September X , 2018

1. Human Research, Clinical Trials, and Opportunities for Growth Key Updates and Collaborative Tips for Enhancing your SUNY Research Enterprise September X , 2018

2. Part 1: Collaboration among the Institutional Review Board (IRB), investigators, and sponsored research administrators to ensure regulatory compliance and human research protections Kevin Nellis, Executive Director, Human Research Protections and Quality Assurance Research Foundation for SUNY - Downstate Medical Center

3. Some (not all) Important Changes in the Revised Common Rule*– Effective 1/21/2019 • Certain activities are not research • Exemptions revised • Continuing review is not required in certain circumstances • TIP: Find out if your institution applies the Common Rule to ALL research or ONLY federally funded research • *Common Rule: Each Federal Agency has regulations within the Code of Federal Regulations (CFR). Collectively this is known as the “Common Rule.” Example: Title 45, Subtitle A, Subchapter A, Part 46: Basic HHS Policy for Protection of Human Research Subjects within the CFR, aka 45 CFR 46.

4. Common Rule: Certain Activities are Not Research • Scholarly and journalistic activities… that focus directly on the specific individuals about whom the information is collected • Public health surveillance activities… • … criminal justice… activities authorized… for criminal investigative purposes • Authorized operational activities…

5. Collaborative Efforts: • Certain Activities That Are Not Research • 2 New IRB Decision Aid Applications: http://research.downstate.edu/irb/irb-electronic-submissions.html# • FORM A: Common Activities related to Health Care Operations Activities, when there is no intent to develop or contribute to generalizable knowledge • FORM B: All activities • TIP: Understand your local IRB process

6. Common Rule: Exemptions Revised • Restricted: Exemption #1 • Expanded: Exemption #2, #4, & #5 • New: Exemption #3, #7 & #8 • Unchanged: Exemption #6 (FDA* exemption) • * FDA = Food and Drug Administration

7. Collaborative Efforts with Revised Exemptions • All Exempt Research at Downstate must be reviewed and approved by the Downstate IRB • IRB application clearly defines criteria: http://research.downstate.edu/irb/irb-electronic-submissions.html • Investigators and Post-Awards consult with IRB for guidance and determinations • TIP: Understand your local IRB process

8. Common Rule: Continuing Review Is Not Required in Certain Circumstances • Research eligible for expedited review, approved after 1/20/2019, unless IRB justifies why continuing review would enhance protections • Research initially approved by the full board after 1/20/2019 that has progressed and is now limited to: • Data analysis (including identifiers) and/or, • Access to clinical data from clinical care. • NOTE: Still required for FDA-regulated research.

9. Collaborative Efforts with Continuing Review • Revised IRB Policy • Revised guidance on training and conflict of interests • Educated the research community • “Check-in” process established every three years when continuing review not required • Revising automatic reminders in IRB application and reporting system

10. Collaborative Efforts with Continuing Review • TIP: Follow your IRB’s policy regarding frequency of continuing review. • TIP: Ensure annual review is conducted for grandfathered research approved under the previous version of the Common Rule. • TIP: Follow your institutional policies for conflict of interest disclosures and training requirements, as they may no longer be annually reviewed by the IRB.

11. NIH* and Common Rule: Single IRB Review Requirements • NIH: Multi-center studies require Single IRB (sIRB) approval if funded by the NIH (effective 1/25/18) • COMMON RULE: sIRB review will be required for federally funded multi-site studies (Cooperative Research) approved by an IRB on or after 1/20/20 • *NIH = National Institutes of Health

12. Collaborative Efforts with Single IRB Review • Created an “Application for External IRB Oversight” • Establish IRB Reliance Agreements • Pre-Awards may negotiate agreements with preferred IRBs • Downstate IRB: • confirms local research context • can require amendments for external IRB approval • acknowledges external IRB approval • has additional reporting requirements of local investigators

13. Latest FDA, NIH, and Common Rule Clinical Trial Requirements • Responsible Party must register and report findings of Applicable Clinical Trials on www.ClinicalTrials.gov • Post the IRB-approved informed consent form on Federal Web site after the clinical trial is closed to recruitment and no later than 60 days after the last study visit, if study is Federally supported or conducted.

14. Collaborative Efforts with Clinical Trial Requirements • Reminders added to IRB application forms • Pre-Awards manages the Protocol Registration and Results System (PRS) for www.ClinicalTrials.gov • ClinicalTrials.gov Identifier (NCT #) or anticipated registration date is required on IRB application • NCT# required for Downstate Clinical Trials website • Department or Colleges must pay fines • ($10k/day up to $250,000)

15. European Union (EU) General Data Protection Requirements (GDPR) – effective 5/25/2018 • GDPR is an EU data privacy regulation that may impact research conducted in the EU, research sponsored by an EU entity, or transmission of protected data within the EU or between the EU and the US • SUNY General Counsel has issued guidance on GDPR and intends to follow guidance issued by University College London: https://www.ucl.ac.uk/legal-services/ucl-general-data-protection-regulation-gdpr/guidance-notices-ucl-staff

16. Collaborative Efforts with EU-GDPR • Pre-Awards and/or IRB notify all groups of potential GDPR study, including: IRB, Pre-Awards, Data Security Officer, Privacy Officer, and General Counsel • All groups review requirements to determine if we can comply with the study. • Privacy Officer helps with informed consent disclosures • General Counsel provides advice as needed

17. Part 2: Preparing for the Changing Landscape of Clinical Trials • MaryLou Watson, Director of Clinical Research Initiatives, Upstate Medical Center • Kim Brunton, Associate Operational Director, University at Buffalo • Pamela Anderson, Associate Operational Director, University at Buffalo

18. Where SUNY Stands Today Clinical Trial Expenditures – FY 2017 * * Source: NSF Higher Education Research & Development (HERD) Survey

19. The Changing Landscape The Estimated Cost of Bringing a Drug to Market In 2003 $802 million In 2016 $2.6 billion Source: https://www.igeahub.com/2018/08/28/evaluation-of-clinical-trial-costs-and-barriers-to-drug-development/ Source: The Tuft Center for the Study of Drug Development

20. The Changing Landscape 12 years The average time of bringing a drug to market 1 in 5,000 Drugs that enter pre-clinical testing progress to FDA approval Source: https://www.medicinenet.com/script/main/art.asp?articlekey=9877

21. Key Challenges of Clinical Trials • High costs of clinical trials • Lengthy timelines • Difficulties in recruitment of participants • Data collection and analytics • Complexity in maintaining and monitoring safety Source: https://www.igeahub.com/2018/08/28/evaluation-of-clinical-trial-costs-and-barriers-to-drug-development/

22. SUNY Clinical Trials Institute UB, Upstate, Downstate, Stony Brook, Optometry, Binghamton Speed Scale Scope Savings Standardization More competitive and more value as a network

23. SUNY Clinical Trials Institute Network Node 2 More competitive and more value as a SUNY network Node 3 Node 1 Center Hub Node 5 Node 4

24. The Lifecycle of an Industry Sponsored Clinical Trial

26. The Beginning: Initial Contact • Market Dynamics are Changing…Industry and Governmental Change is forcing Adaptation • Industry will not work with underperforming Academic Medical Centers and Sites • Must deliver enrollment numbers • Must activate quickly • Must utilize a central IRB • Industry trend R&D $$$ spend is shifting to Oncology, CNS and rare disease • Do you have a plan in place for this trend?

27. Understanding What defines a High Performing PI/Site

28. What is an Institution Performance Score?

29. Practices of High Performing Clinical Research Sites • Invest in Infrastructure • Hire Research Staff with Strong Management and Interpersonal Skills • Use Data and Information to Support Research Activities • *****Feasibility***** • Be Open to Collaboration, New Ideas and Opportunities • Don’t Overpromise • Recognize that your site is part of a larger team

30. True or False??? We need the Sponsor more than they Need Us???

31. True or False??? • A Phase III, multicenter, IND clinical trial may require an aggregate of 5000 project management hours to complete subject recruitment. • That is roughly $250,000/month or $62,500/week until target enrollment is reached… • Source: Kelly Willenberg LLC, 2019

32. Study Preparation: You were site selected, now what?? • The email that starts it all- • Receipt of Regulatory Packet from Sponsor: • Draft Budget & Contract • Protocol, draft consent and support documents • Regulatory Binder documents

33. Study Preparation: Contract and Budget Contract: must be entered into PACS/CLICK Agreements module for negotiation of terms Budget: the ‘who’ that will be negotiating may differ at each campus

34. Study Preparation: Protocol, Draft Consent, Support Documents • Elements of the IRB Submission must be prepared by study staff • The protocol, Investigator Brochure or Instructions For Use documentation, IND/IDE documents are not altered by site staff • Must be entered into PACS/CLICKIRB module for review of Human Subjects Protection

35. Study Preparation: Regulatory BinderDocuments The Regulatory Binder is one of the most important elements in Industry –Sponsored Research and must be maintained throughout the life of the trial. It contains: FDA Form 1572, (or Investigator Statements), IRB roster, submissions, communications and approvals, delegation of authority logs, training logs, medical licenses and signed CVs for each study member, sponsor-site correspondence, the protocol and approved consent, laboratory manual, laboratory certification, director’s signed CV/license, and normal ranges, Pharmacy manual and accountability logs, Investigator Brochure or IFU documents, safety reports …….

36. Study Preparation: Additional Elements • Laboratory requirements • Pharmacy requirements • Imaging needs • Hospital billing/finance involvement • Submission to PACS/CLICK Grants module for award set up • Attendance at Investigator Meeting • Site Initiation Visit • CTMS study build

37. Study Preparation: Complete • Signed contract/budget • IRB Approval • CTMS Build • Site-Initiation Visit • Drug or Device receipt • Regulatory document completion and submission to sponsor • All personnel lined up, documented, trained and ready to go

38. Study Activity • Who is doing what? • Is there a process in place at your campus for how industry supported clinical trials are managed?

39. Study Activity (cont.) The money just comes in right?

40. Study Activity (cont.) • Vendor payments radiology services, lab services, currier services • How are these visits or procedures confirmed?

41. Not a One and Done • Throughout the study Communication, Cooperation and Coordination between site and SPS is imperative in order to ensure we are capturing all our fees

42. Study Closure • Who is responsible for reconciling account? • Compare the budget with funds received • Final invoicing Don’t leave money on the table!

43. September X , 2018