Module 3

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Module 3: The IRB Review Process

Institutional Training for Human Subjects Research

Learning Objectives

Upon completion of this lesson, you should be able to identify:

1. Whether policies for the protection of human subjects apply to your research

2. When IRB review and approval are or are not required

3. What you are expected to do if your research involves human subjects, but you believe it is exempt from IRB review and approval.

4. Steps you must take before you collaborate in research involving human subjects at other institutions

Before beginning a research activity, you need to answer three critical questions about it:

1. Is the activity in which you will be engaged defined as RESEARCH?

2. Will the activity involve HUMAN SUBJECTS?

3. Does the activity require IRB REVIEW and APPROVAL

The following decision tree will help you answer these questions.

**The Institutional Review Board (IRB) will ultimately determine if the proposed project is exempt from review and approval, not the investigator

Question 1. Is the proposed activity RESEARCH?

The definition of research in the KWU IRB policies is: a systematic investigation designed to develop or contribute to generalizable knowledge. Compare your proposed activity with the definition of research. And ask yourself the following questions:

Is the activity designed to produce generalizable knowledge? In other words, will the information derived from the activity be applicable to other cases?

Will the information be gathered systematically? In other words, will it be arranged so that conclusions can be drawn, and so that others can review those conclusions (i.e. activities which may later be published or publicly presented)?

If your answers to the previous questions are NO, then your proposed activity does not meet the definition of Research, and the KWU IRB does not apply to the activity.

However, if your answers to the previous questions are YES, then the activity IS research and you should proceed with Question #2 of the decision tree.

Important clue: The intent to publish the results of an activity, almost always means that it is research.

Question 2. Does the proposed activity involve HUMAN SUBJECTS?

If the activity is defined as research, then you need to ask, does the research involve any Human Subjects? A human subject is involved if:

The person is alive and

Data pertaining to the person will be obtained through:

Intervention (e.g., taking a blood sample)

Interaction (e.g., taking a medical or personal history).

A private/confidential source (e.g., from medical or personnel records).

Types of activities that are NOT covered by the definition of Human Subjects and are NOT subject to the IRB include research use of:

Samples from dead or cadaverous individuals

Samples or data available from commercial or public repositories or registries

Established cell lines available to qualified scientific investigators

Self-sustaining free-cell derivative preparations including viral isolates, cloned DNA or RNA

Note: Some of these activities may be subject to other laws or regulations. In most cases, the determination as to whether a particular research activity involves human subjects or not is not difficult.

Sometimes, the issue is not so clear. When in doubt, contact the Chair of the IRB for help or clarification.

If your proposed activity is RESEARCH, AND involves HUMAN SUBJECTS, you must submit a proposal to the KWU IRB. The KWU IRB will decide if your proposed activity is EXEMPT from review.

Question 3. Is your proposed activity exempt from IRB review and approval?

** Remember that the KWU IRB makes the final determination if a project is exempt or not.

There are six categories of Research involving Human Subjects that are EXEMPT from the provisions of IRB review and approval. The general rationale behind the six exempt categories is that, although the research involves human subjects, it exposes them only to very small physical, social, or psychological risks that are similar to the risks they take in everyday life - such as applying for a job, answering telephone surveys, tasting food, etc. Adults who engage in these and similar activities can be expected to understand and accept the small risks they are taking. Therefore, for this reason, they need no special protection offered by IRB review and approval.

Some of the most frequently conducted research activities that are EXEMPT from IRB review involve the study or collection of existing records or samples (e.g., pathological specimens, data) if these sources are publicly available or if the information is recorded by the investigator so that subjects cannot be identified directly or through identifiers linked to subjects. The Six Exemptions from 45 CFR 46 are:

1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as research on regular and special educational instructional strategies; or effectiveness of, or the comparison among instructional techniques, curricula, or classroom management methods.

2. Research involving the use of educational tests (cognitive diagnostic attitude achievement), survey procedures, interview procedures or observation of public behavior, unless information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers, linked to the subjects, and any disclosure of the human subjects responses outside of the research could reasonably place the subjects at risk of criminal or civil liability, or be damaging to the subjects financial standing, employability, or reputation.

3. Research involving the use of educational tests (cognitive diagnostic attitude achievement), survey procedures, interview procedures or observation of public behavior that is not exempt under #2 if the human subjects are elected or appointed public officials or candidates for public office or federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

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.

5. Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine public benefit service programs, procedures for obtaining benefits or services under these programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs.

6. Taste and food quality evaluation and consumer acceptance studies if wholesome foods without additives are consumed, or a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, an agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

An example of an exempt project: research analysis of stored human blood samples from which all identifiers have been completely removed. In this hypothetical example of exempt research, the samples stored are “existing,” (e.g., they are stored in a freezer), and there are NO IDENTIFIERS, therefore, subjects cannot be identified. Note that the identifiers can include names, initials, social security numbers, patient numbers or codes, or student ID numbers. Investigators should be cautious when using such identifiers in their research and should not assume that the use of codes renders research data exempt from IRB review.

Even if you believe your proposal is Exempt from IRB review and approval, you must complete the IRB Application for Review for a project involving Human Subjects.

Research Protocol Format

The format for a research protocol submitted by the principal investigator (PI) to the Committee on Research Involving Human Subjetcs (IRB) includes:

A description of, and scientific rationale for the proposed research activity

A discussion of the human subjects protection issues which addresses at a minimum:

The risks to subjects.

All experimental procedures that may be a risk.

The anticipated benefits to subjects, if any.

The usual format for a research protocol submitted by the principal investigator (PI) to the IRB includes:

Subject selection, recruitment procedures, and the anticipated number of subjects.

The proposed consent document and process to be used.

Appropriate additional safeguards if potentially vulnerable subjects are to be enrolled. Potentially vulnerable subjects include the elderly, prisoners, children, cognitively impaired people, or people who are economically or educationally disadvantaged.

IRBs review research from the vantage point of protecting the rights and welfare of human research subjects and are required to evaluate proposed research activities using the following criteria:

1. The design of the study is consistent with sound scientific principles, ethical guidelines, and legal requirements.

2. Risks to subjects are minimized by using procedures that are consistent with sound research design and do not unnecessarily expose subjects to risk.

3. Risks to subjects are reasonable relative to anticipated benefits, if any, to subjects and the importance of the knowledge that may reasonably be expected to result.

4. The necessary elements of informed consent have been met and documented, and additional elements added when appropriate.

5. Additional appropriate safeguards have been provided if potentially vulnerable subjects are to be studied (e.g., children, prisoners, financially or educationally disadvantaged people).

6. Subject selection is equitable, with attention to the inclusion of minorities and both genders in study populations so that research findings can be applied to all persons at risk for the disease or condition under study.

In exercising their authority, IRBs may approve, disapprove, or table research protocols. However, IRBs are obligated not to approve any protocol that does not meet the criteria previously presented. Most often, the IRB approves a research protocol with required changes, referred to as stipulations. Research may not begin until the stipulations have been met in writing by the P.I. Once the IRB approves your protocol and you reply to any stipulations that are required by the committee, you will receive an approval letter authorizing you to proceed with your project as described in your protocol. As part of its statutory responsibility to monitor ongoing human subjects research activities on campus, you will be required to update the committee at least annually on the status of your project.

Collaborative Research

Special provisions must be made if you intend to collaborate in non-exempt research involving humans at sites other than KWU. These provisions are required because when you collaborate, you accept some measure of responsibility for protecting the rights and welfare of the human subjects involved.

What constitutes “collaboration” by an investigator? Collaboration exists if the investigator expects “something in return” as a result of having participated in a research activity. “Something in return” could include data, authorship on a publication, samples, or even patent rights. KWU views authorship as prima facie evidence of collaboration. Collaborative activities may include but are not limited to:

Collection of specimens

Visits to institutions to perform research activities or clinical research

Exchange of information containing personal identifiers

Preliminary data collection activities involving human subjects

Substantive intellectual contributions to research techniques, protocol design, or interpretation of data.

More remote participation -- such as supplying important reagents, performing laboratory analyses, or analyzing data, may also constitute collaboration.

The degree of review required for collaborative research projects depends on the nature and the extent of the collaboration. In order to collaborate in research where subjects are enrolled other than at KWU, you should ask your collaborator if his/her institution has an IRB. Most organizations with which you are likely to collaborate will have a Multiple Project Assurance (MPA). A list of MPA-holding institutions is at a National Institures of Health (NIH) web site at http://helix.nih.gov:8001/ohsr. When you are collaborating with an investigator in an institution with an MPA in non-exempt research with human subjects, research may begin only when both you and your collaborator have formal documentation of IRB approval. When you want to collaborate in research at any non-MPA domestic site or in foreign countries, you need assurance that the rights and welfare of human subjects involved are appropriately protected. This is done by negotiating a Single Project Assurance (SPA). An SPA is a formal agreement between an institution and the NIH’s Office for the Protection from Research Risks (OPRR) that the institution will abide by the ethical principles of The Belmont Report and 45 CFR 46 in its conduct of a specific collaborative research project.

Summary of Important Points in this Lesson

1. The requirements of the KWU IRB apply to all research involving human subjects, including collaborative activities that enroll subjects at sites other than KWU.

2. If you apply the decision tree shown in this lesson, you will be able to analyze whether or not a particular research activity involves human subjects.

3. When your research involves human subjects, you should not begin until it has received IRB review and approval OR is determined by the IRB to be exempt from IRB review.

4. The mandate of the IRB is to review research in order to protect the rights and safeguard the welfare of human subjects at KWU.