1. Primer: Clinical Trial Basics: What You Need to Know to Manage an Industry Sponsored Clinical Trial

2. Presenters: Cheryl K. Williams, Associate Director, Office of Research and Project Administration, University of Rochester Donna Galloway, Division Administrator, Infectious Diseases Division, University of Rochester Doreen M. Francis, RN, CCRC, Vaccine Research Unit, Infectious Diseases Division, University of Rochester

3. Milestones in Clinical Trial and Ethics Development 1 Research Ethics Milestones Presidents Council on Bioethics 2000 National Bioethics Advisory Commission 1990 Common Rule CIOMS Guidelines HHS/FDA Human Subject Regulations 1980 Belmont Report Trigger Events Gene Transfer Subject Death The Syphilis Study (Expose)

4. Research Ethics Milestones 1970 Declaration of Helsinki Kefauver-Harris Amendments1960 1950 Nuremberg Code 1940 1930 Trigger Events The Beecher Article (NEJM) Milgram Study The Thalidomide Tragedy Human Radiation Experiments (begin) The Nazi Experiments The Syphilis Study (begins) 1 Dunn, C.M., Chadwick, G.L. Protecting Study Volunteers in Research, Third Edition, p 27, (2004)

5. Game Changers in Clinical Trials Nazi Concentration Camp Atrocities The Milgram Study – Obedience Study The Thalidomide Catastrophe – Sedative PHS Study of Untreated Syphilis in the Negro Male Human Radiation Experiments – Plutonium Injections – Intentional Releases of Radiation U Penn Gene Transfer Experiment - FCOI

6. Harmonization Ideally, your institution has a central office to review, negotiate and approve clinical trials Reality: Central sponsored programs office negotiates clinical trial agreement (CTA) IRB reviews, approves protocol and ICF Department reviews, negotiates budget Possible Result: contradictory documents and bad timing – CTA negotiated, but IRB approval Missing or budget still under review

7. You Know You’re Going to Work on a Clinical Trial When... 1.Your PI brings a Confidential Disclosure Agreement (CDA) to you 2.Your PI starts talking about the patient base 3.Your PI leaves town to go to an investigators’ meeting in the Caribbean 4.An unacceptable budget with an exceptionally expensive protocol lands on your desk

8. The CDA – see Handout 1 for sample Should be reviewed by your central office Concerns: 1.Definition of confidential information – narrow the scope – eliminate any mention of intellectual property requirements – this is a CDA only 2.Time limit to hold confidential – 1 year standard (obligation no greater than 5-7 years) 3.Only the PI should be bound by agreement

9. The CDA Should be reviewed by your central office Concerns: 4.If a CTA results, it will supersede the CDA 5.Believe it or not, Export Control – don’t accept any information that could be subject to this law 6.Refuse to receive any trade secrets 7.Governing law

10. The CTA – see Handout 2 for sample Negotiated by the Central Office Issues: 1.CTA with Institution, not PI 2.Signatories should be sponsor, Institution, with PI signing as “read and understood” 3.Statement of work section should reference attached protocol 4.Payment terms should reference attached negotiated budget

11. The CTA 5.Sponsor will supply drug/devise in sufficient quantity 6.Investigator and sponsor assure that study will be conducted in accordance with all laws and regulations 7.HIPAA 8.In an age of electronic everything, watch out for CFR, Title 21, Part 11, Electronic Records compliance

12. The CTA 9.Time limitation on requirement to keep confidential 10.Under data ownership and IP, make sure all original records or work, including patient medical records, laboratory records and reports scans, films and pre-existing information in Institution’s databases remain Institution property – everything else belongs to sponsor 11.Free to publish after sponsor review 12.Site access – know what your institution will accept

13. The CTA 16.Subject Injury – sponsor reimburses institution for cost of reasonable and customary medical treatment for any illness or injury sustained by subject 17.Insurance – get sponsor’s limits – remember, indemnification and subject injury are not limited by sponsor’s insurance limits 18.AAHRPP language, if required by your institution

14. The CTA 19.WARRANTIES – institution should make no warranties, express or implied regarding the results 20.Governing law – should be your state’s

15. The Protocol and Informed Consent Form Protocol – Provided by sponsor – Usually in final version – Review for feasibility to assist in budget preparation and to compare with consent

16. The Protocol and Informed Consent Form Consent – Template provided by sponsor – Modifications per institutional policy SOP for Consent Process – Consent quiz used to confirm subject understanding and tool to aid discussion – see Exhibit C

17. Other Considerations Protocol may need to be reviewed by others: Institutional Biosafety, ED Committee or other department review Applications to be completed – 2 at our institution Local IRB WIRB – IBC – Research Match – Other committee-required applications

18. Other Documents Consent quiz (see Handout 3 for sample) Phone screen Advertisements – Email/internet – Newspaper/flyer – Radio TV spots 1572

19. Other Documents CV Assembly/Medical Licenses Financial Disclosure form Conflict of Interest statements – COI Management Plan if applicable

20. Other Coordinator Duties Set up any testing need with appropriate dept – Lab – X-ray – Cardiology, etc. All this information must be in the budget!

21. The Budget Event grid – used to develop budget Event grid - populated with time and costs – Nurse time has been rounded (salary and benefits) to $50/hr) – PI time at $200/hr Bullet list of pass-through costs See Handout 4 for samples