New Investigator Instructions

Required Reading for All New Investigators

Table of Contents

Historical Background
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 participants.
  • Beneficence. This principal requires researchers to maximize potential benefits to participants and to minimize the potential of harm.
  • 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 manner.

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 community members.

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 policy.

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).

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IRB Review
Review by the Laboratory’s 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 or facility.
  • The activity involves the use of LLNL’s nonpublic information to identify or contact human research subjects or prospective subjects.

Definitions

Research—“a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.”
Human subjects—“living 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 LLNL’s 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 human subjects?

All research involving human subjects must be screened by the Laboratory’s IRB Office to determine whether further review and approval by the IRB is required. This review must take place before the research activity is initiated.

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 purposes.
  • Research projects that require human subjects to participate in physical activities.
  • 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.

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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 test articles

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.

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