WHAT IS AN IRB AND WHY SHOULD I CARE?

BETH TARABAN

RESEARCH INTEGRITY OFFICE

IRB--DEFINITION

An Institutional Review Board is a committee whose primary responsibility is to protect rights and welfare of human research participants.

IRB review is required for all federally-funded research involving human participants. The procedures for research review are set out in the Code of Federal Regulations (CFR).

IRB DEFINITION--CONTINUED

Most institutions (including TTUHSC) have elected to abide by the CFR regulations for human research review even for research that is not federally funded.

The FDA also requires IRB review and approval of research for any research involving a drug, a biologic or a medical device.

FEDERAL REGULATIONS--GENERAL

Biomedical IRBs are regulated by two groups:

Department of Health & Human Services (DHHS)—Office of Human Research Protection (OHRP)

DHHS rules for IRBs can be found in 45 CFR 46 and subparts B,C, and D which offer special protections for pregnant women, fetuses/neonates, prisoners and children

And by the Food and Drug Administration (FDA) FDA rules can be found in 21 CFR 50 and 21

CFR 56

THE “COMMON RULE” (45 CFR 46) The Common Rule is a federal policy regarding Human subjects Protection that applies to 17 Federal agencies and offices that have signed the agreement and is enforced by OHRP

The main elements of the Common rule include requirements for:1. Assuring compliance by research institutions2. Researchers’ obtaining and documenting informed consent 3. Institutional Review Board (IRB) membership, function,

operations, review of research, and record keeping

The Common Rule includes additional protections for certain vulnerable research subjects

• Subpart B-Pregnant women and fetuses• Subpart C- Prisoners• Subpart D- children

FEDERAL REGULATIONS--CONTINUED

Failure to follow either the DHHS regulations or the FDA regulations can result in penalties for individual researchers and for the institutions themselves—a single rogue researcher can halt ALL HUMAN RESEARCH at an institution!

WHAT IS RESEARCH?

Research is defined as any systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.

Source: 45 CFR 46.102(2)

WHAT IS HUMAN RESEARCH

Human subjects are defined as living individuals about whom an investigator conducting research obtains

1) Data through intervention or interaction with the individual or

2) Identifiable private information

Source: 45 CFR 46.102(f)

SO, IS THIS RESEARCH OR NOT??

When in doubt, Contact your local IRB AdministratorLubbock—Karen Douglas—806-743-

4753Amarillo—Kathy Thomas—806-354-5419

OR

Check the very cool decision trees at the OHRP website:

http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html

OK, IT’S HUMAN RESEARCH, I NEED IRB APPROVAL. NOW WHAT?

Training requirements for ALL study personnel involved in human research at TTUHSC :

CITI Biomedical Investigator Course

(13 modules) Retraining required every 3 years

CITI Financial Conflicts of Interest Course

(2 modules) Retraining required every 4 years

www.citiprogram.org

I FINISHED CITI. NOW CAN I SUBMIT MY PROJECT? Not yet. First, you need to get access to

the iRIS program—this is an internet based program through which all communication TO and FROM the IRB takes place.

Obtain iRIS access by clicking the “Request a New Account” button at the iRIS website: www.sobmrimedris.ttuhsc.edu

Training specific to using iRIS can be arranged through the IRB office.

A LITTLE MORE ON CITI

Registering at www.citiprogram.org is pretty simple.

However, if you would like step-by-step instructions, with pictures, you can find answers at the CITI Support Center.

Here is the link to the “How do I enroll in a CITI course for the first time?” instructions (updated 1/24/14)

http://citiprogram.desk.com/customer/portal/articles/163300-how-do-i-enroll-in-a-citi-course-for-the-first-time-

I HAVE CITI AND IRIS.

Can I send my study for IRB review NOW?

Almost! You are SO CLOSE! Do you have an up-to-date financial disclosure form on file?

YES, goshdarnit—and believe me, that’s not the word I was really thinking!!

OK. You can submit your research project for IRB review now.

IRB COMPOSITION

Federal regulations govern IRB composition:

At least 5 membersAt least one “scientist” memberAt least one “non-scientist” memberAt least one member who is otherwise

unaffiliated with the institutionAt least one member who is considered a

“participant advocate.” Diversity regarding gender, background, etc. to

represent the types of research reviewed

TTUHSC IRB COMPOSITION

TTUHSC has 2 IRBs (Lubbock/Odessa/Midland and Amarillo/Dallas/Abilene)

Most IRB members are TTUHSC facultyThe members spend, on average 4-6

hours per month preparing for and attending the IRB meeting

Current list of members available on IRB website: www.ttuhsc.edu/research/hrpo/IRB

IRB REGULATIONS—RESEARCH APPROVAL• Risks to subjects are minimized• Risks are reasonable in relation to potential

benefits• Selection of subjects is equitable• Informed consent will be sought and

documented for each subject• Ongoing monitoring will occur to ensure

subject safety • Adequate provisions exist to protect privacy• Special safeguards are in place for

vulnerable subjects

WHAT IS THE IRB LOOKING FOR?

TTUHSC IRB reviewers are looking for:

1) Protection of subject safety and well- being)

1a) Scientific validity of the research project

1b) Qualification of investigators to conduct research

1c) Adherence with federal regulations and TTUHSC policies.

TYPES OF IRB REVIEW

Exempt projects

Expedited Full Board review

IRB REVIEW--EXEMPT PROJECTS

Exempt studies are “exempt” from the federal regulations Generally, these are:

a) studies that are done as part of normal classroom procedures for which you don’t collect any identifying information

b) surveys or questionnaires of adults in which you don’t get any identifying information and don’t ask any sensitive questions or

c) retrospective research in which all of the data are already in existence and you won’t be recording any identifying information.

A-HA! MY STUDY IS EXEMPT FROM IRB REVIEW, SO I DON’T HAVE TO SUBMIT ANYTHING TO YOU, RIGHT?

~~WRONG~~

The federal regulations say that the investigator can not be the one to decide if a project is exempt.

TTUHSC has decided that the IRBs will make that decision.

SUBMITTING AN EXEMPT STUDYIf it’s a retrospective chart review, you need to

submit:

Your IRB application

Your protocol

Be sure in your protocol to clearly state the following two things:

1) The data are all in existence AS OF THE DATE of the IRB application. Often people will say something like, “Medical records dated 1/1/2003 through 12/31/2013 will be examined” The important part is that the end date is from a time BEFORE your submit your IRB application

2) You will not be recording any identifiable information—this includes DATES associated with the patient

Your data collection sheet

A HIPAA Waiver of Authorization form (allows you access to medical records for research purposes)

SUBMITTING AN EXEMPT STUDY--CONTINUEDIf it’s an anonymous survey, you need to

submit:Your IRB applicationYour protocolYour survey (or a link to the survey if it’s

web-based)Any flyers or letters that you’ll be using to

recruit respondents

MY STUDY ISN’T EXEMPT—WHAT ELSE COULD IT BE?

Your study might meet criteria to be expedited. This means that the study can be reviewed by one or two experienced IRB reviewers and you don’t have to worry about deadlines or meeting dates.

Expedited studies are always minimal risk

studies--no investigational drugs, no protected populations, no very sick people and no highly sensitive procedures.

EXPEDITED REVIEWS

Note that an “expedited” review doesn’t necessarily mean a “quick” review. Regulations require that an expedited review be given the same scrutiny that a submission to the full board would receive.

An expedited reviewer can APPROVE or REQUIRE MODIFICATIONS to a study but can not disapprove a study.

MY STUDY IS NEITHER EXEMPT OR EXPEDITED

In this case, your study will require Full Board review. You will need to submit all required materials by the deadline date. You can find all IRB deadline dates and IRB meeting dates on the TTUHSC IRB website: www.ttuhsc.edu/research/hrpo/irb.

The Full Board reviews proposed research that is greater than minimal risk, uses vulnerable populations, has any unapproved drugs or devices, deception of subjects, surveys with sensitive questions or any other project that doesn’t quite meet the definition for expedited review.

SUBMISSION REQUIREMENTS FOR A FULL BOARD REVIEW:

Complete IRB application formProtocolInformed consent and HIPAA Authorization formRecruiting materialsLetters of support from collaborating sitesData collection formsGrant applicationsAll surveys, questionnaires, videotapes, etc.

For investigational drug or device studies, we also needIND or IDE number from the FDAInvestigator’s brochureDocumentation of approval by other committees (Radiation

Safety; Institutional Biohazard Committee; Conflict of Interest Committee)

IRB REVIEW—FULL BOARDTwo (or more) reviewers will be assigned to read and

review all of the materials you’ve submitted. Prior to the meeting, the PRIMARY reviewer will write an objective summary of your project and both reviewers will add a subjective review of the project

All of the other IRB members will have access to the materials in iRIS and they, too, can add information (subjective or objective) to the review.

At the IRB meeting, the primary and secondary reviewers will present the study along with their recommendations about what should happen to the study.

Principal investigators may ask or be asked to attend the IRB meeting at which their study is presented.

FULL BOARD REVIEW--CONTINUED

The members will discuss the study and then vote on it. The Board can vote to:

APPROVE the study as it isREQUEST ADDITIONAL INFORMATION prior to approval

orDISAPPROVE the study. You will receive an e-mail through iRIS, usually within

24 hours of the IRB meeting, telling you the outcome of the review.

If the Board requests additional information, the email will provide detailed STIPULATIONS—things that need to be addressed prior to approval. You have 30 days to respond to the stipulations.

FULL BOARD REVIEW--CONTINUED

If the Board disapproves the study, you will be provided written notification of the reason for the disapproval. You can request reconsideration within 10 days of receiving the notice. If, after reconsideration, the Board still disapproves the project there will be no further activity—TTUHSC officials can not approve research that has been disapproved by the IRB (45 CFR 46.112)

THEY ASKED FOR ADDITIONAL INFORMATION AND I ANSWERED THEM—NOW WHAT?

Depending on how many stipulations you had and the nature of the stipulations, either one IRB member or the Full Board will review your responses. If everything has been adequately addressed, your informed consent and HIPAA documents will be stamped and you will get an official Approval Letter from the IRB.

Once you have that approval letter in your hand (AND NOT BEFORE!!) you are ready to start your study.

USING PHI IN RESEARCH

Protected health information (PHI) is any information, including demographic information, that is transmitted or maintained in any medium (electronically, on paper, or via the spoken word) that is created or received by a health care provider…that relates to or describes the past, present, or future physical or mental health or condition of an individual… and that can be used to identify the individual.

IDENTIFIABLE PHINamesMedical Record NumbersGeographic subdivisions smaller than a State Dates (except year) directly related to an individual including

Date of birthAdmission date, discharge date, date of deathAll ages over 89, including dates and year

Telephone numbers, fax numbers, E-mail addresses, internet URLs, IP addressesSocial security numbers

Account numbers, Certificate/license numbersLicense plate numbers/VIN numbersDevice identifiers and serial numbers, Finger and voice prints, Full face photographic images and any comparable imagesAny other unique identifying number, characteristic, or code

SO, WHAT DO I HAVE TO DO?

If you need PHI to do your research (and most biomedical research does), you MUST do one of two things:

1 Obtain written authorization from your potential participants allowing you to access their medical record for research purposes. Can generally be done as part of the informed consent process

Or

2) Ask for (and be approved for) a WAIVER OF AUTHORIZATION.

You must attest that:

• there is minimal risk to the privacy of the research participants (generally because you will not be recording any personally identifiable information);

• you will not reuse or disclose any of the PHI that you access;

• the research could not practicably be conducted without access to PHI; and

• the research could not practicably be conducted without the waiver of authorization.

ANYTHING ELSE?

If you want to make ANY CHANGES* to your study from what the IRB originally approved, you must submit a Change/Request Amendment to the IRB (through iRIS). You can’t actually make the change until you get the amendment approved.

* Yes, we do mean ANY changes—changes in study personnel, changes in methodology, changes in where data are stored, ANYTHING that is different from what you originally said in the protocol.

ANYTHING ELSE—PART 2

The IRB also wants to know about any* unexpected events—anything that didn’t go according to plan

The IRB requires ongoing progress reports. The IRB will determine the frequency, but regulations require continuing review at least once every 365 days.

* Yes, ANY…no unexpected event is too minor…

ANYTHING ELSE—PART 3Clinical Trial Registration:

If you are conducting a clinical trial, the project MUST be registered at ClinicalTrials.gov prior to enrolling your first subject.  

Also, the FDA mandates specific language in the consent document regarding ClinicalTrials.gov registration.

For more information, see http://prsinfo.clinicaltrials.gov; or

www.icmje.org/clintrialup.htm or www.fda.gov/cder/guidance/4856fnl.htm 

ANYTHING ELSE—PART 4

Unanticipated events that occur during the study need to be reported to the IRB—PROMPTLY.

Unanticipated event types:

1)Protocol deviations (affect one participant—don’t increase risk of study)

2) Unanticipated Problems Involving Risks to Subjects or Others (Affect the conduct of the study more generally—bigger deal)

3) Serious Adverse Events (defined elsewhere)

4) Unanticipated Adverse Device Effects

IS THIS ALL REALLY AS COMPLICATED AS IT SOUNDS?Nah, not at all. The Office of Research and

IRB really DO want to help you get your research done. Come and talk to us.

OR Check the IRB website:

www.ttuhsc.edu/research/hrpo/irbOR

Check the OHRP website: http://www.hhs.gov/ohrp

TO SUMMARIZE:

If you are going to do research with people, an IRB will be involved.

You will ALWAYS be better off asking

questions first.

The primary goal is always protection of participants, but institutional, state and federal policies and regulations also have to be followed.