1. Human Research Protection Program Training Preparing a Full Committee Application Richard Wagner Associate Director, HRPP Richard.Wagner@ucsf.edu 415-476-1172 January 29, 2009

2. Human Research Protection Program 2 HRPP Training: Upcoming Sessions Preparing an Expedited or Exempt Application –Friday, February 20, 1:30-3:30 p.m., N-225 –Lisa Voss, Assistant Director The Study Coordinator’s Role in Investigator- originated Studies –March 2009 –Diane Davies RN, Manager, Clinical Research Unit, Helen Diller Family Comprehensive Cancer Center CHR Introductory Training –Spring 2009 –Presenter TBD Introduction

3. Human Research Protection Program 3 HRPP Website

4. Human Research Protection Program 4 Change Is Coming New On-Line (iMedRIS) CHR Application –Expected to be fully implemented before the end of 2009 –A single application process with branching questions –Based on current applications, but with simplified questions –New database/document manager –More information about progress of the application will be available on line At present, you must use the current application form and supplements (Downloaded from CHR website, filled out on your computer, submitted in hard copy)

5. Human Research Protection Program 5 Outline for Today Demystifying the CHR review process The Full Committee Application Getting Answers After this Class Open Questions and Answers Introduction

6. Human Research Protection Program 6 HRPP Organization Demystifying the CHR Review Process

7. Human Research Protection Program 7 Where does the application go? Assessment/Screening   Review by Full Board   Post-Review Correspondence   Approval Demystifying the CHR Review Process

8. Human Research Protection Program 8 What do CHR members consider when reviewing a new study? Risks to subjects are minimized –Procedures are consistent with sound research design and do not unnecessarily expose subjects to risk. –Study utilizes procedures already performed for diagnosis/treatment. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result. Selection of subjects is equitable –Inclusion/Exclusion criteria are adequate –Research purpose and setting is appropriate –Recruitment process is fair Demystifying the CHR Review Process

9. Human Research Protection Program 9 What do CHR members consider when reviewing a new study? Informed consent will be sought in accordance with 45 CFR 46.116 Informed consent will be documented in accordance with 45 CFR 46.117 Provisions for monitoring collected data are adequate to ensure the safety of subjects Provisions to protect privacy of subjects are adequate Provisions to maintain confidentiality of data are adequate Vulnerable populations are adequately protected by additional safeguards –Children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons Demystifying the CHR Review Process

10. Human Research Protection Program 10 Process FAQ How are studies assigned to CHR meeting agendas? How do I get more information about the review status of the study I submitted to CHR? Demystifying the CHR Review Process

11. Human Research Protection Program 11 Full Committee Application One application for clinical and behavioral research Research poses more than minimal risk, or Poses minimal risk but –Does not fit an expedited review category –Requires a full committee determination Demystifying the CHR Review Process

12. Human Research Protection Program 12 Minimal Risk Risk of daily life of a healthy individual Not relative risk Demystifying the CHR Review Process

13. Human Research Protection Program 13 The Full Committee Application PI, Co-PI, Contact Person Key Personnel Financial Interests Part 1: Administrative Requirements The Full Committee Application

14. Human Research Protection Program 14 The Full Committee Application Sites –VAMC –SFGH –CCRC’s Funding Scientific or Scholarly Review Part 1: Administrative Requirements The Full Committee Application

15. Human Research Protection Program 15 The Full Committee Application Drugs, Devices & Biologics –Include one copy of the Investigational Brochure –Document IND/IDE numbers –Is an IND/IDE needed? Part 1: Administrative Requirements The Full Committee Application

16. Human Research Protection Program 16 The Full Committee Application Synopsis vs. Design vs. Procedures Hypotheses Specific Aims Background vs. Preliminary Studies Part 2: Study Design The Full Committee Application

17. Human Research Protection Program 17 The Full Committee Application Differentiating between research and standard of care activities Identify any difference between local procedures and sponsor’s protocol Adding tables/charts Tissue Banking Part 3: Procedures The Full Committee Application

18. Human Research Protection Program 18 Full Committee Application Part 4: Alternatives Be sure to identify standard or usual care at UCSF Also identify other available alternatives Consent form must say if study drug or treatment is available off study

19. Human Research Protection Program 19 The Full Committee Application A. Risks and Discomforts 1. Description of risks 2. Steps to minimize risks –Reference to inclusion/exclusion criteria –Subject monitoring –Rules for withdrawing participants from study B. Data and Safety Monitoring Plan (DSMP) Part 5: Risks and Benefits The Full Committee Application

20. Human Research Protection Program 20 The Full Committee Application Explain the plan to monitor study progress and safety Describe who will perform the monitoring reviews and at what frequency Describe the type of data and events (i.e., efficacy data, adverse events, unanticipated problems involving risk to participants or others) reviewed under the monitoring plan. Part 5. B. Data Safety Monitoring Plan The Full Committee Application

21. Human Research Protection Program 21 The Full Committee Application How will results of monitoring reviews be communicated to the study sponsor and the CHR? As appropriate: Plan for conducting and reporting interim analyses Study stopping rules Part 5. B. Data Safety Monitoring Plan The Full Committee Application

22. Human Research Protection Program 22 When is a DSMB needed? Phase III Clinical Trials Phase II Clinical Trials when Randomized and blinded, or High Risk The Full Committee Application

23. Human Research Protection Program 23 More on Risks and Benefits Adequacy of Resources Confidentiality and Privacy Information Security Benefits Risk/Benefit Analysis The Full Committee Application

24. Human Research Protection Program 24 The Full Committee Application CHR Supplements Inclusion and Exclusion Criteria Be specific Explain differences from sponsor’s protocol Determining Eligibility Non-regulated vulnerable populations Part 6: Subject Information The Full Committee Application

25. Human Research Protection Program 25 The Full Committee Application Respect for privacy Lack of pressure Unbiased presentation The “Therapeutic Misconception” Be sure to include all pertinent details in Part 7.B. Part 7: Recruitment The Full Committee Application

26. Human Research Protection Program 26 The Full Committee Application How, Where, When and By Whom? Ensuring Understanding Waiver of Consent Supplement Part 8: Informed Consent The Full Committee Application

27. Human Research Protection Program 27 The Full Committee Application Payment of Subjects Costs to Subjects Part 9: Financial Considerations The Full Committee Application

28. Human Research Protection Program 28 Treatment and Compensation for Injury Three options: 1.Standard UC wording naming both UC and the sponsor 2.Standard UC wording naming only UC 3.Standard UC wording naming only UC, followed by a very limited statement about the sponsor’s policy The Full Committee Application

29. Human Research Protection Program 29 Attachments Consent and Assent forms Sponsor’s protocol Investigator’s brochure Survey instruments Recruitment and contact materials The Full Committee Application

30. Human Research Protection Program 30 CHR Supplements Inclusion of Children and Minors Human Biologic Specimen Collecting and/or Banking for Future Research IRB Approval Certification for UCSF Researchers Involving Non-UCSF Affiliated Sites Disclosure of Investigator’s Financial Interests Supplement Waiver of Informed Consent/Authorization for Minimal Risk Research or Screening The Full Committee Application

31. Human Research Protection Program 31 CHR Supplements (continued) Non-Significant Risk Determination for an Investigational Device Surrogate Consent Inclusion of Prisoners Human Gene Transfer / Recombinant DNA Research Supplement Human Stem Cell Research Emergency Medical Research Waiver of Informed Consent The Full Committee Application

32. Human Research Protection Program 32 Top Tips for Speeding Up Your CHR Approval Please see brochure available at this presentation. Brochure is also available at CHR website, Applying and Reporting to the CHR, Overview of Application Process, Top Tips for Speeding Up Your CHR Approval Top Tips for Speeding Up CHR Approval

33. Human Research Protection Program 33 Where to Go for Help Call the HRPP Office at 476-1814 –Explain your concern to the person who answers the phone –Specialists handle various areas such as renewals, modifications, and adverse event reporting –For complex problems, ask to speak to the Analyst of the Day. Visit the HRPP Website at www.research.ucsf.edu/chr/

34. Human Research Protection Program 34 More Resources CITI Training (Required Education for Key Personnel) https://www.citiprogram.org CTSI: Clinical and Translational Science Institute http://ctsi.ucsf.edu/ RKS: Regulatory Knowledge and Support http://ctsi.ucsf.edu/rks/request/ Marlene Berro –Marlene.Berro@ucsf.edu; 476-3426Marlene.Berro@ucsf.edu BREAD: Biostatistics, Research Ethics and Design Program CtsiBread@ucsfmedctr.org, 502-7893CtsiBread@ucsfmedctr.org Open Questions and Answers