Regulatory Science Virtual Symposium: “Clinical Research Career Pathways” Session 4: Understanding Clinical Research Management at Academic Institutions (2021)

1. Big Questions: Where do you fit in a clinical trial as part of an academic institution? What roads can you take, and what things do you need to improve on? What is needed to run a successful clinical trial?
2. General Lifecycle of a Clinical Trial
   1. Approved Protocol → Investigator Selection → Approval Process → Patient Recruitment and Participation → Data Entered and Reviewed → Statistical Analysis → Presentation and Publication of Report → Data Filed and Registration Obtained
3. Main Categories of Clinical Trials done in Academia
   1. Industry-Sponsored
      1. Pharmaceutical/Biotech/Medical Device Company is the Sponsor contracting with community practice/medical provider or academia to conduct the investigation
   2. Federally Funded
      1. Federal entity (like NIH, NCI, etc.) is the Sponsor, providing grant funding to community practice/medical provider or academia to conduct the Investigation (i.e. Cooperative group)
   3. Investigator Initiated (IIT)
      1. The same entity is both the Sponsor and the Investigator, who conceives the research, develops the protocol, as well as conducts the study.
4. Successful Clinical Trial Requirements:
   1. Contract and Budget
      1. Review protocol calendar for budget task completed by calendar builder (federally funded, IIT, industry)
      2. MCA analysis task completed by MCA analyst (federally funded, IIT, industry)
      3. Budget development task completed by budget specialist (fixed budget, IIT, industry)
      4. Contract task completed by contract manager (overall grant, IIT, industry)
   2. Regulatory Oversight
      1. FDA (Industry/Federal)
         1. IIT Specific
            1. IND: Drugs (CDER) and Biologics (CBER)
            2. IDE: Medical Device & Radiological Health (CDRH)
            3. Not under FDA oversight
               1. Prevention, epidemiology, sociology, and psychology, etc. not under FDA oversight
         2. Institutional Review Board (IRB)
            1. Local vs. Central
            2. Important to maintain ethical standards with a secondary party
         3. Specialty Committee
            1. Biosafety (biologics, i.e. live vaccine)
            2. Radiation Safety (radiology/scans/radiation treatment/procedure more frequency than SOC)
               1. CCC Approval Requirements

                  
                  

                  1. Scientific Committee Review and Approval (CIC at USC)
               2. Submission to the FDA is completed by the site regulatory team in IIT’s, the sponsor in industry studies, and the federal agency in federally funded studies
               3. Submission to the local IRB (and the Bio & Radiation Safety Committee) is always completed by the site regulatory team in all studies
               4. Submission to the central IRB is completed by the site regulatory team in IIT studies; it is also completed by the site regulatory team in industry and federally funded studies for site-specific standards, but the sponsor completes the main submission in industry studies and the federal agency completes the main submission in federally funded studies
               5. The CIC coordinator is responsible for the scientific committee in all studies
   3. Regulatory Compliance Requirements

      
      

      1. GCP & CFR 21 (& ICH)
         1. Required training and documentation
      2. SOPs

         
         

         1. Internal (development, implementation, and maintenance)
         2. External (protocol and industry, and federal requirements)
      3. FDA Interaction

         
         

         1. inspections
            1. Routine (prior to NDA)
            2. For cause
         2. IIT Specific

            
            

            1. Safety reporting
            2. Annual submissions
      4. Quality Assurance (QA)

         
         

         1. Routine monitoring
            1. 100% source data verification (SDV)
            2. Risk based monitoring
         2. Internal Audits
         3. External Industry and Federal Funding Agency Audits
            1. Routine (annual, triannual)
            2. For cause
            3. In preparation for filing with FDA
      5. Data and Safety Monitoring (DSMC)

         
         

         1. IIT vs Industry and Federal
   4. Safety Oversight: Data and Safety Monitoring Plan

      
      

      1. CIC: Main Committee
         1. Main Charge: PRMS with focus on science
         2. Activities: Initial scientific review for all studies, and amendments on IITs
      2. CIC: SPC
         1. Main Charge: Accrual Monitoring
         2. Activities: Review of accrual for all active studies
      3. Safety and Data Monitoring: QAC
         1. Main Charge: Compliance, Data Accuracy, and Quality
         2. Activities: Performance and review of internal audits; review of all violations
      4. Safety and Data Monitoring: DSMS
         1. Main Charge: Subject Safety
         2. Activities: IIT: focus on toxicity profile, overall safety, and any study conduct issues that may impact patient safety; review of all SAEs
      5. Safety and Data Monitoring: Phase I Committee
         1. Main Charge: Oversight of dose escalation with focus on subject safety
         2. Activities: Adjudication of DLTs and decisions regarding dose escalation for IITs
   5. For resources and infrastructure, staffing needs across all trials includes a regulatory manager, researcher coordinator, data manager, specimen coordinator, admin and management, and research pharmacist

      
      

      1. IIT will also require a protocol writer, study statistician, and quality assurance 
      2. FF will also require a quality assurance
   6. IIT-Specific Management
      1. Data-Management
         1. Investigator, biostatistician, and quality assurance staff is responsible for case report development (CRF)
         2. Informatics (IT) is responsible for the database built
         3. Biostatistician and investigator are responsible for data analysis
         4. Investigator is responsible for the publication
      2. Multisite Management

         
         

         1. USC Clinical Trial Unit and multisite coordinator are responsible for CDA task
         2. PI and multisite coordinator are responsible for the site selection, and regulatory review & approval 
         3. PI, multisite coordinator, DSMS, and the QAC are responsible for the oversight of study conduct
         4. USC Clinical Trial Unit is responsible for the contract and budget
   7. Examples of Academia Org (CISO @ USC)

      
      

      1. Regulatory Affairs Unit
         1. Feasibility and protocol development
         2. Navigation through approval process Interaction with sponsor, internal and external stakeholders
         3. Maintenance of study & update of regulatory requirements)
      2. Clinical Research Operations Unit 

         
         

         1. Study execution
         2. Patient enrollment
         3. Quality of data and supervision
         4. Monitoring of study progress
         5. Committees Support
      3. Administration Business Management Unit
         1. Assistance with budget development
         2. Interaction with institutional entities
         3. Review of department budgets
         4. Assistance with hiring staff
   8. Resources and Infrastructure
   9. Facility
      1. outpatient clinic, inpatient facility, infusion center, laboratory, radiology, pathology, BMT, pharmacy, research office space, research specimen processing lab, monitoring room, medical records storage
      2. Equipment
         1. office equipment, software, lab equipment, data storage, electronic clinical trial management system, electronic data capture with capabilities for multi-site trials
   10. Questions
       1. There is 90+ employees in the Clinical Investigators Support Office (CISO)
       2. Strategies to ensure continuity of projects in a rapid staff turnover environment include assigning projects to multiple people to avoid assigning to responsibility to a single person; it’s important to prevent the halting of projects as a result of staff turnover

Accompanying text created by Omer Baker, BS Human Biology Candidate | omerbake@usc.edu | Edited by Annie Ly, MS Regulatory Science Candidate | lyannie@usc.edu