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

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

2. 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 Vanderbilt-Ingram Cancer Center

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

4. 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 Preclinical Phase I Animal or laboratory studies that provide information regarding safety. Evaluation of data determines whether safety to start human subject clinical trials. Phase II 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 Phase III Experimental study drug or treatment is given to a larger group (30-100) to see if it is effective and to further evaluate safety Approval To Market Experimental study drug or treatment given to large groups to confirm effectiveness, side effects, compare to common treatments, and collect safety information After completing trials successfully, new drugs go to market. Roughly 20% of all new drugs that enter Phase I trials are approved for marketing. Up to 4.5 years Up to 8.5 years Up to 1.5 years

5. 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) Information Users 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. • 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.) Safety Monitoring

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

8. 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 Phase I Team and Information Gaps

9. 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 Clinical Trial Sponsor Clinical Trials Shared Resources (CTSR) Overall trial management SAE Vanderbilt-Ingram Cancer Center Health Care System Patient Info. SAE Directives Resources Compiled CRF OnCore Master File Regulatory and Data Management Patient SAE Resources Patient Info Patient LEGEND Data/Event Trial Protocol EMR Resources Directives Workflow, Processes Patient Patient Health Care Delivery Cancer Care Clinics

10. 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

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

12. 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

13. Improved reporting procedures will increase the transfer of information between sponsors and PI’s and Research Nurses. Recommended process improvement 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. Successful implementation of the conference call reporting tool will: Measuring Implementation Success