1. PRE-AWARD PAPERWORK FOR CLINICAL TRIALS SERIES 4, SESSION 8 OCTOBER 28, 2014 Applicants and Administrators Pre-Award Luncheon Series

2. Presented By: Kathleen Benoit – Research Administrator, OFFICE OF RESEARCH ADMINISTRATION, BOSTON

3. Overview What is a Clinical Trial? Clinical Trial Phases Preparing the Proposal Payment Terms and Budgeting

4. What is a Clinical Trial? A study on human subjects to answer questions about biomedical or behavioral interventions  novel vaccines  drugs  treatments  functional foods  dietary supplements  devices or new ways of using known interventions

5. Clinical Trial Phases Phase I – dose finding toxicity Phase II – efficacy & safety Phase III – compare to standard treatment Phase IV – post marketing after FDA approval

6. Breakdown of the Phases Phase I – Testing in a small group of people (roughly 50 subjects) to determine efficacy and evaluate safety  e.g. determine a safe dosage range and identify side effects Phase II – Study in a larger group of people (roughly 100 subjects) to determine efficacy and further evaluate safety

7. Breakdown of the Phases, cont. Phase III – Study to:  determine efficacy in large groups of people (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions  monitor adverse effects; and  collect information to allow safe use  includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy; and community trials and other population-based intervention trials

8. Breakdown of the Phases, cont. Phase IV – Studies done after the intervention has been marketed. Designed to:  monitor the effectiveness of the approved intervention in the general population  collect information about any adverse effects associated with widespread use One phase must be completed before the next phase can begin

9. The Phases - Overview Phase IPhase IIPhase IIIPhase IV PurposeDose finding toxicity Efficacy & safetyCompare to standard treatment Post marketing after FDA approval Number of Participants  50  100  100 into the thousands Any number LocationPhase I Center or University University, Large Medical Center or Private Office Private Office or Medical Center GoalDetermine safe dose & possible indications Efficacy in specific clinical situations Evaluate in comparison to standard or no treatment New indications or long term impact on quality of life Common Study Design Dose escalating cohorts One arm, may be stratified Randomized, blinded, multi-arm may be placebo controlled Open labeled; expanded access

10. The Protocol How a clinical trial will be conducted (objectives, design, methodology, statistical considerations and organization) Number of study subjects depends on the required sample size Criteria for selection and exclusion of subjects, assessment of efficacy and safety, study monitoring plan, and quality control & assurance Ethics and handling of adverse events Data handling and recordkeeping Publication plan, literature reference, timetable PI is responsible for the welfare of the study subjects, study data, compliance with regulations

11. Developing a Budget Budget needs to be somewhat flexible and must cover all costs Fixed and upfront costs are incurred whether or not subjects are enrolled Costs related to subject visits depend on the number of participants Analyze the study timeline to identify items that will generate expenses for the site Create detailed budget by visit and by study cycle

12. Budget Items  Required professional charges for the tests being performed  Inclusion of one-time charges  IRB  Investigational drug (IND) pharmacy start-up fee  Human subjects charges  Advertisement/Recruitment  Stipends  Travel  Meals  Parking  Laboratory assessments and pharmacy fees  Don’t forget F&A (use ‘other on-campus rate of 37%)

13. Cost-Related Considerations Realistic number of subjects that can be recruited Number of subjects that need to be screened to identify an eligible participant Difficulty of meeting eligibility criteria and additional recruitment effort Delayed start will increase costs

14. Subject Screening and Costs Most allow for up front fees (inclusive of one time charges) to be paid in full before the study begins When determining per patient costs, be mindful of:  Initial screening  Failure after screen and/or during the life of the study  Drop-out rates  Full completion  Does the sponsor require a final amount of patients (i.e. must see 100 patients for successful completion)?  Is this number flexible?

15. Tracking Costs Ensure that all costs are tracked accurately for invoicing Sponsored Programs Accounting relies on the accuracy of the information provided by the Project Coordinator and Administrator Understand all terms from the Sponsor before beginning  Are the study and fees feasible for the institution?

16. Clinical Trials Registration All clinical trials must be registered in the US Clinical Trials database: https://clinicaltrials.gov/https://clinicaltrials.gov/  provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies  maintained by the National Library of Medicine (NLM) Information is provided and updated by the sponsor or PI Studies are submitted to the website (that is, registered) when they begin, and information is updated throughout the study  in some cases, results are submitted after the study ends

17. Clinicaltrials.gov Request registration from your Signing Official (SO)at ORA to receive access Once information is entered or updated, the SO will have to release the information Clinicaltrials.gov staff maintain quality control and may reject incomplete information or request edits before posting Information must be updated in a timely fashion Record must be closed once the trial is completed

18. Take-Aways Work closely with the sponsor to design the study Be realistic about subject recruitment Analyze the timetable to create adequate budget Monitor costs closely to avoid problems Clinical trials registration is mandatory

19. Questions ??? Questions? Please feel free to call Kathleen Benoit at 617-636-0414 or email kathleen.benoit@tufts.edukathleen.benoit@tufts.edu