1. Study Development and Design Suzanne Adams RN MPH Director, Clinical Operations Jefferson Clinical Research Institute

2. Study Design: Industry vs. Academic The Industry clinical research process can be long and expensive. Investment over $1 billion (15.2 m phase I / $41.7 m phase II / $115.2 m in phase III 10-15 years for a compound or device to advance from benchtop to bedside Subjects may be assigned to take one or a combination of:  Investigational drugs  Approved drugs  Placebo* Academic Research Intramural funding / Support for pilot studies – informing larger grant development Resources and sharing Value of Academic Capital NIH Clinical and Translational Science Awards Requirements for Reporting Results

3. Likelihood of Approval by Phase and Disease Group Nature, 2009

4. Study Design: Types and Characteristics Observational Registry Interventional Prospective Retrospective Cross-sectional Cohort RCCT Randomization Crossover/Stratified Blinding / Double Blind Single Site or Multi-Center RCC with Enrolling Sites Adaptive Design Patient-Centered Patient Reported Outcomes Comparative Effectiveness Big Data Analyses

5. Clinical Trial Design: Phase I and II Phase I Test investigational drug for the first time in humans Small number of healthy volunteers Evaluate safety - Determine safe dosage range - Identify adverse effects. NOTE: Due to toxicity of the agent, cancer trials may do Phase I studies on subjects with advanced disease who have not responded to SOC treatment Phase II Investigational drug given to a larger number of people People have a particular disease or condition Determine effectiveness - Further evaluate safety IIa Pilot clinical trials may focus on dose-response, type of patient, frequency of dosing, or numerous other characteristics of safety and efficacy IIb Well controlled trials representing the most rigorous demonstration of efficacy Sometimes referred to as pivotal trials

6. Clinical Trial Design: Phase III and IV Phase III Several hundred to several thousand people Participants have the appropriate disease or condition Additional testing for safety, effectiveness, side effects, comparative effectiveness IIIa Trials conducted after efficacy of the medicine is demonstrated, but prior to regulatory submission of a New Drug Application (NDA) Also conducted in special groups or under special conditions dictated by the nature of the medicine and disease. Provide information for package insert and labeling IIIb Clinical trials conducted after regulatory submission of an NDA or other dossier, but prior to the medicine's approval and launch. These trials may supplement earlier trials, complete earlier trials, or may be directed toward new types of trials (e.g., quality of life, marketing) Phase IV After a drug is available by prescription, FDA requires reporting of additional information to assess longer-term risks, benefits and use Post-marketing Surveillance or Pharmacovigilance

7. Industry vs. Federal Grants vs. Investigator-Initiated CONSIDERATIONS Funding Source (Commercial, Federal, Foundation) Duration of Study Size and Scope Conflicting or Competing Studies Specific Aims/Exploratory Aims Endpoints and Outcomes Investigator Role/Expectations FDA Interactions for IND/IDE / Exemption “Waiver” Contract Research Organizations Trial Networks DSMB/DSMP Enrollment Goals and Timelines/Milestones Data Quality Monitoring

8. Assessing Feasibility Internal Financial Estimates and Projections Cost to Institution Potential for / Level of Success Data Management / EDC Use vs. AE / SAE Reporting Requirements Scientifically Sound - Subject Safety Training and Education Needs Site Feasibility Questionnaires – Level of Specificity Experience Access Capabilities Past Performance Audit Record

9. Feasibility: Assessment of Subjects, Staff, and Stuff Subjects Number / Availability of Subjects Access to Subject Population Subject Burden Staff Sufficient Research Staff Skill Set/ Experience of Research Staff Research Staff Burden Investigator Training and Experience Investigator Effort and Availability Investigator Engagement Resources Equipment Facilities (Lab etc.,) Accommodations

10. Budgeting and Financial Feasibility Staff Effort IRB/IEC fees (including continuing review and amendments) Study start-up administrative costs SAE reporting Monitoring plan Long-term document storage Study maintenance fees Subject reimbursement Organizational overhead Translation services Pharmacy charges

11. Protocol Evaluation and Assessment Objectives that address specific questions or a hypothesis statement Scientific background and study rationale providing the basis for the trial Trial design consistent with study goals and depicted in a study schema Subject selection and enrollment using specific inclusion and exclusion criteria Procedure and events schedule: treatment plan, visits, clinical procedures, laboratory tests, questionnaires, other measures Management of AEs, expected AEs, and actions to be taken or stopping rules Statistical considerations/ rationale for study design, sample size, and analysis plan Methods for quality control and quality assurance Methods for human subjects protection and safety

12. Operational Analysis Tools for Pre-Screening and Screening Equipment: Acquisition, Care, and Feeding Coordinator Training Standard of Care Overlap Subject Injury Language Investigational Product/Device Control Management/Cooperation/Resources needed for required labs or tests Safety Assessments Subject Retention Clean Data / Data Query Resolution Analysis Responsibilities

13. Feasibility: Assessment of Start up Time and Effort Individual Project Metrics CDA Turnaround Regulatory Document Submission IRB packet–Development, Submission, Approval Contract Review and Execution Account establishment Time to first subject enrolled Meeting Enrollment Goals Data Quality Report Meeting Endpoints General Performance Metrics Number of Studies coming in Time in Pipeline Meeting Enrollment Goals Account Balances/Residuals Balance/Flow to support personnel Overall Site Performance

14. Information and Resources FDA and CFR IRB Guidance Investigator Drug/Device Brochure CORE Lab/Operations Manual JCRI Standard Operating Procedures JCRI Business Operations (Grants and Contracts) RACE Federal Grant Management TJU/H Websites

15. Questions and Comments Thank You !