Investigator-InitiatedClinical 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
Objectives • To begin to be able to … • Describe the differences between investigator-initiated clinical research and sponsor-initiated clinical research. • Successfully planyour own clinical research project and assume ownership for your work and achievement. • Thoroughly developyour research proposal.
Objectives • Successfully initiate and conductyour clinical research program. • Complywith institutional, federal, and other policies, guidances, and regulations in managing your clinical research program. • Counton the Offices of Clinical Trials and BioStatistics to assist you.
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!!
(1) Examples of Investigator-Initiated Research • Sponsor-Investigator or Investigator-IND • Investigator submits a Letter of Intent (LOI) to industrial sponsor and OCT/BioStatistics • Your interest!! • Project proposal – You’re the expert • Technical and logistical support – Kinetics, clinical/therapeutic section, investigational drug, Drug Master File (Inv.-IND), GCRC, etc. • Address Federal regulatory requirements!! • OCT will help you • Human research participant population?? • Possible funding?? • Data ownership??
(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??
(3) Institutional Supported Research • Department funded – possiblyno outside funding • LOI • Resources • Assistance from BioStatistics • Assistance from OCT and GCRC
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
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!!
So, how do you go about doing this? Take ownership Devote sufficient time and initiative Don’t lose focus of your objective Ask yourself – “Do I really want to do this?” Work with OCT & BioStatistics Work with Sponsored Projects and the IRB Plan for the long-haul
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
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?
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
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
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?
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
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
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
Steps to Ensure Success • Study conduct and Monitoring • KNOW YOUR OBLIGATIONSand 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
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
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