Human Subjects Overview

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

Does it require IRB review? Systematic investigation and designed to develop or contribute to generalizable knowledge RESEARCH Research about a living individual either through intervention/ interaction or identifiable private information HUMAN SUBJECT IRB Review 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 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 Review at a full IRB meeting 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 Identifiable data will be recorded Expedited Prospective chart review

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

Does it require IRB review? Examples 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 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

Does it require IRB review? Failure to Obtain 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

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 Complete submission Pre-review: Each department assigned to HSO team Completeness and understandability Review (depending on level of review) Provisions/concerns addressed (if necessary) 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: Reporting Unanticipated Problems Noncompliance 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 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 Responsibilities FDA-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

Additional Investigator Responsibilities FDA-Regulated Studies 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 Responsibilities FDA-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

CTSI-supported Indiana Biobank Goal: 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