Webcast
Perspectives on Patient Recruitment
Sponsors:
Moderator:
Christiane
Truelove
Editor‐in‐Chief,
R&D Directions
Speakers:
Dr. Bradley Vince, D.O.,
President and Medical Director, Vince and Associates
Clinical Research
Jeffrey M. Zucker
Senior Director and Global Head, Patient Recruitment, Kendle
www.kendle.com
Kathy Chase, Pharm.D.
IRB chair, MidLands
IRB; Director, Provider Services,
Cardinal Health ‐
Pharmacy Solutions
www.mlirb.com
PresentersPresenters
Dr. Vince has participated in over 325 clinical trialsHis focus is Phase 1 to Proof of ConceptDr. Vince was involved in the design and construction of their new 90 bed Early Development Unit. The objective of this new facility is enhanced recruitment of patient population trials and studies with long-term confinement periods.
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Discussion Topics:OverviewFinalizing the ProtocolFeasibilityRecruitmentMedical OversightRetention
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Special populations are being enrolled earlier in the clinical trials process More Phase I trials (including FIH and MAD) are:
Incorporating patient populations into the study design Often consolidating SAD/MAD/POC studies into one protocol with an adaptive design
This depends on: Safety profile of the compoundTherapeutic area
This approach conserves development time and provides an earlier read on potential efficacy and tolerability
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Early Physician Feedback Critical Ensures that:
Safety measures are acceptableExecution is realisticStudy populations are recruitable
Quick Turn Around (1 week) from the PI or Medical DirectorShould be provided as a no-cost service to clients
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Feasibility AssessmentsSpeed important, but accurate feedback is more importantIn-depth feasibility protects against expensive rescue effortsPI involvement necessary to validate protocol feasibility at the siteAdditional review from clinical operations, regulatory, recruitment, lab and others minimize costly mistakes prior to study startVerify accuracy of the metrics from the siteUnfortunately, sites often over-commit Always have Plan B
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Considerations for Special Population Feasibility Assessments
Competing trials (not just at the site but in the region)Competition from marketed drugsSubject compensationTime of yearRisk Benefit RatioLikelihood of placebo
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Special Population Volunteers ≠
HNV Recruitment is more challengingCompensation is not always the priorityConfinement periods are more problematicEvening call center hours are imperativeScheduling flexibility (including evenings and weekends)
Usually not “professional” volunteers
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Accountability – Who is accountable at site level?Database
Verify itBigger is not always better
AdvertisingUnderstand the site’s planAdvertising dollars should be specific to YOUR study (not generic)If additional advertising funds are needed…
↑ funds ≠ ↑ recruitmentMarket saturationCompeting trialsSkin in the game
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Competition is good (multi-center studies)Emails, NewslettersFSFV Milestone, Most RandomizedCall the PI
Confirm AppointmentsWelcome packets and handholding
Physician Referrals – Beware
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Special population volunteers ≠
HNV
Existing medical co-morbiditiesRequire additional medical oversightConcomitant medicationsAE assessment
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Special population volunteers ≠
HNV
More family involvementRequire more personal attention of P.I.Have more medical questions
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Staff (Warm and Empathetic)
Meals (Hot and Tasty)
Lighting (Bright with Natural Light)
Dorm Size and Assignments (Room to Roam)
Mattresses (Sounds Trivial)
Technology (70’s, 80’s or today?)
Entertainment (Wifi, Movies, How many TVs?, Activities)
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Customer Service Training (Serve, Serve, Serve)
Full-time Housekeeper (White-glove inspection)
Bathrooms (Individual and private)
Medical Safety (Highly visible nurses station)
Physician Availability (That’s my P.I.)
Access Outdoors (Sunshine)
Visitors (Welcome; but have a plan and process)
Compensation (Important, but only part of the answer)
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Beyond PaperUsing data-driven expertise to enhance patient recruitment
Jeffrey Zucker, MSSenior Director and Global Head, Patient RecruitmentKendle
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a19
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Components to successful recruitment planning
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Role of Feasibility
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Use of internal resources
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Accessing external data
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Applying the data to simulate recruitment timelines
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Factoring in recruitment tactics
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Optimizing timelines
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Measuring success
Agenda
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Components
Patient Recruitment
Marketing
Investigator Consult
Key Opinion Leaders
Regulatory Medical Affairs
Feasibility
Vendors
Internal Expertise
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Pillars of feasibility
Internal data
• Previous trials conducted –
database/CTMS• Previous experience with investigators• Regulatory and contract timelines• Expertise of internal staff and lesson’s learned
External data
• Standard of care for indication and country• Competing clinical trials• Disease incidence/prevalence• Benchmarking/clinical trial intelligence
Site-specific questionnaires
• Validate assumptions• Confirm investigator availability and build interest in trial• Explore potential patient recruitment strategies
Medical review and engagement
• Detailed examination of protocol medical team• Identify and engage key opinion leaders as needed• Develop relationships with key advocacy/support groups• Internal expertise and relationships
Feasibility
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a
Full review of I/E criteria
Identify barriers and opportunities
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Study design review
Burden on subject and site
Compare to standard of care
Comparison to past trials
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Identify site requirements
Specialty
Geography
Patient access
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MedicalInternal resource Medical
Affairs
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a23
MarketingInternal resource Marketing
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Evaluate current therapeutic market globally
Opportunities for emerging markets
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Identify key physicians
Can influence other investigators
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Access to prescription data
Identify “hot spots” for med use
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Competitive information
Pipeline information on other companies
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a
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Regulatory timelines are often underestimated
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Need full review of protocol to evaluate for country requirements
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Various tactics are not allowed in certain countries…
…but some are just not typically used
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RegulatoryInternal resource Regulatory
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a25
KOLs
and Investigator consultExternal resource
• Clinical protocol guidance
• Standard of care
• Medical trends
• Operational guidance
• Recruitment issues
• Competitive landscape
Investigator Consult
Key Opinion Leaders
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VendorsExternal resource
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Media buying
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Material development
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Recruitment planning
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Database driven outreach
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Prescription data
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Chart reviewing at sites
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Recruitment workshops
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Website design and maintenance
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Site selection
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Text messaging
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New services emerging daily
Vendors
Recruitment simulation Using data to predict success
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Timeline modeling
250 patients were enrolled in 16 months or less 50% of
the time
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a29
Recruitment curve
250 patients were enrolled in 16 months or less 50% of
the time
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a30
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Change country mix
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Different distribution of patient allocation
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Over allocate patients/sites
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Back up sites/countries
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Entering additional recruitment tactics
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Propose protocol changes
Optimizing probability of success
Re-run the model with new assumptions
N o r t h A m e r i c a • E u r o p e • A s i a / P a c i f i c • L a t i n A m e r i c a • A f r i c a31
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During the trial, clear milestones and contingencies need to be
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Every program needs and after action review
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Identify success, failure, barriers, and opportunities
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Make it an official document that is engrained into the process
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Conduct a team meeting to review results
Measure performance
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Be sure to use all internal and external resources
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All data is helpful –
just be sure you know the validity and reliability
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Use data to support your decisions around study planning
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Modeling recruitment using the data is helpful to generate discussion
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Specific and measureable
recruitment tactics
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Work into the model and re-run simulation
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Learn from experience
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Minimize repetition of mistakes
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Leverage knowledge to identify opportunities
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Use common sense when analyzing data and results
Summary
IRB Considerations in Proof‐of‐Concept Trials
Kathy Chase, Pharm.D.Chair, MLIRB
Proof‐of‐Concept Research Study
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Proof‐of‐principle / concept study
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First time in humans
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Target disease state
Basic Elements of IRB Review
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Protocol •
Informed consent form•
Recruiting materials•
Safety reports•
Ongoing results
Fundamental Responsibility of IRB
Assure the rights &welfare of the subject is protected
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IRB membership
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Review process
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Initial review
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Ongoing review
IRB Evaluation
Drug Product•
Experience
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Animal studies
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In vivo studies
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Human studies
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Data source
IRB Evaluation
Research Protocol•
Objectives/Purpose
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Study Design
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Risk vs
benefit
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Healthy vs
disease
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Subject Selection
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Inclusion criteria
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Exclusion criteria
IRB Evaluation
Research Protocol•
Study Methods/Procedures/Plan
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Diagnostic testing
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Dose escalation
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Adverse Events/Deviations
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Definitions
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Prescriptive action
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Evaluation Methods/Statistical Analysis
IRB Evaluation
Informed Consent Form
IRB Evaluation
Informed Consent Form•
Readability
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Eighth grade reading level
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Format
IRB Evaluation
Informed Consent Form•
Purpose
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Easy to read
The purpose of this study is to measure how much of the study drug gets into the blood stream and how long it takes the body to get rid of it.
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“First time in Humans”
IRB Evaluation
Informed Consent Form•
Description of procedures
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Schedule of tests and drug administration
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Diagnostic tests
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Blood draws
Frequency
Amount
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Diaries
IRB Evaluation
Informed Consent Form•
Risks
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Animal studies
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In vivo studies
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Human studies
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Similar agents
IRB Evaluation
Informed Consent Form•
Risks
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Pregnancy risks
Women
Men
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Diagnostic test risks
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Psychological risks
IRB Evaluation
Informed Consent Form•
Benefits
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Alternative Therapy
IRB Evaluation
Subject Recruitment•
Vulnerable populations
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Children
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Prisoners
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Chronic disease
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Inducement
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IRB oversight
Ongoing IRB Actions
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Safety analysis
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Protocol deviations
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Progress reports
IRB Evaluation
Safety Reports•
Serious adverse events•
Report to IRB•
IRB actions▫
Informed consent modifications
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Protocol modifications▫
FDA report
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Subject follow up
IRB Evaluation
Protocol Deviations•
IRB review▫
Description of deviation
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Intended deviation▫
Unintended deviation
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IRB responsibility
IRB Evaluation
Progress Report•
Frequency of Review•
IRB Analysis▫
Safety
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Protocol deviations▫
Audit results
Questions Q&A…
Thank you for joining us today for our
webcast
on ‘Perspectives on Patient Recruitment’!
If you have any other questions, feel free to contact us at:
Webcast
Bradley Vince, D.O.President and Medical [email protected]
Kathy Chase, Pharm.D.Chair
www.mlirb.com
Rimmy
JundayAccount [email protected]
www.kendle.com