CATCH22 INTENDED USE DEFINITION

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CATCH-22 INTENDED USE DEFINITION
The Second Annual Medical Device Regulatory,
Reimbursement and Compliance Congress - March
28-30, 2007
The FDA and CMS Changes in Regulatory and
Surveillance Proximity Beverly H.
Lorell, MD, FACC Senior Medical Policy
Advisor King Spalding LLP Washingto
n, D.C.
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FDA and CMS A Changing Proximity

• Device and Drug Innovation Tensions between
  Regulatory and Public Expectations
• Ensuring rapid access to new devices and drugs
  for unmet clinical need, and
• Freedom from late low-frequency serious safety
  events (near-complete safety), and
• Physician use for individual patient benefit
  through practice-of-medicine, and
• No additional cost (or, maybe, ?Value ? benefit
  / ? cost compared to current therapy).

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FDA and CMS A Changing Proximity

• The Evolution of CMS Oversight and Authority in
  the Federal Research Agenda
• CMS and FDA interaction past and present
• Mandates for conduct and evaluation of clinical
  research
• Payment for research
• Coverage with Evidence Development
• Challenges
• Outsourcing of responsibilities to external
  partners
• The challenge of rapid innovation Case example

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FDA and CMS A Changing Proximity

• The Statutory Basis for FDA and CMS Separation
• 1976 Medical Device Amendments FDA risk-based
  regulation of devices
• Premarket Approval (PMA) for Class III (highest
  risk) devices reasonable assurance of safety
  efficacy
• 
  
• Premarket Notification for Class I and II
  devices Substantial equivalence to a device
  already marketed
• Social Security Act Section 182(a)(1)(a) CMS
  National Coverage Decision determination on a
  national level of items and services that are
  reasonable and necessary

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FDA and CMS A Changing Proximity

• FDA and CMS Interaction in the Federal Research
  Agenda
• Categorization of Investigational Devices for
  Coverage under Medicare Sept, 1995 - The
  HCFA/FDA Interagency Agreement Nov, 1995 - The
  related HCFA Final Rule.
• FDA categorizes all IDE devices
  Category A (experimental/
  investigational) Category B
  (nonexperimental/ investigational)
• 
  
• CMS contractors determine coverage of Category B,
  whereas Category A non-coverage
• CMS Clinical Trial Policy
• Sept, 2000 - Routine costs implemented through
  the NCD process following a June 2000 Executive
  Order
• July, 2006 - Now under reconsideration
  Redefinition and expansion of good clinical
  studies that qualify for coverage

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FDA and CMS A Changing Proximity

• Tensions between FDA and CMS Perspectives
• FDA reasonable safety and efficacy
  determination does not equal
• CMS determination of reasonable and necessary,
  or
• Beneficiary entitlement to an FDA approved device
• Determinations can differ from the FDA-approved
  labeling
• Coverage with Evidence Development (CED) April,
  2005 -Patient data collection as a Condition of
  Coverage
• MCAC
• Dec, 2006 - Now MedCAC (Medicare Evidence
  Development Coverage Advisory Committee)
• New charter and expanded focus on CED collection
  and evaluation of clinical data

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FDA and CMS A Changing Proximity

• Ongoing Changes in the Congressional Agenda
• The Medicare Data Access and Research Act
  (S.3897)
• Sept 14, 2006 - Introduced by Senators Charles
  Grassley and Max Baucus (Chairman and Ranking
  Member of the Finance Committee) Likely to be
  reintroduced this session.
• Require the Secretary of HHS to enter annual data
  release agreements with the FDA, CMS, CDC, AHRQ
  and NIH
• Link hospital and ambulatory care data to CMS
  data on benefits to Medicare beneficiaries, and
  permit federal agencies and qualified researchers
  to analyze drug safety and health care use
• More concretely, analyzing the Medicare claims
  data can help agencies, such as the FDA, identify
  situations like the one involving Vioxx more
  quickly and provide a new valuable tool to enable
  the FDA to take swifter action to protect the
  publics health and well-being. Senator
  Grassley, Sept 14, 2006

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FDA and CMS A Changing Proximity
Could
Should
Must!
National Guidelines
Clinical Trials
FDA Regulatory Approval
JCAHO Credentialing
Post-Approval Studies



CMS National Coverage Decision
Coverage with Evidence Development
Peer-review Publication
Performance Benchmarks
Clinical Value Enablers Does Science Support It?
Economic Value Enablers Will Someone Pay for It?

Social Value Enablers Public Health Mandates
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FDA and CMS A Changing Proximity

• The CMS Authority to Mandate CED -
• The statutory authority for linking coverage
  decisions to the collection of
• additional data is derived from Sec.1862(a)(1)(A)
  of the Act, which states
• that Medicare may not provide payment for items
  and services unless they are
• reasonable and necessary for the treatment of
  illness or injury. In some
• cases, CMS will determine that an item or service
  is only reasonable and
• necessary when specific data collections
  accompany the provision of the service. In these
  cases, the collection of data is required to
  ensure that the care provided to individual
  patients will improve health outcomes.
• The Purpose of CED - CMS Guidance Document July
  12, 2006
• Document appropriateness of use in beneficiaries
• Consider future changes in coverage
• Generate clinical information that will improve
  the evidence base on which providers base medical
  recommendations.

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CMS National Coverage With Evidence Development
FDA and CMS A Changing Proximity
Broad National Coverage
Yes
Is existing evidence sufficient to support
Medicare coverage?
Limited Coverage with Evidence Development (ICD
Registry)
Coverage with Evidence Development (colon cancer
drugs)
No
Non-coverage
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FDA and CMS A Changing Proximity

• National Coverage Determination CED
• Cochlear Implantation None scheduled at present
• 2. Chemotherapy Colorectal Cancer National Cancer
  Institute Clinical Trials Covered Under
  the Medicare Anti-Cancer Drug NCD
• 3. PET (FDG) for Brain, Cervical, National
  Oncologic PET Registry
• Ovarian, Pancreatic, Small Cell Lung,
• and Testicular Cancers
• Implantable Cardioverter Defibrillators American
  College of Cardiology- National
  Cardiovascular Data Registry
• Carotid Stenting American College of
  Cardiology-NCDR
• PET (FDG) for Dementia and Medicare-Approved
  PET for Dementia
• Neurodegenerative Diseases Trial
• 6. Long term oxygen treatment NHLBI

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FDA and CMS A Changing Proximity

• FDA Clinical Standards for Reasonable Efficacy
  and Safety are Better Defined than those of CED
• Clinical evidentiary standards Prospective,
  randomized, blinded clinical trial as highest
  clinical standard of proof-of-efficacy
  (predefined questions to be tested and endpoints)
  
• Control of bias in the groups to be compared
• Formal adjudication of events, and stopping rules
• Evidence needed for decision making 2
  confirmatory studies (drug approval)
• p lt .05 Statistical standard the level of
  confidence required to conclude that the result
  is not due to play of chance

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FDA and CMS A Changing Proximity

• Clinical Evidentiary Standards for CED Registry
  Research are Still Rudimentary and Evolving
• Registry Strengths
• Demographics and patterns of real-world use
• Registry Weaknesses - Less consensus regarding
• Methods of monitoring and analysis
• Acceptable statistical boundaries of certainty
• Bias
• Adjudication
• Stopping rules - Does a CED registry ever end?
• Longitudinal patient data and protection of
  privacy
• Poor tools to ask the REAL QUESTION
  Does it really work? or," Does A work
  better than B? or,
  Is A safer than B?

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FDA and CMS A Changing Proximity
Outsourcing of CED data collection, American
College of Cardiology-National Cardiovascular
Data Registry, a confidential quality measurement
program for cardiac and vascular facilities.
It now
operates four national registries.
ICDs
Carotid Artery Stents
Angioplasty and Drug Eluting Stents
Acute Coronary Syndrome Drugs, Devices, Processes
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FDA and CMS A Changing Proximity

• Drug Eluting Stents - A Case Example
• Emerging combinatorial science
• Novel combination products drug, polymer, device
  
• Reduce coronary restenosis (and need for 2nd
  invasive procedure) compared with bare metal
  stents
• FDA approval 2003 (Cypher) and 2004 (Taxus)
• CMS anticipatory reimbursement New DRG
• Postmarket surveillance
• FDA condition-of-approval 5-year follow-up of
  patients enrolled in pivotal premarket trials,
  and
• Single-arm real world registries at least 2000
  pts followed for one year (but, no control group)
  

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FDA and CMS A Changing Proximity

• Drug Eluting Stents - A Case Example
• Postmarket challenges for FDA and CMS
• Rapid penetrance gt80 of coronary stent use
• Practice-of-medicine gt60 of real world use is
  in complex patients and complex arteries
• Variable use of adjunctive drugs (aspirin and
  Plavix)
• Detecting late and rare safety signals late
  stent thrombosis
• Determining causality vs. the play of chance
• FDA - Dec 2006 public panel Jan 2007 safety
  statement including consideration of change in
  product labeling

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FDA and CMS A Changing Proximity
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FDA and CMS A Changing Proximity
Life Cycle of Device Approval Iteration
FDA Postmarket Surveillance
CMS Coverage Decision
FDA Approval
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FDA and CMS A Changing Proximity
Life Cycle of Continuous Change in BenefitRisk
New Clinical Information
Increased Interagency Interaction
Physician Practice Iteration
Changes In Patient Choice
Evolution of CMS Policy
Evolution of FDA Policy
Changes in Practice of Medicine
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FDA and CMS A Changing Proximity

• What are the Opportunities to Enhance FDA and CMS
  Interaction to Improve Patient Care and Assure
  Innovation?
• Recognize Strengths and limitations of
  registries
• Align FDA condition-of-approval and CMS CED
  clinical data collection
• Innovate Use the Medicare claims data base to
  ask specific questions
• Simplify Avoid redundant postmarket clinical
  data collections
• Assure Transparency for all stakeholders

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FDA and CMS A Changing Proximity

• Thank you

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FDA and CMS A Changing Proximity

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