irb’s top ten* investigator responsibilities what every investigator (and his/her research staff)...

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IRB’s Top Ten* Investigator Responsibilities What Every Investigator (and his/her research staff) Should Know about Conducting Human Research Activities *Based on David Lettermen’s Top Ten

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IRB’s Top Ten*Investigator

Responsibilities

What Every Investigator

(and his/her research staff)

Should Know about

Conducting

Human Research Activities

*Based on David Lettermen’s Top Ten

PI Responsibility #1

• In designing the study, the investigator should take into consideration the three underlying ethical principles for conducting research with human subjects as delineated in the Belmont Report.

Belmont Report?What’s that?

My research is ethical!

• The Belmont Report outlines the ethical underpinnings of all of the federal regulations governing the use of human subjects.

Ethical Principles

• Respect for Persons– Each person is autonomous– Respect for the person’s privacy

when identifying him/her as a potential subject

– Respect for the person’s autonomy includes obtaining consent for research procedures

– Respect for the person’s willingness to share confidential information

Ethical Principles

• Beneficience– The research will do no

intentional harm– The research will provide

opportunity for benefit, either to the individual, to the group which the individual represents, or to society

– The risks associated with the research are minimized as much as possible

Ethical Principle

• Justice– That the burdens (i.e., the risks)

of the research will not be put upon any one particular group because of convenience, vulnerability, or lack of autonomy

– The benefits of the research will not be exclusive to any one particular group but will be made available to anyone who might reap those benefits.

PI Responsibility #2

• Research investigators should acknowledge and accept their responsibility for protecting the rights and welfare of human research subjects and for complying with all applicable federal regulations dealing with protection of human subjects.

Federal Regulations?What regulations apply

to my research?Which ones can I

avoid?• Common Rule (Federal Policy

for the Protection of Human Subjects– Effective August 19, 1991– Adopted by 16 Federal Agencies– Based on Subpart A 45 CFR 46

Department of Health and Human Services

• Core Requirements • (Subpart A) • Fetuses and Pregnant Women

(Subpart B) • Prisoners (Subpart C)• Children (Subpart D)• Institutionalized Mentally

Disabled (Proposed Subpart E)

Food and Drug Administration

• Informed Consent

21 CFR 50• Institutional Review Board

21 CFR 56

Are there ever times when I do not have to

apply these regulations?

• There are certain categories of research that are exempt from DHHS regulations. The regulations do not have to be applied when the only involvement of human subjects falls within one or more categories on the following list.

Exempt Categories1. Research conducted in established

or commonly accepted educational settings, involving normal educational practices.

2. Research involving the use of educational tests, survey procedures, interview procedures, or observation of public behavior, unless: (1) Information obtained is recorded in such a manner that human subjects can be identified directly or through identifiers linked to the subjects; AND (2) any disclosure of the human subjects’ responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects financial standing, employability, or reputation.

Exempt Categories, cont.

3. Research not exempt under “2” may be exempt if: (i) the human subjects are elected or appointed public officials or candidates for public office; or (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research thereafter (e.g., Department of Justice and National Center for Educational Statistics)

Exempt Categories, cont.

4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to subjects.

Please note: according to OHRP to quality for this exemption the data, documents, records, or specimens must be in existence before the project begins.

5. Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment of benefits or services under those programs.

Exempt Categories, cont.

6. Taste and food quality evaluation and consumer acceptance studies: (I) if wholesome food without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the FDA or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the US Department of Agriculture.

Exempt Categories, cont.

PI Responsibility #3

• Investigators are responsible for ensuring that all research involving human subjects is submitted to and approved by the appropriate Institutional Review Board (IRB).

So, what needs IRB review?

*The IRB has purview over all research that involves human

subjects.

HUMAN SUBECT is defined as a living individual about whom

an investigator conducting research obtains (1) data through intervention or

interaction with the individual or (2) identifiable private

information. [45CFR46.102(f)]

When is it research?

“RESEARCH”

Research is a systematic investigation designed to develop or contribute to generalizable knowledge

[45CFR46.102(d)]

Does that mean I need IRB review

for chart reviews?

What about poster presentations?

The answer to both questions is “YES”!!

• Chart reviews are the systematic collection of identifiable private information

• If you are sharing your findings with anyone outside the research team, it is considered meeting the definition of “generalizable knowledge.

Applicability: FDA

• Clinical Investigations• Regulated Products

–Drugs–Devices–Biologics–Food/Color Additives

What is designated as a “clinical

investigation”?• Involves use of a Test

Article• One or more Human

Subjects• Meets requirements for

Prior Submission to FDA or

• Results intended to be part of an Application for Research or Marketing Permit [21 CFR 56.102(c)]

PI Responsibility #4

• Investigators are responsible for complying with all applicable IRB policies, procedures, decisions, conditions, and requirements.

• OKAY, OKAY – so I need IRB review. What do I do next and what does all that mean?

Complete an IRB Application

http://www.research.usf.edu/cs/irb.htm

Mechanisms for Review• Expedited Review• Full Review

Expedited Review Criteria

• No More Than “Minimal Risk”

• Falls in One or More Federally Specified Categories

• Minor Change in Previously Approved Research

Definition of Minimal Risk

“Minimal Risk” mean that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves from those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. 45 CFR 46.102(i)

What are the “federally specified categories” that qualify my research for

expedited review?

• Clinical studies that no not require an IDE or IND

• Collection of blood samples • Noninvasive prospective collection of

biological specimens• Noninvasive data collection used in clinical

practice• Data, documents, records, specimens collected

for non-research purposes• Voice, video, digital, or imaging recordings for

research• Research on individual or group

characteristics• Continuing Review (under certain conditions)

My research involves other kinds of procedures.

Now what happens?

• Full Review Requirements– Conducted at Convened Meeting– Quorum Present– Nonscientific Representative– 45 CFR 46.111 Satisfied– Approval by Majority– Conflict of Interest Abstain from

Vote/Leave Room– PI Informed of Outcome In

Writing

What Does it Take to Get My IRB Application

Approved?

Criteria for IRB Approval of Research

[45 CFR 46.111]

To approve research, an IRB should determine that all of the

following conditions exist:

Risks to subjects are minimized;

Risks are reasonable in relation to anticipated benefits, if any, to subjects and to the advancement of knowledge;

Selection of subjects is equitable;

Informed consent will be sought;

Informed consent will be documented;

Where appropriate, research plan makes adequate provision for monitoring the data collected to ensure safety of subjects;

There are adequate provisions to protect the privacy or subjects and to maintain the confidentiality of the data;

Where any of the subjects are likely to be vulnerable to coercion or undue influence, additional safeguards have been included in the study to protect subjects.

In addition, local IRB policies and requirements apply.

Statement from Actual Informed Consent

Document

“…investigator may at his/her absolute discretion terminate the procedures and/or investigators at any time.”

And Yet Another Statement from an

Actual Consent Form

“…will be permanently able to perform sexual acts.”

And Finally….from an actual consent form…

“We will insert three catheters, one in each arm.”

» ARENA Newsletter, 1989

What has to go in my consent form to make sure it is approved?

General Requirements

45 CFR Part 46.116

Basic Elements

45 CFR Part 46.116(a)

Additional Elements

45 CFR Part 46.116(b)

Alteration or Waiver

45 CFR Part 46.116(d) Documentation

45 CFR 46.117

Investigator Responsibilities #5

& #6Unless otherwise authorized by the IRB, investigators are responsible for obtaining and documenting informed consent in accord with federal regulations (45 CFR Part 46.116 and .117 and 21 CFR Parts 50.25 and 50.27) and as approved by the IRB.

General Requirements• Obtained from the subject or the

subject’s legally authorized representative

• Language understandable to the subject/representative

• Obtained under circumstances that provide subject w/opportunity to consider whether or not participate and that minimize coercive influences

• Not include language through which the subject appears to waive his legal rights or which releases the investigator, sponsor, or institution from liability for negligence

Basic Elements• The study involves research!• Explanation of the purpose• Duration of subject’s participation• Description of procedures• Identification of experimental

procedures• Description of risks or discomforts• Description of potential benefits to

subject or others• Disclosure of alternatives available• Extent of confidentiality that can be

made (FDA statement)

Basic Elements, cont.• If research is greater than minimal

risk, explanation of compensation and availability of medical treatment

• Whom to contact (3 contacts)Contact for questions about

the researchContact for questions about subject rightsContact if research-related injury should occur

• Statement that participation is voluntary, refusal to participate involves no penalty or loss of benefits, and that subject may discontinue at any time.

Additional ElementsIf required by the IRB, one or more of the following should be provided to the subject:

•Statement that there may be unforeseen risks

•Description of circumstances under which subject’s participation may be terminated

•Additional costs to subject•Consequences of withdrawing from study

•Statement that significant new findings which may related to the subject’s willingness to participate will be shared

•Approximately number of subjects involved in the study

“Do I always have to obtain consent? My study is so low

risk!!”An IRB may waive consent or alter

the elements IF it finds and documents the following:

• Research involves no more than minimal risk;

• Rights and welfare of subjects will not be adversely affected;

• Research could not be practicably carried out without waiver or alteration; and

• If appropriate, subjects will be provided pertinent information after participation.

Documentation of Informed Consent

• Informed consent will be documented using:– A written form approved by the

IRB (in our case and appropriately stamped with the IRB approval period)

– Signed by the subject or his legal representative; and

– A copy of the form will be given to the person signing the form. (Be sure to document in the research/medical records that the form was given to the subject.)

“I can’t get written consent in a telephone survey. What do I do?”

• IRB may waive documentation of informed consent if:– The only record linking the subject

and the research is the informed consent document and the principle risk would be harm resulting from breach of confidentiality; each subject must be asked whether he/she wants documentation (not included in FDA regulations); or

– The research presents no more than minimal risk and involves no procedures for which written consent is normally required.

“What’s the difference in requesting a waiver of documentation and a requesting a waiver of

consent?”

• Waiver of documentation will usually mean that the IRB requires that you provide the subject with written information but don’t obtain a signature.

• Waiver of consent means that you meet the 4 criteria previously described and there is no consent process.

“What can I do to make sure subjects really do

understand the research?”

• Train individuals obtaining informed consent (they should be able to answer questions the subjects may have about the research)

• Use technology or innovative approaches

• Be sensitive to subjects’ needs• Make adjustments in the process, as

necessary• Obtain IRB approval for

substantive changes and a plan to re-consent, when necessary

“We were in a hurry; we just grabbed the

only copy of the consent form we could

find.”• It must be the most recently IRB

approved form or it’s just not valid!• The subject or legally authorized

representative must date and sign the form.

• The subject must be given a copy of the form.

• Maintain documentation!!!! If it isn’t documented, it didn’t happen.

Investigator Responsibility #7

The investigator is responsible for ensuring that the research is implemented as specified in the approved protocol and for promptly submitting to the IRB a modification to the previously approved protocol prior to initiating the change.

In lay terms…“I changed my mind - do I need to tell the IRB?”

“The protocol says I will only enroll subjects with blue eyes but this subject has green eyes – can I enroll him?”

Modifications – need to obtain prior IRB approval!

Exceptions – need to obtain sponsor and IRB approval!!

Investigator Responsibility #8

Research investigators are responsible for reporting progress of approved research to the IRB, as often as and in the manner prescribed by the approving IRB on the basis of risks to subjects, but no less than once per year.

“Why do you keep sending me those letters

about my IRB approval?”

• Federal regulations [45 CFR 46.109(e) and 21 CFR 56.109(e)] state that an IRB “shall conduct continuing review at intervals appropriate to the degree of risk, but not less than once per year…”

It is the PI’s responsibility to seek a new approval if the study is to continue.

However, USF will help you out. We will send you a reminder notice approximately 75 days before your IRB approval is to expire.

If you ignore the reminder notice and IRB approval expires, you will have to stop all research procedures and data collection.

http://www.research.usf.edu/

cs/download01.htm/• Download the Continuation

Review Form• Complete the form and submit

the required information (copies of the application, the informed consent, abstract or progress report, etc.)

• Call the Division of Research Compliance if you have questions (813-974-5638) and have your IRB number ready.

“How does the IRB decide if a study can

continue?”The criteria for issuing continuing approval is the same as that for initial review.

The questions on the application are there for a reason. If the application is incomplete, it may slow your review or cause your approval to lapse.

The IRB will take into consideration the progress that has occurred on the study to determine if there has been a change to the risk/benefit ratio and if the study continues to be appropriate for the intended population.

Investigator Responsibility #9

Research investigators must promptly report to the IRB and to the sponsoring Federal department any injuries, adverse events, or other unanticipated problems involving risks to subjects and others, in accord with IRB polices and requirements.

“What do I report and when do I report it?”

• https://irb.research.usf.edu/ers/o6-start.asp

• Gives you all the information you need about reporting AE’s, injuries, and unanticipated events.

• USF IRB Policy 706: http://www.research.usf.edu/cs/irb_policies/706.pdf

Investigator Responsibility #10

Research investigators are responsible for retention of signed consent documents and IRB records for at least five years past the completion of the research activity.*

*Sponsors may require that study documentation be retained for a longer period of time.

“I am running out of space. How much

longer do I need to keep all of this paper and

what do I need to keep?”

•Research protocols•All IRB and sponsor correspondence•Continuing Review reports•Original Data•Signed Consent/Assent Forms

Remember, if it isn’t documented or you can’t produce documentation, the feds (and in worse case scenarios, lawyers) won’t consider it done!

Investigator Top 10 Responsibilities

• Design Ethical Research• Comply with Federal Regulations• Obtain Prior IRB Approval• Obtain Informed Consent/Assent• Document Informed

Consent/Assent• Implement Research As Approved

and Obtain Prior Approval for Modifications

• Submit Progress Reports• Report Unanticipated Problems• Retain Records for 5 years after

study closes

USF Division of Research Integrity & Compliance

• Web site:http://www.research.usf.edu/cs/irb.htm

• Phone: (813) 974-9343

• Location:University Professional Center3702 Spectrum Blvd., Suite 155Tampa, Florida 33613

• Mail:USF Division of Research Integrity and Compliance12901 Bruce B. Downs Blvd., MDC 035Tampa, FL 33612-4799