Feature Article
WHAT IS AND WHAT IS NOT HUMAN SUBJECTS RESEARCH
June 2014 Issue
By John F. Ennever, MD, PhD, CIP, Director, BUMC IRB
Authors has nothing to disclose with regards
to commercial support.
WHAT IS AND WHAT IS NOT HUMAN SUBJECTS RESEARCH
One of the more confusing areas to our research community is, “What makes an activity human subjects research (and, therefore, subject to IRB oversight); and what makes an activity NOT human subjects research?” The confusion exists not just among our researchers, but also with grant administrators, project officers at funding agencies, journal editors, and many others. The default at BU/BMC as well as many other institutions has been to require that the IRB (or more correctly, staff within the IRB Office) make the determination that a specific activity is “not human subjects research,” abbreviated “NHSR.” The purpose of this article is to help you understand how we in the IRB Office make this determination. Armed with this understanding, you might recognize ways you can change the research design of a proposed study that would make your study “NHSR” and, thus, not subject to further IRB oversight.
The federal regulations that cover human subjects research are found in 45 CFR 46. These regulations are also called the “Common Rule” because they have been adopted by most of the departments and agencies of the Federal Government.
The Common Rule carefully defines what is meant by “research” and what is meant by “human subjects.”
RESEARCH means “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy…”
Ambiguity about whether an activity is research most commonly arises when someone is doing quality assurance or quality improvement work (QA/QI) that could also be used to contribute to generalizable knowledge. A discussion of this issue has been previously discussed in the CR TIMES, see April, 2008 issue. An updated discussion of QA/QI will be the subject of a subsequent CR TIMES article.
The far more confusing area is what constitutes a “human subject.” The following is the definition in the Common Rule.
HUMAN SUBJECT means “a living individual about whom an investigator conducting research obtains:
(1) Data through intervention or interaction with the individual, or
(2) Identifiable private information.”
This leads to four further definitions:
Intervention includes both physical procedures by which data are gathered (e.g., venipuncture, having a subject perform a task on a computer or run on a treadmill); and manipulations of the subject or the subject's environment that are performed for research purposes (e.g., placing color coded nutritional information on packaged sandwiches, acting like a homeless person at a bus stop).
Interaction includes communication or interpersonal contact between investigator and subject for the purpose of gathering data (e.g., interview, email survey).
Private information means information that is generated in a context in which an individual can reasonably expect that no observation or recording is taking place; and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (e.g., behavior in a person’s home, answers to a survey where confidentiality was promised, medical records).
Obtaining private information per se does not constitute involvement of human subjects unless this information is “identifiable.”
Identifiable means that the identity of the subject is or may readily be ascertained by the investigator or associated with the information.
In summary, human subjects research is obtaining data by intervening or interacting with living subjects or obtaining identifiable private information about living subjects.
All other research is not human subjects research (NHSR).
There is research going on throughout the University and BMC that has not been officially determined to be NHSR by the IRB because the investigators are absolutely certain that what they are doing is not human subjects research. For example, many years ago I worked with bilirubin and human serum albumin (both purchased from a chemical supply house). Even though I used HUMAN serum albumin, I was confident that what I was doing was NHSR.
Often, it is not as clear whether or not a project is NHSR. An approach to how we make the decision is illustrated by the questions below. You begin with the first question and if the answer is “b” you move to the next one. As long as the answer is “b” you keep going. If an answer is “a” you have the answer as to whether or not a project is Human Subjects Research or Not Human Subjects Research.
- Will this research cause any intervention or interaction with living individuals? (Are there living individuals who will do something different because of this research?)
- Yes => this IS human subjects research
- No => continue to 2
- Will this research involve obtaining specimens from living individuals and/or obtaining any information about living individuals?
- No => this is NOT human subjects research.
- Yes => continue to 3
- Will this research only involve obtaining information that is publicly-available? (Will no specimens be obtained, and will all the information that is obtained be readily accessible to everyone?)
- Yes => this is NOT human subjects research.
- No => Continue to 4
- Will anyone on the research team be able to identify who gave any of the specimens or information? (Could the identity of any individual who gave the specimens or information be directly or indirectly deduced?)
- Yes => this IS human subjects research
- No => Continue to 5
- Will a key exist anywhere linking the specimens or information to the identity of the people who gave them?
- No => this is NOT human subject research
- Yes => Continue to 6
- Is there written documentation that the holder of the key will not disclose the key to the research team under any circumstances (and the holder of the key is NOT part of the research team)?
- No => this IS human subjects research
- Yes => this is NOT human subject research
In the following examples, I have given the answers to the above questions to illustrate how this tool could be used to make a Human Subject Research or Not Human Subject research determination.
Typical categories of “Not Human Subjects Research (NHSR):
- Analysis of anonymous specimens – “anonymous” meaning no one could link the information or specimens to the people who gave them.
1-B, 2-B, 3-B, 4-B, 5-A
- Analysis of coded patient information – “coded” meaning that they are not inherently identifiable, but a key exists linking the identity to the specimens or information. The researchers do not have the code, and there is written documentation that the researchers will never be given the code.
1-B, 2-B, 3B, 4-B, 5-B, 6-B
- Analysis of publicly-available political contribution data from the federal election commission (http://fec.gov) that includes name, address, and amount contributed.
1-B, 2-B, 3-A
- Data obtained by observation in public places without interaction with any participants.
1-B, 2-B, 3-A
Examples of research that DOES meet the definition of human subjects research. I have included the reason why the research is human subjects research and what changes could be made to make the research NHSR:
- Retrospective or prospective chart reviews. (The researchers are obtaining personally identifiable private information)
1-B, 2-B, 3-B, 4-A
NOTE: this would change to NHSR if someone else had recorded data from the charts (with IRB approval) and the BU/BUMC researcher were looking only at unidentifiable data. - An additional blood draw will be taken from individuals, but only the blood with no identifiers will be sent to the BU/BMC researchers. (The interaction with these individuals will occur only because this research is being conducted.)
1-A
NOTE: this would change to NHSR if already-collected blood samples were sent to the BU/BUMC researcher without any identifiers, i.e., the samples were not obtained specifically for the BU/BMC researcher.
- One or more members of the research team have access to the code linking the specimens or information to the individuals who originally gave them. (The individuals can be identified.)
1-B, 2-B, 3-B, 4-B, 5-B, 6-A
NOTE: this would change to NHSR if access to the code were removed for all members of the research team.
- Existing specimens are being obtained with a verbal agreement not to share the key code. (The documentation that the key will not be given for coded data must be in writing.)
1-B, 2-B, 3-B, 4-B, 5-B, 6-A
NOTE: this would change to NHSR if access to the agreement not to share the code were put in writing.
- Individuals will take an Internet survey and no names or other identifiers will be collected. (The individuals are doing something that they would not have done if it weren’t for the research.)
1-A
NOTE: this would change to NHSR if the survey had already taken place (with IRB approval) and the BU/BUMC researcher were only looking at unidentifiable data.
- Infection control posters are placed in a public hospital waiting areas, and the investigator records the use of hand sanitizer. (The investigator manipulates the environment, so this is an intervention.)
1-A
NOTE: this would change to NHSR if the study compared existing waiting areas with posters that had been placed for non-research purposes.
The IRB has responsibility for research that meets the regulatory definition of Human Subject Research. Research that does not meet this definition is termed Not Human Subject Research (NHSR). The purpose of this article is to help you understand how we in the IRB office analyze a particular project to determine whether or not it is NHSR.
When there is ever a question about whether or not an activity is human subject research, you should consult with us in the IRB office. We can ask for help by sending an email to medirb@bu.edu, or by calling us at 617-638-7207.
Quiz
This Quiz applies to the current recertification period from July 1, 2013 to June 30, 2015. We recommend that you take this quiz now so you can stay up-to-date.