What Happens After Your Device is Approved? Collecting Data in the Real World

What Happens After
Your Device Is Approved?
Collecting Data in the Real World.
Part of the Complex Medical Devices Series

What Happens After Your Device Is Approved? Collecting Data in the Real World.
Speakers and Agenda
Medpace Device Speakers Agenda
Deborah Schmalz
Executive Director
• Early planning for post-market success
including regulatory considerations and study
design
Lee Walke
Vice President, eClinical
• Special considerations for collection of post
approval data
Kristi Schaefers
Associate Director, Medical Devices
• Patient identification and retention strategies to
improve evidence collection

Presented by:
Deborah Schmalz
Executive Director
Early Planning for
Post-market Success
including Regulatory
Considerations
and Study Design

Evidence Needs
Efficacy Safety Value
Pre-market Post-market
Regulators Market Users
Approval Status
Key Audience
Source: FDA News: Observational Studies

Collecting Data in the Real World
Continued Viability &
Acceptance
Experiences
Effects
Usage

Identifying your Audience(s) and
Their Unique Needs
 Regulatory agencies
 CMS/payors
 Hospital purchasing
 Physicians
Alignment of endpoints and the audience value proposition is
key to a successful post-market study
• Safety signals
• Applicability to age 65+
• Cost-effectiveness
• Defining the possibilities

Defining Your Goals
“You start out with a beautiful green
tree that should be admired and then
everybody in the family wants to put
an ornament on it…and no one will
take Grandma’s ornament off the tree.
So you end up with a protocol that is
impossible to do and distracts you
from answering the question you
originally had.”
Dr. Robert Califf, Mind the Gap Seminar,
“Innovative Approaches to Clinical Trials”

Experiments
 Treatment is applied to
experimental units, often
by chance
 Investigator observes the
effect of the treatment on
the units
 Evidence of causation
Observational Studies
 Treatment is beyond the
control of the investigator
 Investigator observes
subjects and measures
variables of interest
 Evidence of association
Begin With the End in Mind
Finding the right place on the continuum
FDA
CMS
Market Adoption
Purchasing Organizations

Consider your Options
Experimental Observational
Subject selection Defined inclusion/exclusion criteria
Prospective enrollment
All comers
Prospective or retrospective
Consent Always required Waiver of Consent may be possible
Follow-up Usually defined Variable based on Standard of Care
Data quality Consistent Variable and/or not available
Cost $$$ $
Time to complete +++ +
Messaging Peripheral Stent XYZ provides a 25%
better outcome than Stent ABC
Peripheral Stent XYZ is associated
with a 25% improvement over Stent
ABC
Research Question:
What is the relative long-term vessel patency of Peripheral Stent XYZ vs. Stent ABC?

Results & Outcomes from Observational Studies
“In practice, a shift to causal language can occur
at any stage: writing, editing or headline
composing, with similar effects on meaning.
Without attention to the underlying study design,
distortions of wording can creep in that would
lead readers to over-estimate the meaning of a
given study and possibly make life choices that
the evidence does not warrant.”
Zweig, Mark, M.D et al., Observational Studies—Does the Language
Fit the Evidence? Association vs. Causation, Undated Article from
Health News Review

Mandated Post Market Surveillance
 Recognized burden and
lack of incentives for
clinicians and patients to
participate in PMS studies
 Adds “Comprehensive,
Linked, Registry-Based
Surveillance” to list of
acceptable study designs

Use of Post-market Data to Extend Label Claims

Waiver of Consent Considerations
 United States considerations
• Expect that you will need to educate your sites on this waiver as the
law is not well understood {21 CFR 46.116(d)}
• Must be universally applied to all cases at the site
• Data must be de-identified and retrospective in nature
• Informed consent process would prevent collection of data
 EU considerations
• Generally similar to US law
• Picture is muddied because of recent changes in data protection laws
• Waiver is still possible but will require approval by both site specific EC
and Data Protection Body (country specific)

Presented by:
Lee Walke, Vice President eClinical
How Technology is Evolving
Special Considerations for
Collection of Post-Approval Data

Unique Challenges of Real World Data Collection
 Study design – Standard of Care
 Prescribers vs Investigators
 Retrospective data
 Off-label surprises
 Reliance on Patient Reported Outcomes and diaries
 Reduced onsite monitoring and source document verification
 High demand for immediate results
 Some studies can last for decades

The Selection and Sourcing of Data Fields:
eCRF Content
Study
Design
Every
endpoint
must be
supported
Feasibility
of Data
Collection
Avoid
superfluous
data
collection
 Collect the minimum amount of
data to support the protocol
objectives and endpoints
 Challenge habitual, “standard”
pages – physical exam, free text
adverse events, medical history
 Create a map showing how every
protocol endpoint is supported
 If an eCRF field is not on the map,
ask why

eCRF Navigation & Retrospective Data Collection
Traditional eCRF navigation
• Enter a field
» System checks missing, range,
and logic
• Next field
» Systems checks missing, range,
and logic
• And so on, in chronological
order
Retrospective eCRF navigation
 “Flat”, not hierarchical
• See where you need to go
• Few Clicks to get there
• Enter data and move on
 Fast, lightweight pages
 Structured to mimic a real chart
» H and P sections (History and Physical)
» MAR (drug section)
» Labs
» Imaging
» Procedures
» Surgeries

Breaking Habits in eCRF Design
 It’s very easy to habitually include CDASH AE and CONMED
forms in the eCRF Draft
 Open text collection of medications and adverse events is
difficult and costly
• High volume of complex open-text
• Related fields are opportunities for inconsistency and queries
• Medical coding required for analysis
• Reconciliation with other forms and databases
 Ask: Can we satisfy safety endpoints with targeted
checkboxes?

Avoiding Off-label Solicitation
 Checkboxes are great! Unless they lead the investigator to
believe that the product is approved for off-label use
 Despite the Vascular Solutions case, FDA
has not updated the rules on off-label solicitation
 A sponsor may not promote off label use
 This can include a checkbox on a CRF
 Be certain to solicit Standard of Care
 Use a layered approach

The Patient as Data Source
 System considerations
• Integrated, yet private
• Encryption
• Use modern browsers for portability
 Instruments
• Validated
• Relevant
• Lightweight
 Modalities
• Adjust for differences in use and delivery
• Reminder rules

Decision Support
Need for valuable data, on demand, in a meaningful format
 Stakeholders
» Health care providers
» Key Opinion Leaders
» Medical monitors
» Risk-based monitoring
» Medical science liaisons
 Value:
» Derived data
» Integrating clinic and patient
sourced
» Aligned with statistical
analysis

Very Long-term Registry Considerations
Drivers
 Changes in standards
of care
 Reporting regulations
 Aging patient populations
 Sub-studies
 Cost pressure
 Well-planned data
migration processes
• Include all stakeholders
• Detailed checklists
 Redundant technology
 Smart database design
 Smart analysis
programming
Mitigations

Presented by
Kristi Schaefers
Director, Clinical Operations
Patient Identification and
Retention Strategies to
Improve Evidence
Collection

Patient Identification and Retention
Clinical
Research
Clinical
Practice

Patient Identification
Technology
»EMR/EHR
»Insurance/billing claims (UB04s)
»Product reimbursement forms
»Patient/product registries
»Device usage reports
»Patient-centered outcomes databases
This all assumes you’ve selected the right study sites….

Overcoming Enrollment Obstacles
 How to avoid turning an 18 month study into
one with no end in sight…
Improper screening
Lack of site training
Missed enrollment
Not aligned with SOC
Inadequate staffing
….
Reliable
enrollment
Efficient
execution
Risk Identification/
Management

Patient Retention
Patient
Retention
Patient &
Family
Email/Text/
Phone
Utilize
Technology
Reminder
Postcards
Fridge
Magnets
Snow-bird
Logistics
Incentives
Money and
knowledge

1. Informed consent waiver
» Geographic differences in definitions
» IRBs/ECs desire to “try” for consent if at
all possible
2. Retrospective determination
» Patient must be at least 3M out from
implant
» IRB definition of retrospective is from
today’s date vs. approval date
3. Data definitions
» Terms intentionally ambiguous to allow
for broad spectrum sponsor use
» Consistency required (both across
geographies and site personnel)
Case Study
Interventional
Cardiology:
Global Registry
Challenges

Case Study: Mitigation Strategies
Informed Consent Waiver
• Assist with IRB application to answer “Why is waiver requested?”
• Ensure protocol clearly defines minimal risk, retrospective nature
Retrospective Determination
• Letters written, approved & signed by sponsor provided to IRB/EC
proactively (with submission) to mitigate their concerns
• Rolling IRB approvals, annual renewals
Data Definitions
• Sponsor encouraged to clearly define terms (e.g. “high-risk PCI”) by
utilizing steering committee/internal medical experts
• Data entry guidelines/completion instructions (inc. “hover help”)

What Happens After
Your Device Is Approved?
Collecting Data in the Real World.
Part of the Complex Medical Devices Series
COMPLIMENTARY
DOWNLOADS
Complex Medical
Device Series
http://www2.medpace.com/com
plex-medical-device

What Happens After Your Device is Approved? Collecting Data in the Real World

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Editor's Notes