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

UCSF Fresno Building, Suite 290 IRB Office Staff UCSF Fresno Building, Suite 290 Jessica Klusener 559-499-6553 Jackie Denmon 559-253-3251 Veronica Bath 559-499-6651 Anabel Jayme 559-499-6552

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

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

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

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

WHY STUDY ETHICS IN RESEARCH?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Minimal Risk Study: Retrospective Chart Review Injuries Due to Falling Coconuts Barss, P, Journal of Trauma. 1984 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.

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

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

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

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.

What must the Board determine? (cont.) 4. Additional safeguards required for subjects likely to be vulnerable to coercion or undue influence. 5. Informed consent is obtained from research subjects or their legally authorized representative(s). 6. Risks to subjects are minimized. 7. Subject privacy & confidentiality are maximized.

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.

Training in the Protection of Human Subjects (Required for all investigators & study staff) Web-based training Required for ALL those involved in research www.CITIprogram.org 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

Where to Start?

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

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

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 email any attachments to IRB@communitymedical.org 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.

Submitting to CyberIRB Log into CyberIRB: http://www.cyberirb.us/cmc  First time logging into CyberIRB: Contact your study coordinator for your username and password No study coordinator - contact the IRB Office

CyberIRB

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

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

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

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

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 499-6553.

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 499-6553 if you need assistance with incident reporting.

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

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

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

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!

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

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

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