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Draft Guidance for the Public, Industry, and CMS Staff Coverage with Evidence Development in the context of coverage decisions

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Date:

11/29/2012

Public Comment Period:

11/29/2012 - 01/28/2013    View Public Comments

Draft Guidance for the Public, Industry, and CMS Staff


Coverage with Evidence Development in the context of coverage decisions

Document Issued on November 29, 2012

For questions about this draft guidance, please contact Rosemarie Hakim, PhD, at rosemarie.hakim@cms.hhs.gov.

Please see the Coverage Center website: http://www.cms.hhs.gov/center/coverage.asp for information about specific national coverage determinations (NCDs,) local coverage determinations (LCDs) or other coverage materials.

Public comments may be submitted via the "COMMENT" button at the top of this page. Information on comment submission can be found on the Coverage website at http://www.cms.gov/Medicare/Coverage/InfoExchange/publiccomments.html. Please refer to this draft guidance document when submitting comments. CMS will accept comments until January 28, 2013.

This draft guidance represents the Centers for Medicare & Medicaid Services' (CMS') current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind CMS or the public. Where warranted by unique circumstances, CMS may consider a modified approach if it satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, please contact CMS staff responsible for this guidance.

I. Purpose of this guidance document

Recognizing that both CMS and the public have accumulated a body of practical experience with CED before and since the July 12, 2006 publication of the guidance document National Coverage Determinations with Data Collection as a Condition of Coverage: Coverage with Evidence Development, we sought public input with a goal to improve the application of CED. We asked particularly for comment on the following areas.

  • Implementation of CED through the national coverage determination (NCD) or other avenues under Part A and Part B;
  • Potential impact of CED on the Medicare program and its beneficiaries; and
  • Suggested approach to CED to maximize benefit to Medicare beneficiaries.

On November 7, 2011 CMS solicited public comment on CED, with the aim to make revisions to the 2006 document in light of lessons learned. In developing this draft guidance, we considered the submitted public comments and the public testimony and panel recommendations made at the public meeting of the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) on May 16, 2012. A record of that meeting is available at http://www.cms.gov/medicare-coverage-database/details/medcac-meeting-details.aspx?MEDCACId=63. All public comments are available at http://www.cms.gov/medicare-coverage-database/details/mcd-view-public-comments.aspx?MCDId=8

II. Background

A. Goals

On April 26, 2012, the White House published the National Bioeconomy Blueprint. In part the Blueprint stated:

Expanding the Coverage with Evidence Development Program to Drive Innovation: Reimbursement for medical treatments is a powerful driver of industry investment. Under the Coverage with Evidence Development (CED) program, Medicare reimburses for promising new technologies that do not currently meet the standard for full coverage. The CED program requires more evidence to be collected to determine full potential benefit of new technologies. The CED authority has existed for more than a decade but has been applied sparingly. The Centers for Medicare & Medicaid Services (CMS) is poised to implement the next phase of CED by better defining the parameters and guidance for CED so it can be used more widely and effectively as a driver of innovation. CMS believes that the lessons learned during the initial implementation of CED can inform its more frequent use and create predictable incentives for innovation while providing greater assurance that new technologies in fact fulfill their initial claims of benefit

The full text of the Blueprint is available at the following link. http://www.whitehouse.gov/sites/default/files/microsites/ostp/national_bioeconomy_blueprint_april_2012.pdf

CMS relies on clinical evidence to determine whether particular items and services are reasonable and necessary (see 1862(a)(1) of the Social Security Act). The available evidence may not support confident conclusions of clinical benefit for all uses of potentially beneficial items and services. While newly emerging true “first in class” technological innovations may be more likely to have limited evidence of real world benefit in typical patient care settings, we may find similar challenges with older technologies whose initial findings are called into question by subsequent study. When we have had reasonable grounds, based on the available evidence, to question whether improved health outcomes reported in narrower settings would be realized by our beneficiary population, which includes the elderly, the chronically disabled, and those patients with end stage renal disease who are treated with dialysis, we have used CED to provide for Medicare coverage while further evidence is developed.

We have also found instances where new research or evolving scientific thought raises important questions about the clinical usefulness, and thus the medical necessity, of older established technologies. While our need to reconsider an evidence base may be disconcerting to some stakeholders we believe that such review is our ongoing responsibility to respond to changes in the body of evidence that informs our policies.

CED will help us to meet these goals.

B. History

As CMS (then known as the Health Care Financing Administration) embraced an evidence based medicine coverage paradigm approximately 12 years ago, the agency was challenged to develop coverage policies for certain items and services in cases where we believed that the enthusiasm of interested parties was disproportionate to the persuasiveness of the then-current evidence base.1 At the same time, we believed that we should support innovative technologies that are likely to show benefit for our population, but where the available evidence base was not yet mature. In addition, we learned that coverage in the context of ongoing clinical research protocols can expedite earlier beneficiary access to innovation while ensuring that systematic patient safeguards are in place to reduce the risks inherent to new technologies, or to new applications of older technologies. Coverage conditioned on clinical study enrollment came about as a result of these considerations.

For example, in 1996, CMS covered lung volume reduction surgery (LVRS) when furnished within the NIH-sponsored National Emphysema Treatment Trial (NETT). Through the mid- 2000s, CMS published a number of national coverage determinations (NCDs) requiring data collection as a condition of coverage, e.g., cerebral artery stenting to reduce stroke risk, ventricular assist devices (VADs) and positron emission tomography scans for diagnosis and staging of cancer, with the intent of using the information to fill evidence gaps. CMS subsequently applied the term Coverage with Evidence Development (CED) to describe this paradigm in the 2006 National Coverage Determinations with Data Collection as a Condition of Coverage: Coverage with Evidence Development guidance document. These NCDs are available at http://www.cms.gov/medicare-coverage-database/indexes/ncd-alphabetical-index.aspx.

While this guidance document will focus on CED in the context of coverage decisions, we remind the reader that CMS supports the following evidence development activities as well.

Clinical Trial Policy: The clinical trial policy (Routine Costs in Clinical Trials) supports research by paying for the routine costs and the investigational item or service in a clinical trial if and when the criteria outlined in the clinical trial NCD are met. (See section 310.1 of the NCD manual.)

Investigational device exemption (IDE) policy: The IDE rule allows Medicare to make local decisions on certain IDEs in the context of an FDA approved clinical trial (see 42 CFR 405.211).

C. CED Authority

Fundamentally, CED is a determination that an item or service is reasonable and necessary, based on the best available evidence, under an explicit condition that patients be enrolled in a research study that evaluates outcomes, effectiveness, and appropriateness of the item or service in question. The reasonable and necessary standard and its subparts are found in Section 1862(a)(1) of the Social Security Act (the Act). CMS has referred most often in coverage policy to sections 1862(a)(1)(A) and 1862(a)(1)(E) which read:

(a) Notwithstanding any other provision of this title, no payment may be made under part A or part B for any expenses incurred for items or services—

(1)(A) which, except for items and services described in a succeeding subparagraph or additional preventive services (as described in section 1395x(ddd)(1) of this title), are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member,

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(E) in the case of research conducted pursuant to section 1142, which is not reasonable and necessary to carry out the purposes of that section,

Section 1142 describes the authority of the Agency for Healthcare Research and Quality (AHRQ) to conduct and support research on outcomes, effectiveness, and appropriateness of services and procedures to identify the most effective means to prevent, diagnose, treat, and manage diseases, disorders, and other health conditions. Under section 1142, AHRQ is required to assure that research priorities appropriately reflect the needs and priorities of the Medicare program under Title XVIII, as set forth by the CMS Administrator.

III. Public Comment

We received approximately 50 comments in response to the solicitation for public comment on Coverage with Evidence Development, which was opened on CMS’ website on November 7, 2011 and closed on January 20, 2012. The following themes were raised during the public comment period. Commenters asked CMS to address the following themes. This document responds to those themes.

  • CMS needs clear evidentiary criteria for applying CED, including when the CED would end.
  • Whether CED should be required only within the context of the coverage process.
  • Whether local contractors should have the discretion to apply CED in local coverage.
  • How CED could be applied in the context of FDA-CMS alignment.

IV. Statutory Basis

In the previous guidance, CMS described two types of CED, based on two sources of authority: section 1862(a)(1)(A) (for the “coverage with appropriateness determination” or CAD form of CED) and section 1862(a)(1)(E) (for the “coverage with study participation” or CSP form of CED). CMS’ thinking on the scope of, and basis for, CED has evolved based on six years of experience with the application of CED. The Agency believes that the principal function of CED is to generate new evidence on the benefit or harm of an item or service among the Medicare beneficiary population based on rigorous scientific inquiry. Our more recent CED NCDs have all been designed around research questions. Although it is important to ensure that items and services covered by Medicare are being used appropriately, the CAD form of CED does not fundamentally encompass the concept of research. As such, we will no longer use the term CAD to describe CED. We will rely on the authority under section 1862(a)(1)(E) for future CED NCDs; and apply CED when evidence is insufficient to support coverage under 1862(a)(1)(A).

V. Coverage with Evidence Development

CMS developed CED to address coverage of items and services that were believed to be promising but whose ultimate impact on Medicare beneficiary health outcomes remained unconfirmed. Using section 1862(a)(1)(E) authority, the CED concept considers the item or service to be reasonable and necessary only while evidence is being developed pursuant to AHRQ’s authority under section 1142 of the Act. Under section 1142, AHRQ can conduct and support research on the outcomes, effectiveness, and appropriateness of health care services and procedures to identify the manner in which diseases, disorders, and other health conditions can be prevented, diagnosed, treated, and managed clinically. In addition, AHRQ can conduct or support evaluations of the comparative effects, on health and functional capacity, of alternative services and procedures utilized in preventing, diagnosing, treating, and clinically managing diseases, disorders, and other health conditions.

A. Applying CED

The following factors are among the reasons why Medicare considers applying CED to various items or services.

  1. Relevance to health outcomes in the Medicare population: available evidence is limited to narrow but otherwise methodologically rigorous protocols that did not adequately evaluate clinical outcomes relevant to affected Medicare beneficiaries, e.g. the protocol studies the impact of a technology on a laboratory test result whose manipulation is not clearly experienced by the patient as a meaningful clinical improvement.

  2. Representativeness of available evidence: available evidence is not based on subjects who are representative of the affected Medicare beneficiary population, e.g. the enrollment criteria excluded older individuals with significant, relevant comorbid conditions.

  3. Evolution and reevaluation of evidence base: new evidence or reasonable reinterpretation of existing evidence calls into question past conclusions about the impact on patient health outcomes of a covered item or service, e.g. additional clinical study subsequent to initial coverage identifies significant harms or lack of meaningful benefit.

  4. Generalizability of study results to typical settings: evidence supporting clinical benefit of a new item or service was developed in a setting that does not represent the typical community based setting in which a Medicare beneficiary receives care, e.g. expert practitioners following strict research protocols furnished the care in specialized research centers.

We believe that, although not all of these factors were mentioned in previous CED Guidance, the historic invocation of CED has been consistent with these factors. Representative examples are listed below.

CMS has applied CED to develop evidence on:

  • Stroke, mortality and quality of life for implanted cardiovascular devices;
  • The use of pharmacogenomic testing for anticoagulant management of the affected Medicare beneficiary population, where commonly found clinical characteristics of beneficiaries are believed to supersede the usefulness of the test;
  • The new use of an accepted therapeutic device as a diagnostic tool for sleep apnea;
  • New uses of inhaled oxygen therapy for non-cardiopulmonary disease; and
  • The clinical impact of advanced radionuclide imaging for oncologic conditions.

An approved CED study must be designed and conducted prospectively to produce evidence to inform future Medicare coverage. Payment for items and services covered under CED will be limited to those furnished to Medicare beneficiaries involved as human subjects in approved studies.

We believe that adherence to the following standards of scientific integrity and relevance to the Medicare population should be demonstrated in all CED studies.

  1. The principal purpose of the study is to test whether the item or service meaningfully improves health outcomes of patients who are represented by the enrolled subjects.
  2. The rationale for the study is well supported by available scientific and medical information, or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
  3. The study results are not anticipated to unjustifiably duplicate existing knowledge.
  4. The study design is methodologically appropriate and the anticipated number of enrolled subjects is sufficient to answer the research question(s) being asked in the study.
  5. The study is sponsored by an organization or individual capable of completing it successfully.
  6. The study is in compliance with all applicable Federal regulations concerning the protection of human subjects found at 45 CFR 46.
  7. All aspects of the study are conducted according to appropriate standards of scientific integrity set by the International Committee of Medical Journal Editors (http://www.icmje.org).
  8. The study has a written protocol that clearly demonstrates adherence to the standards listed here as Medicare requirements for coverage with evidence development.
  9. The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Such studies may meet this section (i) only if the disease or condition being studied is life threatening as defined in 21 CFR §312.81(a) and the patient has no other viable treatment options.
  10. The study is registered on the ClinicalTrials.gov website and/or the Registry of Patient Registries (RoPR) by the principal sponsor/investigator prior to the enrollment of the first study subject.
  11. The study protocol specifies the method and timing of public release of results on all pre-specified outcomes, including release of negative outcomes. The release should be hastened if the study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors (http://www.icmje.org). However a full report of the outcomes must be made public no later than three (3) years after the end of data collection.
  12. The study protocol must explicitly discuss subpopulations affected by the item or service under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial. If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
  13. The study protocol explicitly discusses how the results are or are not expected to be generalizable to subsections of the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

Consistent with section 1142 of the Social Security Act (the Act), the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that meet the above-listed standards and address the above-listed research questions.

B. Ending CED

As an overarching principle, CED for identified use(s) of an item or service will end when one of the following conditions are met.

  1. No CED studies are approved within the timeframe required by the CED decision.
  2. Approved CED studies are not completed within the timeframe required by the CED decision.
  3. CED studies are completed.

As an example of how CED affects policy, in 2009, based on published CED results, we ended CED for many uses of FDG-PET in the initial management of most tumor types and were able to nationally noncover for one specific initial use, adenocarcinoma of the prostate.

We recognize that clinical studies are planned to run for various durations and it is not unusual to take months or even years to enroll the full number of planned study subjects, complete observation period and analyze and publish the results in a peer reviewed journal. Under CED, there is a potential period of noncoverage between the end of the study and the agency’s review of the scientific results.

We may address the issue of ongoing coverage by working with investigators to develop integrated research strategies during the planning of CED studies. For example CED studies may be designed to accommodate the complementary roles of randomized controlled trials (RCTs) and practical observational studies to close outstanding evidence gaps and allow coverage after an RCT ends where appropriate. An interim analysis, based on pre-agreed public criteria, would serve to open or close enrollment in the follow up study.

C. CED in the context of FDA CMS coordination

CMS and FDA have executed a memorandum of understanding (MOU) and have jointly published Federal Register notices on parallel review. The parallel review pilot program, announced in a Federal Register notice posted for advanced viewing on October 7, 2011, is voluntary and does not change the existing separate and distinct review standards for FDA device approval and CMS coverage determination. These documents are available online at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/ucm255678.htm

CMS has found historically that various products may be approved or cleared by FDA though significant Medicare-relevant evidentiary questions are unresolved. We also note that FDA has at times required ongoing research and data submission as a condition of approval. While the alignment of CED with an FDA post approval study requirement presents an opportunity for greater research efficiency, we believe that this is simply an example of a CED application rather than a new CED paradigm.

VI. The Role of the Agency for Healthcare Research and Quality (AHRQ)

As noted earlier, section 1862(a)(1)(E) of the Act authorizes Medicare coverage in the context of research conducted and supported by AHRQ under section 1142. Section 1142(b) in pertinent part includes the following language.

(3) Relationship with Medicare program.—In establishing priorities under paragraph (1) for research and evaluation, and under section 914(a) of the Public Health Service Act for the agenda under such section, the Secretary shall assure that such priorities appropriately reflect the needs and priorities of the program under title XVIII, as set forth by the Administrator of the Centers for Medicare and Medicaid Services.

Commenters have noted implementation challenges to the successful conduct of CED studies. These have included among others the lack of clinical study experience or infrastructure in some stakeholder communities, limited financial resources to undertake studies, no clearly authoritative professional society to represent the multiple physician specialties whose members manage certain conditions, and a culture that historically may not have embraced evidence based patient care. AHRQ may help implement practical solutions to some of these challenges.

We believe that AHRQ’s role will continue to develop as both agencies gain more experience with CED, and that the two agencies may address the implementation challenges together. AHRQ’s authority and resources complement CED in that AHRQ:

  • has the ability to convene stakeholders to design clinical research studies for CED; and
  • has the capacity to establish public/private partnerships to financially support CED studies; and
  • has the ability to invoke certain confidentiality protections regarding certain uses of data.

VII. Formal Evidentiary Criteria for CED

Pursuant to the November 2011 –January 2012 call for public comment, we received 20 comments that advocated the development of more formalized evidentiary criteria for CED. We convened the May 16, 2012 MEDCAC to hear recommendations on this topic, and the panel conclusions are summarized below.

  • An evidentiary threshold can be defined to invoke CED
  • An evidentiary threshold can be defined to trigger an evidentiary review to determine if CED should cease, continue or be modified.
  • An evidentiary threshold would be influenced by general and particular characteristics of the item or service, the disease, and the availability of acceptable alternatives. There may be meaningful interaction of these characteristics.
  • Generalizability (to additional settings, practitioners or other clinical indications) may comprise the primary evidence gap for some bodies of evidence.

There was discussion of how one or more evidentiary thresholds might be developed. A member of the panel noted that in other settings, the presence of an evidentiary standard, i.e. a standard of proof, does not eliminate the requirement for consideration of factors specific to each case. Examples such as the legal standards of “preponderance of the evidence” and “beyond reasonable doubt” were cited, accompanied by a conclusion that such standards do not remove the need for individuals to make situation specific judgments.

Some recommended that every instance of CED be preceded by a MEDCAC meeting. We do not believe this can be practically implemented with reasonable resources unless the MEDCAC paradigm itself were to be revised. Under current circumstances, we believe such a requirement would effectively delay or prevent beneficiary access to items and services that would otherwise be covered with a more agile CED paradigm. That said, we recognize the importance of active engagement with the public stakeholder community with ongoing opportunities for public comment on CED.

VIII. Medicare Administrative Contractors (MACs) and coverage of items and services in clinical research

The Medicare program directs that providers, practitioners and suppliers submit claims for payment to local administrative contractors that process and review those claims. This includes claims arising pursuant to beneficiary participation in clinical research studies.

Section 310.1 of the NCD manual (Routine Costs in Clinical Trials) directs MACs to make payment for specified types of items and services furnished in clinical trials that meet relevant criteria. To the extent that the NCD does not identify specific clinical trials or routine costs, nor does it identify investigational items and services that are covered outside of the clinical trial, these determinations are left to the MACs.

    Routine costs of a clinical trial include all items and services that are otherwise generally available to Medicare beneficiaries (i.e., there exists a benefit category, it is not statutorily excluded, and there is not a national non-coverage decision) that are provided in either the experimental or the control arms of a clinical trial except:

    • The investigational item or service itself, unless otherwise covered outside of the clinical trial;
    • Items and services provided solely to satisfy data collection and analysis needs and that are not used in the direct clinical management of the patient (e.g., monthly CT scans for a condition usually requiring only a single scan); and
    • Items and services customarily provided by the research sponsors free of charge for any enrollee in the trial.

    Routine costs in clinical trials include:

    • Items or services that are typically provided absent a clinical trial(e.g., conventional care);
    • Items or services required solely for the provision of the investigational item or service (e.g., administration of a noncovered chemotherapeutic agent), the clinically appropriate monitoring of the effects of the item or service, or the prevention of complications; and
    • Items or services needed for reasonable and necessary care arising from the provision of an investigational item or service in particular, for the diagnosis or treatment of complications.

    This policy does not withdraw Medicare coverage for items and services that may be covered according to Local Coverage Determinations (LCDs) or the regulations on category B investigational device exemptions (IDE) found in 42 CFR 405.201-405.215, 411.15, and 411.406. For information about LCDs, refer to http://www.cms.gov/medicare-coverage-database/, a searchable database of Medicare contractors' local policies.

In addition, CMS has generally delegated to MACs the routine determination of coverage for items and services furnished in FDA category B IDE trials, i.e. the contractors exercise local coverage discretion to the extent that they do not conflict with national coverage policy.

IX. Transparency of CED

CMS expects that results of all CED approved studies will be analyzed and published in peer reviewed clinical journals. CMS has used and will continue to use the results of published CED studies to inform new or revised coverage decisions. CMS intends to maintain information on ongoing CED research studies on its website along with links to the ClinicalTrials.gov maintained by the National Library of Medicine and/or the Registry of Patient Registries (RoPR) maintained by AHRQ. We also plan include links to CED study results.

X. Summary

  1. Definition of CED

    We no longer believe that Coverage with Appropriateness Determination (CAD) falls under CED. We believe that Coverage with Study Participation (CSP) is more consistent with our current conceptualization of CED. We describe CED under the authority of section 1862(a)(1)(E) of the Act in Section IV of this document.

  2. National coverage determinations (NCDs) and strength of evidence for NCDs

    This section of the 2006 document is deleted. If CED is considered in the context of an NCD, CED is just one result of that process.

  3. Evidentiary Criteria for CED

    The 2006 document lists some of the evidentiary findings that might result a CSP/CED decision. We modified that list and shortened it. The list can be found in Section V of this document.

  4. Standards of scientific integrity and relevance to the Medicare population

    We list 13 standards that must be demonstrated in all CED studies.

  5. Role of the Agency for Healthcare Research and Quality (AHRQ)

    This document more clearly describes the role of AHRQ in CED.

  6. Ending CED

    We more specifically discuss ending CED and acting on CED results. The 2006 document describes ending registries at length. We no longer discuss specific study designs in this guidance. Study designs and time frames are generally specified in particular CED decisions.

  7. CED in the context of FDA CMS coordination

    This document introduces potential interactions between CMS and FDA in support of CED.

  8. CED MEDCAC on May 16, 2012

    We briefly summarize the panel recommendations.

  9. Medicare Administrative Contractors (MACs)

    We summarize the roles of the MACs in determining coverage of items and services in clinical research in several contexts. This is not an exhaustive list of potential MAC activities in this regard.

  10. Principles governing the application of CED (in the 2006 document)

    This section of the 2006 document is deleted because some of the “principles” are now moot.

  11. Researchers access to CMS’ CED data (in the 2006 document)

    This section of the 2006 document is deleted based on our experience with data ownership and privacy regulations. This issue is specific to each CED decision.

  12. Other uses of data collected under CED (in the 2006 document)

    This section of the 2006 document is deleted because it is more specific to CAD.

XI. Where to submit public comments

Public comments may be submitted by using the orange "COMMENT" button at the top of this page. Information on comment submission can be found on our Coverage website at http://www.cms.gov/Medicare/Coverage/InfoExchange/publiccomments.html. Please refer to this draft guidance document when submitting comments.


1 http://www.cms.gov/Medicare/Coverage/DeterminationProcess/Downloads/FR04271999.pdf

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