Vanderbilt-Ingram Cancer Center Clinical Trials Shared Resources (CTSR)

VANDERBILT- INGRAM CANCER CENTERCLINICAL TRIALS SHARED RESOURCES (CTSR)

Jennifer S. NoviaINFO 643March 6, 2011

VANDERBILT-IN

GRAM CAN

CER CENTER

Mission

To alleviate cancer death and suffering through pioneering research; innovative, patient-centered care; and evidence-based preservation, education and community activities.

Vision

To be the preeminent cancer center in the Southeast and a recognized leader, nationally and globally, in the effort to prevent and treat cancers.

Values

• Discovery and Innovation• Impact and Translation• Relationships and Collaboration• Service and Compassion

CEO, VICC

Assistant Director of Finance

Medical Director Executive Director

Regulatory and Data Management

Clinical Trials Information Program

(CTIP)

Research Compliance and Scientific Review

Analysis

Assistant Director, Clinical Operations

Research Nurses

Assistant Medical Director

CLINICAL TRIALS SHARED RESO

URCES (CTSR)

Information flows to the CTSR under the direction of the Vanderbilt-Ingram Cancer Center CEO.

Drug toxicity and safety is imperative to Phase I clinical trials. This evaluation of users and information gaps is centered on the Phase I Clinical Trials Initiative of CTSR.

CLINICAL TRIAL PHASES

Experimental drug or treatment given for the first time to a small group (15-30) to evaluate its safety, determine a safe dosage range, and identify side effects

Experimental study drug or treatment is given to a larger group (30-100) to see if it is effective and to further evaluate safety

Experimental study drug or treatment given to large groups to confirm effectiveness, side effects, compare to common treatments, and collect safety information

Animal or laboratory studies that provide information regarding safety. Evaluation of data determines whether safety to start human subject clinical trials.

Up to 4.5 years

Up to 8.5 years

After completing trials successfully, new drugs go to market. Roughly 20% of all new drugs that enter Phase I trials are approved for marketing.

Approval

Phase III

Phase II

Phase I

Preclinical

Up to 1.5 years

To Market

INFO

RMATIO

N U

SERSPrimary Information Users

Cancer Center• Patients• Physicians• Research Nurses

Clinical Trials Shared Resources (CTSR)• Clinical Trials Information Program• Biospecimen• Regulatory • Data

External Users• Institutional Review Board (IRB)• Pharmaceutical Sponsors• Food and Drug Administration (FDA)

Secondary Information Users

Safety monitoring is required in clinical trials to ensure subject safety and study integrity. Drug level toxicities are a key component of Phase I safety issues.

SAFETY MO

NITO

RING

Subject Safety

Primary investigators and research nurses ensure subject safety by:

• Implementing the trial protocol as written

• Adherence to inclusion and exclusion criteria

• Continued adherence throughout the study

• Monitoring subject status (subject health, minimization of risk, toxicity tracking and management, etc.)

INFO

RMATIO

N SHARIN

G

Formal Information Sharing

Formal information is gathered to assess the viability of treatment options within the clinical trials program at Vanderbilt University. In the case of the CTSR, this formal information is also used to assess the safety and efficacy of new drugs.

• Physical Examinations• Laboratory Tests• Diagnostic Imaging• Serious Adverse Effect (SAE)

reporting

Informal Information Sharing

Informal information is shared spontaneously, is unofficial and has the potential to be an impromptu way for people to learn how to do their jobs and impact patient care and new drug development.

• Associations in clinics Patient visits – health information,

potential side effects from drug treatment

Interactions between research nurses and primary investigators (physicians)

• Team collaboration Sponsor conference calls Phase I team meetings

Formal and informal information have an impact on patient care and moving new drugs through the pipeline to FDA approval.

PHASE I TEAM AN

D INFO

RMATIO

N GAPS

Phase I TeamVanderbilt University School of Medicine

• Ten physicians who act as primary investigators

Vanderbilt-Ingram Cancer Center• Program Coordinator

Clinical Trials Shared Resources (CTSR)• Four research nurses• Bio-specimen team• Regulatory personnel• Data monitoring and reporting personnel

Information Sharing on Drug Toxicities• Weekly toxicities meeting • Trial sponsor conference calls• Informal exchange of information

Information GapsPoor participation in weekly Vanderbilt Toxicity Meetings by principle investigator

• Only four of ten principle investigators participate

• Personnel issues have impacted demands on research nursing staff

• Serious adverse effect (SAE) information not documented by regulatory and data personnel for notation in monitoring records.

Lack of knowledge transfer from sponsor conference calls results in loss of information regarding:

• External trial site information regarding dose limiting toxicities and unexpected toxicities in patients on the trial drug.

• Conference call information not properly documented and shared with all staff. This information is necessary for proper patient care and diagnosis in the case of a suspected adverse reaction.

• No formal reporting process to the CTSR Medical Director

CURREN

T CLINICAL TRIAL DATA FLO

W PRO

CESSDirectivesS

AE

Pat

ient

Info

Pat

ient

Res

ourc

esD

irect

ives

Pat

ient

Info

.

Res

ourc

es

SA

E

Com

pile

d C

RF

Clinical Trial

Sponsor

Clinical Trials Shared Resources (CTSR)

Overall trial management

Regulatory and Data Management

Patient Health Care DeliveryCancer Care Clinics

Vanderbilt-Ingram C

ancer Center

Health C

are System

OnCoreMaster File

TrialProtocol

SAE

Patient

Patient

Data/Event

Resources

Workflow, Processes

LEGEND

EMR

The current data flow model does not allow for the clear exchange of toxicity information between the principal investigators and staff.

PROBLEM

S WITH CU

RRENT IN

FORM

ATION

FLOW

Informal communications are hindered by the current information process. Lack of reporting to a central point is detrimental to the flow of information and has the potential to impact patient safety.

Decrease in Information

Flow and Patient Safety

No central repository for

reporting conference call

results

Lack of assigned ownership with current process

SAEs not adequately

reported back

PROPO

SED TOXICITY INFO

RMATIO

N FLO

WImproved reporting procedures will increase the transfer of information between sponsors and PI’s and Research Nurses.

Toxi

city

C

onfe

renc

e C

all

Hig

hlig

ht

Clinical Trial

Sponsor

Internal Principle Investigators and Research Nurses

Phase I Toxicity Meetings (Medical Director, Regulatory & Data

Vanderbilt-Ingram

Cancer C

enterH

ealth Care System

OnCoreMaster File

EMR

External Trials Sites

External TrialPatients

SA

EP

t. In

fo

Une

xpec

ted

Toxi

citie

s

Pat

ient

In

form

atio

n

Institutional Review Board (IRB)

Program Coordinator, Phase I Clinical Trials Initiative

Phase I Clinical Trials

Toxicity Report

Pro

toco

l Mod

ifica

tions

or T

rial W

arni

ngs

SAE?NO

YES

Rep

orte

d To

xici

ties

Stop. No further reporting required.

Directives

Data/Event

Resources

Workflow, Processes

LEGEND

INFO

RMATIO

N REPO

RTING TO

OL

Phase I Conference Call Reporting

Study Name

Date of Conference Call

Dose Limiting Toxicities (DLTs)

Pertinent Dose Level Discussions

Unexpected Toxicities

Slots available for VICC

Further Comments

VICC MD/Staff on call

Conference call reporting form not only provides information about safety but also provides planning guidance to regulatory/data personnel for number of patients that can be brought into the trial (slots available).

RECOM

MEN

DED PROCESS IM

PROVEM

ENT

Improved reporting procedures will increase the transfer of information between sponsors and PI’s and Research Nurses.

Sponsor

Principal Investigator or Research

Nurse

Program Coordinator

Phase I Business Meeting

Information from other trial sites is conveyed from the trial sponsor during conference calls.

SAE information is transferred from the Sponsor to Vanderbilt clinical staff directly involved in trial management.

Safety information is collected and assembled in a reportable style by Phase I, Program Coordinator.

SAE information is discussed in business meeting by clinical team and decisions for further reporting or action are made.

MEASU

RING IM

PLEMEN

TATION

SUCCESS

Successful implementation of the conference call reporting tool will:

Accurately reflect number of patient slots with trial sponsor for screening/consenting patients

Convey safety issues from sponsor to CTSR management

Create a centralized repository for SAE information for historical purposes