PROJECT MANAGEMENT: VEGF TRAP CLINICAL TRIALS California State University Los Angeles Winter 2011 Presented by: Sahar Shahiem, Michael DeSalvio, Kevin.

PROJECT MANAGEMENT: VEGF TRAP CLINICAL

TRIALS

California State University Los Angeles

Winter 2011

Presented by: Sahar Shahiem, Michael DeSalvio, Kevin Ip,

Neha Padwal, Rukshan Thenuwara

COMPANY OVERVIEW AND INTRODUCTIONPresented by Sahar

Phase 3-Integrated Systems (P3-IS): Who Are We?

• Successful Small Business• $50 million in annual revenues

• Over 20 yrs in PM consulting

• Many areas of expertise in PM • Life sciences, healthcare, biotechnology, medical devices

• Well known for subcontracting clinical trial projects

• Provide distinct deliverables with clear beginning and end

P3-IS – Our Values• We avoid costly delays, inefficiencies and frustrations  

No longer worry about: We deliver:

• Miscommunication

• Cross-functional disconnects

• Inconsistent processes

• Competing priorities

• Missing deadlines

• Cut timelines in half

• Objective facilitation

• Precision planning from beginning to end

• Industry best practices

• Improved collaboration

• Skilled PM work on-site

P3 Integrate Systems - VEGF Trap Team

• Mike DeSalvio – Project Manager (PM)• 8 yrs experienced PM• Lead many successful high profile

projects

• Kevin Ip – Assistant PM• 7 yrs exp.• Worked on high profile projects

• Neha Padwal – Clinical Recruitment Manager• 7 yrs exp. in Phase II and III

recruitment• Managed recruitment for many drug

development companies

• Sahar Shahiem – Quality Assurance (QA) & Data Manager• 7 yrs exp. in Phase III clinical trials• Success in quality completion of project

• Rukshan Thenuwara – QA & Risk Analysis Manager • 7 yrs exp. in risk assessment in all

phases of clinical trial

P3-IS Data Collection Complies with FDA Regulations

• Create platform for doc & data management • FDA regulations• 21 CFR Part 11 for Electronic Records & Electronic Signatures

• Comply to Good Laboratory Practice• audit trails, security, data integrity and data archiving.

• P3-IS Document Management functions• fully integrated into the workflow• content and docs may include:

• Analyst certifications, electronic training materials & investigation reports

Fda.gov

Experience in Patient Recruitment

• We have contracts with local nurses & doctors • assist in pt recruitment and observation

• P3-IS dr./nurse requirements• must have 5 years clinical trial experience

• 24 hour on-site availability

Regeneron – VEGF Trap

• Regeneron• Large biotech and biopharm company

• needs help in managing a section of Phase III

• VEGF Trap (Aflibercept)• Blocks new blood vessel growth for

cancer cells

• fusion protein designed to bind to Vascular Endothelial Growth Factor-A (VEGF-A)

• also binds to Placental Growth Factor (PLGF)

Where we come in

WBS & TIMELINE Presented by Kevin

Trial Implementation

Contract with PI and Sponsor

Request for Retainer

Preliminary Screening

Review Case Files &

Treatment Documents

First Round

Screening

Schedule Interviews

Patient Authorization

Patient Recruitment

Get Patient Criteria

Determine Sample

Size

Data Collection

Provide Software/Hardware

Install Hardware

Train Users

Server Maintenance

Data Management

Devote Server Space

Implement Server

Security

Establish SQL

Customize Software

Securities EncryptionUser

PermissionsError

Checks

Validation Rules

Schedule Site Networking

Data Hand Off

Meet with Sites

Perform Audit

Verify System Compatibility

Meet with Statisticians

Create User

Access

Securely Transfer

Data

Verify Post Transfer

Data

Unmask Data

Schedule

Task Time Task Cost (k)

Trial Implementation & Initiation

8 d 0m

Pt Recruitment 12-14 w 77k

Data Collection 4.5 w 200k

Data Management 4.5 w 400k

Custom Software for Regeneron

2.1 w 60k

Schedule

PHASE I: RECRUITMENTPresented by Neha

CLINICAL TRIAL FACTS• $1.76 billion out of $8 billion total annual clinical

research spending dedicated to patient enrollment efforts

• 85% trials fail to finish on time- low patient accrual.

• 30% trial sites- Fail in enrolling even a single patient

• 65%- 80% of trials fail to meet their temporal end points.

Cooley, M.E., Sarna, L., Brown, J.K., Williams, R.D., Chernecky, C., Padilla, G., and Danao, L.L. 2003.Challenges of recruitment and retention in multisite clinical research. Cancer Nursing 26(5):376–84.

RECRUITMENT STRATEGY

RECRUITMENT STRATEGY

Recruitment

CLINICAL TRIAL – SET UP• According to Regeneron specifications

• Pts will receive VEGF trap every 3 hours on Day 1• Tx continues for every 2 weeks • for up to 10-15 courses in absence of disease progression or toxicity

• Blood collection- Pharmacokinetic study

• Analysis- Biological markers (VEGF subtypes)• Follow up for 60 days

CLINICAL TRIAL GOALS

• GOAL: To help recruit 4000 adults ages 25-50 years for double blind, placebo controlled trials over 8 month period conducted at sites across U.S

• OBJECTIVE: Evaluate safety and efficacy of VEGF trap• Evaluate angiogenic properties of tissues.

CRITERIA AND SELECTION PROCESS

• Eligibility:• Age- 25- 50 years• Gender: Both• Accept healthy volunteer: No

• Disease characteristics:• Histologically confirmed multiple

myeloma• Relapsed or refractory disease

• Patient Characteristics:• Life expectancy > 14 weeks• WBC > 3000 /mm^3• Not pregnant• No evidence of coagulopathy• No serious traumatic injury within

past 30 days• No known history of allergy to

compounds of similar chemical or biological composition

PATIENT RECRUITMENT DIRECTOR

REGULATORY AFFAIRS DIRECTOR

QUALITY CONTROL MANAGER

CLINICAL MANAGER

REGULATORY STAFF

CLINICAL TRIAL MANAGER

TRIAL SITE COORDINATOR

CLINICAL TRIAL NURSE

PRINCIPLE INVESTIGATOR

SUPERVISOR

HUMAN RESOURCES

DATA MANAGER

PHYSICIAN

ASSISTING STAFF

CLINICAL SUPPLY MANAGER

CLINICALRESEARCH ASSOCIATE

DATAVALIDATION PM

COMMUNICATION PLAN• Bimonthly Video Conferencing amongst Directors.

• Communication Report• Enrollment Status

• Data Quality• Reports- Tracking, Data monitoring, Data management

• Availability of Resources

• Regulation Compliances• Electronic Records, GLP, GCP, cGMP, Quality system regulation• Consent Forms

Audience Type of communication

Mode of delivery Timing of delivery

Authority responsible for delivery

Regeneron Project Status Report Email and Video conferencing

Monthly PI & Supervisor

Regeneron Budget Report Email and Video conferencing

Monthly HR Manager

Regeneron Enrollment Report Email and Video conferencing

Monthly PI & Supervisor

PI & Supervisor Project Status Report Email and Conference Meeting

Bi-weekly Data Manager, Pt Recruitment Director, Clinical Manager, QC

Director

PI & Supervisor Enrollment Report Conference meeting Bi-Weekly Pt Recruitment Director

Data Manager Data Clarity Report E-mail Weekly Data validation manager & Clinical Trial Nurses

Clinical Manager Site investigation Report

Conference meeting Monthly Trial Site Coordinator

Clinical Manager Pt Initial Screening Reports

E-Mail Weekly UC system

Physician Patient Secondary Screening Reports

E-Mail, CRF Weekly Clinical Trial Nurse

Regulatory affairs Director

Regulation Compliance Report

E-mail and Conference meeting

Monthly Regulatory Staff Lead and members

Department Director and or

Supervisor

Conflicts Conference meeting Monthly Team leader having conflicting interests

RISK MANAGEMENT

Presented by Rukshan

Risk Management Plan

• Risk management is an ongoing process.• Plan to minimize the probability and impact of adverse

events.• Reference insurance on budget

When a risk is identified the degree of impact:• SCHEDULE• SCOPE• COST• QUALITY

Risk Identification

Risk priority rating of 1,2,3

A risk priority assigned:

1 = significant resources to mitigate

2 = considerable resources to mitigate

3 = less assigned resources to mitigate

Element Ref. Risk Risk Priority

Likelihood (H,M or L)

Impact (H,M or L)

1 Patient Injury 2 L M

Patient Care 2 Patient Attrition 1 H H

3 Data or Property Theft 5 L H

Project Nature 4 Data Loss 3 L H

5 Staff Injury 4 L M

Project Staff 6 Staff Attrition 6 L M

Risk Assessment Chart

Priority Title DescriptionChance

of Impact

Schedule Scope Quality Cost

1Patient Attrition

Loss of pts: death or withdrawal 70% High High High High

2 Patient Injury

Pt injured during tx or clinical site 40% High Low Low High

3 Data LossData is wiped from

servers or individual data

recording devices

10% High High Medium High

4 Staff Injury Staff injured at clinical site

30% Medium Low Medium Low

5Data or Property

Theft

Data stolen from data recording

devices or servers

5% Medium High Medium High

6 Staff Attrition

Resignation or termination of Staff

15% Low Low High Medium

MitigationRisk Mitigation Activity

Patient Attrition• Well established inclusion/exclusion criteria.• Incentives and patient care.• Staff training.

Patient Injury •Patient information sessions/injury reporting •Staff training on injury prevention

Data Loss • Series of drives hardwired to a secure server.

Staff Injury • Insurance policy and training. • Annual facility audits.

Data or Property Theft

• Two identical/separate servers.• Secured wireless uplink to an offsite location

Staff Attrition • Hire trained workers• Staff incentives. • Staff evaluations

Contingency PlanRisk Activity

Patient Attrition •Patients recruited all at once and start simultaneously.

•Patients enter in a “batch” mode.

•Patients are recruited continuously until desired sample size is achieved.

•Patients are recruited until a fixed date is reached.

Patient Injury •Patient evaluation and injury coverage.

•Immediate dismissal from trial if too severe.

Contingency Plan Cont.

Risk Activity

Data Loss • Restore lost data through striping array

Staff Injury • Rehabilitation and time off

• Shift coverage and replacement

Data or Property Theft

• iPads remotely wiped

• Instantaneous backup/lockdown prevent data leaks

Staff Attrition • Subcontract clinical site staffing agency

• Database of qualified candidates

PHASE II: DATA COLLECTION

Presented by Mike

Overview

• Highly regulated due to sensitivity of the data

• Must be masked until stats are performed

• Kept highly secure and encrypted

• Must maintain chain of custody• No compromises

• Puts all data into question

• Track changes and restrict edits

• No single person has full access!

Strategy• Multiple Servers both on and off site• Collected with iPad tablets• Multitude of servers, processors, UPS backups etc.• Tailored to the trial

• Restricted access• Reliable collection

http://www.futt.org/wp-content/uploads/2008/07/server-picture.png

Methods• Installed:

• On site for data storage• Off site for secure backups

• Redundant copies

• Networking• Secure in-house access• Off-site access is contingent• Limits potential for hacks and malicious software penetrations

• Off site storage

http://communities.vmware.com/servlet/JiveServlet/showImage/38-6564-11783/PCoIP+View+Security+Server+1.png

Risks & Mitigation• Data Loss-

• Frequent Backups, backup power sources, redundant drives and striping data recording

• Data Theft-• Server security• SQL security• Encryption on all servers, drives and recording devices• Firewall

• Hacking/ Malicious Software-• Firewall• Encrypted access • Frequent security and IP scans

Contingency• Data Loss-

• Striping allows for lost data to be recovered• Performed on 10 drives, data written across all 10.

• If lost, data can be recovered by server clone• Same drive configuration across 10 drives• Exact clone as the first server• Both kept in-house

• If lost, data can be recovered at off site dual backup• Secured facility, encrypted access only• Confidential location• “Off the grid” and environmentally stable

PHASE III: DATA MANAGEMENTPresented by Sahar

P3-IS Quality Data Control

• It may seem negligible• BUT small discrepancies can make a significant difference to data

interpretation

• So, data quality control is a must• Especially with data that is used to drive life altering

decisions/conclusions

P3-IS Data Management Control

P3-IS provides scientists and clinicians with:

• Each clinician (2) will have laptops

• can securely store and share complete scientific reports

• Will input data at the same time

• Notification appears if data input is conflicting

• Access codes (login and pw) required

• Everything will be timestamped

• Highlight data corrections, changes etc

Data validation checkpoints (about 5)

• To integrate and analyze correct data input

• practices Good Laboratory Practice

Obtain final authorization on final data

Assistance in correcting errors

• 800 number of program provider

INTEGRATE & ANALYZE

Continue Producing Data Listings

Data Entered into P3-IS program

1st POE Validation by technician

Data Collection (2 clinicans)

P3-IS program datasets Generated

Integrate all data into the datasets

3nd Validation of Clinical Data Review

Adverse Event / Medical Coding

Final Database Review for Completeness get Authorization

Authorization to Deliver Datasets

Data Received

Coding Dept.

Final Data Review for Completeness

Resolution Obtained

Error Identified

2nd Validation Internal Program Check

P3-IS Program Advantage

• Cheaper

• Tables/charts easily pasted into spreadsheets or Word

• Very User Friendly• So training will not be tedious nor

expensive.

• Spreadsheets similar to excel

• Better graphics

• Documentation is better

• Better clarity on algorithms used for statistical procedures

• Good stats analysis (Regeneron)

Our Goal of DM/ Quality Control

• To VALIDATE, VALIDATE, & VALIDATE!

• Recall, Value of the data is only as good as its DM

• Reducing our risk of incorrect interpretations• by increasing quality control

Conclusions

• Meet demands of pt recruitment & data collection

• Practicing GLP

• Subcontracted for section of Phase III• Area I - Patient Recruitment

(~3400 nationwide)

• Area II – Data Collection/Management

• Perform recruitment to clients specifications

• Collect Data

• Manage Data• Maintain integrity • Maintain protection

• Pass off to Statisticians (Regeneron)

• Get Paid!

Questions