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 AgendaMedpace 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 SchmalzExecutive Director

Early Planning for Post-market Success including Regulatory

Considerations and Study Design


Evidence Needs

Efficacy Safety ValuePre-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 MindFinding the right place on the continuum

FDACMS

Market Adoption Purchasing Organizations


Consider your Options

Experimental ObservationalSubject selection Defined inclusion/exclusion criteria

Prospective enrollmentAll comersProspective 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

Schaefers, Kristin

Julie - can you snazz this up? I just wanted a simple graphic that shows a bridge between clinical research and clinical practice - my talking points are as outlined below in hte notes section


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 screeningLack of site trainingMissed enrollment

Not aligned with SOCInadequate staffing

….

CHAOSRisk 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

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

Devices & Hardware