VANDERBILT-INGRAM CANCER CENTER CLINICAL TRIALS SHARED RESOURCES (CTSR) Jennifer S. Novia INFO 643 March 6, 2011

V ANDERBILT -I NGRAM C ANCER C ENTER 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 DirectorExecutive 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 C LINICAL T RIALS S HARED R ESOURCES (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. C LINICAL T RIAL P HASES 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

I NFORMATION U SERS 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

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. S AFETY M ONITORING 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.)

I NFORMATION S HARING 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.

P HASE I T EAM AND I NFORMATION G APS Phase I Team 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 Information Sharing on Drug Toxicities Weekly toxicities meeting Trial sponsor conference calls Informal exchange of information Information Gaps 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

C URRENT C LINICAL T RIAL D ATA F LOW P ROCESS Directives SAE Patient Info Patient Resources Directives Patient Info. Resources SAE 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 SAE 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.

P ROBLEMS WITH C URRENT I NFORMATION F LOW 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

P ROPOSED T OXICITY I NFORMATION F LOW Improved reporting procedures will increase the transfer of information between sponsors and PI’s and Research Nurses. Toxicity Conference Call Highlight Clinical Trial Sponsor Internal Principle Investigators and Research Nurses Phase I Toxicity Meetings (Medical Director, Regulatory & Data Vanderbilt-Ingram Cancer Center Health Care System 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. Directives Data/Event Resources Workflow, Processes LEGEND

I NFORMATION R EPORTING T OOL 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).

R ECOMMENDED PROCESS IMPROVEMENT 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.

M EASURING I MPLEMENTATION S UCCESS 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