Grants, Human and Non-Human Subjects, and the IRB

This page is designed to provide guidance for Biostatistics faculty members who are submitting grant applications for methodological research on the IRB’s determination of non-Human Subjects.

If you have any questions, or if you would like some help, please see Peggy Schuyler.

Note: If a PI receives an award through a grant, contract, or cooperative agreement for research activities on human subjects that are carried out at another institution, and the PI receives only de-identified data or a limited data set, then a non-Human or Exempt Application will not be sufficient. A full Institutional Review Board (IRB) approval and is required, since the award was made to the PI. In other words, follow the money for the answer. Full IRB approval and yearly reviews will be required at the institution that receives the grant.

The final arbiter of whether a study involves human subjects rests with the IRB. You will need to have approval for your study from the IRB even if your grant application claims no human subjects. As well, the Just in Time requirements include documentation of IRB approval.

A helpful decision tree to determine whether you have human subjects or non-human subjects:

http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html#c5

Whether the research involves human or non-human subjects will depend upon the following:

• Source of the data
• Presence of identifying elements
• Whether data or samples will be collected specifically for the proposed research
• Intent of the analysis of the data

Methodological research involving clinical data generally will not involve any primary research or collection of data or samples and will not fall under the definition of human subjects.

Generally the biostatistician will use one of two types of data sets:

De-identified data sets

• All HIPAA identifiers have been removed
• Publicly available databases are usually de-identified
• A designation of non-human subjects can be claimed with the use of de-identified data

Limited data sets (LDS)

"Recognizing that some research, for example epidemiological research, requires some, but minimal, identifying information, the HIPAA Privacy Rule provides an alternative to the extremes of de-identified data and Protected Health Information. …With the limited data set, Health and Human Services attempted to strike a balance between privacy and facilitating highly valuable epidemiological research. Thus, limited data sets do not have a “free pass” like de-identified data but neither do they require the approval that is necessary for Protected Health Information.”

Dunn CM, Chadwick GL, Protecting Study Volunteeers in Research: A Manual for Investigative Sites. 3rd ed: CHapter 15: Implementing the HIPAA Privacy Rule in Research. Thomson Centerwarch. Boston. 2004, page 167.

Protected Health Information is individually identifiable information that contains HIPAA identifiers.

For LDS:

• Dates (including dates of birth, admission, etc.), town/city, and/or 5-digit zip codes may be retained.
• Many clinical data sets not publicly available will involve dates (birth, admission, etc.) or locations.
• The use of a LDS requires a Data Use Agreement between the institution supplying the data and the investigator. The Data Use Agreement specifies who has access to the LDS and the recipient’s responsibilities.
• A designation of non-human subjects can be claimed with the use of a LDS.

The applicant should specify which type of data set will be used and whether a Data Use Agreement will be signed. VUMC policy on de-identified and limited data sets: http://vumcpolicies.mc.vanderbilt.edu/E-Manual/Hpolicy.nsf/AllDocs/3C23BD359506762886256CC30051DDEE

To receive a designation of non-human subjects, submit IRB form 1122, Request for Determination of Non-Human Subject or Non-Research. With this form you will be required to submit a list of the data elements you will be using and any data use agreements with other institutions. An IRB Protocal Analyst II or higher can approve the request; yearly reviews will not be necessary. You can apply for a determination before or after you submit your grant. After you receive your notice of grant award, the Just in Time requirements must be met, including a letter of approval from the IRB.

You are required to have your IRB Human Subjects training up to date before any requests can be approved by the IRB, even for a determination of non-Human Subjects. The CITI IRB training modules can be found at http://www.citiprogram.org/default.asp?language=english. If you have CITI training at another institution, you can change your affiliation to Vanderbilt. Before you change it, print out your completion certificates for your training. If you do not do this, see Peggy Schuyler, who may be able to have the certificates sent from your former institution's IRB.

The staff of the IRB is agreeable and willing to informally help a researcher understand their policies and procedures. They are your ally and not a stumbling block.

The face page of the grant application has a check box to designate human or non-human subjects. If no human subjects are designated, then the investigator cannot instruct their COEUS administrator (who makes out this face page) to claim any of the exemptions noted in the PHS 398 or SFR 424 grant instructions. Grants & Contracts will not approve an application designating non-human subjects with a claim of Exemptions 1, 2, 3, 4, 5, or 6

Even though the PHS 398 Instructions appear to indicate that these exemptions can be claimed, nevertheless, according to Grants & Contracts, these exemptions cannot be claimed. You will not change their minds on this issue.

Sample Human Subjects section

E. Human Subjects Research

The proposed research meets the definition of No Human Subject Research.

E.1. The proposed study does not involve human subjects for the following reasons:

1. No data will be specifically obtained for the proposed research through any interaction or intervention with a living individual. 2. The investigator cannot readily identify any individual involved in the two studies from which the de-identified datasets were obtained because:

a. The analysis dataset from the Heart Institute (See Section B.1.1) will not contain individually identifiable private information (i.e., HIPAA identifiers). The investigator does not have access to a coding system by which an individual can be directly or indirectly identified. Data will be supplied by Darby Conley, MD from Johns Hopkins University. Dr. Conley has agreed to serve as a consultant on the scientific context of the data. The investigator will sign a Data Use Agreement with the Heart Coordinating Center at Johns Hopkins University, stipulating the use of the data for research purposes only and the responsibilities of the investigator to safeguard the privacy of the data.

b. The analysis dataset from the Thoracic Aneurysm Study (see Section B.2.1) will not contain individually identifiable private information (i.e., HIPAA identifiers). The investigator does not have access to a coding system by which an individual can be directly or indirectly identified. The dataset will be supplied by Rob Wilco, PhD of Vanderbilt University. Dr. Wilco has agreed to serve as a consultant on the scientific context of the data.

c. Analysis datasets will only be used to develop ___________. (If the grant’s aims are methodologic: No direct clinical applications are planned for the results of this study.)

d. We will obtain approval as non-human subjects for the proposed research from the Institutional Review Board of Vanderbilt University

Note: the following headings are required only if you have human subjects:

E.2. Protection against risk: The only risk to the data involves the confidentiality of the data. No individual in the de-identified databases will be identified or contacted. The risk that someone in this study will gain access to information through which an individual could be identified is negligible. Data will be stored on a Linux workstation in the Department of Biostatistics at Vanderbilt University. The confidentiality of this data is protected through the secrecy of the computer password required to gain access to the data and the manner in which the data are encoded. Paper records will be kept under lock and key.

E.3. Security measures: Data will be stored on a Linux workstation in the Department of Biostatistics at Vanderbilt University. The confidentiality of this data is protected through the secrecy of the computer password required to gain access to the data and the manner in which the data are encoded. Paper records will be kept under lock and key.

E.4. Potential benefits of the proposed research to the subjects and others: This research may lead to improved methods for _________. The negligible risks and real potential benefits justify the conduct of this study.