Preparing a complete IRB protocol

Preparing the application
Designating the principal investigator
Specifying the number of research subjects
Payments to subjects
Advertising and recruitment
Using investigational new drugs
Using investigational new devices
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 Preparing the Application

To submit a project to the IRB for review, you must draft a complete protocol describing all proposed human research activities.

A full protocol will include:

  1. A complete IRB Form #1, available here

  2. Any relevant appendices, available here 

  3. A lay summary describing the purpose of the study

  4. A description of the study population, criteria for including and excluding participants, the number of and the process of identifying subjects, and any other plans related to the selection of subjects

  5. A description of the tasks that subjects will be asked to perform

  6. A full description of the anticipated risks and benefits of participating in the study

  7. An outline of strategies for minimizing risks

  8. Documentation of provisions to care for subjects in case of accident, injury, or risk of harm to self or others, when applicable

  9. A full description of procedures for maintaining confidentiality

  10. A description of the process by which informed consent will be obtained from the appropriate individuals (for example, subjects, parents, cooperating institutions)

  11. Documentation of any required approvals or applications for approval from other committees and from cooperating institutions

  12. All supporting materials and documents, including interview schedules, solicitation letters, advertisements, descriptions of any medications, and any survey instruments that will be used

  13. Original signatures, including an academic advisor's signature for student research

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Designating the Principal Investigator

A human research project must be led by a Principal Investigator (PI).  The PI is the person who directs the project and bears ultimate responsibility for its conduct. Brown’s policy defines who may serve as a PI on a Brown University human research protocol as an individual who is a Brown University:

(a) faculty member (including clinical, postdoctoral, adjunct, visiting, conducting the research project in his/her capacity as a faculty member); or

(b) graduate student or medical student (conducting the research project in his/her capacity as a graduate student or medical student); or

(c) staff member (conducting the research project in his/her capacity as a staff member)

[Note that undergraduate students (including those in the Program in Liberal Medical Education) may not serve as PI on a human research protocol.]

The IRB must ensure that PIs have the training and experience that the project requires. Researchers are given considerable latitude, however, in designating the PI. The IRB may have concerns about a human research project if it appears that the PI lacks training and experience in human subject research, or has a conflict of interest that could impact the PI’s ability to objectively ensure subjects' well-being.

Some research projects include a provision to delegate much of the recruitment or intervention to research associates. In those instances, an explanation of the training of the associates must be included in the protocol application.

Whenever there is a change in the PI or in the PI's status that affects the project, the IRB must be notified by way of an amendment to the protocol.

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Specifying the number of research subjects

The IRB is required to protect subjects from the first contact for possible recruitment. All subjects who go through the recruitment process even if they fail or decline participation screening must be accounted for. When asking for subjects please ask for a number large enough to account for this group.

The application must specify the number of study subjects to be recruited and undergo study activities. Exceeding the recruitment limits approved by the IRB is a violation of the protocol. The IRB must give prior written approval for any increase in subjects.

If it is difficult to predict how many subjects will be eligible or be attracted to a study, the optimum number should be specified. Responses such as "don't know" or "as many as we can recruit" to questions about the number of subjects are not acceptable.

Multicenter studies, in which data will be pooled and recruitment may vary, present a special problem for investigators. The application should provide information about the total picture, including both the number of subjects to be studied at the University or by University researchers and information on overall recruitment goals.

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Payments to subjects

Researchers may pay research subjects for their participation, but payment arrangements must be disclosed to and approved by the IRB and are subject to review. Subjects are not paid to assume risk, but can be compensated for the time and inconvenience involved in participating. Payment arrangements affect the fairness of recruitment plans, the balance of risks and benefits, and the adequacy of informed consent. Although there are no fixed formulas for determining whether payment plans are acceptable, the IRB restricts payment arrangements that appear to be coercive or present undue influence. Payment should not encourage subjects to participate or continue to participate against their better judgment.

The amount paid to subjects must correspond to the burdens of participation. For example, payment might defray parking charges or transportation costs. Payments may also be scaled to the time that subjects spend in a study or to the biological materials they donate.

Researchers are encouraged to offer gift certificates/gift cards or grocery vouchers rather than cash or checks. When children and adolescents are the subjects, researchers are encouraged to reimburse parents for parking or transportation and give a token payment or gift certificate to the child subject. Drawings and raffles are subject to the state laws and regulations governing games of chance and are generally discouraged.

Subjects must receive at least partial payment if they withdraw from a study. Withholding all payment until participation is complete is coercive. A modest lump sum can be paid after the subject's participation is complete if the arrangement is thoroughly documented in the consent form. An end bonus cannot exceed half the total payment provided to subjects.

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Advertising and recruitment

Advertisements are part of the informed consent process and subject selection process. Samples of all advertisements, such as flyers, newspaper ads, radio and television announcements, URLs, bulletin board tear-offs, and posters, along with an explanation of other methods of recruiting subjects, must be submitted to the IRB.

Advertisements should be submitted with the application or as soon as the principal investigator decides to use them. The content of advertisements should be limited to:

  • names of the investigators and the university identified by name along with contact information,

  • purpose of the research,

  • general eligibility criteria, and

  • straightforward and truthful descriptions of potential benefits, payment, or free treatment.

Advertisements should include the word "research" and should not claim, explicitly or implicitly, that the research is treatment or is superior to any current practice. Extravagant attention-getting devices such as extremely large, bold typefaces and dollar signs are prohibited. Statements of payment should not be in larger type than the rest of the ad. Advertisements should not pressure readers into participating.

The IRB's authority for review and approval of advertising is supported specifically by the FDA, 21 CFR 56.111(a) (3): PHS Information Sheet, January 1988.

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Using investigational new drugs

Researchers who employ a test article classified by the Food and Drug Administration as an investigational new drug must assure the IRB that they are complying with the FDA's IND regulations (21 CFR 312). The IND number assigned to the test article must be filed with the IRB when the application for review is submitted.

Experimental drugs require an IND number if they are used to develop information about their safety or efficacy.

Approved, marketed drugs may also require an IND, if proposed use is:

  • different from its previously FDA-approved use,

  • administered by an unapproved route or method of delivery, or

  • an altered dosage form,

  • shipped by interstate commerce in order to conduct a clinical trial.

The FDA has published several exemptions to the IND requirements. Roughly, a clinical investigation may be exempted from the IND requirements if the drug is lawfully marketed in the U.S. and all the following apply:

  • the results will not be reported to the FDA to support a new indication for use nor to support any other significant change in the labeling of the drug;

  • the investigation will not be used to support a significant change in the advertising of a prescription drug that is already on the market;

  • the investigation does not involve a route of administration, dosage level, use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;

  • the investigation is conducted in compliance with the requirements for institutional review set forth in Part 56 and with the requirements for informed consent set forth in Part 50; and

  • the investigation is conducted in compliance with the requirements of section 312.7, which concerns the promotion and sale of investigational drugs.

The IRB requires detailed discussion of all these points when an exemption from IND requirements is requested.

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Using investigational new devices

Researchers who employ a significant risk device classified by the Food and Drug Administration (FDA) as an investigational device must assure the IRB that they are complying with the FDA's Investigational Device Exemptions(IDE) regulations (21 CFR 812 or 814). The IDE number assigned to the test article must be filed with the IRB when the application for review is submitted.

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