R&D Directions Webcast June Final[1]

Webcast

Perspectives on Patient Recruitment

Sponsors:

Moderator:

Christiane

Truelove

Editor‐in‐Chief, 

R&D Directions

[email protected]

Speakers:

Dr. Bradley Vince, D.O., 

President and Medical Director, Vince and Associates

Clinical Research 

[email protected]

Jeffrey M. Zucker

Senior Director and Global Head, Patient Recruitment, Kendle

[email protected]

www.kendle.com

Kathy Chase, Pharm.D. 

IRB chair, MidLands

IRB; Director, Provider Services,

Cardinal Health ‐

Pharmacy Solutions

[email protected]

www.mlirb.com

PresentersPresenters

3

Bradley Vince, D.O.President and Medical [email protected]

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.

4

5

Discussion Topics:OverviewFinalizing the ProtocolFeasibilityRecruitmentMedical OversightRetention

6

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

7

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

8

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

9

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

10

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

11

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

12

Competition is good (multi-center studies)Emails, NewslettersFSFV Milestone, Most RandomizedCall the PI

Confirm AppointmentsWelcome packets and handholding

Physician Referrals – Beware

13

Special population volunteers ≠

HNV

Existing medical co-morbiditiesRequire additional medical oversightConcomitant medicationsAE assessment

14

Special population volunteers ≠

HNV

More family involvementRequire more personal attention of P.I.Have more medical questions

15

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)

16

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)

17

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

•

Components to successful recruitment planning

•

Role of Feasibility

•

Use of internal resources

•

Accessing external data

•

Applying the data to simulate recruitment timelines

•

Factoring in recruitment tactics

•

Optimizing timelines

•

Measuring success

Agenda

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 a20

Components

Patient Recruitment

Marketing

Investigator Consult

Key Opinion Leaders

Regulatory Medical Affairs

Feasibility

Vendors

Internal Expertise

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 a21

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

•

Study design review

Burden on subject and site

Compare to standard of care

Comparison to past trials

•

Identify site requirements

Specialty

Geography

Patient access

22

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

•

Evaluate current therapeutic market globally

Opportunities for emerging markets

•

Identify key physicians

Can influence other investigators

•

Access to prescription data

Identify “hot spots” for med use

•

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

•

Regulatory timelines are often underestimated

•

Need full review of protocol to evaluate for country requirements

•

Various tactics are not allowed in certain countries…

…but some are just not typically used

24

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

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 a26

VendorsExternal resource

•

Media buying

•

Material development

•

Recruitment planning

•

Database driven outreach

•

Prescription data

•

Chart reviewing at sites

•

Recruitment workshops

•

Website design and maintenance

•

Site selection

•

Text messaging

•

New services emerging daily

Vendors

Recruitment simulation Using data to predict success

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 a28

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

•

Change country mix

•

Different distribution of patient allocation

–

Over allocate patients/sites

•

Back up sites/countries

•

Entering additional recruitment tactics

•

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

•

During the trial, clear milestones and contingencies need to be

•

Every program needs and after action review

–

Identify success, failure, barriers, and opportunities

•

Make it an official document that is engrained into the process

•

Conduct a team meeting to review results

Measure performance

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 a32

•

Be sure to use all internal and external resources

–

All data is helpful –

just be sure you know the validity and reliability

•

Use data to support your decisions around study planning

–

Modeling recruitment using the data is helpful to generate discussion

•

Specific and measureable

recruitment tactics

–

Work into the model and re-run simulation

•

Learn from experience

–

Minimize repetition of mistakes

–

Leverage knowledge to identify opportunities

•

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

•

Proof‐of‐principle / concept study

•

First time in humans

•

Target disease state

Basic Elements of IRB Review

•

Protocol •

Informed consent form•

Recruiting materials•

Safety reports•

Ongoing results

Fundamental Responsibility of IRB

Assure the rights &welfare of the subject is protected

•

IRB membership

•

Review process

▫

Initial review

▫

Ongoing review

IRB Evaluation

Drug Product•

Experience

▫

Animal studies

▫

In vivo studies

▫

Human studies

•

Data source

IRB Evaluation

Research Protocol•

Objectives/Purpose

•

Study Design

▫

Risk vs

benefit

▫

Healthy vs

disease

•

Subject Selection

▫

Inclusion criteria

▫

Exclusion criteria

IRB Evaluation

Research Protocol•

Study Methods/Procedures/Plan

▫

Diagnostic testing

▫

Dose escalation

•

Adverse Events/Deviations

▫

Definitions

▫

Prescriptive action

•

Evaluation Methods/Statistical Analysis

IRB Evaluation

Informed Consent Form

IRB Evaluation

Informed Consent Form•

Readability

▫

Eighth grade reading level

▫

Format

IRB Evaluation

Informed Consent Form•

Purpose

▫

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.

▫

“First time in Humans”

IRB Evaluation

Informed Consent Form•

Description of procedures

▫

Schedule of tests and drug administration

▫

Diagnostic tests

▫

Blood draws

Frequency 

Amount

▫

Diaries

IRB Evaluation

Informed Consent Form•

Risks

▫

Animal studies

▫

In vivo studies

▫

Human studies

▫

Similar agents

IRB Evaluation

Informed Consent Form•

Risks

▫

Pregnancy risks

Women

Men

▫

Diagnostic test risks

▫

Psychological risks

IRB Evaluation

Informed Consent Form•

Benefits

•

Alternative Therapy

IRB Evaluation

Subject Recruitment•

Vulnerable populations

▫

Children

▫

Prisoners

▫

Chronic disease

•

Inducement

•

IRB oversight

Ongoing IRB Actions

•

Safety analysis

•

Protocol deviations

•

Progress reports

IRB Evaluation

Safety Reports•

Serious adverse events•

Report to IRB•

IRB actions▫

Informed consent modifications

▫

Protocol modifications▫

FDA report

•

Subject follow up

IRB Evaluation

Protocol Deviations•

IRB review▫

Description of deviation

▫

Intended deviation▫

Unintended deviation

•

IRB responsibility

IRB Evaluation

Progress Report•

Frequency of Review•

IRB Analysis▫

Safety

▫

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

[email protected]

www.mlirb.com

Rimmy

JundayAccount [email protected]

www.kendle.com