University of Wisconsin–Milwaukee

Under federal regulations, certain types of research may be exempt from Full Board IRB review if the study involves no more than “minimal risk” and falls into one or more of six categories (45 CFR 46.101 (b)). Minimal risk, as defined in 45 CFR 46.102 (i), means that "the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests."

At UWM, a project that is exempt:

• is not subject to the submission deadlines for Board meetings,
• does not require full review by a convened Full Board, and
• does not need to be reviewed annually under 45 CFR 46.109 (e).
• meets the criteria for one or more of the Exemption Categories 1-6 defined below.

General characteristics of all exempt research include the following:

• With very few exceptions, private identifiable information cannot be recorded by the investigator or members of the research team

Exemptions do not apply to research involving:

• Prisoners
• Fetuses
• Pregnant Women
• Human In Vitro Fertilization

An exempt protocol can be reviewed by either a decentral reviewer prior to IRB office submission, or for those departments/colleges that do not have a designated decentral reviewer, a central reviewer designated by the IRB (usually the IRB Chairperson) will review the study. The decentral reviewer examines the protocol and makes recommendations for approval. The submission is then submitted to the IRB Office. The IRB Administrator reviews the protocol a final time for compliance with federal regulations and administrative policies, and may recommend additional conditions to the approval.

CATEGORY #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.

Note: This category may be applied to research involving children.

CATEGORY #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 that could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.

Note: Surveys on sensitive or personal topics which may cause stress to study participants are not exempt from IRB review.
Note: The section of this category pertaining to standardized educational tests may be applied to research involving children. This category may also apply to research with children when the investigator observes public behavior but does not participate in that behavior or activity.
Note: This section is not applicable to survey or interview research involving children.

CATEGORY #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.

CATEGORY #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.

Note: Investiagtors should be aware that review of private records involving the recording of identifiable information is not exempt from IRB Review and requires written consent of the study subject. Existing public records do not require prior consent of subjects to review the record.
Note: This category may be applied to research involving children.

CATEGORY #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.

CATEGORY #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.

Under federal regulations, research that is considered "minimal risk" may be reviewed in an expedited manner. Minimal risk, as defined in 45 CFR 46.102 (i), means that "the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests."

To qualify for expedited review, a research study must (1) involve no more than minimal risk AND meet the criteria for one of the categories listed below, OR (2) be a minor change in previously approved research during the period of 1 year or less for which approval is authorized by the IRB. Categories and requirements for expedited review are listed below.

At UWM, a project that is expedited:

• Is not subject to the submission deadlines for Board meetings.
• Does not require full review by a convened Full Board.
• Needs to be reviewed annually under 45 CFR 46.109 (e).
• Categories one (1) through seven (7) pertain to both initial and continuing IRB review. Categories eight (8) and nine (9) pertain to continuing IRB review only.
• Standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or convened--utilized by the IRB.

General characteristics of all expedited research include the following:

• Considered minimal risk as defined previously.

Exemptions do not apply to research involving:

• Where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects= financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.
• Classified research involving human subjects.

At UWM, a subcommittee of one or two Board members is assigned by the IRB Administrator to review the protocol. The subcommittee may exercise all of the authorities of the Full Board IRB, except that it may not disapprove the research. The subcommittee may either approve the research study, request revisions, or refer it to the full Board for discussion and review.

The categories in this list apply regardless of the age of subjects, except as noted.

CATEGORY #1:
Clinical studies of drugs and medical devices only when condition (a) or (b) is met. (a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.) (b) Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

CATEGORY #2:
Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows: (a) from healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week; or (b) from other adults and children2, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these subjects, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week.

CATEGORY #3:
Prospective collection of biological specimens for research purposes by noninvasive means. Examples: (a) hair and nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine patient care indicates a need for extraction; (d) excreta and external secretions (including sweat); (e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization.

CATEGORY #4:
Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)

Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject=s privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.

CATEGORY #5:
Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)

CATEGORY #6:
Collection of data from voice, video, digital, or image recordings made for research purposes.

CATEGORY #7:
Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.)

CATEGORY #8: (Continuing Review Only)
Continuing review of research previously approved by the convened IRB as follows: (a) where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or (b) where no subjects have been enrolled and no additional risks have been identified; or (c) where the remaining research activities are limited to data analysis.

CATEGORY #9: (Continuing Review Only)
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.

**Source: 63 FR 60364-60367, November 9, 1998.**

Informed consent is the knowing consent of an individual or her/his legally authorized representative, obtained without undue influence, force, deceit, or other forms of constraint or coercion. A well-drafted consent form documents the researcher's process in obtaining informed consent from a subject, with emphasis on the process of obtaining informed consent rather than the consent form itself.

Note: One of the most common reasons for delay in approval of a protocol is an inadequate consent form.

The consent form should be a statement addressed to the subject and should read as such. Ordinarily, it is best worded in the first person when talking about the researcher (I am Dr. Mary Smith, and I am conducting research on . . .) and the second person when talking about the subject (You will be asked to complete a survey about . . .). It must be in language that the subject can understand, avoiding jargon, defining technical terms, and adjusting for the educational background and age of the subject. A translation in another language may be necessary for subjects who do not read or speak English. Separate forms may also be required for different subject groups (parents, children, UWM students, etc.), as well as for release of particular kinds of information (photographs, videotapes).

Research investigators are responsible for obtaining informed consent and for insuring that no human subjects will be involved in the research prior to obtaining their consent. In obtaining informed consent, investigators must avoid the possibility of coercion or undue influence. Unless otherwise approved by the IRB, investigators are responsible for insuring that effective informed consent is obtained in the following manner:

1. It is obtained from the subject or the subject's legally authorized representative;
2. It is in language understandable to the subject or the representative;
3. It is obtained under circumstances that offer the subject or the representative sufficient opportunity to consider whether the subject should or should not participate; and
4. It does not include exculpatory language through which the subject or representative is made to waive or appear to waive any of the subject's legal rights, nor does it release or appear to release the research investigator, the sponsor, the institution or its agents from liability for negligence.

As stated in 45 CF 46.116(a) the basic elements of informed consent contains the following information:

(2) A description of any reasonably foreseeable risks or discomforts to the subject;

(3) A description of any benefits to the subject or to others which may reasonably be expected from the research;

(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;

(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;

(6) For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;

(7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and

(8) A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

As stated in 45 CF 46.116(b) the additional elements of informed consent when appropriate contains the following information:

(1) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;

(2) Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;

(3) Any additional costs to the subject that may result from participation in the research;

(4) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;

(5) A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and

(6) The approximate number of subjects involved in the study.

Only in special and/or unusual circumstances can the consent of the subjects be obtained orally. Oral presentation of the elements of informed consent should be used only when it is the most appropriate means of conveying relevant information to the subject, thus adapting the presentation to the subject's capacities. The presentation may be made in either of two ways: 1) A written consent document that sets forth the required basic components of informed consent may be read to the subject or the subject's representative and the investigator will allow the subject or representative ample time to read and consider the document before it is signed; or 2) the IRB may approve a short written form describing the particulars of required informed consent that are to be presented orally to the subject or representative.

Where oral consent is allowable, investigators shall insure that:

1. a witness is present at the oral presentation;
2. the short form is signed by the subject or the representative;
3. the witness signs both the short form and a copy of the written summary of the oral presentation;
4. he person obtaining consent signs a copy of the summary;
5. a copy of both the short form and summary is given to the subject or the representative;
6. the written summary of what is to be said to the subject or the representative receives the prior approval of the IRB.

It is important to note that federal regulations nor UWM's IRB do not support the concept of passive consent. For example, a research study's subject population consists of grade school students. The investigator sends a letter to each of the students’ parents. The letter explains that if parents do not complete and return the form (meaning they do not want their child to be a part of the study), the investigator will assume the parents are giving the investigator permission to ask their child to participate.

UWM's Board does not, in general, approve of the use of passive consent in research with minors. Investigators who propose the use of passive consent in a study to be conducted in an elementary or secondary school must:

1. Obtain permission from the relevant research review mechanism for that school (e.g., school district),
2. Provide the IRB with documentation of such approval prior to initiation or recruitment,
3. If the research involves a change of curricula by the school or school district, provide written documentation on official letterhead from the participating school or school district indicating that the school district's procedures for adopting the curricula have been followed. The letter documenting curricula adoption must be submitted with the protocol to allow review with passive parental consent,
4. Request a waiver of informed consent, and
5. The investigator must provide the parent(s) with a written document containing all the required elements of informed consent.

Adequate provisions for assent from the child participant must be developed by the researcher. However, the IRB may waive the assent requirement if some or all of the children lack the capacity to give meaningful assent, or the research holds out the prospect of direct benefit that is important to the health or well-being of the children that is available only in the context of the research.

The federal regulations do not set a minimum age at which a child's assent must be solicited but instead say that assent is required whenever in the judgment of the IRB the children are capable of providing assent, taking into account their ages, maturity, and psychological state. At UWM, the IRB has stated that it considers "school age" children to be capable of assent.

Consent (permission) from parent(s) or guardian.
If the research involves only minimal risk, or it poses more than minimal risk but promises to benefit the child directly, permission must be obtained from at least one of the child's parents, or the child's guardian. If the research poses more than minimal risk and no direct benefit to the child, both parents or the child's guardian must give permission for the child to participate in the research. However, the permission of a parent who is deceased, unknown, or incompetent, or not reasonably available, or who does not have legal responsibility for the care and custody of the child is not required.

If a research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the children (for example, neglected or abused children), the IRB may waive the requirement that parental permission be sought, provided that there is an appropriate alternative mechanism for protecting the children which is not inconsistent with the law. The choice of an appropriate alternative mechanism depends on the nature and purpose of the activities described in the protocol, the risk and anticipated benefit to the children, and their age, maturity, status and condition. In such cases the researcher should propose an alternative mechanism, explaining why it will protect the children. The IRB will then review the adequacy of this proposal.

Information that must be provided in requests for assent and consent, & documentation of informed consent. When parents or guardians are asked for consent (permission) and children are asked for assent, they must be given the same information that is generally required when informed consent for participation in research is sought, and their permission and assent must be documented in writing.

The assent form for children should, of course, be written in language appropriate to their age and understanding. If the parents are not also research subjects themselves, it may be appropriate to have them sign the same form their children sign. If the parents are also research subjects, ordinarily a separate form should be drafted for them, addressing their own participation as well as that of their children.

Researchers may request that the IRB waive or alter the requirements for seeking consent (permission) and assent when children are subjects.

Some research studies can be carried out without the investigator having to obtain informed consent (e.g., observational studies, dataset studies, etc.). The IRB may waive the requirement to obtain informed consent provided the IRB finds and documents that:

1. The research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is 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; and
2. The research could not practicably be carried out without the waiver or alteration.

The IRB may also waive the requirement to obtain informed consent provided the IRB finds and documents that:

1. The research involves no more than minimal risk to the subjects;
2. The waiver or alteration will not adversely affect the rights and welfare of the subjects;
3. The research could not practicably be carried out without the waiver or alteration; and
4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Occasionally, there may be incidences where documenting (signed by subject or subject's legally authorized representative) informed consent may be waived (e.g., surveys conducted over the mail/ telephone, research conducted over the internet, etc.). In order for such a waiver to be granted, the IRB must find either:

1. That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or
2. That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.

The IRB may approve a consent procedure which does not include, or which alters, some or all of the required elements of informed consent (e.g. abbreviated scripts for telephone surveys).

1. The research or demonstration project is to be conducted by or subject to the approval of state or local government officials and is 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; and
2. The research could not practicably be carried out without the waiver or alteration.

The IRB may also approve a consent procedure which does not include, or which alters, some or all of the required elements of informed consent if the IRB finds and documents that:

1. The research involves no more than minimal risk to the subjects;
2. The waiver or alteration will not adversely affect the rights and welfare of the subjects;
3. The research could not practicably be carried out without the waiver or alteration; and
4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Health, education and social science professionals work under the constraints of laws and professional ethics codes that require the reporting of certain types of activities that become known to them to the appropriate agencies or authorities. If a researcher belongs to one of these professions, or believes that data collected from their research participants may reveal reportable activities, a statement revealing this duty to report must be incorporated into the informed consent document.

Likewise, there are many guidelines about maintaining the confidentiality of client information or file materials. The guidelines under which a researcher is acting should be referenced in both the protocol procedures and the informed consent.

Guidance about what kind of language to include in either of these circumstances can be obtained by contacting the IRB Administrator, or a member of the IRB.

When research subjects are children, federal regulations impose additional requirements on the researcher. Two such limitations include (1) some research which would fall in the exempt category if the subjects were all competent adults is not exempt, and (2) some research involving more than minimal risk to the subjects is prohibited. The informed consent process also requires some additional steps.

1. Categories of exempt research when the subjects are children
Some types of research are considered exempt even when children are subjects. However, some types of research considered exempt when subjects are competent adults are not exempt when children are subjects. Research involving survey or interview procedures is not exempt when children are subjects. Research involving observation of public behavior is exempt only if the researcher does not participate in the activities being observed. All other research with children must be reviewed by the IRB. In all cases, the assent of the children, and consent of parent(s) or guardian, must be obtained prior to conducting the research.

2. Special considerations in research when subjects are children
The HHS regulations at 45 CFR part 46, subpart D permit IRBs to approve three categories of research involving children as subjects:

45 CFR 46.404 - Research not involving greater than minimal risk to the children.

To approve this category of research, the IRB must make the following determinations:

• the research presents no greater than minimal risk to the children; and
• adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.

45 CFR 46.405 - Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual child subjects involved in the research.

To approve research in this category, the IRB must make the following determinations:

• the risk is justified by the anticipated benefits to the subjects;
• the relation of the anticipated benefit to the risk presented by the study is at least as favorable to the subjects as that provided by available alternative approaches; and
• adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.

45 CFR 46.406 - Research involving greater than minimal risk and no prospect of direct benefit to the individual child subjects involved in the research, but likely to yield generalizable knowledge about the subject's disorder or condition.

In order to approve research in this category, the IRB must make the following determinations:

• the risk of the research represents a minor increase over minimal risk;
• the intervention or procedure presents experiences to the child subjects that are reasonably commensurate with those inherent in their actual, or expected medical, dental, psychological, social, or educational situations;
• the intervention or procedure is likely to yield generalizable knowledge about the subject's disorder or condition which is of vital importance for the understanding or amelioration of the disorder or condition; and
• adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.

A fourth category of research requires a special level of HHS review beyond that provided by the IRB.

45 CFR 46.407 - Research that the IRB believes does not meet the conditions of 45 CFR 46.404, 46.405, or 46.406, but finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children.

If the IRB believes that the research does not meet the requirements of 45 CFR 46.404, 46.405, or 46.406, but finds that it presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children, it may refer the protocol to HHS for review. The research may proceed only if the Secretary, HHS, or his or her designee, after consulting with a panel of experts in pertinent disciplines (e.g., science, medicine, education, ethics, law) and following an opportunity for public review and comment, determines either: (1) that the research in fact satisfies the conditions of 45 CFR 46.404, 46.405, or 46.406, or (2) the following:

• the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;
• the research will be conducted in accordance with sound ethical principles; and
• adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians, as set forth in HHS regulations at 45 CFR 46.408.
  

The IRB has adopted special rules that apply when research subjects are mentally disabled. Most of the general requirements for approving research with human subjects apply, but with some exceptions and additions. The major exceptions are that (1) some research which would fall in the exempt category if the subjects were all competent adults is not exempt, and (2) some research involving more than minimal risk to the subjects is prohibited. Additional requirements pertain to informed consent. For the purpose of these requirements, a "mentally disabled" person is a person who, because of mental illness, mental retardation, emotional disturbance, or senility, is incapable of giving informed consent.

Of course, some persons who have these conditions are also able to give informed consent, but the IRB cannot determine the capacity of persons with these conditions on the basis of labels alone. Therefore, whenever proposed research involves subjects who have been diagnosed with one of these conditions or who may have such a condition, the researcher should explicitly tell the IRB whether the subjects are able to give informed consent because of the condition. If the subjects are able to give informed consent, the special rules in this section do not apply, and only the general requirements for research with human subjects must be satisfied.

Categories of exempt research when the subjects are mentally disabled.
Some types of research are considered exempt even when subjects are mentally disabled (refer to exemption categories). However, some types of research considered exempt when subjects are competent adults are not exempt when subjects are mentally disabled. Research in Category 1 (conducted in established or commonly accepted educational settings involving normal educational practices) is exempt only if the research involves no changes in the content of instruction, location of instruction, or procedures used during instruction from those a subject would normally experience. Research involving survey or interview procedures is not exempt. Research involving observation of public behavior is exempt only if the researcher does not participate in the activities being observed. All other research with mentally disabled subjects is subject to review by the IRB.

Special considerations in research when subjects are mentally disabled.
1. Research that poses only minimal risk to the subjects requires no special limits, except that adequate provisions must be made for obtaining assent of the mentally disabled subjects and permission from their representatives.

2. Research that poses more than minimal risk but which promises to benefit the individual subject directly will be permitted if:

• the risk is justified by the expected benefit to the subject;
• the relationship between the risk and benefit is at least as favorable to the subject as that presented by other available approaches; and
• adequate provisions are made for obtaining assent of the mentally disabled subjects and consent (permission) from their representatives, as described below.

3. In addition, if the mentally disabled subjects are wards of the state or any other agency, institution, or entity, they may be the subjects of research that poses more than minimal risk only if the research is: (1) related to their status as wards, or (2) conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of the subjects involved are not wards. Furthermore, if the research poses more than minimal risk, an advocate must be appointed for each mentally disabled person who is a ward. The advocate must be a person who has the background and experience to act in, and agrees to act in, the best interests of the mentally disabled person for the duration of the person's participation in the research. The advocate cannot be associated in any way with the research, the investigator(s) or the guardian organization. A person can be the advocate for more than one person. The requirement for an advocate is in addition to any other person acting on behalf of the mentally disabled person as guardian.

4. Research that poses more than minimal risk and does not promise to benefit the individual subject directly will be permitted if:

• the risk is only slightly greater than minimal;
• the research will expose the subject to experiences that are reasonably commensurate with those inherent in the subject's actual or expected medical, dental, psychological, social or educational situation;
• the research is likely to yield generalizable knowledge about the subject's disorder or condition which is of vital importance to understanding or ameliorating the subject's disorder or condition; and
• adequate provisions are made for obtaining assent of the mentally disabled subjects and consent (permission) from their representatives, as described below.
• In addition, if the mentally disabled subjects are wards, the requirements described previously apply.

Assent of the subjects.
Ordinarily, a mentally disabled person may not be the subject of research unless the person gives assent. The IRB may waive the assent requirement if: (1) the capability of some or all of the subjects is so limited that they cannot reasonably be consulted, or (2) the intervention involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the subjects that is available only in the context of the research.

Consent (permission) from competent adults acting on behalf of the subjects.
Ordinarily, a mentally disabled person may not be the subject of research unless consent (permission) is obtained from the person's guardian. For purposes of these rules a guardian cannot be associated in any way with the research or the investigator(s). If the mentally disabled person is a ward of the state or any other agency, institution or entity, a person associated with the entity cannot be a guardian for purposes of these rules.

The parent of a mentally disabled person below the age of 18 is presumed to be the person's guardian. If the mentally disabled person is older than 18, the parent is not automatically the guardian. If the subjects are mentally disabled adults who have not formally had legal guardians appointed for them, the researcher should propose a procedure for securing permission from a competent adult acting solely in the interests of the mentally disabled person. This procedure must be consistent with federal, state, and local law.

Information that must be provided in requests for assent and consent (permission ) & documentation of informed consent. Mentally disabled subjects and the competent adults acting on their behalf must be given the same information that is generally required when informed consent for participation in research is sought, and their permission and assent must be documented in writing. The assent form for the mentally disabled subjects should, of course, be written in language appropriate to their level of understanding.

Waiving assent and consent:
Researchers may request that the IRB waive or alter the requirements for seeking consent (permission) and assent when the subjects are mentally disabled.

Pregnant Women & Fetuses - 45 CFR 46, Subpart B

Pregnancy encompasses the period of time from confirmation of implantation (as evidenced by missed menses or a medically acceptable test) until expulsion or extraction of the fetus. Fetus means the product of conception, from the time of implantation until a determination is made, following expulsion or extraction, that it is viable.

Activities Directed Toward Pregnant Women
No pregnant woman may be involved in a research activity unless: (a) the risk to the fetus is minimal, or (b) the purpose of the activity is to meet the health needs of the mother and the fetus will be placed at risk only to the minimum extent necessary to meet such needs.

Additional Consent Requirements
Research activity permitted above may be conducted only after fully informing the mother and father of any possible impact on the fetus and obtaining informed consent from the legally competent mother and father. Consent by the father need not be secured if:

1. the purpose of the study is to meet the health needs of the mother;
2. the identity or whereabouts of the father cannot be reasonably ascertained;
3. the father is not reasonably available;
4. the pregnancy resulted from rape.

Prisoners - 45 CFR 46, Subpart C

Prisoner means any individual involuntarily confined or detained in a penal institution. The term applies to those sentenced to such an institution, those detained in other facilities as alternatives to prosecution, and those detained pending arraignment, trial, or sentencing.

Prisoners may be under constraints because of their incarceration that affect their ability to make a truly voluntary decision whether or not to participate as subjects in research. Additional safeguards are required, therefore, when prisoners are proposed as subjects.

IRB Membership Regarding Research with Prisoners
At least one member of the IRB shall be a prisoner or prisoner representative, with appropriate background and experience. If the research is reviewed by more than one IRB, only one need have a prisoner representative.

Types of Research Permitted
When using prisoners as subjects, only the following types of research are allowable:

• Study of possible causes, effects, or processes of incarceration or of criminal behavior;
• Study of prisons as institutional structures or of prisoners as incarcerated persons;
• Study of conditions particularly affecting prisoners as a class, including research on relevant social and psychological problems such as alcoholism, drug addiction, and sexual assault;
• Study of practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the prisoner subjects.

In all cases, the research is to present no more than minimal risk and inconvenience to subjects. For research in the latter two categories above, consultation may be necessary to determine possible need for approval by experts in penology, medicine and ethics.

Additional Considerations
When using prisoners as subjects the following additional concerns must be addressed:

• Selection of subjects within the prison is to be fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners;
• Unless providing justification otherwise, control subjects must be selected randomly from an appropriate population of prisoners;
• Any advantages accruing to a prisoner subject, when compared to standard prison conditions, are not to be of such magnitude as to impair the prisoner's ability to weigh appropriately the risks of research participation in the limited choice environment of prison;
• The risks involved should be commensurate with risks that would be accepted by non-prisoner volunteers;
• Adequate evidence exists that parole boards will not take into account a prisoner's participation or non-participation in research and prisoners are informed in advance that participation or non-participation in the research will have no effect on parole decisions;
• Information is provided to prisoners in language they can understand;
• Where the IRB finds there may be a need for follow-up examination or care of subjects after participation, adequate provision is made, taking into account the lengths of subjects' sentences, and subjects are informed regarding these provisions.

It is the obligation of researchers to conduct activities in a manner and at such locations as will assure the proximity of adequate medical attention if warranted, and to provide appropriate referrals to subjects for adequate facilities and professional attention should subjects suffer physical, psychological or other injury.

The seriousness of a risk to subjects is a function of the magnitude of the harm and the probability of the harm. A risk may be serious or significant because it has a probability (even a low probability) of great harm (e.g., a low probability of death), or because it has a high probability of slight harm (e.g., a near certainty of physical discomfort or psychological distress).

The risks of participation in research may be part of the research design or may be a consequence of the research procedures, or both (e.g., the risks of an adverse reaction to an investigational drug are part of the research design, while the risk of hematoma from blood drawn in the research is not part of the design but a consequence of the research procedures). Risks may be a consequence of the methods of recording, maintaining, or reporting data, and they may be a consequence of methods of obtaining informed consent.

Occasionally, some degree of deception is involved in a research study. Minor deception, such as failing to tell the subject what the specific points of interest are, in an attempt to prevent biasing the results, can be acceptable provided the subject is fully debriefed after participating. Risks stemming from major deceptions, such as leading a subject to believe that s/he has committed a crime or has a disease, must be clearly counterbalanced by the benefits of the research. Withholding information cannot be used as a means to secure the participation of subjects in research.

The use of deception imposes special responsibilities on the investigator. One of these responsibilities is to provide appropriate debriefing to the subjects. In each case, the UWM IRB will require information sufficient to understand why deception is needed, how the potential benefits justify its use, and how debriefing will be done.

If information was temporarily withheld from the subject during the study, or if deception was employed, a separate debriefing statement should be presented at the end of the procedure. This statement should clearly indicate why information was withheld during the study, and/or the purpose of the deception.

In all research involving human subjects, confidentiality of identifiable information is presumed and must be maintained unless the investigator obtains the express permission of the subject to do otherwise. Subjects have the right to be protected against injury or illegal invasions of their privacy and to preservation of their personal dignity. The more sensitive the research material, the greater the care that must be exercised in obtaining, handling, and storing data.

Investigators should be cognizant of the following guidelines to ensure confidentiality:

1. acquisition of personal information should be limited to that which is absolutely essential to the activity;
2. data should be securely stored and accessible only to the investigator and authorized staff;
3. data should be coded as early in the activity as possible, and plans for the ultimate disposition of the data should be made;
4. identities of individuals should not be released without express permission of the individual;
5. use of stored data which was originally obtained for different purposes and which involves identifiable subjects, requires examination of the risk involved, a determination of whether the new use is within the scope of the original consent or whether obtaining additional consent is necessary and feasible, and provision made for the preservation of anonymity of the subjects.

Voluntariness begins with recruitment. Potential subjects must not feel that they have been coerced into participating, nor must they fear the loss of some benefit to which they are otherwise entitled if they choose not to participate (such as on-going support by a social agency).

Special care must be taken if the person doing the recruiting is a person who is in a position of authority (such as a teacher recruiting his or her own students) or makes decisions about the provision of services (such as a director of a training clinic). It is the researcher's responsibility to ensure that a person's decision to participate or not participate, will have no other effect on an existing relationship.

Students in UWM classes are occasionally asked to participate in research. In such cases, the researcher should ask the instructor to give her/his permission to use class time to conduct a study. Because students in classrooms comprise a captive audience, care should be taken to respect their rights as subjects and as students. If participation as a subject is part of the academic work of a student, it must not be a coercive requirement, and informed consent, if appropriate, must be obtained. Alternate means of receiving credit if a student chooses not to participate or chooses to withdraw during the course of the study should be provided.

To assure that students feel free to refuse to participate without concern that the evaluation of their classroom performance will be affected, the instructor should not be present during any research activities. Furthermore, the instructor should not be informed nor be aware of who participates. When researchers wish to audiotape or videotape university classes, students have the right to refuse participation. At the same time, students should not be penalized by losing significant classroom instruction, in the event they decide not to be taped. The following procedures should be used:

1. The investigator must notify students in advance that the class session will be taped;
2. Taping must be stopped long enough before the end of the class to allow students to ask questions without appearing on the tape;
3. Students must be given a full explanation of the project after the recording and given the option to arrange for deletion of their participation on the tape.

Because research involves time that would otherwise be used for instructional activities, departments may wish to promulgate policies with regard to classroom research. The IRB recognizes that participating in research and receiving information about the research may be instructionally relevant.

The researcher shall not ask institutions to directly identify potential subjects for a research study. Rather, the investigator shall ask an intermediary (doctor, case worker, school administrator) to first approach potential subjects (or their guardians, as appropriate) and inform them about the research. If a potential subject agrees to participate, the intermediary should provide her/him with the information necessary to contact the researcher, in such a way that the institution is unaware whether the subject chooses to participate in the research. The intermediary should not obtain consent from potential subjects.

The researcher shall not ask institutions to release records or anecdotal information either for the purposes of identifying subjects, or for examination by the investigator, unless this information is public. An investigator wishing to examine records must first obtain permission of the subject via an intermediary. If a potential subject agrees to release his or her records, the intermediary should provide the information necessary to contact the researcher. This provision does not apply to records with all identifiers removed (see exemption 4).

If advertising for subjects, investigators must follow these guidelines:

1. Information must not be misleading to subjects, especially when a study will involve vulnerable populations;
2. Include the name and address of the investigator, the purpose of the research and eligibility criteria for participation as subjects, a clear description of any benefits and/or risks of participating, the affiliation of the researcher, the location of the research, and whom to contact for further information
3. If a drug or device is to be used in the research, no claim should be made as to its superiority, safety or effectiveness.
4. A copy of the advertisement must be included with the protocol.

If you plan to pay research subjects using prizes, raffles, or awards, please review the guidance from UWM's Legal Affairs Office.

Additional Guidance for Online Research Activities on what is considered private v. public websites and consent options.

The IRB recommends researchers utilizing the Internet as a research tool to address the following in their protocol procedures and informed consent:

1. State whether the Internet site is considered public or private space. State whether you have obtained permission from the list owner or administrator to recruit subjects from, or post messages on, the site. Researchers shall also obtain permission to use archived data from a list or site. (Permission may be verified by an email from the list owner or administrator, and a copy should be included in your protocol.)
2. Inform the subjects that online communications, in general, are considered public in nature. Electronic records of such communications may therefore be subject to open records requests.
3. Inform the subjects that there is no completely secure interaction online. The following statement must be inserted into the informed consent document, as it relates to keeping collected data confidential and the risk/benefit of participation in the study: As an online participant in this research, there is always the risk of intrusion by outside agents, i.e., hacking, and therefore the possibility of being identified.
4. State that subjects provided with an online email account are allowed to change passwords at regular intervals.
5. If the researcher uses encryption software, a thorough set of instructions shall be included in the protocol and provided to the subjects.
6. The protocol will describe how subjects will be identified in written reports, whether by use of their screen names or pseudonyms.
7. The researcher will state that the data and identifiers shall be kept on different servers.
8. Researchers shall provide a forum for participants to ask questions online before consenting to participate in a research project.
9. Researchers shall identify how confidentiality will be safeguarded on a forum where some participants consent while others do not.
10. The researcher will provide a yes/no statement in the online format to substitute for a signature on the consent form.
11. Online research with minors is strongly discouraged. If minors are recruited for online research, a written, signed informed consent by a parent or guardian is required.

Research in foreign countries also presents special concerns regarding the rights and welfare of human subjects. In general, the IRB accepts the standards of the location in which the research is taking place, unless those standards grossly violate the basic ethical principles of human subject research. In addition, the following issues apply to international human subject research:

1. All materials, including consent forms must have English language translations included with the protocol.
2. Documentation of permission from local authorities and/or research visa are generally required before approval can be granted.

Student research conducted purely for instructional purposes is generally not reviewed by the IRB. If, however, there is a possibility that the data will be published or maintained for later use, the project should be approved by the IRB prior to human subjects involvement. The Board is unable to give post facto approval.

Even though classroom initiated research is not reviewed for risk by the IRB at this time, it is important that instructors and students discuss the guidelines and ethics for protection of research subjects and incorporate these into their methodology.

Particular emphasis should be place on:

1. Developing an awareness of the types of risks subjects may be exposed to in various types of research projects, i.e., psychological, social, physical, economic, legal, etc.
2. Obtaining voluntary informed consent to participate in a way that truly informs subjects of the purpose and potential risks and benefits of the research.
3. Protection of the privacy and confidentiality of the subjects.
4. Management of potential risks to subjects.
5. Identification of benefit to be derived from participation in the research.
6. A risk/benefit analysis for all populations, with special consideration of vulnerable populations (children, pregnant women, fetuses, mentally disabled, institutionalized persons, prisoners, etc.).

Regardless of how minor it is, approval from the IRB is required for any modifications or amendments to a previously approved protocol or consent form. Changes to the study can be reviewed either by a Full Board or through Expedited status.

Expedited Review: Minor changes to previously approved protocols may be reviewed in an expedited manner by the IRB Administrator and designated IRB board member. Minor changes include those that pose no greater than minimal risk to the participant and do not negatively impact the risk-benefit ratio of the research. Examples of amendments that consist of simple changes include:

• Change of PI, addition/deletion of co-investigators, or personnel updates.
• Administrative changes - correction of administrative errors, title changes, version changes, change in wording for clarification purposes.
• Advertisements.

Full Committee Review: When proposed changes in a research study do not meet the requirements for expedited review, the IRB must review changes at a convened meeting of the full IRB Committee before they can be implemented. The only exception is the rare circumstance in which a change is necessary to eliminate apparent immediate hazards to the research participants. In this case, the IRB should be promptly informed of the change following its implementation.

Federal regulations require protocols receive continuing review not less than once per year. 45 CFR 46.109(e). UWM does not annually review Exempt protocols. Study original reviewed and approved as either Full Board or Expedited are reviewed at least annually. Two (2) months before the 1 year approval period on a protocol expires, the IRB office will send the principal investigator a notification letter reminding them of continuing review.

If the study is considered active by the investigator (i.e., still enrolling, performing research procedures, recording/analyzing data, etc.) and submission for continuing review has not been filed and reviewed by the IRB before the date of IRB expiration, the study will automatically be "Terminated". Federal regulations make no allowances for grace periods.