1

V-0950 Protocol 001

Phase IFIM Safety/Immunogenicity Vaccine in AD

Patient Recruitment and Patient Recruitment and RetentionRetentionKathleen OxberryClinical Operations Specialist09-Jan-07

2

Topics of DiscussionTopics of Discussion

Goals of Patient Recruitment Timelines Patient Funnel Patient Profile Recruitment Planning Recruitment Challenges and Solutions Patient Sources and Locating Methods Recruitment to Retention Conclusion

3

Participating Countries

US 40 patients US: 8 sites

ExUS 30 patients France: 2 sites Netherlands: 1 site Sweden: 2 sites

WW Total: 70 randomized patients

4

Goals of Patient Recruitment Goals of Patient Recruitment PlanningPlanning

Planning Predictability

Productivity Ability to Meet Study Timelines

Imp

roves

Imp

roves

Improves

Improves

5

Protocol Timelines

US exUS FSR: 24-Jan-2007 31-Jan-2007 FPS: 29-Jan-2007 05-Feb-2007 FPI: 12-Feb-2007 19-Feb-2007 SR80: 09-Mar-2007 SR100: 10-Apr-2007 LPS: 17-Jul-2008 LPI: 31-Jul-2008 LPO: 31-Jul-2011

6

Patient Recruitment Funnel Estimates “Out of 200 pre-identified patients”

RESULTS: of those RESULTS: of those randomized, ~10-11randomized, ~10-11

will complete studywill complete study

~ 12- 14 will enter ~ 12- 14 will enter randomizationrandomization

~4-5 will fail screening or ~4-5 will fail screening or run-inrun-in

~16-18 potential patients 16-18 potential patients will sign the consentwill sign the consent

~25 potential patients will follow-up ~25 potential patients will follow-up with the site and schedule a visitwith the site and schedule a visit

7

Recruitment: Target population

>55 years of age; male and female Mini-Mental State Examination (MMSE)

score between 16-25 (inclusive) at the time of screening

Undetectable or low levels of pre-existing Aβ-specific antibodies at enrollment will be included in the primary immunogenicity analysis.

MRI scan at screening w/ dx of AD

8

Key Elements in Patient Recruitment Planning

Identify Recruitment Challenges & Opportunities Protocol specific Site specific

Identify Patient Sources Health care system General Public

Know Recruitment Methods Activities Materials Resources

Develop Screening Procedures On-site Phone screen

9

Key Elements in Patient Recruitment Planning (continued)

Site Resource Planning Available Staff Other ongoing

activities Black-out periods

Deployment of Methods Timing Frequency Combination of

methods

Progress Monitoring Plan vs. actual Understand

deviations to plan Modify Involve all staff Communicate

10

Recruitment Solutions:Best Practices

Educate and discuss with patients the study procedures and safety issues

Early identification of patients through planned recruitment strategy

Careful screening and patient history review

Ensure site has a recruitment plan available

11

Recruitment:

“Carefully managed competitive enrollment” “staggered dosing” FDA request Wait at least 48 hours between dosing

individual patients within a panel Expect AEs manifest within 6 hours Staggering interval may change

12

Recruitment: “carefully managed”

Screen failure rate ~25% Drop out rate ~25% Drop outs will be replaced External eroom / spreadsheet

CRAs: Review MUL contact info Panel 1 Vaccine release 11-Jan-07

Enough for 20 patients

13

Recruitment: “carefully managed”

Draft process is evolving Site email KOxberry after patient has

completed V1 and meets I/E criteria Site #, BN, anticipated date of V2.

Review xls in external eroom Site may need to postpone visit for a

few days to avoid multiple randomizations on the same day

10 patients per panel

14

Recruitment: “carefully managed”

HQ Randomization Guidelines Order of notification - first to arrive Decisions made every 24 hours FPI at site is priority

Site 1 email precedes Site 2 by <24 hours (i.e., HQ reviews on same day) and both request same dosing date

Site 2 may still get chosen if FPI at Site Maintain split: 30exUS/40US Stick to enrollment timeline

15

Recruitment: External eroom

Requirements in IM binder Supported Platforms: Windows XP: Internet Explorer 6.0 Windows 2000: Internet Explorer 5.5

SP2 and Internet Explorer 6.0 Windows 98: Internet Explorer 6.0 Post requirements to FSA

16

Recruitment: External eroom

17

Recruitment: Visit Predictor Calendar

18

Recruitment: External eroom

19

Recruitment: Visit Predictor

Visit Predictor calendar: posted to FSA

20

CTMS: DRAFT Visit Design

Sam Bratic

21

Patient Enrollment within Panel

Patient #1

M0 M6

12 weeks

Patient #10

M6M3M0

≥6 weeks

≤6 weeks

•Analysis of all patients within panel through Month 3 to inform GO for Month 6 vaccination

•Calls for enrollment of panel within 6 weeks of FPI.

22

23

Patient Enrollment: Stages

2 0 0 7 2 0 0 8

J F M A M J J A S O N D J F M A M J J A S O N D

1 # G

2 # G

3 # G

4 #

STAGE

LPO JUL2011

LPI 31JUL2008Data for full panel out to Month 3

also informs dose escalation.

# = FPI within panel

G = “Go” decision to move to next panel

24

Site’s Initial Challenges and Solutions

Caregiver compliance/availability/motivationCaregiver compliance/availability/motivation• Flexible scheduling: Plan visits for the first

3 months and then at least 3 months prior to the next visit, based on caregiver schedule; Utilize the Visit Predictor

• Focus on taking time with the caregiver to explain and support throughout the consent process and the entire study

Length of Study: 3.5 yearsLength of Study: 3.5 years• Maintain contact with the patient and

caregiver.• Birthday cards, holiday cards, phone

callsLength of Visits: Cognitive testingLength of Visits: Cognitive testing

• Plan for comfortable waiting area for caregiver and subjects; Provide snacks

25

Generalized Challenges with Simple Solutions

Pre-screening activities Consenting Goals – A well informed

caregiver/family/patient is more likely to enroll Acknowledge consent process doesn’t end once the document is signed. Allow adequate time for patient/caregiver to consent

– Consider that families may be hesitant to allow their loved one to be in this study

Frightening procedures: MRI, LP Discuss at the very beginning; explain the importance

26

Potential Sources of Patients

Site

Memory Clinics

Referrals/Colleagues

Database/Charts

Church Groups

Senior Centers/Wellness Centers

LocalAlzheimer’s Assoc.

Advertising

Health Fairs/Memory Screenings

27

Matching Methods to Patient Sources

Site

Memory Clinics

Referrals/Colleagues

Database/Charts

Church Groups

Senior Centers/Wellness Centers

LocalAlzheimer’s Assoc.

Advertising

Health Fairs/Memory Screenings

Database Search

Flyers/ Posters

Letters/Phone Calls

Lectures/ Posters

Lectures/ Posters

Booths/Posters

Penny Saver

Lectures

28

Retention ChallengesChallenge

Caregiver stress Frightening

procedures Potential AE’s Travel

Solution Educate and explain

benefits of participation Create retention plan to

keep pt/caregiver motivated

Be flexible, be patient, and show concern with patients

Continue regular encouragement and communication

29

Conclusion Be Creative

If you were a potential patient, how would you arrive at your doctor’s office?

Use the CommunityDistribute materials to “hot spots”You are encouraged to create and implement

tools to help with recruitment (Please contact your CRA before using them.)

We are available to each of you and want to assist in your success in this trial

THANK YOU

30

Questions

31

Backup Slides

32

11 Site Ready Deliverables

Trial Level Deliverables Last Vendor agreement signed Clinical Data Management Deliverable

complete EDC collector deployed eCRFs, PROs available

Vaccine Supplies available Panel A: T 11-Jan-2007

33

11 Site Ready Deliverables (cont)

Country Level Deliverable Regulatory Approval

Site Level Deliverable IRB/IEC Approval Site and/or Country

(protocol, IC) Financial Aspects complete (not required to

ship vaccine) Clinical Data Management Deliverables

Complete at Site Paper or eCRFs Password to access EDC

34

11 Site Ready Deliverables (cont)

Site Level Deliverable (cont) Initiation Essential Documents

approved (includes import approval) Site Trained (not required to ship

vaccine) Vaccine at site Vendor supplies at site

35

Site Training Requirement: AE and GCP

Must be completed by all site staff members once a year

Training can be accessed through OneMerck US: https://www.merckclinicaltrials.com/ exUS: https://www.msdclinicaltrials.com/

CRAs: Please document site’s completion of AE/GCP training in the narrative of the Monitoring Visit Report

36

Site Training Requirement:PBMCs

LabCorp: 5 sites Non-network: 8 sites

France - Netherlands – TC training complete Sweden - US Arizona – TC 18-Jan-07 US New York -

Posted xls to FSA in “PBMC Training Materials” “PBMC Training Site Reagents…”

37

Definitions

FSR: First Site Ready FPS: First Patient Screened FPI: First Patient In (First Patient Visit) SR80: 80% of the Sites are Ready SR100: 100% of the Sites are Ready LPS: Last Patient Screened LPI: Last Patient In (Last Patient Visit) LPO: Last Patient Out

38

Definitions

Visit window: the amount of flexibility you have to schedule a patient visit. V2 has a +14 day window; should occur

14 days after visit 1 but can be scheduled up to 28 days after V1 (14D + 14D = 28D)

V5 has a ±2 day window; should be scheduled 30 days after V2, but could be scheduled 28 or 32 days after V2 (30D – 2D = 28D or 30D +2D = 32D)

39

Definitions

EDC: Electronic Data Capture eCRF: Electronic Case Report Form PRO: Patient Reported Outcome

eCRF (MMSE, CANTAB, CSR, VRC)