1299 Pennsylvania Ave, NW
Washington, DC 20004
August 9, 2012
Jeffrey Roche MD, MPH
Lead Medical Officer
Stuart Kaplan, RN, MAS
Coverage and Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244
RE: Request for Public Comment on Reconsideration of the National Coverage Determination for Positron Emission Tomography (PET) (CAG-00065R2)
Dear Dr. Roche and Mr. Kaplan:
GE Healthcare (“GEHC”) appreciates this opportunity to comment on the reconsideration of the National Coverage Decision (“NCD”) for Positron Emission Tomography (“PET”) which the Centers for Medicare and Medicaid Services (“CMS”) announced on July 11, 2012. It is our understanding that during this 30-day public comment period CMS is particularly interested in comments that include scientific evidence and that address the breadth of the request by the Medical Imaging & Technology Alliance (“MITA PET NCD Request”).
GEHC, a division of General Electric Company, has expertise in medical imaging and information technologies, medical diagnostics, patient monitoring systems, performance improvement, drug discovery, and biopharmaceuticals manufacturing technologies. GEHC’s broad range of products and services enables healthcare providers to offer patients earlier and more accurate diagnosis and treatment of cancer, heart disease, neurological diseases, and other conditions that threaten the quality and length of life. Worldwide, GEHC employs more than 53,000 people committed to serving healthcare professionals and their patients in more than 100 countries.
GEHC is a member of MITA and has participated in that group’s effort to develop the MITA PET NCD Request. We re-affirm our support for MITA’s proposed modification to the Medicare Coverage Manual Section 220.6, as stated below:
This manual section 220.6 lists all Medicare-covered uses of PET scans based on the tracers rubidium, ammonium, sodium fluoride, and fluordexoglucose. Except as set forth below in cancer indications listed as “Coverage with Evidence Development,” a particular use of PET scans with these tracers is not covered unless this manual specifically provides that such use is covered. Although this section 22.06 lists some non-covered uses of PET scans, it does not constitute an exhaustive list of all non-covered uses of these tracers. Coverage of other FDA-approved PET radiopharmaceuticals is at the discretion of the local Medicare Administrative Contractors unless specifically addressed under a National Coverage Determination.
We believe this proposed modification is appropriate for several reasons.
- It creates the conditions for trained expert clinicians to take a patient-centric approach to the use of PET.
- It is suitable for the new generation of diagnostic radiopharmaceuticals being investigated for more targeted uses and personalized medicine for appropriate patient populations.
- It recognizes that radiopharmaceuticals now face a far more rigorous regulatory environment.
- It acknowledges the appropriate clinical evidence threshold for diagnostic medical innovations.
- It harmonizes the coverage determination criteria for all diagnostic radiopharmaceuticals.
- It removes inappropriate coverage restraints from providers working to succeed under new pay-for-performance (P4P) models of care.
We discuss each of these reasons below, and although each is addressed separately, we underscore that they all work together to create the conditions for a new approach to PET coverage. Our comments re-emphasize some of the information included in the MITA PET NCD Request because it provides important justification for the proposed coverage modification. We also provide additional rationale to support this reconsideration of the PET NCD.
1. Proposed Modification Creates the Conditions for Trained Expert Clinicians to Take a Patient-Centric Approach to the Use of PET.
Today, unless specifically covered in the current PET coverage policy, CMS categorically denies other uses of PET radiopharmaceuticals for all Medicare beneficiaries (often referred to as the exclusionary clause). We believe this “one-size-fits-all” non-coverage approach for new FDA-approved PET radiopharmaceuticals is inconsistent with the recently published Department of Health and Human Services (“DHHS”) National Quality Strategy (“NQS”) which calls health care providers and payers to redirect their attention to patient-centered care. Specifically, the first aim under the Triple Aim as stated in the NQS is to “Improve the overall quality, by making health care more patient-centered, reliable, accessible, and safe”1 (emphasis added). [Note: We address reliability and safety aspects of the Triple Aim in Section #3].
Historically, the Medicare program has enabled patient-centric coverage determinations using the criterion that if a particular service or item falls within a benefit category, it is eligible to be covered. When there is no specific coverage policy, a local Medicare Contractor can decide to cover the service or item on a case-by-case basis, based on documentation it requests from the physician to assess the medical necessity and reasonableness of the service for his/her particular patient. We believe that CMS’s current restrictive approach for new FDA-approved PET radiopharmaceuticals, regardless of the patient-specific circumstance, is not in step with DHHS’s new emphasis on accessible, patient-centered care.
We also believe that removing the exclusionary clause for new uses of PET and new radiopharmaceuticals still leaves several safeguards in place for both CMS and patients. There is a well-established common principle that unnecessary services are unpayable, as formalized by an Administrator’s Ruling.2 Thus, association guidelines or other commonly available review standards can be applied by Medicare Administrative Contractors, Recovery Audit Contractors, and Zone Program Integrity Contractors, in lieu of a specific local coverage determination (“LCD”). As stated in the MITA PET NCD request, professional societies, including the American College of Radiology (“ACR”), and the Society of Nuclear Medicine and Molecular Imaging (“SNMMI”), are committed to developing appropriateness criteria guidelines to assist referring physicians and other providers in making appropriate decisions regarding PET.3
2. Proposed Modification is Suitable for the New Generation of Diagnostic Radiopharmaceuticals Being Investigated for More Targeted Uses and Personalized Medicine for Appropriate Patient Populations
As summarized in the MITA PET NCD Request, the original context of PET coverage was to address the broad use of the generic tracer, fluorodeoxyglucose F-18 (“FDG”) for which there was no specific FDA labeled indication and for which there was limited published literature for the majority of proposed indications. In contrast, modern diagnostic PET radiopharmaceuticals are studied in adequate and well-controlled in clinical trials as a basis for review of safety and efficacy by the FDA and have more precise and specific mechanisms for detecting and quantifying pathophysiology as one element in the clinical decisions for patient management. These innovations are opening the door to more personalized medicine.
Accelerating the development of and access to technologies that personalize medicine are clear objectives of the President, as stated in the White House National Bioeconomy Blueprint (“Blueprint”).4 The Blueprint notes the report by the Personalized Medicine Coalition which states in its introduction that “what is different about medicine today, and the reason the word “personalized” has been added for emphasis, is that technology has brought us much closer to exquisite precision in disease diagnosis and treatment.”5 The Blueprint calls for reducing regulatory barriers to adoption of new technology, which in addition to targeted use of coverage with evidence development and regulatory parallel reviews, we believe includes revisiting outdated coverage policies. In this instance, the proposed modifications to the PET NCD will reflect the current environment, which includes among other things, much more rigorous FDA requirements for radiopharmaceuticals. This is addressed in the next section.
3. Proposed Modification Recognizes that Radiopharmaceuticals Now Face a Far More Rigorous Regulatory Environment
The MITA PET NCD Request summarized the history of regulatory approvals for PET radiopharmaceuticals. In sum, for each of the four longstanding PET radiopharmaceuticals — rubidium Rb-82, ammonia N-13, fluorodeoxyglucose F-18, and sodium fluoride F-18, there was generally a lack of FDA-supervised phase II and phase III trials, clear metrics for reporting, or a clear landmark to signify a satisfactory achievement of clinical evidentiary standards as to when clinical use should begin. Rather than review the developer/manufacturer’s exhaustive dossier of data, as is familiar today, in 2000 the FDA issued a public notification of labeling for FDG in oncology (“to assist in evaluating malignancy”) and ammonia N-13 (for myocardial blood flow), as it began to implement 1997 legislation to “establish appropriate procedures for the approval of PET drugs.”6,7 Today, the FDA requirements are much more rigorous including requirements to demonstrate (i) accuracy & reliability; (ii) clinical usefulness; (iii) competent image interpretation & radiology training; and (iv) GMP standards for PET radiopharmaceutical manufacturing.
Evidence of this is the FDA’s recent approval of AmyvidTM8, which was approved only after issues of image interpretation were addressed. The FDA label provides substantive information to physicians to guide them in the use of Amyvid, including information on limitations of use and requirements for special training for readers of Amyvid images.9 Provision of guidance in drug labeling is not unusual for drugs, generally.
The ability to visualize amyloid in-vivo is an important discovery and is playing a vital role in advancing our understanding of Alzheimer’s Disease (AD). This technology not only identifies individuals with and without amyloid deposition which, when taken with other diagnostic information, is proving useful for early and differential diagnosis of AD,10,11 it is playing a role in our understanding of the cascade of events that leads to the clinical expression of the disease.12 Recently amyloid imaging has been incorporated into therapeutic trials of disease modifying anti-amyloid treatments.13,14 This neuroimaging technique may prove important for subject selection and stratification in therapeutic trials and in monitoring treatment effects.15
FDA’s more rigorous requirements for radiopharmaceuticals, especially FDA’s requirement for demonstration of clinical utility and the accuracy and reliability of radiologist interpretation, establish a solid basis of evidence for coverage of the labeled use(s). These requirements also satisfy the other components of the aforementioned first aim of the Triple Aim, namely, ensuring that uses of new FDA approved PET radiopharmaceuticals are safe, effective, and reliable.
4. Proposed Modification Acknowledges the Appropriate Clinical Evidence Threshold for Diagnostic Medical Innovations.
CMS has frequently stated in previous PET NCD Decision Memoranda that diagnostic tests should not be evaluated with the same standards as therapeutics, but rather a diagnostic test should be evaluated on the basis of its clinical usefulness to change patient management, i.e. “a diagnostic test affects health outcomes through changes in disease management brought about by physician actions taken in response to test results.”16 In other words, if a new radiopharmaceutical is approved under rigorous regulatory requirements, and this new FDA-approved PET radiopharmaceutical leads physicians to prescribe different treatment than they would otherwise have prescribed, leading to a greater likelihood of improved health outcomes (either clinically or in quality of life, as per the demonstrated efficacy of the therapeutic intervention planned), the standard of evidence for coverage has been met. We believe relegating new FDA-approved PET radiopharmaceuticals to immediate non-coverage without even de minimis review by CMS disregards CMS’s standard evidentiary requirements for diagnostics by assuming that new FDA-approved PET radiopharmaceuticals do not meet the evidentiary standard for diagnostics.
5. Proposed Modification Harmonizes the Coverage Determination Criteria for All Diagnostic Radiopharmaceuticals
Other nuclear medicine coverage policies, such as the policy for Single Photon Emission Computed Tomography (“SPECT”), do not impose categorical non-coverage restrictions on new uses of the nuclear medicine procedure or new FDA-approved radiopharmaceuticals. The SPECT national coverage policy lists several clinical conditions for which SPECT is useful for diagnosis, and defers to the discretion of local Medicare Contractors, coverage decisions for remaining patient conditions.17
6. Proposed Modification Removes Inappropriate Coverage Restraints from Providers Working to Succeed under New P4P Models of Care
The transition under both public and private health reform initiatives from volume-based to value-based reimbursement often means paying for bundles of services rather paying separately for each service. For example, under one of Medicare’s most far-reaching innovations, the Pioneer Accountable Care Organization (“ACO”) program, those Pioneer ACOs that show savings over the first two years will be eligible to move to a population-based payment model in the third year of the program, where payment is a per-beneficiary per month payment amount. This capitated bundle is intended to replace some or all of the ACO’s fee-for-service payments with a prospective monthly payment.18 The goal for all of these initiatives is to support the Triple Aim: Better Care, Healthy People/Healthy Communities, Affordable Care, all of which are objectives of DHHS’s National Quality Strategy.19
To participate in these initiatives, and others like them (e.g., Medicare Shared Savings Program, Bundled Payment for Care Improvement), CMS requires provider organizations to have governing processes in place to document and support adherence to evidence-based medicine.20,21 For this reason, it seems inconsistent that CMS would tie the hands of the very providers to whom it is giving more flexibility in choosing the most appropriate health care services for a patient. Again, we believe non-coverage of future FDA-approved radiopharmaceuticals without even de minimis review by CMS is incongruous with these new models of care, and will stifle adoption of new technologies in these initiatives.
In summary, much has changed over the last several years that we believe makes the current national non-coverage policy for new radiopharmaceuticals outdated and inconsistent. The new focus on patient-centric care and personalized medicine; the more rigorous regulatory standards for radiopharmaceuticals to ensure safety, reliability, and clinical utility; the continued acknowledgement that the role of diagnostic tests to change patient management as a step towards improved health outcomes; and the push for payment incentives that give providers and patients flexibility to choose the most appropriate health care services all call for revising the current PET national coverage determination. We believe that the proposed modification which removes the exclusionary clause for the breadth of future new FDA-approved PET radiopharmaceuticals is appropriate for conditions of today’s health care market and which will be in play for the foreseeable future.
GEHC very much appreciates the opportunity to submit comments on these important issues. If you have any questions on our comments, please do not hesitate to contact me at firstname.lastname@example.org or (609) 933-0007.
Richard Frank, MD, PhD.
Global Clinical Strategy and Policy
1 DHHS. Report to Congress: National Strategy for Quality Improvement in Health Care. March 2011.p.2.
2 Administrator’s Ruling 95-1. https://www.cms.gov/Rulings/CMSR/list.aps. Medicare contractors can rely on “acceptable standards of practice” which are reflected in “consensus of expert opinion” and “published medical literature” that is “well-recognized.” Services failing these standards may be non-payable.
3 For example through a joint task force, the SNM and the Alzheimer’s Association, are already developing recommendations for the use of amyloid imaging for physicians, imaging and other medical specialists, Alzheimer families and the general public. Alzheimer's Association statement on FDA approval of florbetapir (Amyvid). April 6, 2012. Last accessed July 31, 2012 at http://www.alz.org/news_and_events_approval-of-florbetapir.asp
4 The White House. National Bioeconomy Blueprint. April 2012, p. 9.
5 Personalized Medicine Coalition. “The Case for Personalized Medicine.” p. 2. last accessed on July 27, 2012 at www.personalizedmedicinebulletin.com/files/2011/11/Case_for_PM_3rd_edition1.pdf
6 65 Fed. Reg. 13002, March 10, 2000, implementing the 1997 FDA Modernization Act, § 121(c).
8 Amyvid™ is a registered trademark of Eli Lilly and Company.
9 FDA Label for Amyvid. Last accessed July 31, 2012 at
10 Laforce R Jr, Rabinovici GD. “Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications.” Alzheimers Res Ther. 2011 Nov 10;3(6):31.
11 Fodero-Tavoletti MT, Cappai R, McLean CA, Pike KE, Adlard PA, Cowie T, Connor AR, Masters CL, Rowe CC, Villemagne VL. “Amyloid imaging in Alzheimer's disease and other dementias.” Brain Imaging Behav. 2009 Sep;3(3):246-61
12 Jagust WJ, Mormino EC. “Lifespan brain activity, ß-amyloid, and Alzheimer's disease.” Trends Cogn Sci. 2011 Nov;15(11):520-6.
13 Reiman EM, Langbaum JB, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, Quiroz YT, Kosik KS, Lopera F, Tariot PN. “Alzheimer's Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments.” J Alzheimers Dis. 2011;26Suppl 3:321-9.
14 Cummings JL. “Biomarkers in Alzheimer's disease drug development.” Alzheimers Dement. 2011 May;7(3):e13-44.
15 Scheinin NM, Scheinin M, Rinne JO.”Amyloid imaging as a surrogate marker in clinical trials in Alzheimer's disease”. Q J Nucl Med Mol Imaging.” 2011 Jun;55(3):265-79.
16 CMS. “Decision Memorandum for PET for Initial Treatment Strategy in Solid Tumors and Myeloma (CAG-00181R3). August 4, 2010. p. 10
17CMS. National Coverage Determination (NCD) for Single Photon Emission Computed Tomography (SPECT) (220.12).
18 CMS. “Fact Sheet: Pioneer Accountable Care Organization Model: General Fact Sheet.” December 19, 2011.
19 DHHS. Report to Congress: National Strategy for Quality Improvement in Health Care. March 2011. p. 2.
20 CMS. Federal Register. 76(212) November 2, 2011. p. 67826 (Medicare Shared Savings Program Final Rule.)
21 Center for Medicare and Medicaid Innovation. “Bundled Payments for Care Improvement Initiative
Request for Application.” August 22, 2011. V4, p. 33.