1. Jennifer S. Novia INFO 643 March 6, 2011
Vanderbilt-Ingram Cancer Center Clinical Trials Shared Resources (CTSR)
Jennifer S. Novia
INFO 643
March 6, 2011

2. Vanderbilt-Ingram Cancer Center
Mission
Vanderbilt-Ingram Cancer Center
To alleviate cancer death and suffering through pioneering research; innovative, patient-centered care; and evidence-based preservation, education and community activities.
Vision
Values
To be the preeminent cancer center in the Southeast and a recognized leader, nationally and globally, in the effort to prevent and treat cancers.
Discovery and Innovation
Impact and Translation
Relationships and Collaboration
Service and Compassion

3. Clinical Trials Shared Resources (CTSR)
Information flows to the CTSR under the direction
of the Vanderbilt-Ingram Cancer Center CEO.
Clinical Trials Shared Resources (CTSR)
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

4. Drug toxicity and safety is imperative to Phase I clinical trials
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
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
1.5 years
To Market

5. Information Users Primary 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

6. 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 Monitoring
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.)

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

8. Phase I Team and Information Gaps
Vanderbilt 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
Poor 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
Information Sharing on Drug Toxicities
Weekly toxicities meeting
Trial sponsor conference calls
Informal exchange of information

9. Current Clinical Trial Data Flow Process
The current data flow model does not allow for the clear exchange of toxicity information between the principal investigators and staff.
Current Clinical Trial Data Flow Process
Directives
SAE
Patient Info
Patient
Resources
Patient Info.
Compiled CRF
Clinical Trial Sponsor
Clinical Trials Shared Resources (CTSR)
Overall trial management
Regulatory and Data Management
Patient Health Care Delivery
Cancer Care Clinics
Vanderbilt-Ingram Cancer Center
Health Care System
OnCore
Master File
Trial
Protocol
Data/Event
Workflow, Processes
LEGEND
EMR

10. Problems with Current Information 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.
Problems with Current Information Flow
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

11. Proposed Toxicity Information Flow
Improved reporting procedures will increase the transfer of information between sponsors and PI’s and Research Nurses.
Proposed Toxicity Information Flow
Toxicity Conference Call Highlight
Clinical Trial Sponsor
Internal Principle Investigators and Research Nurses
Phase I Toxicity Meetings (Medical Director, Regulatory & Data
Health Care System
Vanderbilt-Ingram
Cancer Center
OnCore
Master File
EMR
External Trials Sites
External Trial
Patients
SAE
Pt. Info
Unexpected Toxicities
Patient Information
Institutional Review Board (IRB)
Program Coordinator, Phase I Clinical Trials Initiative
Phase I Clinical Trials
Toxicity Report
Protocol Modifications or Trial Warnings
SAE? NO
YES
Reported Toxicities
Stop.
No further
reporting
required.
LEGEND
Data/Event
Resources
Directives
Workflow, Processes

12. Information Reporting Tool
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).
Information Reporting Tool
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

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

14. Measuring Implementation Success
Successful implementation of the conference call reporting tool will:
Measuring Implementation Success
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