Protecting Human Subjects Guide

3. How to Apply for Review

The central task of the Institutional Review Board (IRB) is to ensure that a project's risks are justified by its benefits. 

3.1 The IRB process

The IRB reviews a proposal by first assessing the risks and benefits of research participation. After determining that the research benefit outweighs the risks involved, the IRB turns to the consent process to ensure that subjects are fully aware of the risks and the benefits and that they participate in the project voluntarily. The consent form is a key element in this review.

After reviewing the application and its supporting materials, the IRB may require revisions in the protocol. When the investigator revises a project, the IRB reviews the project again to see whether its concerns have been adequately addressed. A project may undergo several reviews.

To fully protect subjects, the IRB must approve a project before investigators start to work on it--even before they begin to recruit subjects, since recruitment strategies are part of the review. Although there are different types of review, many projects require "full" committee review. The initial full review will occur within two weeks of submission if the application is complete. All IRB actions are communicated in writing to the investigator by the IRB staff.

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3.2 Primary types of review

Research projects are reviewed at one of three levels, according to the IRB's determination of the project's potential risk to the human subjects and the federal guidelines that define the categories of review, which are:

• screening for exemption from full IRB review,
• expedited IRB review, and
• full convened IRB review.

The level of review is determined only by the IRB.

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3.3 Screening for exempt status

Investigators do not have the authority to determine whether research involving human subjects is exempt from full review 45 CFR 46.101(b) and (c)  & 21 CFR 56.104(c) and (d). Hence, while research that involves only minimal risk to human subjects is sometimes exempt from full IRB committee review, it is still subject to IRB review. Researchers must file an application requesting that the IRB determine exempt status for a project.

In general, the federal guidelines for research on human subjects allow a project to be exempt from full review only if the research involves no risk to the subject and the procedures are limited to the following criteria:

1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:
   (i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and
   (ii) any disclosure of the human subjects' responses outside 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, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if:
   (i) the human subjects are elected or appointed public officials or candidates for public office; or
   (ii) 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:
   (i) Public benefit or service programs;
   (ii) procedures for obtaining benefits or services under those programs;
   (iii) possible changes in or alternatives to those programs or procedures; or
   (iv) 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,
   (i) if wholesome foods without additives are consumed or
   (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or 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.

Projects that involve contact with subjects may still qualify as exempt. Copies of the written consent form should be filed with the application or justification for a waiver of written documentation should be provided. See 45 CFR 46.117.

The application form, titled Exempt Screening Application Form, is available from the Human Research Protection Program office or its Web site.

The IRB administrator decides whether the project qualifies as exempt, and the decision is confirmed in writing, most often within one week. If the project does not qualify as exempt, it is referred back to the investigator with the appropriate application forms.

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3.4 Expedited review

To qualify for expedited review, a research procedure must be limited to the activities that are federally approved (from 63 FR 60364-60367, November 9, 1998.) for expedited review and incur no more than minimal risk for participants, or be a minor change in previously approved research that involves no additional risk to the research subject.

The activities approved in the federal regulations for expedited review are:

1. Clinical studies of drugs and medical devices
2. Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture
3. Prospective collection of biological specimens for research purposes by noninvasive means
4. Collection of data through noninvasive procedures
5. Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes
6. Collection of data from voice, video, digital, or image recordings made for research purposes
7. Research on individual or group characteristics or behavior
8. Continuing review of research previously approved by the convened IRB
9. Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified

The researcher must demonstrate in the application how the proposed project activities fall into one or more of these categories.

To apply for expedited review, investigators complete complete either the Health & Medical/Biological or the Social & Behavioral Sciences Application Form and indicate that they are requesting expedited review in the appropriate section.

The IRB administrative staff assures that all of the elements essential for review, including consent forms and supporting information, have been submitted. The application is then forwarded to a designated committee member for review and decision. Either the research is approved (perhaps with stipulations) by the committee member or it is forwarded for full review.

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3.5 Full review

A project that involves greater than minimal risk requires approval by an IRB panel composed of members qualified to review research in that field. Research that requires full committee review includes:

• research that involves greater than minimal risk
• non-exempt research that involves children or other vulnerable populations;
• research that involves experimental drugs or devices;
• research that involves invasive procedures; and
• research that involves deception.

Survey research that involves sensitive questions or information about sexual practice or illegal behavior is subject to full review, in keeping with federal guidelines. Any survey or interview that is likely to be stressful for the subject requires full committee review. IRB staff will make this determination.

All applications are screened by the administrative staff before they are assigned to an IRB panel; if the application is incomplete, it is returned to the investigator. After review by the IRB panel, the application will be:

• approved as submitted;
• approved with minor suggestions for changes;
• approved with stipulations (conditions that must be met before final approval is granted) - most common;
• deferred, pending receipt of additional information or major revisions; or
• not approved.

All non-exempt research is subject to continuing review at least annually[see 6.1 Continuing Review]. If research involves significant risk to subjects, the IRB may require more frequent review and may ask to be kept apprised of all research activity. For example, researchers in acute care settings or whose research involves novel therapies are asked to submit their protocols for frequent review.

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3.6 Class Protocols for Research Methods Courses

If the overall objective of a course assignment is to learn about the design and conduct of research projects, and if data will be collected and analyzed for classroom learning only, a request for approval of a Class Protocol should be filed with the IRB office by submitting an application.

If the same Class Protocol will be used in several courses during an academic year, the IRB may be able to approve all uses with a single application. The protocol must be reevaluated annually, however, to ensure that the guidelines are maintained and to bring the protocol up to date with any changes in the federal guidelines.

Very ambitious projects and projects that involve sensitive topics and vulnerable populations are not suited to the Class Protocol process. These must be pursued as individual projects.

An example of an acceptable Class Protocol is a course in psychology taught several times per year by different faculty members. The course involves a cluster of independent projects conducted by the students. In this case, students complete IRB application forms and submit them to their instructors for review and approval. The Course Protocol adheres to the following terms:

• the instructor will direct students to complete basic level training for human subject protection
• student projects will be reviewed by course faculty;
• students will draw their research subjects from the student population (if extra credit points are awarded to subjects, a faculty member will determine whether the points awarded are appropriate in light of the time spent by the subject);
• student projects will not involve any personal, sensitive, or incriminating topics or questions that could place subjects at risk;
• the projects will not manipulate the behavior of students in any way beyond the range of normal classroom activity or college life; and
• the projects will not involve physically or psychologically invasive contact with the subjects.

Please see section 2.5 to find more about research in classes and research conducted by students.

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3.7 Application forms and original signatures

All forms that an investigator must file with the IRB to apply for review are available, with specific instructions, on the Web at http://www.research.umn.edu/subjects, or from the Human Research Protection Program (HRPP) office. The HRPP staff can help researchers determine which level of review is appropriate for a project. The forms are: 

• Exempt Screening Application Form
• Health & Medical/Biological Application Form (expedited or full review)
• Social & Behavioral Sciences Application Form (expedited or full review)

Providing original signatures

A signature page provides space for the signature of the principal investigator and co-investigators. Original signatures are required here. An original signature certifies that the investigator will be actively involved in the research project and has made a commitment to protect the research subjects according to the federal regulations.

Others besides the investigators need to sign, too. Academic advisers must sign all student research proposals, and department heads must sign all faculty, staff and student proposals. Some colleges and campuses have imposed additional signature processes. Check with your local department to assure compliance.

All other documents submitted to the IRB (such as interim reports, requests for changes in protocol, reports of adverse events, requests for renewal of approval) must be accompanied by correspondence signed by the principal investigator. Staff signatures are not accepted. The principal investigator remains ultimately responsible for protection of subjects.

Finally, before submitting the application with original signatures, investigators must:

• make a copy of the application for their own records, and
• make multiple copies for the IRB:


For full IRB review, attach:
1. 12 copies of the application,
2. 12 copies of the consent form,
3. 1 copy of the complete protocol, and
4. any additional information.

For expedited review, attach:
1. 3 copies of the application,
2. 3 copies of the consent form,
3. 1 copy of the complete protocol, and
4. any additional information.

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3.8 Preparing the application

To submit a project to the IRB for review, an investigator must complete the application form according to detailed instructions and enclose supporting material as necessary.

A fully completed application form will include:

1. an up-to-date version of the appropriate application form (available on web site),
2. answers to every question on the form,
3. appropriate appendices to the application,
4. a lay abstract describing the purpose of the study,
5. 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,
6. a description of the tasks that subjects will be asked to perform,
7. a full description of the anticipated risks and benefits of participating in the study,
8. an outline of strategies for minimizing risks,
9. documentation of provisions to care for subjects in case of accident or injury,
10. a full description of procedures for maintaining confidentiality,
11. a description of the process by which informed consent will be obtained from the appropriate individuals (for example, subjects, parents, cooperating institutions),
12. documentation of any required approvals or applications for approval from other committees and from cooperating agencies,
13. all supporting materials and documents, including protocol, interview schedules, solicitation letters, advertisements, descriptions of any medications, and any survey instruments that are rarely used or are designed by the investigator (common standardized instruments can be merely cited), and
14. appropriate original signatures, including an academic adviser's signature for student research and department head signatures for all research.

The application form alone will be used as background information for all future reviews of the study; therefore, "see protocol" is not an adequate response to any application question.

No form can adequately address the wide diversity of research at such a large institution. Principal investigators should use the form to convey the nature and specifics of the project proposed attaching appendices as necessary.

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3.9 Designating the principal investigator

A research project is headed by a principal investigator (PI). At one time, federal regulations for human subjects research allowed the PI to shoulder most of the responsibility for a project. Recently, though, the regulations have emphasized that the whole research team shares responsibility, even though the PI directs the project and bears ultimate responsibility for its conduct.

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 is most likely to have concerns about projects in which the principal investigator appears to lack training and experience in human subjects research or has a conflict of interest that could make it difficult for him or her to ensure the subjects' well-being. If external funding is being sought, the University's policies on Principal Investigator Eligibility on Sponsored Projects also must be met.

Some research projects include a proposal to delegate much of the recruitment or intervention to research associates. In those instances, an explanation of the training of the associates should accompany the application.

Whenever there is a change in the PI or in the PI's status that affects the project, the IRB must be notified. [See section 6.2 Making changes to research protocols]

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3.10 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 tested, grouped by age, gender, and population diversity. 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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3.11 Women and minorities in study populations

Research benefits and burdens should be distributed fairly. If an individual or group is denied access to a clinical trial that might be beneficial or if some people are singled out to bear the burden of risks associated with a study, the requirement for fairness is not met.

In accordance with the policies of the National Institutes of Health, the IRB requires researchers applying for federal funds to give breakdowns of their subject populations by gender and minority group. Studies with the potential to address issues relevant to both sexes must recruit both genders, and minority populations should be included in a study population wherever feasible. Researchers must justify the exclusion of any group of individuals. The IRB makes exceptions if there is adequate scientific justification for exclusion, such as when a disease predominates in one gender or the focus of the research question is on a specific group.

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3.12 Students or employees as research subjects

Though the researcher may be careful to avoid potentially coercive behavior, the very nature of the relationship with the subject can create the appearance of coercion. For this reason, researchers should be aware of the potential for coercion that exists when a research subject is also a student, employee, colleague, or subordinate of the researcher. For this reason, researchers should avoid using their own students or employees as research subjects.

If there is a good scientific reason to include their own students, researchers should:

• Make sure students clearly understand that their participation will not influence class standing, grades, or other benefits under the control of the researcher.
• Limit the use of extra credit points as a reward for participating; points should be used only when the research is closely tied to the course subject matter and they should not raise a student's grade by a whole step (for example, from a B to an A).
• avoid using class time to recruit subjects or complete study instruments.

Researchers who include colleagues or subordinates as research subjects, must be able to provide a rationale other than convenience for selecting them and must show that the recruitment method does not lead colleagues to think they will be compromised by not participating. Usually recruitment through bulletin board advertisements or by a third party is preferable.

Information about how students and colleagues will be recruited and how coercion will be avoided should be included in the information submitted to the IRB.

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3.13 Children as subjects

All research conducted is subject to the application of 45 CFR Subpart D. In all cases, inclusion or exclusion of children is reviewed for appropriateness as defined in the regulation.

In general, if research involves greater than minimal risk, children can be included in the study population only if there is direct personal benefit to the child. This restriction applies to research in both the health sciences and the social sciences. A research protocol that involves anything more than minimal risk and that offers no potential benefit to the subject cannot involve children unless all conditions of 45 CFR 46.406 are met. Investigators claiming this provision in 45 CFR 46.406 should be prepared to provide rigorous justification.

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3.14 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 a stringent 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. 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. The minimum wage provides a ready baseline for hourly rates for participation, and the Blood Bank's payment scale for plasma and other blood products offers a guideline for compensating subjects for biological materials.

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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3.15 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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3.16 FDA regulations for designating the principal investigator (PI)

Some additional requirements for PI designation apply to projects that fall under the guidelines of the Food and Drug Administration. The FDA defines an "investigator" as an individual under whose immediate direction a test drug or device is administered or dispensed to a subject. "Subinvestigators" are team members who may help design and conduct the investigation but are not charged with overseeing the investigation. Some team members such as pharmacists, research coordinators, and others who do not deal directly with subjects would not be listed as investigators.

Investigators involved in drug studies must sign an FDA State of Investigator agreement (Form FDA-1572), which documents the investigator's commitment to supervise the investigation. No standard agreement exists for device studies. Instead, the device study sponsor prepares a draft agreement and negotiates its terms with the investigator, following the FDA's regulations for investigational devices. Principal investigators should provide current copies of 1572 to the IRB.

The University IRB needs to be notified when a U of M faculty/staff member or student is identified on an FDA investigator agreement, so it can make sure that its records agree with the FDA's.

The relevant federal regulations are 21 CFR 312 and 21 CFR 812, as well as the March 1995 FDA "Information Sheet."

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3.17 Women in clinical trials

Food and Drug Administration guidelines implemented in 1993 give IRBs broad discretion to encourage the entry of women into the early phases of clinical trials.(see the NIH's Women's Health Initiative for more information)

The guidelines now encourage women with childbearing potential to participate in entry phase 1 and early phase 2 trials. FDA believes that early drug trials can be safely conducted on women, even before all animal studies are completed, through sound protocol design. Studies can include pregnancy monitoring, pregnancy testing, and counseling about contraceptives or abstinence. Participants can also be referred to gynecologic consultants for advice.

The guidelines also direct sponsors to collect gender-related data during research and development and to analyze the data for gender effects. New drug applications must include a characterization of drug effects by gender.

The guidelines stress that pharmacokinetic data on demographic differences should be collected beginning in phase 1 and 2 studies. When it is feasible, three pharmacokinetic issues should be considered when women subjects are involved:

1. the effect on the stages of the menstrual cycle,
2. the effect of exogenous hormonal therapy including oral contraceptives; and
3. the effect on the pharmacokinetics of oral contraceptives.

Consent forms should include a statement that there may be unknown risks to the fetus if a woman becomes pregnant while participating in a clinical trial.

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3.18 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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3.19 Using investigational new devices

Researchers who employ a significant risk device classified by the Food and Drug Administration 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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3.20 Labeling investigational drugs

Requirements for labeling investigational products are similar to those required for prescription medications. FDA regulations for labeling (21 CFR 312.6) indicate the following:

1. The immediate package of an investigational new drug intended for human use shall bear a label with the statement "Caution: New Drug?Limited by Federal (or United States) law to investigational use.
2. The label or labeling of an investigational new drug shall not bear any statement that is false or misleading in any particular and shall not represent that the investigational new drug is safe or effective for the purposes for which it is being investigated.

In addition, state regulations for labeling prescription drugs apply to investigational drugs (see Minnesota Statutes 151.06 subd 1, 151.212 subd 1):

All drugs dispensed to or for a patient (other than an inpatient of a hospital) shall be labeled with the following:

1. Name, address and telephone number of clinic dispensing
2. Subject's name or identifying number
3. Prescription number, or way of tracking the dispensing
4. Name of prescribing physician
5. Directions for use
6. Name of manufacturer of the finished dosage form (there may be an exception due to investigational status)
7. Auxiliary labels as needed, e.g. "Take on empty stomach."
8. Date of original issue or renewal
9. Generic or trade name of drug and strength or study name to identify drug

There may be some flexibility allowed for labeling due to the unique nature of investigational studies, particularly studies involving a placebo.

Sample label:

Univ of MN Clinic Name Address, Phone number       Tracking Number (ie visit number) Subject ID (name or initials) Date of issue: Prescribing MD, or PI if MD Drug name and strength or study acronym (Manufacturer)     Directions for use.

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3.21 Research involving ionizing radiation

To facilitate the review of applications for research involving radiation exposure, the IRB and the Human Use Subcommittee of the All University Radiation Protection Advisory Committee (HUS-AURPAC) have revised the applications to both committees.

Projects involving higher levels of radiation exposure, or exposure of vulnerable subjects (e.g. pregnant and/or breast feeding subjects, or minors), and/or subjects who receive a radiation dose above 100 millirem, require full review by the HUS-AURPAC. Projects that involve low-level radiation exposure (100 millirem or less) or routine clinical care and that have been approved by the IRB qualify for expedited review by the HUS-AURPAC chairperson.

IMPORTANT: if the radiation dose received by a subject in a study is a part of their normal medical care, and would be received even if they did not participate in the study, the study does not require review by the HUS-AURPAC.

Radiation exposures which may qualify for expedited review by the HUS-AURPAC chairperson are listed in Section 2. of the HUS application form entitled, "Conditions for Accelerated HUS Review". The HUS application form is available on-line at http://www.dehs.umn.edu/rpd/forms/HUS.pdf Listed below are some examples of ionizing radiation procedures for which accelerated review by the HUS may be authorized:

1. Single plane-film radiographic procedures that do not involve cineradiography, fluoroscopy, or any form of tomography, such as (a limited number of) X-rays of: joints; cervical spine; PA or lateral chest; PA, AP or lateral skull; AP scapula or shoulder; femur; AP, PA or lateral abdomen, AP pelvis; mammogram.
2. A limited number of nuclear medicine labeling procedures including Tc-99m and Xe-133.
3. Bone mineral analyses (DEXA scans).
4. Cancer therapy studies with a protocol that has already been reviewed by a national study group (for example, RTOG or CALGB), provided the study group's review criteria have been approved by the HUS-AURPAC.

Research conducted at another site requires review by the radiation review committee at that site. Our University IRB should receive documentation of that review.

Application sheets for HUS-AURPAC review are available on-line (http://www.dehs.umn.edu/rpd/forms/HUS.pdf) or from the HRPP office and from the Radiation Protection Division (612/626-6764). If assistance is needed in completing dose calculations for HUS-AURPAC review, contact a medical physicist in the University's Department of Radiology (612-626-6805).

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3.22 Emergency waivers

Physicians sometimes decide they must administer a drug, biologic, or experimental agent that has not yet been approved for marketing by the FDA. In such cases, the IRB can grant a waiver for an "emergency use." "Emergency use" is defined as the use of an experimental device on a human subject in a situation that is life-threatening, in which no standard acceptable treatment is available, and in which there is not enough time to obtain full IRB board approval.

When a physician must employ experimental medicines or devices to care for a patient in a life-threatening situation, neither the IRB nor the clock nor the calendar should interfere.

The IRB trusts physicians to exercise their best clinical judgment, to use experimental medications when necessary, and subsequently to take the appropriate steps to request approval or inform the IRB.

When emergency medical care must be provided without prior IRB review and approval, the patient may not be considered a research subject. The emergency care may not be claimed as research, nor may the outcome be included in any report of research activity.

Procedures during business hours

If the need for emergency use arises during the business day, the procedure to secure a waiver is as follows:

1. The physician notifies the IRB office by telephone of a pending request for emergency use.
2. The IRB administrative staff refers the physician to the IRB chair, or to a physician designated by the chair, to secure oral approval.
3. Within five working days of the request, the physician provides the IRB office with written documentation of the oral approval, a copy of the unsigned consent form used to document informed consent of the subject, and a report of the experience.
4. The IRB provides the physician with written confirmation of its approval. This should be maintained with the physician's records.

Many drug companies require IRB certification of approval to release drugs or biologics. The investigator is responsible for the paperwork required by sponsors, drug companies, and the FDA.

Procedures outside of business hours

If the need for emergency use arises when the IRB office is not open, the physician should:

1. secure approval, or agreement, from another physician who is not involved in the treatment of this particular patient,
2. alert the IRB office of the intended use by voice mail at 612-626-5654 or email at irb@umn.edu, and
3. report the action to the IRB office in writing within five working days.

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Next Section: 4. The Process of Consent