diagnostic radiopharmaceuticals and the many other items and services which are covered by Medicare. Removing the unnecessary delay in access to new radiopharmaceuticals for Medicare beneficiaries will benefit the Medicare population when they are used for the right patient at the right time as they can vastly improve the diagnosis of disease which can have a positive impact on patient management. Rest assured, we are not advocates of “screening” or unfettered use of new radiopharmaceuticals which are not medically necessary and may provide little to no benefit to the referring physician in making care management decisions. More importantly, we do advocate for appropriate use resulting in a positive impact on patients and on healthcare in general.”

We are surprised by the exclusion of cardiac radiopharmaceuticals from the decision memo. Cardiac radiopharmaceuticals have been in use for many years and while they are included in section 220.6 of the National Coverage Determinations manual they are also subject to numerous local coverage determinations and/or educational articles prepared by the local contractors. We feel this should give CMS sufficient comfort that coverage for newly approved cardiac PET radiopharmaceuticals could be appropriately determined by the local Medicare Administrative Contractors (MACs). Further, there is robust support from numerous cardiology societies regarding when these radiopharmaceuticals are appropriately utilized through both the American College of Cardiology Foundation Appropriate Use Task Force as well as published guidelines for myocardial PET imaging from the American Society of Nuclear Cardiology. We were also disappointed that neurology indications were excluded from the decision memo. Beta amyloid imaging is subject to another ongoing reconsideration to section 220.6 of the NCD; however, as reiterated above, we feel that the breadth of the MITA reconsideration request was appropriate.

We are concerned by the reasons provided for excluding non-oncologic PET radiopharmaceuticals; specifically, the way in which the guidelines were analyzed. It is reasonable to expect that a new radiopharmaceutical may not have guidelines in place upon FDA approval; however that should not preclude a new radiopharmaceutical from coverage. New proprietary radiopharmaceuticals will benefit from having a sponsor company who can be relied upon to help educate referrers and interpreting physicians on when a scan is appropriate and provide guidance on how to interpret the images. The most commonly used radiopharmaceutical today, F-18 FDG which proliferated primarily in academic institutions, did not have a consistent use pattern nor would it be expected to as there was not even a label indication at the time of the first CMS coverage. New radiopharmaceuticals are being approved under a more rigorous FDA approval process today which was absent when the currently covered radiopharmaceuticals were evaluated. We feel that the FDA process as well as the fact that new proprietary radiopharmaceuticals will benefit from a level of consistent education that was not existent before provides enough baseline for local Medicare contractors to make informed decisions on how to cover these new radiopharmaceuticals.

In closing, we would like to thank you for the opportunity to comment on this reconsideration request and we continue to believe that all new FDA approved PET radiopharmaceuticals should be included in the final decision. Coverage decisions for all other diagnostic radiopharmaceuticals are left to the local Medicare contractors; we urge you to treat all diagnostic PET radiopharmaceuticals in the same manner.

For any questions regarding our comments, please contact Terri Wilson at (407) 790-8287 or terri.wilson@cardinalhealth.com.

Sincerely,

Aaron Pitts
Sr Vice President, Nuclear Pharmacy Services
Cardinal Health

Less

January 11, 2013

Louis Jacques, M.D.
Director, Coverage and Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244

RE: Proposed Decision Memo for Positron Emission Tomography (CAG-00065R2)

Dear Dr. Jacques:

The Society of Nuclear Medicine and Molecular Imaging (SNMMI), the American College of Radiology (ACR), the American College of Cardiology (ACC) and the American Society of Nuclear Cardiology (ASNC) appreciate the opportunity to share our comments on the Centers for Medicare & Medicaid Services (CMS) recent proposed decision memo for positron emission tomography (PET) (CAG-00065R2). This proposal would remove the national non-coverage decision for PET for FDA-approved oncologic applications. While we believe this to be a step in the right direction, we do not think it is comprehensive enough. We respectfully request that CMS modify the proposed decision and finalize that local Medicare Administrative Contractors (MACs) may determine coverage within their respective jurisdictions for positron emission tomography (PET) using radiopharmaceuticals for their labeled indications that are approved by the FDA. The effect of this decision, with change, would be to remove the national non-coverage for any future PET radiopharmaceuticals that have not been more specifically determined nationally. Thus this change would not apply to any use of PET using radiopharmaceuticals FDG (2-deoxy-2-[F-18] fluoro-D-Glucose (fluorodeoxyglucose)), NaF-18 (fluorine-18 labeled sodium fluoride), ammonia N-13, or rubidium Rb-82. This would not prevent CMS from determining national coverage for any of these uses in the future, and if such determinations are made, a future determination would supersede local contractor determinations under §1862(a)(1)(A) of the Social Security Act (the Act).

SNMMI, ACR, ACC, and ASNC previously supported the Medical Imaging Technology Alliance’s (MITA) letter that requested a limited revision of the PET national coverage determination (NCD) which would maintain the integrity of the NCD for tracers reviewed within, but would foreclose the inappropriate extension of non-coverage to new FDA-approved tracers that have not received even minimal review by the agency. As a result, we believe CMS’s recent proposal, which would allow local Medicare administrative contractors to determine coverage for new oncologic agents for PET within their respective jurisdictions, to be a positive step.

However, we believe this proposal is too limited, and should not be confined to oncologic applications. In our previous letter, dated August 10, 2012, the societies provided examples of how this policy would be beneficial to additional indications, such as clinical cardiac PET. Unless there are specific national restrictions, we believe CMS should expand this proposal beyond oncology to cover all areas. The MACs’ expanded authority in this area does not preclude further CMS action. CMS would have the option to specifically exclude indications and products when necessary. Finally, the lengthy process to update national coverage generally requires over a year to complete. The proposed decision memorandum will unnecessarily/unintentionally delay coverage to Medicare patients who would benefit from new FDA-approved indications.

We remain committed to working with CMS and other stakeholders in creating a clear and open dialogue to provide peer-reviewed information for new PET radiopharmaceuticals. Additionally, we plan to work with other organizations to develop educational resources to help ensure appropriate utilization of PET/computed tomography by referring physicians, as well as nuclear medicine physicians and radiologists.

We appreciate your consideration of our recommendations. Should you have any questions, please contact Sue Bunning, Director of Health Policy and Regulatory Affairs at sbunning@snmmi.org or (703) 326-1182.

Respectfully Submitted,

Frederic H. Fahey, DSc
President, SNMMI

Harvey L. Neiman, MD, FACR
CEO, ACR

William A. Zoghbi, MD, FACC
President, ACC

James Arrighi, MD
President, ASNC

Less

The World Molecular Imaging Society (WMIS) appreciates the effort by the Centers for Medicare & Medicaid Services (CMS) over the past year to revise the national coverage policy for Positron Emission Tomography (PET) imaging. WMIS strongly supports the Proposed Decision Memorandum proposal to permit local contractors to determine coverage for new oncologic PET radiopharmaceuticals approved by the U.S. Food and Drug Administration (FDA).

However, WMIS remains concerned that the scope of the proposed decision is unnecessarily limited to oncology. We believe that there is no clinical basis that justifies the proposed requirement that every future FDA-approved cardiac and neurological PET radiopharmaceutical must seek a case-by-case National Coverage Determination (NCD) for an exemption from the non-coverage language of NCD 220.6. As is the case for oncology, we believe a more flexible coverage policy is also clinically appropriate for cardiology and neurology.

* Background on WMIS

WMIS is an international scientific and educational organization dedicated to the understanding of biology and medicine through multimodal in vivo imaging and the utilization of quantitative molecular imaging in patient care. The foremost and authoritative society in molecular imaging, WMIS was formed in 2011, as a result of the merger of two of the premier molecular imaging societies—the Academy of Molecular Imaging (AMI) and the Society for Molecular-Genetic Imaging. Between 2006 and 2011, AMI was the sponsor of the original NOPR, and since 2011, WMIS has continued to sponsor the current iterations of the registry, NOPR 2009 and NOPR (NaF-PET). WMIS is also a cosignatory to the March 30, 2012 NCD reconsideration request.

* WMIS Supports Ending the National Non-Coverage Policy for New Imaging Agents

WMIS strongly supports the proposal to permit local Medicare Administrative Contractors (MACs) to determine coverage for oncologic PET that uses new radiopharmaceuticals for their labeled indications as approved by the FDA. As we articulated in our previous comments, for more than a decade, significant data have been accumulated to demonstrate both the clinical accuracy of FDG-PET and its impact on patient management. To date, each change in PET coverage has required a lengthy NCD reopening and review. Based on the past reviews of FDG-PET, and now NaF-PET, it is appropriate that FDA-approved imaging agents, in the future, should not face a de facto national non-coverage policy following their approval.

In the United States and internationally, the molecular imaging clinical community and the radiopharmaceutical industry are undertaking clinical trials on numerous new oncologic imaging agents that hold great promise for the treatment and management of patients with cancer. In the next few years, we expect that several other PET radiopharmaceuticals for oncologic imaging will obtain FDA approval. These include agents for assessing tumor proliferation rates, hypoxia, angiogenesis, amino acid transport, and estrogen, androgen and somatostatin receptor status, as well as several radiolabeled monoclonal antibodies directed against receptors and other cellular antigens. These agents all hold promise for improved cancer care by individualizing therapy. Moreover, they likely will enable more cost-effective application of expensive therapies to those patients in whom the likelihood of therapeutic benefit can be established by imaging biomarkers before (or soon after) the start of treatment. For instance, Ga-68 DOTATOC or DOTATATE have been used worldwide for imaging somatostatin receptor expression in neuroendocrine tumors. These PET methods are more accurate and, at the same time, less expensive than currently covered conventional planar scintigraphy and SPECT with In-111 pentetreotide.

Most recently, in September 2012, the Mayo Clinic received FDA approval for Choline C-11 Injection to help detect sites of recurrent prostate cancer. C-11 Choline is a radioactive tracer involved chiefly in a metabolic pathway leading to the synthesis of cell membrane lipids. Since cancer cells take up more choline than do normal cells, the images can be used to help determine areas of probable cancer in patients with biochemical recurrence of their disease when bone scintigraphy, computed tomography or magnetic resonance imaging is non-informative. The review that preceded FDA approval was rigorous and exhaustive, and is publicly available. ^[1]

* CMS Should Expand the Final Decision to Include Cardiology Tracers

The FDA’s standards for new radiopharmaceuticals in oncology do not differ from its standards for approval of tracers in other diseases. Therefore, WMIS is highly concerned that the Proposed Decision only lifts the national non-coverage policy in the field of oncology (with the possibility of an extension to include cardiology).

The Proposed Decision memorandum requests public comments on lifting the national non-coverage policy for cardiac PET imaging agents. For several decades, members of WMIS have generated an extensive body of clinical research, and by now have over a decade of clinical practice, with cardiac PET. Chronic cardiac disease is associated with one of the highest morbidities among Medicare recipients, and several new cardiac PET imaging agents that may be highly relevant to the Medicare population are currently advancing through clinical trials.

WMIS believes that new PET tracers for myocardial perfusion imaging, such as F-18 flurpiridaz, should be open to coverage review by MACs following their FDA approval for the same indications for which Rb-82 and N-13 ammonia are currently covered. Requiring each one of the new FDA-approved agents for myocardial imaging to proceed through a lengthy and administratively burdensome NCD reconsideration process would be unnecessarily duplicative and would delay the availability of safe, FDA-approved tracers to Medicare beneficiaries. This would be unfortunate, because the longer half-life of F-18 flurpiridaz means that this agent should be readily distributable as unit doses (like FDG) and thus be more widely available to Medicare beneficiaries than either Rb-82 or N-13 ammonia.

In addition to perfusion radiotracers, new PET molecular imaging agents are being evaluated in humans with various forms of cardiovascular disease. For example, PET with F-18 galacto-RGD to target avß3 integrin is undergoing human evaluation to detect vascular inflammation in atherosclerosis and angiogenesis in left ventricular remodeling that occurs following myocardial infarction. Successful detection of these processes has the potential for more targeted and earlier intervention of patients with atherosclerosis and its complications. Abnormalities in myocardial fatty acid metabolism are central to the pathogenesis to various forms of heart failure, particularly those secondary to cardiometabolic disease such as obesity and diabetes mellitus. To this end, several F-18 radiolabeled fatty acid imaging agents are undergoing early phase clinical trials. The availability of these imaging agents has the potential to provide both new prognostic markers in heart failure patients and an imaging surrogate for new therapies entering the clinic designed to modulate myocardial metabolism in these patients.

WMIS requests that the Final Decision memorandum include cardiology along with oncology as categories where MACs may determine whether (or not) the use of PET scans with such new FDA-approved radiopharmaceuticals is reasonable and necessary.

* CMS Should Not Foreclose Local Coverage for Future Imaging Agents for Neurology

WMIS strongly recommends that the most appropriate framework for the next generation of PET tracers in oncology, cardiology, and neurology (including dementia and Alzheimer’s disease), is the elimination of tracer-by-tracer and indication-by-indication national coverage reviews. Coverage should be reviewed through the local contractor process and, when appropriate, through a national coverage analysis.

In the Proposed Decision memorandum, CMS has summarily foreclosed the possibility of coverage of neurological PET tracers except on a case-by-case basis through the NCA process. While this is the approach already taken for beta-amyloid imaging, it seems unnecessarily restrictive to repeat the same process over and over for all future FDA-approved neurological PET tracers, and for review of each indication for each of the widening spectrum of tracers. If CMS is not prepared to delegate neurological PET imaging (other than beta-amyloid imaging) to the MACs at this time, we believe CMS should open a review of the national non-coverage policy for neurology following the completion of the current national coverage analysis Beta Amyloid Positron Emission Tomography in Dementia and Neurodegenerative Disease.

Although fewer PET radiopharmaceuticals are currently under clinical development for neurologic applications (other than for amyloid imaging), a notable exception is in tracers for evaluation of patients with movement disorders due to Parkinsonian syndromes. These agents will allow for earlier and more accurate diagnosis, prognosis, and treatment selection. The majority of these PET agents assess specific targets present in neurons in the brain that use the neurotransmitter dopamine, and can quantify the loss of this neuronal population due to neurodegeneration. These PET tracers are clearly superior for detecting the loss of dopaminergic neurons compared to the SPECT agent, I-123 ioflupane, which is FDA-approved for distinguishing Parkinsonsian syndromes from essential tremor and other non-degenerative causes of movement disorders. The overall cost of performing studies with PET tracers for the brain dopaminergic systems would likely be similar to — or less than — the cost of I-123 ioflupane SPECT.

Moreover, in the Proposed Decision, CMS has affirmatively retained the express option to supersede or preclude local coverage decisions on specific uses of neurological PET where CMS believes centralized control is warranted. Indeed, CMS has already exercised this option in the review of beta-amyloid PET. Given the ample regulatory authorities and safeguards that exist, there appears no compelling reason for CMS to preclude preemptively any possibility of local coverage for FDA-approved neurological PET tracers by leaving in place the categorical exclusion for one or another specific group of Medicare’s beneficiaries.

There is a genuine and growing concern in the medical community that the United States is falling behind Europe and the rest of the world in terms of clinical molecular imaging. The continuation of blanket national non-coverage policies for new FDA-approved PET imaging agents discourages continued domestic research and investment in molecular imaging, the adverse impact of which is borne by the patients and Medicare beneficiaries who stand to benefit from such technological advances.

* WMIS Plans to Work with Medicare Administrative Contractors

Over the past decade, WMIS has had extensive experience working with MAC medical directors on PET coverage, coding and payment issues. The years of indication-by-indication review of FDG-PET — and the subsequent multiple phases of Coverage with Evidence Development (CED) for FDG-PET — raised numerous coverage implementation issues for local MACs and Medicare Advantage plans. At the same time, PET imaging has undergone near-annual coding and reimbursement methodology policy changes, each of which has in turn created new implementation issues for MACs.

As CMS introduces this new and more efficient coverage framework for new PET radiopharmaceuticals, WMIS stands ready to work closely with CMS, local medical directors, and other stakeholders in advance of the FDA approval of any new imaging agent, in order to provide technical assistance and help mitigate any coverage implementation issues that may arise at the local level.

* Conclusion

WMIS strongly supports the proposal in the Proposed Decision to permit local contractors to determine coverage for new oncologic PET FDA-approved radiopharmaceuticals, and respectfully requests that the Final Decision memorandum provide local contractors with the same latitude for cardiac and neurologic PET imaging agents as well.

WMIS appreciates the opportunity to comment on the Proposed Decision, and looks forward to continuing to work collaboratively with CMS to make innovative imaging technology available to the providers and Medicare beneficiaries who will benefit most from its use. We are of course pleased to provide CMS with any additional information that it may find useful in reaching its Final Decision.

Sincerely,

/s/

Zaver Bhujwalla, Ph.D.
President, WMIS

[1] http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203155Orig1s000TOC.cfm

Less

Dear Dr. Jacques:

Lantheus Medical Imaging, Inc. (Lantheus) appreciates the opportunity to submit comments to the Centers for Medicare and Medicaid Services (CMS) regarding the above-referenced Proposed Decision Memo for Positron Emission Tomography (PET).

Lantheus is the developer and manufacturer of a number of radiopharmaceuticals used for nuclear cardiology and nuclear medicine procedures, including Cardiolite® (Kit for the Preparation of Technetium Tc99m Sestamibi for Injection) for SPECT myocardial perfusion imaging (MPI), Thallium 201 (Thallous Chloride Tl201 Injection) also for MPI, and TechneLite® (Technetium Tc99m Generator).

As you know, Lantheus is currently conducting a Phase III, multi-center clinical program with a new positron emitting agent, flurpiridaz F 18, to assess myocardial perfusion by PET imaging in patients with known or suspected coronary artery disease (CAD). This clinical study includes Medicare beneficiaries and is designed to determine the clinical efficacy and safety of flurpiridaz F18 PET MPI among Medicare beneficiaries and other patients.

As you recall, Lantheus representatives initially met with you and your staff in April 2009 to present results of a Phase I clinical study with flurpiridaz F 18 and to ask for your/CMS comments on the Lantheus design for a Phase II clinical study with this new positron emitting agent. Subsequently, in April 2011, Lantheus representatives met with you and your staff to present results of a Phase II clinical study with flurpiridaz F 18, describe how your/CMS comments were incorporated, and again asked for your/CMS comments on the Lantheus design for a Phase III study. We at Lantheus are very interested in continuing this open exchange of information with you and others in the CMS Coverage and Analysis Group.

In the spirit of continued open communication and alignment, Lantheus offers the following comments and recommendations in response to the Proposed Decision Memo for PET:

• The performance of PET MPI in patients with known or suspected coronary artery disease is well-established and this imaging procedure has been covered by Medicare for many years. Deferring to regional Medicare Administrative Contractor (MAC) discretion to determine whether PET MPI is reasonable and necessary for known or suspected coronary artery disease when performed using novel PET imaging agents that have been approved by the US Food and Drug Administration (FDA) for this purpose will:
  1. provide physicians with a choice of safe and effective imaging agents,
  2. result in timely patient access to new agents,
  3. provide a level playing field among developers and marketers of FDA-approved PET imaging agents, and
  4. conserve CMS resources by eliminating the need to open individual national coverage analyses each time a new PET MPI agent is approved by FDA.

• Guidelines for the appropriate use of PET MPI are well-established for both treating physicians and those who perform PET imaging. It has been shown that adherence to appropriate use criteria can effectively control the utilization of MPI assuring that these procedures are used when reasonable and necessary. Such criteria and guidelines may be relied upon by regional MACs to establish Local Coverage Determinations (LCDs) for PET MPI using novel PET imaging agents when these agents are approved by the FDA.

Lantheus’s detailed comments on the Proposed Decision Memo for PET coverage are outlined below:

I. PET MPI with a Novel Cardiac PET Imaging Agent FDA-Approved for Patients with Known or Suspected Coronary Artery Disease Should be Considered Reasonable and Necessary for Medicare Beneficiaries as long as there is Sufficient Clinical Evidence in Medicare-eligible Study Subjects

We support the CMS proposal that local MACs may determine coverage within their respective jurisdictions for PET using radiopharmaceuticals for their labeled indications for oncologic imaging that are approved by the U.S. Food and Drug Administration (FDA).

However, we strongly believe that CMS should expand the proposal to include new FDA approved cardiac PET radiopharmaceuticals with FDA approved indications for use in patients with known or suspected coronary artery disease when these agents are approved, consistent with the indications for PET MPI that are currently covered in the PET NCD.

CMS has determined that noninvasive imaging of the perfusion of the heart for the diagnosis and management of patients with known or suspected coronary artery disease using the FDA-approved radiopharmaceuticals Rubidium 82 or Ammonia N 13 is covered if:

The PET scan, whether at rest alone, or rest with stress, is performed in place of, but not in addition to, a single photon emission computed tomography (SPECT);

or

The PET scan, whether at rest alone or rest with stress, is used following a SPECT that was found to be inconclusive. In these cases, the PET scan must have been considered necessary in order to determine what medical or surgical intervention is required to treat the patient. (For purposes of this requirement, an inconclusive test is a test(s) whose results are equivocal, technically uninterpretable, or discordant with a patient's other clinical data and must be documented in the beneficiary's file.)

This coverage determination was based upon CMS’s review of clinical evidence showing that PET MPI using these agents is reasonable and necessary for the diagnosis and management of patients with known or suspected coronary artery disease.

When the FDA approves a new cardiac PET radiopharmaceutical with an indication for use in patients with known or suspected coronary artery disease, this reflects a determination that the agent has been found to be safe and effective for this purpose based upon substantial evidence consisting of adequate and well-controlled trials. Combining this determination by the FDA regarding the novel cardiac PET agent with CMS’s determination that PET MPI is reasonable and necessary, provides a firm evidence chain to support a conclusion that PET MPI using the novel cardiac PET agent is reasonable and necessary for patients with known or suspected coronary artery disease. The remaining question would be whether sufficient numbers of Medicare-eligible subjects were included in the clinical evidence base to allow a regional MAC to conclude that the novel agent is reasonable and necessary for Medicare beneficiaries.

CMS’s deferring to the regional MACs to make this determination would seem reasonable. It would allow for Medicare coverage of novel agents upon FDA approval without requiring expenditure of the substantial resources and delay involved in a National Coverage Determination for each PET imaging agent that may be approved by FDA for known or suspected coronary artery disease.

II. There Are Robust Appropriateness Criteria, Guidelines for Use, and Accreditation Programs for Cardiac PET MPI to which Regional MACs Can Refer to Support Local Coverage Determinations for PET MPI Using Novel PET Agents

In section VI of the Proposed Decision Memo, CMS stated:

“Thus, our analysis speaks to whether we believe that physician understanding of the role of PET imaging, and the evidence base on these uses as it has evolved since our first PET NCD, have reached a point where coverage may commonly be determined successfully at the local contractor level with respect to the use of potentially new radiopharmaceuticals.”

In section VIII of the Proposed Decision Memo, CMS stated:

“There is a risk of imaging in a haphazard manner due to the absence of evidence based diagnostic algorithms.”

Cardiac PET MPI has a substantial evidence based supporting the use of this imaging technology, and the procedure has matured to the point where there are now extensive, detailed professional society imaging guidelines, professional society Appropriate Use Criteria (AUC), and accreditation organizations focused on imaging quality.

1. The American College of Cardiology Foundation (ACCF) Appropriate Use Criteria (AUC) Task Force, consisting of the American Society of Nuclear Cardiology (ASNC), the American College of Radiology (ACR), the American Heart Association (AHA), the American Society of Echocardiography (ASE), the Society of Cardiovascular Computed Tomography (SCCT), the Society for Cardiovascular Magnetic Resonance (SCMR), and the Society of Nuclear Medicine (SNM)and endorsed by the American College of Emergency Physicians, has published “Appropriate Use Criteria for Cardiac Radionuclide Imaging” which covers 67 different clinical indications including both SPECT and PET (MPI). These criteria have gained widespread acceptance in the cardiology community as these were developed jointly by imagers and treating physicians. These criteria may be relied upon by regional MACs in establishing LCDs to limit coverage of PET MPI with a novel imaging agent to ensure the right patient receives the right scan.

The 2009 ACCF AUC cover both PET and SPECT MPI and do not distinguish appropriate use criteria by imaging modality or radiotracer. The criteria apply to all forms of radionuclide MPI — whether by SPECT or PET and covering all radionuclides used for these procedures. These guidelines have been assessed in clinical practice and have been found to be feasible for use to readily identify practice patterns and targets for educational and quality improvement initiatives.

2. Separately, the American Society of Nuclear Cardiology published its own “ASNC Imaging Guidelines for Nuclear Cardiology Procedures for PET myocardial perfusion and metabolism.” This detailed 30 page guide addresses PET instrumentation, PET crystal types, PET time of flight imaging, PET attenuation correction, PET Quality Control, PET acquisition and processing, PET dosing considerations, PET image reconstruction, PET patient preparation, PET perfusion imaging, cardiac image display, analysis and interpretation.

3. There has been extensive interest by nuclear cardiology laboratories to demonstrate their commitment to quality care by gaining accreditation from the Intersocietal Accreditation Commission (IAC). The purpose of the IAC Nuclear/PET accreditation program is “to ensure high quality patient care and to promote health care by providing a mechanism to encourage and recognize the provision of quality nuclear cardiology, nuclear medicine and PET diagnostic evaluations by a process of accreditation.” Through the accreditation process, facilities assess every aspect of daily operations and its impact on the quality of health care provided to patients. While completing the accreditation application, facilities may identify and correct potential problems, revise protocols and validate quality assurance programs. Because accreditation is renewed every three years, a long-term commitment to quality and self-assessment is encouraged and more likely to be developed and maintained than if regular re-accreditation was not required. Facilities may use IAC Nuclear/PET accreditation as the foundation for creating and achieving realistic quality health care goals.

According to the IAC, there are 3,811 accredited nuclear cardiology sites, 100 of which are accredited PET sites. As part of the accreditation process, they must engage in an evaluation of their adherence to ACCF AUC.

4. Separately, the American College of Radiology has a quality accreditation program. The goal of the ACR Nuclear Medicine and PET Accreditation Program is to set quality standards for facilities and to help them continuously improve the quality of care given to patients. The ACRs voluntary, modality specific accreditation programs offer nuclear medicine and PET physicians an opportunity for comprehensive review and evaluation of their nuclear medicine and PET facilities, personnel qualifications, image quality, equipment, quality control procedures, and quality assurance programs through a confidential, peer review mechanism. The program is designed to be educational in nature, focusing on the primary factors that have an impact on the quality of clinical images and the quality of patient care.

According to the ACR, there are 3,240 sites accredited for nuclear medicine and 1,450 accredited for either cardiac or oncologic PET.

CMS found over 100 guidelines relevant to PET imaging for oncology, noted that fewer cardiology imaging guidelines were identified. However, this is to be expected as cancer is a diverse disease involving different tumor types and stages. On the other hand, MPI to diagnose or manage coronary artery disease is a more focused clinical indication and allows for a simpler process to write comprehensive guidelines than for PET used for oncologic indications. Regardless, and as described above, there are well-established, multi-disciplinary appropriate use criteria, guidelines, and accreditation programs for PET MPI on which regional MACs can rely to establish LCDs for coverage of novel PET MPI agents. Most of these programs evolved over the past decade and did not exist in the early days of PET imaging when the PET NCD was established.

* * *

Based upon the information summarized above, Lantheus requests that CMS allow regional MACs the discretion to develop LCDs consistent with the coverage of Rb-82 and ammonia N 13 PET MPI in the correct PET NCD to cover novel cardiac PET radiopharmaceuticals for MPI for the diagnosis and management of patients with known or suspected coronary artery disease, when the novel PET MPI agent is both FDA-approved and there is sufficient clinical evidence in Medicare-eligible subjects to support a conclusion that PET MPI with the novel agent is reasonable and necessary. Please note, we are NOT requesting that CMS propose to defer to regional MACs for all novel PET imaging agents that may be used for cardiac indications. We are requesting that CMS defer to regional MACs solely for PET MPI procedures for known or suspected coronary artery disease meeting the criteria of the current PET MPI NCD when these procedures are performed using FDA-approved novel PET MPI agents for this purpose.

Lantheus appreciates your consideration of these comments, and we would be pleased to provide you with additional information regarding any of these issues. Please contact Paul Radensky, MD, JD at (202) 756-8794, or PRadensky@mwe.com with any such requests or questions.

Sincerely,

Donald R. Kiepert, Jr.
President and CEO

Cc: American College of Cardiology
Association of Black Cardiologists
American Society of Nuclear Cardiology

Less

Louis Jacques, MD
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
7500 Security Boulevard
Baltimore, Maryland  21244

RE:     Proposed Decision Memo for Positron Emission Tomography (CAG-00065R2)

Dear Dr. Jacques:

The American Society of Nuclear Cardiology (ASNC) and American College of Cardiology (ACC) appreciate the opportunity to submit comments to the Centers for Medicare and Medicaid Services (CMS) regarding the above-referenced Proposed Decision Memo for Positron Emission Tomography (PET). 

ASNC is a 4,700 member professional medical society, which provides a variety of continuing medical education programs related to nuclear cardiology and cardiovascular computed tomography develops standards and guidelines for training and practice, promotes accreditation and certification within the nuclear cardiology field, and is a major advocate for furthering research and excellence in nuclear cardiology and cardiovascular computed tomography.  The ACC is a 40,000-member nonprofit medical society composed of physicians, nurses, nurse practitioners, physician assistants, pharmacists and practice managers, and bestows credentials upon cardiovascular specialists who meet its stringent qualifications. The ACC is a leader in the formulation of health policy, standards and guidelines, and is a staunch supporter of cardiovascular research. The College provides professional education and operates national registries for the measurement and improvement of quality care.

In a letter submitted to CMS in August 2012, ASNC and ACC joined with other medical societies in requesting that CMS remove the current non-coverage language as it pertains to new PET radiopharmaceuticals that receive approval from the Food and Drug Administration (FDA).  The letter noted newly approved PET radiopharmaceuticals are subjected to rigorous, well-controlled clinical trials that are demonstrative of the safety and efficacy of the FDA approval process.  Recent advances in imaging and CMS’ past experience with PET coverage no longer support a rationale for a pre-emptive national non-coverage policy for new PET radiopharmaceutical agents that undergo rigorous FDA review and approval.

We are concerned by the agency’s contention that removing the non-coverage language will lead to “a real risk that imaging may proceed in a haphazard manner.”  Cardiology has been at the forefront of the development of Appropriate Use Criteria (AUC).  The American College of Cardiology Foundation (ACCF), in concert with key subspecialty societies, developed AUC with a rigorous foundation in scientific evidence and practice experience.  AUC publications reflect an ongoing effort by medical societies to critically and systematically create, review, and categorize clinical situations where diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular disease.  AUC documents provide a valuable tool based on a broad range of clinical experiences and evidence-based data to guide the efficient and equitable allocation of healthcare resources in cardiovascular imaging.  Therefore, CMS can be confident that regional Medicare Administrative Contractors have a robust set of reference guidelines to support Local Coverage Determinations for PET myocardial perfusion imaging procedures performed with new PET imaging agents that have been approved by the FDA for use in patients with known or suspected coronary artery disease.

Moreover, medical societies and healthcare professionals with no direct ties to cardiovascular imaging played an integral role in the development of AUC documents.  The ACC represents the entire field of cardiology and is not driven by the interests of cardiovascular imaging.  The American Heart Association (AHA), for example, was a key participant in the development of the “2009 Appropriate Use Criteria for Radionuclide Imaging.”  The AHA has a broad focus on cardiovascular disease that extends far beyond imaging (arrhythmia, cholesterol, congenital heart defects, etc.).  In addition, the American College of Emergency Physicians (ACEP) endorsed this 2009 document and had a representative on the Technical Panel, Anthony J. Dean, MD, FACEP.  Peter Goldbach, MD, Medical Director for Blue Cross/Blue Shield Massachusetts, was a member of the Technical Panel as well.  The diverse participation in the development of AUC documents is not a random occurrence; rather, the ACCF consciously seeks an appropriate balance with respect to expertise in the specific modality, referring physicians, academic versus private practice, health services research, and specialty training. 

Cardiac AUC documents display substantial rigor and input from diverse stakeholders, and this founding principle ensures the focus remains on prompt, efficient, and patient-centered care.  Our additional quality initiatives will further ensure a patient-centered focus.  For instance, the clinical data registry will provide a platform for support communities to share best practices, develop lab-based tools that can be easily used to foster innovation, and allow for continuous quality improvement.  The registry will also develop data and metrics to lead policy development.

Removing the non-coverage language will not create a risk of haphazard imaging.  Therefore, ASNC and ACC reiterate the multi-society request that CMS remove the current non-coverage language as it pertains to new PET radiopharmaceuticals that receive approval from the FDA.  In particular, we urge CMS to allow regional MACs to cover PET myocardial perfusion imaging for patients with known or suspected coronary artery disease when performed using new, FDA-approved PET radiopharmaceuticals.

We appreciate the opportunity to provide comments on this key issue.  Should you have any questions, feel free to contact Andrew McKinley, Associate Director of Health Policy, at (301) 215-7575 or amckinley@asnc.org.

Sincerely,

James Arrighi, MD  
President   
American Society of Nuclear Cardiology       

William Zoghbi, MD
President
American College of Cardiology

Less

Allowing MAC discretion for coverage of oncologic applications for PET drugs is a very positive move forward. Any drug being put through the current FDA approval process whether generic or a new molecular entity must show safety and efficacy for a relatively narrow range of applications.
These actions help streamline the process for coverage post approval and will streamline access to these powerful diagnostic compounds for clinicians and patients.

I am hoping that CMS will allow pass through status for payment rates until such time as an orange book price can be established for these new products.

Less