Andy Bertolatus MD2/22/10

Preparing an IRB Application

Learning Objectives Know when an IRB application needs to be

submitted Understand the workflow of IRB

applications through the Human Subjects Office (HSO)

Understand criteria for IRB approval

Institutional Review Boards (IRBs) Mandated by federal research regulations

DHHS and 19 other federal agencies (“the Common Rule”) – NIH, VA

FDA The federal regulations apply:

If there is federal funding If the research is FDA regulated, or Your institution has decided to apply some or

all of the rules to all research (which is true at Iowa and most major research universities)

When to submit an IRB application Whenever you are doing “human subjects

research” (HSR) as defined in the federal (DHHS and FDA) regulations, you need IRB approval

If you have any doubt about a particular undertaking, call the HSO and speak to the staff or one of the chairs

The decision about whether something is, or is not, HSR should generally be made by an IRB person, not the investigator

At the University of Iowa, “Human Subjects Research” is defined as an activity that either:

Meets the DHHS definition of “research” and involves “human subjects” as defined by the DHHS regulations; OR

Meets the FDA definition of “research” and involves “human subjects” as defined by FDA regulations.

DHHS regulations define research as a systematic

investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Intent to publish or present results often used

as an “indicator” of research

FDA regulations define research as any experiment that involves a

test article and one or more human subjects A test article means any drug (including a

biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the Federal Food, Drug & Cosmetic Act

an experiment is any use of a drug (or device) except for the use of a marketed drug in the course of medical practice. Note: not limited to use of investigational drugs

Human subject DHHS regulations define a human subject

as a living individual about whom an investigator (whether professional or student) conducting research obtains either: (a) data through intervention or interaction

with the individual, OR (b) identifiable private information.

So, we conclude from this that:

Human subjects research, cont’d Research on the dead not subject to the

Common Rule regulations Research on medical records IS subject to

the regulations (identifiable private information)

Research on data or samples which are not identified MAY NOT be subject to the regulations

Human Subject FDA regulations define human subject as

an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient. For research involving medical devices, a human subject is also an individual on whose specimen an investigational device is used.

Examples of some things that may not be human subjects research Research on cadavers or autopsy

materials Research on data and/or samples which

are provided to an investigator as truly “deidentified” or anonymous

Note that this means no possible link back to identified subject, i.e. “coded” not the same as “anonymous”

In IRB-speak, “coded/linked” “deidentified”

Data/Tissue repositories Under current federal guidance, work done

by secondary users of data or samples from a repository may be considered as “not human subjects research” Samples usually obtained with consent by

“owner/operator”. Link to subject could be maintained

But: secondary users get no identifiers and have to sign that they will not try to re-identify subjects.

If we decide “NOT HSR”: Currently not tracked/entered into the

electronic HawkIRB system (but about to change)

A chair can give you a letter or memo indication the “Non-HSR” decision, if you need it. (We will probably ask for a short signed description of what you want to do, at a minimum)

IF your work IS “HSR” You need to fill out an electronic IRB

application on HawkIRB The interactive application is driven by

your responses to a series of questions; optional sections will open up as needed.

Note the presence of hyperlinks to advice or help – this often quotes verbatim from regulations, may help you in knowing what to say

In the HSO Application screened for completeness

All necessary documents attached? Protocol, IDB or package insert, recruitment

materials All team members have certification?

(automatic, I think you can’t list them if not)

Decision re: type of review Initially driven by your application, i.e. you

will be asked if you think study is exempt, or can be expedited

Exempt: Not same as “not human subject research” Will not need continuing review

Expedited: by chair or designee Full Board

For all types of studies Initial “pre-review” by staff Usually there will be questions or

requested revisions from staff; these will be send back to you within HawkIRB electronic system

The faster you get stuff back to IRB, the faster it is dealt with.

Exempt/expedited studies: will be approved by a chair or designate

Expedited review (chair or chair designate) for specific categories Blood sampling (within limits) Noninvasive biologic samples (e.g. urine) Noninvasive monitoring techniques

No radiation or microwaves MRI is OK but not if sedation or gad used

Existing data or samples obtained in clinical care

Survey/questionnaire methods

“Existing” in IRB-speak Per federal guidance “existing” data

and/or samples exist: AT THE TIME YOU SUBMIT YOUR IRB

APPLICATION.

For full board review: Study will go to specific “prereviewers” in

IRB office; experienced folks who know the regulations and general IRB expectations

If they find problems, inconsistencies, missing information, or have questions, you will get notified by HawkIRB/email

Quicker you get things back, faster they can go to meeting.

After Pre-Review, Scheduled for full board review at a

convened meeting Investigators not routinely invited to

meetings; may be invited at chairs’ discretion for: Controversial or complicated studies Tabled studies.

Only the full board can disapprove a study (i.e. a chair cannot unilaterally disapprove anything, even an “expeditable” study)

Regulatory criteria for IRB approval (1) Risks to subjects are minimized:

(i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and

(ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

(2) 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.

Regulatory criteria for IRB approval (3) Selection of subjects is equitable. …the IRB … should be

particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons. [Special rules for children, prisoners]

(4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative...

(5) Informed consent will be appropriately documented, in accordance with, and to the extent required by §46.117.

(6) The research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

(7) There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

Range of IRB actions: Approve Approve with required changes

The changes must be items that are a matter of simple “assent” by the investigator

Anything else requires tabling and re-review, e.g. “clarify…”; “re-write consent to make more clear”; “describe plans for safety monitoring”

Disapprove Table (usually happens if questions are raised

that bear on risk/benefit ratio that can’t be answered during meeting)

After approval: Max period is 1 year Everything (except exempt) needs

continuing review at least 1x per year.