Required Reading for All New Investigators
Table of Contents
In 1945, information came to light about unethical experiments conducted
by Nazi physicians on concentration camp prisoners. In that same decade,
a study in Tuskegee, Alabama used disadvantaged rural black men to study
the untreated course of syphilis. These subjects were not offered effective
treatment until long after such treatment became generally available.
These issues heightened awareness of the need to protect human subjects
and to assure their informed voluntary consent to participate in human
subjects research. The principles that underlie the protection of human
subjects today are found in three main documents:
These three documents served as the cornerstone for the drafting of the
Federal Policy for the Protection of Human Subjects (known as the Common
Rule). The Common Rule was adopted in 1991 by 17 Federal agencies that
conduct, support, or otherwise regulate human subjects research. For DOE,
the Common Rule is implemented in Title 10 Code of Federal Regulations
(CFR), Part 745. For the U.S. Department of Health and Human Services
(DHHS), the Common Rule is implemented at 45 CFR 46. Laws governing human
subjects research are continuing to evolve rapidly.
Common Rule regulations are based upon the three ethical principles outlined
in the Belmont Report:
- Respect for Persons. This principal requires investigators
to obtain informed consent and to protect the privacy of human research
- Beneficence. This principal requires researchers to maximize
potential benefits to participants and to minimize the potential of
- Justice. This principle requires that the selection of human
subjects should be fair and equitable and that the risks and benefits
of research should be distributed among subjects in a fair and equitable
The Institutional Review Board (IRB)
Under the common rule, each institution that engages in human subjects
research must establish an Institutional Review Board. The IRB is a board
of people from differing backgrounds and perspectives who are charged
with the responsibility of reviewing and approving, requiring modification
in or disapproving all proposals that involve human subjects in research.
The board is comprised of scientists, non-scientists, LLNL employees and
The function of the IRB is to assure that risks to human research subjects
are minimized and reasonable in relation to the anticipated benefits,
and to protect the rights and welfare of research subjects in accordance
with applicable federal regulations, state laws, DOE directives, and LLNL
LLNL has provided to the Department of Health and Human Services (DHHS)
written assurance that it will comply with the requirements of the Federal
Policy for the Protection of Human Subjects (known as the Common Rule).
Review by the Laboratorys Institutional Review Board is required
for research projects that involve human subjects if:
- The project is sponsored, in part or entirely, by LLNL.
- Some or all of the activity is conducted by, or under the direction
of, any LLNL employee or subcontract worker in connection with his or
her Laboratory duties.
- Some or all of the activity is conducted by, or under the direction
of, any LLNL employee or subcontract worker using any LLNL property
- The activity involves the use of LLNLs nonpublic information
to identify or contact human research subjects or prospective subjects.
Researcha systematic investigation,
including research development, testing and evaluation, designed
to develop or contribute to generalizable knowledge.
Human subjectsliving individual(s) about
whom an investigator (whether professional or student) conducting
research obtains (1) data through intervention or interaction
with the individual, or (2) identifiable private information.
LLNL IRB review is necessary even if LLNLs only contribution to
the research is to provide LLNL instrumentation. There is no distinction
based on whether the researcher collects the specimens or receives them
from another source. Indeed, if specimens are collected by one organization
and analyzed by another organization, typically the IRBs of both organizations
must review and approve the research.
Before a study involving human subjects begins, the Principal Investigator
must complete the following steps:
1. Identify the need to receive IRB review
In defining human subjects research activities, two separate determinations
must be made. The first determination is whether or not the activity can
be considered research. If the answer is yes, investigators
must follow up with a second determination: does the research involve
All research involving human subjects must be screened by the Laboratorys
IRB Office to determine whether further review and approval by the IRB
is required. This review must take place before the research activity
The term human subjects research potentially covers a broad
range of activities. The following list provides a few examples of research
activities that require IRB review and approval:
- The use of human-derived data.
- The use of human cell cultures.
- Projects or pilot studies in which the investigator is the only subject.
- Research projects in which information is sought or obtained either
directly from the subject (e.g., through an interview or questionnaire)
or indirectly (e.g., through observation of human subjects or access
to identifiable private records).
- Collaborative studies in which human material or information is collected
at another institution and sent to investigators at the Laboratory.
- Requests for information from third parties interested in conducting
human subjects research or concerning existing human subjects research.
- Donation of tissues, organs, fluids, or other bodily material for
- Research projects that require human subjects to participate in physical
- Evaluation of medical devices that are being developed to evaluate
health or detect disease.
- Research involving experimental or licensed pharmaceuticals.
When an investigator is unsure whether or not an activity involves human
subjects or should be considered research, s/he should contact the IRB
Office. The IRB Office will review supporting documentation of the
activity and promptly notify the investigator of the results of the review.
2. Complete IRB required training.
3. Make preliminary determination of level of
IRB review needed.
When an investigator is unsure of the level of review needed s/he should
contact the IRB Office for an administrative
review. The IRB Office will review supporting documentation of the activity
and promptly notify the investigator of the results of the review.
4. Submit the appropriate request for review
to the IRB office.
If your study is eligible for Administrative Review, please submit a
Request for Exemption Form to the IRB office.
If you are submitting a new proposal for either full board or expedited
review, please review the following instructions:
If you are developing an informed consent document, please review:
Please review other factors to take into consideration
before submitting your protocol for review if your study involves:
- Large-scale DNA sequencing
- Foreign collaborations
- FDA-regulated studies
- Inclusion of vulnerable populations in research
- Federally sponsored studies
- Use of surveys, questionnaires, or interviews
- Use of advertisements, press releases, or bulletin board announcements
- Studies involving human embryonic stem cells, germ cells, and cell-derived
All IRB Forms are available for downloading
on this Web site.
5. The IRB will review the study and report
back its findings in writing to the PI. For information on the process
and deadlines, please review:
6. During the study, the PI must agree
to conduct the study in an ethical manner and meet certain regulatory
requirements. These requirements include:
For additional information and guidance please see Information, Policies, and Procedures
for the Review and Ethical Conduct of
Human Subjects Research.