Human SubjectsOverview

Human Subjects Office - Mission• Create an atmosphere of respect for, and awareness of, the rights

and welfare of human research participants• Continue to inform established researchers about the application of

the federal regulations and ethical principles to their particular area of research in an effort to keep researchers current with evolving standards.

• Educate students, faculty, and staff who conduct research about the ethical principles and federal regulations guiding research with humans.

• Develop new approaches that better serve the overarching mission of the HRPP, such as state-of-the-art educational materials, more efficient methods for processing applications, tracking and monitoring research activities, and assessing the overall effectiveness of the HRPP

IU’s HRPP

• Nationally accredited• Two campuses, one office• Six Institutional Review Boards (IRBs)

• 2 Social/Behavioral Boards• 4 Biomedical Boards• IRB Executive Committee

• Supported by the Office of Research Administration

Role & Authority of IRB: Protecting Human Subjects

• Approve or disapprove research and require modifications

• Conduct initial and continuing review at least annually (Except Exempt)

• Must approve any changes in research before they can be implemented

• Evaluate unanticipated problems and noncompliance

• Suspend or terminate approval of research

RESEARCH

Systematic investigati

on and designed

to develop or

contribute to

generalizable

knowledge

HUMAN SUBJECTResearch about a living

individual either

through intervention/ interaction

or identifiable

private information

IRB Revie

w

Does it require IRB review?

Questions to ask:– Is it research?– Does it involve human subjects?– Does the activity involve deceased individuals?– Is it subject to FDA regulations?– Is it a student project involving risk to human subjects?

Does it require IRB review?Levels of IRB Review

No Review Exempt(Minimal Risk)

Expedited(Minimal Risk)

Full Board

Type of Research

• Non-human subjects research

• Student projects

• Observation of public behavior

• Collection of existing data

• Surveys

• Prospective collection of data

• Non-invasive or standard of care procedures

• Focus groups

• Most drug or device studies

• Invasive procedures• Clinical trials

IRB Requirements

• Registration only if necessary

• Confirmation of exempt status

• Undocumented informed consent

• Prospective approval of any changes

• Review by an IRB member

• Written informed consent (unless waived)

• Annual review• Prospective approval

of any changes

• Review at a full IRB meeting

• Written informed consent (unless waived)

• Annual review• Prospective approval

of any changes

Minimal Risk: the risks of harm anticipated in the proposed research are not greater considering the probability and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological exams or tests

Does it require IRB review?Research with Existing Data

Example Level of Review

• Review of deidentified data or specimens

• Investigators have no access to identifiable data

None – not human subjects research.

• Retrospective chart review• Access to identifiable data• Data will be recorded in a

deidentified manner

Exempt

• Retrospective chart review• Access to identifiable data• Identifiable data will be recorded

Expedited

• Prospective chart review Expedited

Does it require IRB review?Student Projects

• Class assignments • Generally not intended for publication and are not considered

research• Projects which may be more than minimal risk AND involve a

vulnerable population should be reviewed by the HSO• Application for Non-Research Student Projects

• Thesis/Dissertation projects• Are considered research and should be submitted to the HSO as a

new study• Faculty sponsor is required and have ultimate responsibility for

ensuring the project is conducted appropriately

Example #1: You want to analyze existing, coded tissue samples from 10 patients collected before and after treatment with an investigative agent. Pre- and post- tissue samples are labeled only with a code to correspond the pre-treatment sample with the same patient’s post-treatment sample; code is not associated with or linked to subject. You want to look at the efficacy of a certain treatment in patients from which the tissue was previously collected by recording differences between the tissues.

Systematic investigation Contributing to generalizable knowledge Interaction with living individuals and/or identifiable information

IRB review NOT required

Does it require IRB review?Examples

Does it require IRB review?Examples

Example #2: You want to evaluate the effectiveness of a surgical technique by analyzing data collected by a surgery registry and conducting telephone interviews with a sample of senior citizens. You would like to make a poster presentation of your findings at your next professional society meeting.

Systematic investigation Contributing to generalizable knowledge Interaction with living individuals and/or identifiable information

IRB review required – probably expedited

Does it require IRB review?Examples

Example #3: You want to evaluate whether an investigational device is more efficacious than an already approved device for treating a specific condition. You will be randomizing subjects to either of these devices and will be monitoring them with various procedures and blood draws.

Systematic investigation Contributing to generalizable knowledge Interaction with living individuals and/or identifiable information

IRB review required – full Board review

What can happen if research is not reviewed and approved by the IRB?

The data collected may not be used for research purposes, i.e. the research can not be published or presented (more journals are checking)

The IRBs can impose or have imposed sanctions on investigators that conduct research without prospective IRB approval

IRBs must notify the federal government of any serious or continuing noncompliance

Does it require IRB review?Failure to Obtain

Submitting to the IRB

• Make all submissions to irb@iu.edu • Complete submission requirements

All investigators submit conflict of interest disclosures

All investigators complete CITI modules

Required documents submitted

• Incomplete submissions will be returned to you with a list of requirements to be completed, weekly follow-up from staff

IRB Review Process

1. Complete submission

2. Pre-review: • Each department assigned to HSO team• Completeness and understandability

3. Review (depending on level of review)

4. Provisions/concerns addressed (if necessary)

5. Approval documents sent

Ongoing Review

• Continuing review: required annually for non-exempt studies

• Amendments: all changes must be prospectively approved prior to implementation

• Including Co-Investigators (key personnel)• Research personnel updates (non-key) do

not require approval; notification only

• Reporting

Ongoing Review: ReportingUnanticipated

ProblemsNoncompliance

What to Report Any event meeting the definitions listed on the Prompt

Reporting Form

ALL noncompliance

When to Report Within 5 business days of discovery

Within 5 business days of discovery

How to Report Prompt Reporting Form Noncompliance Form

IRB Determinations

Unanticipated problem involves risk to subjects or

others (UPIRTSO)

Serious noncompliance, Continuing noncompliance, OR

Serious & continuing noncompliance

Possible IRB Actions

– No action– Restrict research activities– Conduct audit– Require remediation, mentoring, education– Require changes to protocol, informed consent process/documents, monitoring– Withdrawal, notification, or reconsenting of subjects– Suspend or terminate research

Principal Investigator Responsibilities Eligibility

• Must meet eligibility criteria• Complete submission requirements

Responsibilities• Management and completion of project• Hiring and assigning employees and resources• Ensuring appropriate training of study staff• Ensuring integrity and security of data• Ensuring consent process• Adherence to protocols and policies (federal, state, insitutional)

Additional Investigator Responsibilities

• Good Clinical Practices A standard by which clinical trials are designed, performed, monitored, audited, recorded, analyzed, and reported so that there is public assurance that the data are credible, and that the rights, integrity, and confidentiality of subjects are protected.

• Auditing• Provided by Clinical Research Compliance Office• Directed and scheduled• General audit process: notification, to site visit, to audit report,

response to findings, and then IRB Review (also see IU SOPs for Research Involving Human Subjects)

• Responsibilities related to external audits

Additional Investigator ResponsibilitiesFDA-Regulated Studies

Additional oversight: FDA• Oversight of clinical research (IND/IDEs, etc.)• Safety reporting• Accuracy of submissions• Patient enrollment• Informed consent• Records retention post approval• Financial disclosures• Inspection rights

Investigational drugs (IND) and devices (IDE)• Provide IRB with IND/IDE number • Devices: provide information regarding

significant Risk/nonsignificant for IRB determination

• If the investigator holds IND/IDE:• Meet with individuals within the Office of Research

Administration to discuss the responsibilities prior to study approval

Additional Investigator ResponsibilitiesFDA-Regulated Studies

IND Enforcement Actions• Illegal Clinical Trial

Synthes, Inc. and four top executives charged with conducting clinical device trials without FDA authorization

Label of bone cement contained a warning against the use being studied

All 4 executives were sentenced prison time – Sentencing exceeded the sentencing guidelines

Additional Investigator ResponsibilitiesFDA-Regulated Studies

CTSI-supported Indiana BiobankGoal: Create a research resource by linking a subject’s

blood sample to their medical record • Subjects consent to broad research use• Consent allows researchers to use past, present and future data in the

medical record• Over 14,000 pediatric and adult subjects already consented and

available for research studies• Studies collecting samples can partner with the Indiana Biobank to

expand this research resource• Investigators consenting subjects and collecting a blood sample for

the Indiana Biobank receive samples from the Indiana Biobank at reduced rates

To participate, contact Dr. Tatiana Foroud (tforoud@iu.edu)

Contact the HSO

• Submit via email to iuirb@iupui.edu • Contact your team:

http://researchadmin.iu.edu/HumanSubjects/hsdocs/HSO_Service_and_Support_Teams.pdf

• Visit our website:

http://researchadmin.iu.edu/HumanSubjects/ • Sign up for email updates:

http://researchadmin.iu.edu/News/email-news.html