Device Postmarket Studies

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Device Postmarket Studies

• Danica Marinac-Dabic, MD, PhD
• Chief, Epidemiology Branch
• Office of Surveillance and Biometrics
• CDRH

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Outline

• CDRH Mandated Postmarket Studies
• Post-Approval Studies
• Postmarket Surveillance (522)
• 2007 Amendments

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Ensuring the Public Health throughout the Total
Product Life Cycle
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Postmarket Authorities

• Define and interpret postmarket requirements
• 21CFR803 - Medical Device Reporting
• 21CFR814.82 - Conditions of Approval
• 21CFR822 - Postmarket Surveillance (522)

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CDRH Postmarket Surveillance Tools

• Adverse event/product problem reporting
• Mandated postmarket studies
• Applied epidemiologic research studies

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Mandated Postmarket Studies

• Post-Approval Studies
• 522 Studies

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Need for Post-Approval Studies

• Address premarket data limitations
• Gather essential postmarket information
• Longer-term performance including effects of
  re-treatments product changes
• Community performance (clinicians patients)
• Effectiveness of training programs
• Sub-group performance
• Outcomes of concern
• Balance premarket burdens
• Account for Panel recommendations

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Legal Authority

• Title 21 Section 814.82
•   (a) FDA may impose post-approval requirements
  at the time of approval of the PMA or by
  regulation subsequent to approval and may
  include        (2) Continuing evaluation and
  reporting on the safety, effectiveness, and
  reliability of the device for its intended use.
  FDA will state the reason and the number of
  patients to be evaluated.
•       (9) Other requirements as FDA
  determines necessary to provide (continued)
  reasonable assurance of the safety and
  effectiveness of the device.

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PAS General Principles

• Objective is to evaluate device performance and
  potential device-related problems in a broader
  population over an extended period of time after
  premarket establishment of reasonable device
  safety and effectiveness
• Post-approval studies should not be used to
  evaluate unresolved issues from the premarket
  phase that are important to the initial
  establishment of device safety and effectiveness

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Post-Approval Studies
vs.
Assurance of Continued Product Safety and
Effectiveness
Least Burdensome Evidence To Support Premarket
Approval
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Vision

• Important postmarket questions are addressed
• Studies are realistic founded on good science
• Studies are timely, accurate, provide useful
  results
• Reports are clearly identified effectively
  tracked
• Stakeholders are kept apprised
• Collaboration is stressed throughout
• Enforcement options are rarely used

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Major Areas of PAS Transformation

• Oversight
• Tracking
• Review
• Design
• Guidance
• Web Posting
• Postmarket Advisory Panel Updates
• Building Public Health Partnerships

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Early Accomplishments
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Oversight

• January 1, 2005 Initial Transfer
• April 2, 2007 Full Transfer
• ODE/OIVD

OSB
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PAS Tracking System

• Developed instituted automated tracking system
  for post-approval study commitments

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Premarket Review Process

• Postmarket Section recommended for each PMA
• Epidemiologist on each PMA team
• Lead the design of PAS study
• Work interactively with sponsors
• Present at Panel meetings
• PAS protocol finalized before or at the time of
  PMA approval

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Postmarket Review Process

• Epidemiologist is the lead on all PAS Reports and
  all PAS Supplements involving changes to PAS
  protocol
• Postmarket Review Team
• Feedback to premarket
• PAS study progress
• Summary and analysis of MDRs
• Literature reviews
• External data analysis

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Post-Approval Studies Guidance

• Guidance for Industry and FDA Staff Procedures
  for Handling Post-Approval Studies Imposed by PMA
  Order (December 21, 2006, revised August 1,
  2007) http//www.fda.gov/cdrh/osb/guidance/1561.ht
  ml

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PAS Web Page

• Went live on April 6, 2007
• Reporting Schedule Status
• PAS Study Progress
• Post 2005 Studies
• http//www.accessdata.fda.gov/scripts/cdrh/cfdocs/
  cfPMA/pma_pas.cfm

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Postmarket Advisory Panel Updates

• Selection criteria
• FDA/sponsor role
• Preparation process procedures
• Confidentiality
• Outcomes

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Building Collaborations
Evolving Initiatives
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FDLI/FDA PAS ConferenceMay 10-11, 2007

• External / Internal stakeholders dialogue
• Premarket /postmarket balance
• FDA/industry interactions
• Role of external public health partners
• Institutional Review Board considerations
• Role of Advisory Panels
• Methodologies used in post-approval studies
• Next steps

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Postmarket Surveillance (PS)

• Under Section 522 of the Federal Food, Drug and
  Cosmetic Act

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The Regulation

• Proposed Rule
• Published August 29, 2000
• Final Rule
• Published June 6, 2002
• Effective July 8, 2002

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The Statute - Simplified

• PS order required
• Device must meet criteria
• class II or class III device the failure of which
  would be likely to have serious adverse health
  consequences
• implanted in the human body for more than one
  year, or
• a life sustaining or life supporting device used
  outside a device user facility.
• 30 days for submission of plan
• 60 days for FDA review
• 36 month limitation

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Postmarket Surveillance (PS) Guidance

• Postmarket Surveillance Under Section 522 of the
  Federal Food, Drug and Cosmetic Act
• Issued April 27, 2006
• Consolidates the three guidance documents issued
  in 1998
• Identifies processes used to identify issues that
  may require postmarket surveillance, determine
  whether PS is appropriate, issue PS orders, and
  review PS plans
• http//www.cdrh.fda.gov/OFFICES/OSB/IMS/postmarket
  522.HTM

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Before we order PS

• Expert Review Team
• Apply statutory criteria
• Delineation of important, unanswered surveillance
  question
• Other considerations
• Ability of other postmarket mechanisms to address
  question (PAS), MDR, etc)
• Practicality of postmarket surveillance
  strategies
• Priority of surveillance question, based on
  magnitude of risk

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The Pre-Order Meeting

• Postmarket Surveillance question
• Potential Public Health impact
• Postmarket Surveillance Plan
• Regulatory/non-regulatory alternatives
• Possible uses of information obtained

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The PS Order

• Postmarket Surveillance question
• Rationale

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PS Plan

• Surveillance approach
• Variables to be measured
• Specific endpoints
• Population to be observed
• Duration

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Surveillance Approaches

• Non-clinical testing
• Telephone or mail follow-up of defined patient
  sample
• Secondary data sets, registries
• Consecutive enrollment
• Cross-sectional (multiple cohorts)

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2007 Amendments

• CONDUCT
• II or class III device
• (i) the failure of which would be reasonably
  likely
• to have serious adverse health
  consequences
• (ii) that is expected to have significant use
  in
• pediatric populations or
• (iii) that is intended to be
• (I) implanted in the human body for more
• than 1 year or
• (II) a life-sustaining or life-supporting
  device
• used outside a device user facility.

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2007 Amendments

• CONDITION
• As a condition of approval or clearance of a
  device

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2007 Amendments

• LONGER SURVEILLANCE FOR PEDIATRIC DEVICES
• Prospective surveillance period of more than 36
  months
• For devices with expected significant use in
  pediatric populations
• To assess the impact of the device on growth and
  development or the effects of growth,
  development, activity level or other factors on
  the safety or efficacy of the device.

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danica.marinac-dabic_at_fda.hhs.gov
[phone]