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Submitting Research Protocols to the
Institutional Review Board

Volume III, Number 4 | September/October 2000
Kenneth Sherman, Pharm.D.

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Figure 1

Introduction

These are challenging times for Institutional Review Boards (IRBs). They are placed in the unenviable position of protecting research subjects in the face of increased pressure to hasten protocol approval times that keep the research machine churning at peak efficiency. The National Institutes of Health (NIH) Office for Human Research Protections (OHRP) has 'turned up the heat' on IRBs. Duke, Rush-Presbyterian-St Luke's Medical Center in Chicago, and the Los Angeles Veteran's Administration Hospital are just three examples of the numerous high-profile institutions that have had clinical research shut down by OHRP in the last year and a half for IRB violations. Conversely, there appears to be no decrease in the number of research protocols that IRBs must evaluate. There was a marked increase in the 1990's in both research spending by pharmaceutical companies and the number of new agents approved by the Food & Drug Administration (FDA). Serving a busy, prominent institution, the IRB at the Cleveland Clinic Foundation (CCF) feels the full weight of these seemingly opposing forces.

The level of scrutiny with which the CCF IRB evaluates protocols will probably not decrease. Therefore, in the interest of timely approvals, it would benefit the researcher to have a general understanding of the function of the IRB and the proper procedures for submitting research protocols. The Federal Regulations from the Department of Health and Human Service's OHRP mandate that an "IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities." The Board of Governors (BOG) at this facility has delegated this authority to our local IRB with the stated goal "to protect the rights and welfare of human research subjects recruited to participate in research activities (at) CCF." The Federal Regulations define research as "a systematic investigation, designed to develop or contribute to generalizable knowledge." The layman's interpretation of this is: all systematic investigations at CCF designed to develop or contribute to generalizable knowledge needs to be approved by our IRB before the project can start.

IRB Submissions (See Table 1): Most projects meeting the above definition of research require a full IRB submission, which includes an IRB application, a corporate compliance checklist, an informed consent document, an investigational drug brochure, and a copy of the grant submission for any projects applying for funding (e.g., NIH funding). If a project is funded by a commercial sponsor, a review and monitoring fee of $1,000 must accompany the submission. The application and corporate compliance checklist are available from the IRB office (ext. 4-2924).

Table 1:  Types of IRB Submissions
Type
Risk
Subject Identifiers Collected or Traceable?
Full Board Review
> minimal
Yes
Expedited Review
<= minimal
Yes
Exempt Review
<= minimal
No

Following a full board submission, a project is evaluated by the IRB using the following three criteria: 1) risks to subjects are minimized, 2) risks to subjects are reasonable in relation to anticipated benefits, and 3) the selection of subjects is equitable. Prior to the IRB meeting, all members of the IRB receive materials regarding each submission on the agenda. A primary reviewer makes comments to the full Board (i.e., a meeting at which a quorum is present) regarding the submission. All other comments are heard, and then the Board votes on the submission. There are four potential outcomes of a vote: approval, conditional approval, tabled, and not approved. If the Board votes to conditionally approve or table a project, modifications or clarifications need to be made based on the Board's comments. Investigators need an approval letter from the IRB before they can begin their research.

There are two types of projects that do not require full IRB approval. The first of these, called an expedited review, is reserved for projects that pose no more than minimal risk to the research subject but do collect subject identifiers. In an expedited review, the IRB Chairperson or his/her designee(s) review the application and approve it. Such reviews are discussed at the next full IRB meeting only if the initial reviewer(s) reject the submission. A comprehensive list of what constitutes no more than minimal risk can be obtained from the IRB office. Examples of such research include (with stipulations) blood draws from otherwise healthy individuals, collection of biologic specimens by noninvasive means, and research involving data that has been collected for non-research purposes (including retrospective chart reviews and drug use evaluations). In all cases, risks related to invasion of privacy and breach of confidentiality must be no greater than minimal. Informed consent procedures also apply for expedited submissions.

The second type of research that does not require full IRB review is an exempt submission. To qualify as exempt research, a study must pose no more than minimal risk and must not collect subject identifiers. Examples of types of research that may be considered for exempt status are chart reviews or drug use evaluations that collect data in a manner such that subjects cannot be identified, either directly or by linked identifiers. Such research is not subject to IRB review, although an abbreviated submission should be made using the Exempt Protocol form that can be obtained from the IRB office. A chart review that collects patient/subject identifiers requires an expedited review. Even though research is approved for exemption from full IRB review, the investigator is still responsible for fully protecting human subjects who are enrolled.

Informed Consent

Generally speaking, before a subject is enrolled into a research project, they must provide informed consent. In most cases this is done by using an informed consent document which the subject or their legal representative must sign. Informed consent is not simply just a signature on a form, but rather a process of information exchanged between the investigator and the research subject. The consent document should serve to foster an exchange of information between the investigator and the subject. It should be written in lay language, avoiding technical terms. The required components of the informed consent document are listed in Table 2. Specific guidelines for informed consent documents can be obtained from the IRB office. There are certain special cases and exceptions to the informed consent process such as consenting non-English speaking subjects and children, and emergency research. Information about these special cases can be obtained from the IRB office.

Table 2:  Required Elements of the Informed Consent Document
Section Purpose
Statement of Research*
Tells subject that they must give informed consent prior to enrolling in research
Encourages Questions
Information on the Research States the purpose of the research and the procedures
Risks and Discomforts A description of any potential discomfort and/or risk, including loss of confidentiality
Benefits A statement of the potential benefits of the research
Alternative Procedures of   Treatment Alternative procedures and courses of therapy
Confidentiality* States who has access to research records and   how confidentiality will be maintained
Research-related Injuries* States that CCF will not voluntarily provide compensation for research-related injuries
States who, if anyone, will provide compensation for
research-related injuries
Questions About Research* States who to call if the subject has questions
Voluntary Participation* States that participation in the research is voluntary and future treatment at CCF is not influenced by participation in or withdrawal from the study
Costs* States that CCF will not pay the costs of research
States who, if anyone, will pay these costs
Signatures* Signature of subject and a witness

 *CCF IRB has standard preferred language for these sections

The informed consent process can be waived only if four criteria are met. First, the research must involve no more than minimal risk. This means that the probability and magnitude of harm involved in the research cannot exceed those ordinarily encountered in daily life. Secondly, waiver of informed consent will not adversely affect subject rights and welfare. Thirdly, the research could not be practicably carried out without waiver. Lastly, subjects must be provided with pertinent information after participation

Conclusion

The IRB submission process can be difficult for investigators. The myriad of regulations can create confusion about when a submission is required and how the submission should be completed. In general, most research protocols need a full IRB submission and informed consent of research subjects. Exceptions to this are defined in the Federal Regulations. When ambiguity exists, the IRB should be consulted for guidance. The IRB at CCF is willing to help investigators through this process while protecting the welfare of research subjects.

References Available Upon Request

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Copyright © 2000-2017 The Cleveland Clinic Foundation. All Rights Reserved.
Center for Continuing Education | 1950 Richmond Road, TR204, Lyndhurst, OH 44124