1. 1 Investigator-Initiated Clinical Research Planning, Developing, Conducting, Managing, and Succeeding Wm. Hirschhorn, M.S. Director, OCT & RQI and Adj. Prof of Regulatory Affairs Office of Clinical Trials & Research Quality Improvement 2-5245 2-3106

2. 2 Objectives To begin to be able to … –Describe the differences between investigator-initiated clinical research and sponsor-initiated clinical research. –Successfully plan your own clinical research project and assume ownership for your work and achievement. –Thoroughly develop your research proposal.

3. 3 Objectives –Successfully initiate and conduct your clinical research program. –Comply with institutional, federal, and other policies, guidances, and regulations in managing your clinical research program. –Count on the Offices of Clinical Trials and BioStatistics to assist you.

4. 4 Isn’t Clinical Research All Alike? Basic science – NIH, bench-top and other. Grant from department or government. Industry (sponsored) - initiated clinical research. FDA regulated. –Usually leads to marketing registration Investigator-initiated research –It’s your project - ownership! –Various funding? –Multiple responsibilities!!

5. 5 (1) Examples of Investigator-Initiated Research Sponsor-Investigator or Investigator-IND Investigator submits a Letter of Intent (LOI) to industrial sponsor and OCT/BioStatistics 1.Your interest!! 2.Project proposal – You’re the expert 3.Technical and logistical support – Kinetics, clinical/therapeutic section, investigational drug, Drug Master File (Inv.-IND), GCRC, etc. 4.Address Federal regulatory requirements!! –OCT will help you 5.Human research participant population?? 6.Possible funding?? 7.Data ownership??

6. 6 (2) Investigator-Initiated Research Funded Proposal (LOI) Resources Application process –NIH funded –Refer to Dr. Steven Houser’s presentation titled “Planning a Successful NIH Research Application” (12/11/03) Other funding (for-profit, private sources) Publications??

7. 7 (3) Institutional Supported Research Department funded – possibly no outside funding LOI Resources Assistance from BioStatistics Assistance from OCT and GCRC

8. 8 Remember!! Wherever you go, whatever you do - your research needs should satisfy … –Your unswerving attention and complete ownership –Department chair’s knowledge and approval –Interaction with Sponsored Projects –Assistance from OCT –IRB review and approval

9. 9 Who is an Investigator? ( Sponsor-Investigator) An individual (not a corporation) who both initiates (plans and designs) and conducts an investigation, and under whose immediate direction the study drug is administered or dispensed. Investigator IND. 21 CFR 312.3 and ICH E-6 (GCPs) 1.54 –Plans, designs, conducts, monitors, manages the data, prepares reports, and oversees all regulatory and ethical matters –21 CFR §312 Subpart D Absolute responsibility and accountability required!!

10. 10 So, how do you go about doing this? 1.Take ownership 2.Devote sufficient time and initiative 3.Don’t lose focus of your objective 4.Ask yourself – “Do I really want to do this?” 5.Work with OCT & BioStatistics 6.Work with Sponsored Projects and the IRB 7.Plan for the long-haul

11. 11 Steps to Success Development – Conduct – Management –Chronological steps Project Development –Letter of Intent –Proposal –Timeline –Protocol development and data collection forms –Budget development –Funding Contract IRB review and approval Study conduct and monitoring Data Review and Analysis

12. 12 Steps to Success What is the Letter of Intent (LOI)? –Statement of your research interest in a particular drug or device –Your interest in conducting a clinical trial with the drug or device –Type of human research participant population –Anticipated time to conduct the trial –Funding source, if known –Who will supply the drug or device?

13. 13 Steps to Success What should be contained in the LOI? –Rationale for the proposed trial –Design for the trial Dose, blinding, schedule, and comparison groups –Characteristics of the population –Patient enrollment feasibility –Any unique features of the proposed trial Who would benefit from the new information? –Patients –Industry –Temple

14. 14 Steps to Success The LOI – Points to Consider –Be clear, brief and to the point –Avoid overuse of jargon –Be unique Here creativity is appropriate –Appeal to your audience(s) –Follow all guidelines –Show that you own the proposal

15. 15 Steps to Success Developing the Protocol –Format from company or OCT –Build in flexibility Revisions will absolutely occur –Make it informative Utilize the appendix section Supply important supplemental reading –See BioStatistics for valuable assistance Consult with experts beside yourself –Carefully edit the final edition –Consult with OCT for template and IRB submission assistance What do I want to do with the data? –Publication? Where? When? Requirements?

16. 16 Steps to Success The Budget –Think about the following things Department interest Industry interest OCT can assist in identifying outside sources Staff resources –Co-investigator, CRC –Consultants and resources (i.e., laboratory, special services, data management, monitoring, technical) OCT benchmarks budgets successfully Complete the SPAF at the appropriate time

17. 17 Steps to Success Some resources I need to identify? –Clinical Laboratory and special lab support –Therapeutic specialties (i.e., cardiology, D.I., G.I., etc –Regulatory guidance –Project management (i.e., QA, timeline adherence) –Patient recruitment and advertising –Data management –Pharmacy –Facility charges –Computer support

18. 18 Steps to Success Project timeline –Development phase – Plan your work and work your plan! Regulatory (IRB, FDA, NIH) and legal (contract) Project conduct phase –Recruitment –Trial conduct –Data collection –Data Quality Assurance Data review and analysis Publication

19. 19 Steps to Ensure Success Study conduct and Monitoring –KNOW YOUR OBLIGATIONS and RESPONSIBILITIES Administrative Federal Temple, State and local –Take charge of your project Champion your expertise Mentor –See it through to completion –Understand the requirement for monitoring and Quality Assurance - OCT

20. 20 Steps to Ensure Success Tips to ensure you have fun and succeed –Frequently review your project for schedule adherence On-track in what areas? Off-track in what areas? Finances Logistics –Prepare for the worst case scenario –Get use to paperwork – it’s a fact of life –Unexpected delays or issues Count on this happening Identify the source Contingency planning – work with OCT/OCR

21. 21 What’s next? In March 2004 – Investigator initiated clinical research –Data management and analysis –Monitoring –Quality Assurance –Study outcomes –Publications Other really exciting and useful topics