Research Using Human Subjects/Materials

(taken in part from "Research on Human Specimens", National Institutes of Health)

A 'human subject' is a living individual about whom an investigator obtains either (1) data through intervention or interaction with the individual, or (2) identifiable private information.  Legal requirements to protect human subjects apply to much broader range of research than many investigators realize, and researchers using human tissue specimens are often unsure about how regulations apply to their research.   Legal obligations to protect human subjects apply, for example, to research that uses -

  • Bodily materials, such as cells, blood or urine, tissues, organs, hair or nail clippings, even if you did not collect these materials

  • Residual diagnostic specimens, including specimens obtained for routine patient care that would have been discarded if not used for research

  • Private information, such as medical information, that can be readily identified with individuals, even if the information was not specifically collected for the study in question.  Research on cell lines or DNA samples that can be associated with individuals falls into this category.

If your research is in these categories, you must...

Compy with your institution's rules and the requirements of your Institutional Review Board (IRB) as well as meeting Federal requirements (Title 45 CFR Part 46) in order to carry out your research.

What is the role of an Institutional Review Board?

The IRB at your institution must review and approve research  if it involves human subjects.  This process is designed to ensure that the research protects the rights and welfare of human subjects - for example, by minimizing risks, selecting subjects equitably, obtaining informed consent and ensuring privacy and confidentiality.  In addition, after your Institution's IRB has approved the work, approval must also be obtained from the ANL IRB before work can begin at the APS.

What consent is required for the use of human tissue specimens?

IRB's are responsible for determining whether or not informed consent is required from the subjects from whom the specimens were obtained.  The IRB may waive the requirements for informed consent if the risk to the subjects is minimal and if certain other conditions are met (Title 45 CFR Part 46.116).  You should not assume that your research poses minimal risk just because it involves tissue specimens.   Loss of confidentiality can cause harm to patients and their relatives; IRBs will consider whether privacy and confidentiality protections are adequate.

Is my research exempt from IRB review?

Research with specimens and data from living persons is exempt from the requirement for IRB approval when it is determined that the research either does not involve human subjects as defined in the Code of Federal Regulations (CFR) or the only involvement of human subjects is in one of the "exempt" categories listed in the Code.  The exemption that is most pertinent to work with human tissue specimens is exemption #4.

As stated in 45 CFR 46.101(b):

"Unless otherwise required by Department or Agency heads, research activities in which the only involvement of human subjects will be in one or more of the following categories are exempt from this policy:
...(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 the subjects."

Some researchers mistakenly believe that any studies on existing pathology specimens are exempt.  Exemption #4 does not apply to specimens that are linked to patient identity, even if the subject identifiers are locked up or kept by someone other than the researcher.  It does not matter if the tissue would otherwise have been discarded.  You should be aware that many institutions require an IRB to determine whether or not the research is exempt.

What is meant by "existing" data or specimens?

Exemption #4 applies to retrospective studies of specimens that have already been collected.  The materials must be "on the shelf" (or in the freezer) at the time the protocol is initiated.

What about specimens obtained from a tissue bank?

Use of tissue specimens obtained from an established tissue repository may be exempt, even though the bank continues to procure new specimens while the research project proceeds.  There are many kinds of tissue banks that operate in different ways.  Your IRB will need to determine whether the bank you are using meets the requirements of the exemption.

What is meant by "publicly available sources"?

This language in the regulation was intended to apply to public sources of data, such as death certificates.  Its meaning with respect to human tissue specimens is widely debated.  Although there are organizations that make human cells and tissues broadly accessible at reasonable cost to the research community, these materials are not usually available to the public at large.  Even if you obtain specimens from such a source, you should not assume that it meets the definition of   "publicly available".  It is up to your IRB to decide.

What is meant by "identifiers linked to the subjects"?

Identifiers such as names, Social Security numbrs or pathology accession numbers permit specimens to be linked to individual people and perhaps also to associated medical information.  Exemption #4 applies most clearly to specimens where such personal information was never collected.  It may apply to specimens provided by a tissue bank or other repository, so long as the specimens are provided without identifiers and the repository has firm policies and procedures, reviewed by its own IRB, to prevent the release of personal information.  It generally does not apply in situations where a researcher receives "coded" specimens from a collaborator if the collaborator retains the key to the code, even though the researcher may have no access to patient identities.

How can I determine if my research is exempt?

Human research information that is most frequently needed is available from the Office of Human Research Protection (OHRP) website will help you to see whether your research falls under the human subjects regulations and if so, whether it is likely to require full IRB review or is a candidate for expidited review.  You should be aware, however that institutions vary in their requirements for IRB review.  Many institutions require some form of IRB review for exempt studies.  You must check with your institutional officials to determine whether full, expedited, or no IRB review is required for you proposed project.

If I obtain all my specimens from collaborators, do the regulations apply?

Yes! Unless your research is exempt, BOTH you and your collaborator(s) must have approvals from the IRBs at your respective institutions.

What if my collaborator is located outside the U.S.?

Your collaborator will need to obtain approval from the IRB at his or her institution.  In addition, your collaborator's institution will probably need to contact OPRR and provide documentation that its IRB meets the requirements defined in U.S. laws.  An assurance coordinator at OPRR can assist you with this process.  In addition, your program official may need to request State Department clearance for you project.

The key is: start early!  Obtaining approvals and assurances takes time, particularly if institutions are located overseas.  No experiment can be run at the APS until the necessary approvals and assurances are in place.

Reviewed and Updated January 10, 2011