1. IRB Applications and Proposals:
The Basics
Jessica Klusener, MHA, CCRP

2. UCSF Fresno Building, Suite 290
IRB Office Staff
UCSF Fresno Building, Suite 290
Jessica Klusener
Jackie Denmon
Veronica Bath
Anabel Jayme

3. Objectives What is an Institutional Review Board (IRB)?
Importance of Study Ethics in Research
The CMC IRB
CyberIRB

4. INSTITUTIONAL REVIEW BOARD
Hospital committee which reviews ALL Research Proposals
Charged with the protection of human subjects in research
Examine the potential risks and benefits to subjects
Recommend modifications to ensure safety to subjects

6. U.S. RESEARCH IS OVERSEEN BY:
Office for Human Research Protections (OHRP)
Food and Drug Administration (FDA)
California Dept. of Health
Institutional Policies

7. Foundation for Ethical Principles in Conducting Research
The Belmont Report
Foundation for Ethical Principles in Conducting Research
Respect for Persons
Autonomy
Beneficence
Benefits outweigh Risks
Justice
Participants share risks/benefits

8. WHY STUDY ETHICS IN RESEARCH?

9. Cleopatra Testing Poisons on Condemned Prisoners (69-30 B. C. )
Cleopatra Testing Poisons on Condemned Prisoners (69-30 B.C.) Artist: Alexandre Cabanel

10. 1947 WWII NAZI WAR CRIMES
Concentration Camp prisoners were experimented upon in the name of “scientific research”
Injected with live viruses
Forcible ingestion of poisons
Immersed in ice water

11. Nuremberg Code Voluntary human consent is essential
Experimental results should result in good for society
Anticipated results should justify the experiment
Avoid all unnecessary physical and mental suffering
No experiment if there is a chance of death/disability
Minimize risk of subjects
Proper preparations and facilities to protect subjects
Experiments conducted only by qualified persons
Subjects can withdraw at anytime
Terminate experiment if results are known or with best judgement

12. Tuskeegee Syphilis Study
1930’s – 1972 – Funded by Public Health Service
African American males with syphilis enrolled so researchers could study the natural history of the disease
Penicillin found to be effective in 1940’s but subjects neither informed, nor treated

13. Fernald Developmental Center
Joint experiments by Harvard University & MIT
Absorption of calcium and iron
Exposed young male children to tracer doses of radioactive isotopes
Boys encouraged to join a “Science Club”
Given large portions of food, parties, and trips to baseball games
Neither children nor parents gave adequate informed consent

14. May 1953 Dear Parent, In previous years we have done some examinations in connection with the nutritional department of the Massachusetts Institute of Technology, with the purposes of helping to improve the nutrition of our children and to help them in general more efficiently than before. For the checking up of the children, we occasionally need to take some blood samples, which are then analyzed. The blood samples are taken after one test meal which consists of a special breakfast containing a certain amount of calcium. We have asked for volunteers to give a sample of blood once a month for 3 months, and your son has agreed to volunteer because the boys who belong to the Science Club have many additional privileges. They get a quart of milk daily during that time, and are taken to a baseball game, to the beach and to some outside dinners, and they enjoy it greatly. I hope that you have no objection that your son is voluntarily participating in this study. The first study will start on Monday, June 8th, and if you have not expressed any objections, we will assume that your son may participate. Sincerely yours, Clemens E. Benda, MD, Clinical Director Malcolm J. Farrell, MD, Superintendent

15. POINTS TO REMEMBER
Investigators bear the ultimate responsibility for their work with human subjects
Society entrusts them with the privilege of using other humans to advance scientific knowledge
Compliance with regulations should be seen as “the right thing to do” because it helps protect the rights and welfare of subjects

16. Community Medical Centers Institutional Review Board
The Board
CMC IRB Chairman – Dr. Robert Libke
CMC IRB Director – Jennifer Trytten, PharmD
Alan Rosa, MBA/HCM
14 Members
Meet 1st Thursday of Every Month
CMC IRB Approval Required
Studies Involving:
CMC Facilities (including CCFMG)
CMC Patients
CMC Patient Data
CMC IRB provides regulatory oversight for 310+ studies

17. 3 Levels of IRB Review
-Determined by level of risk- Exempt Studies- involve Minimal Risk Expedited Studies – involve Minimal Risk Full Board – involve Greater than Minimal Risk

18. EXEMPT RESEARCH Minimal Risk 6 possible categories
Requires IRB oversight
Renewal is every 3 years

19. EXEMPT RESEARCH Examples include:
Surveys of adults without identifiers
Collection of existing data if information is recorded in a manner that subjects can’t be identified, directly or indirectly through links

20. EXPEDITED RESEARCH
Minimal Risk The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests
9 possible categories
Requires IRB approval
Renewal is every year or sooner if required by IRB

21. EXPEDITED RESEARCH
Research on drugs for which an investigational new drug application is not required
Collection of blood considering age, weight and health of subject
Collection of biological specimens by noninvasive means – hair, nail clippings, teeth, sweat, saliva, placenta, mucosal & skin cells
Collection of data through non-invasive procedures (not involving anesthesia or sedation) and excluding x-rays

22. EXPEDITED RESEARCH
5. Materials that have been collected, or will be collected solely for non-research purposes 6. Collection of data from voice, video, digital, or image recordings made for research purposes 7. Research on characteristics or behavior, or employing survey, or interviews

23. Minimal Risk Study: Retrospective Chart Review
Injuries Due to Falling Coconuts Barss, P, Journal of Trauma Nov;24(11):990-1.
A 4-year review of trauma admissions to the Provincial Hospital, Alotau, Milne Bay Province, Papua New Guinea, revealed that 2.5% of such admissions were due to being struck by falling coconuts.

24. Full Board Studies Greater than minimal risk Requires IRB approval
Renewal is every year or sooner if required by the IRB
Application materials are due the 10th of the month prior to the scheduled meeting
New study presentation times are limited

25. Full Board Studies The use of non-FDA approved drugs/devices
The “off-label” use of FDA- approved drugs
Example:
The use of Metformin in
teens with borderline Hgb A1c

26. Ice Cream Evoked Headaches (ICE­H) Study: Randomized Trial of Accelerated versus Cautious Ice Cream Eating Regimen
Maya Kaczorowski, Janusz Kaczorowski
Group 1: Given 100 ml of ice cream and were told to eat it in >30 seconds
Group 2: Given 100 ml of ice cream but were instructed to eat it in <5 seconds

27. What must the Board determine?
The proposed research design is scientifically sound & will not unnecessarily expose subjects to risk
Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of knowledge that may reasonably be expected to result.
Subject selection is equitable.

28. What must the Board determine? (cont.)
4. Additional safeguards required for subjects likely to be vulnerable to coercion or undue influence Informed consent is obtained from research subjects or their legally authorized representative(s) Risks to subjects are minimized Subject privacy & confidentiality are maximized.

29. Who may serve as a Principal Investigator? - Faculty
Fellows
Note to Residents: Have a mentor review your study proposal prior to submission to the IRB.

30. Training in the Protection of Human Subjects (Required for all investigators & study staff)
Web-based training
Required for ALL those involved in research
IRB needs a copy of the Completion Certificate for each member of the study team (if not already on file)
Certification must be renewed every three years – takes approx. 10 minutes to renew

32. Where to Start?

33. The Study Proposal
Your study proposal should include the following components:
Summary
Hypothesis
Specific Aims
Background and Significance
Design of Study
Statistical Analysis
Sample Size
Confidentiality and Privacy
Data Security
References

34. Proposal Elements
Study Title Should be Descriptive: Vancomycin Induced Nephrotoxicity in Children vs. A Retrospective Review of Incidence and Risk Factors of Vancomycin Induced Nephrotoxicity in Children

35. CyberIRB
All IRB submissions to the CMC IRB will be completed through the electronic submission software CyberIRB
Went Live March 27, 2017
Changes in the submission process:
Only 1 application for Initial Review regardless of review type
No need to any attachments to
All correspondence regarding a submission is done in CyberIRB
Investigators will be able to view status of a submission in CyberIRB
Study Modification Form will be the Post Approval Form
Please be aware that CyberIRB has built-in hard-stops, therefore incomplete submission will be automatically returned to Investigators.

36. Submitting to CyberIRB
Log into CyberIRB:
First time logging into CyberIRB:
Contact your study coordinator for your username and password
No study coordinator - contact the IRB Office

37. CyberIRB

38. CYBERIRB
You will be able to submit new exempt, expedited, and full board study submissions by selecting Application for Initial Review

39. CYBERIRB Make sure to send Application to the PI for Signature
The IRB Office will receive the submission once the application is verified and electronically signed by the PI

40. Be sure to attach these documents with your submission in CyberIRB, as applicable:
Study Diaries
Data Collection Forms
Delegation of Authority Log
Recruitment Materials
Screening/Enrollment Logs
- Area Director Agreement form Financial disclosure form for ALL investigators
and study staff HIPAA waiver request paperwork
- CVs and CITI Completion Certificate
- Study Budget
FDA Form 1572

41. RESEARCH MAY NOT BE CONDUCTED WITHOUT FINAL WRITTEN APPROVAL FROM THE IRB

43. Common Problems with Research Studies
Improper consenting process
Unapproved changes to protocol or consent forms
Unintended deviation from protocol
Enrollment of ineligible subjects
Unapproved study advertisements/patient materials
Implementation of study modification without IRB approval
Unapproved study staff working on study
Avoid these problems.
Schedule a Start-Up Consultation by calling the IRB Office at

45. Adverse Events and Incident Reports
Deviations sometimes happen in research
Submit deviations or adverse events to the IRB by completing the Adverse Event & Incident Reporting Form within regulatory timeframe for event
Implement Corrective Actions
Implement Preventative Actions
Call the IRB Office at
if you need assistance with incident reporting.

46. Study Modifications
Use the Post Approval Form to make changes to IRB- approved studies
Examples:
Add study staff
Increase the sample size
Change study time period
Change study visit window
Add materials (study diary, patient info sheet, recruitment material)
Changes to the informed consent or protocol
Be sure to include all supporting materials, as applicable (CVs and CITI completion certificate, new protocol highlighting changes, etc.)
You must receive an IRB approval letter before changes can be implemented

47. CONTINUING REVIEW
Submit Continuing Review through CyberIRB by completing the Study Renewal/Closure
For Expedited and Full Board studies, approval is granted for a maximum of 365 days
A study must be renewed annually even if the data collection phase has ended
It is the Investigator’s responsibility to ensure there is no lapse in study approval

48. CONTINUING REVIEW All study activities must stop if a study expires
CMC IRB will administratively retire studies that expire
Repeated instances of administrative study retirements may result in Continuing Non- Compliance
OHRP has regulations regarding reporting requirements for Continuing Non-Compliance

49. Study Closures Only close your study once it has been completed
You can close your study by completing the Study Renewal/Closure form on CyberIRB
Please submit any publications or presentation slides for your study as attachments to the form on CyberIRB. The Board enjoys learning about the outcome of the studies they approve!

50. Changes Coming Soon to an IRB Near You
Revised Common Rule
OHRP regulations are changing
FDA regulations are not changing
Compliance date of January 21, 2019
Changes to Exempt Categories
Changes to Informed Consent Requirements
Continuing Review  Annual Status Report
Initial Review Application in CyberIRB will be inaccessible from December 1, 2018 to January 21, 2019
In the meantime, work on:
Study Protocol, Consents, & Supporting Docs

51. Changes Coming Soon to an IRB Near You
New Methods to Search for Data – Important to remain compliant with new technologies and applications
Remember: Just because you can access a patient record, does not mean you should be in that record or using it for research purposes
Must obtain IRB approval before looking at any patient data
Accounting of Disclosures Process and Compound Authorization
IRB Routine Reviews of Study Documentation

52. IRB

53. Are You Ready for A Routine Review of Study Documentation?

54. Questions?