• Changes to an Approved Protocol

• Unanticipated Problems

• Cooperative Research/Multi-Campus Research

• Research Involving Vulnerable Subjects

• Research Involving Children and Adolescents

• Research Involving Pregnant Women

• Research Involving Fetuses or Fetal Tissue

• Surrogate Consent

• Determination of decisional capacity

• Research in A Foreign Country

• Medical Research

Changes to an Approved Protocol

Changes in research procedures should not be put into effect before obtaining approval from the UCSC IRB. This requirement includes changes to consent documents. To modify or amend an approved protocol, submit a modification/amendment form to the UCSC IRB.

Unanticipated Problems

The UCSC IRB must be informed promptly of any injuries to human subjects, any data security or confidentiality breaches, any unanticipated problems involving risks to subjects or others, and any serious or continuing noncompliance with UCSC IRB requirements. To report a problem, use the report from available on the forms page.

Cooperative & Multi-Campus Research

Research may involve more than one institution and be within the responsibility of more than one Institutional Review Board (IRB).

A Memorandum of Understanding between the UC campuses allows human subject research projects that are conducted at multiple UC campuses to go through the full IRB review process at only one UC location rather than having to go through the entire process at every UC campus at which the research is taking place. This agreement does not apply to research that requires full committee IRB review or research regulated by the Food and Drug Administration (FDA).

The PI is responsible for filing a Notice of Intent to Rely on Another UC IRB Form with any other campus where the research will take place both at the time of initial and continuing review.  For more information regarding the duties and responsibilities of the principal investigator, email orca<at>ucsc.edu.

Vulnerable Subjects

People who are especially susceptible to coercion or undue influence are considered vulnerable subjects. They may include:

• the mentally or physically infirm
• children
• the illiterate
• prisoners and parolees
• addicts
• the poor, to the extent that they might be coerced into taking risks by payment of a significant economic benefit to take part in the study
• students of an instructor researcher,
• pregnant woman, fetuses & neonates

When research involves vulnerable subjects, the researcher should provide appropriate additional safeguards to protect their wellbeing. Because they are sometimes proposed as research subjects on account of their vulnerability, researchers may be asked to explain the appropriateness of involving them in the research. Whenever feasible, the initial contact with vulnerable subjects should be made by or through people who have no connection with the research, in order to pre serve the subjects' privacy and autonomy. If the subjects are illiterate and the consent presentation is therefore oral, researchers should nevertheless be sure to satisfy all applicable requirements for obtaining documented consent, including submission of a written version of the proposed presentation for UCSC IRB review and approval. Under certain circumstances, it may be desirable for a witness to be present when vulnerable subjects give their consent.

Students of an instructor researcher are considered vulnerable subjects. If participation as a research subject is part of the academic work of students, their participation may not be made mandatory, and the researcher must provide a reasonable academic alternative for students not wishing to participate.

If a research project will involve fetuses, pregnant women, prisoners, or children, Federal law and University policy impose additional requirements. These relate to selection of subjects, risk assessment, obtaining consent, and so forth. Researchers planning to study members of these vulnerable groups may consult the UCSC IRB for more information.

Review of Projects Involving Children and Adolescents

Federal regulations permit the UCSC IRB to approve of the following types of research involving children:

1. Research that involves no more than minimal risk to children if adequate provisions are made for soliciting the assent of the children and the permission of their parents or guardians

2. Research that involves more than minimal risk if:

(a) the research holds out the prospect of direct benefit for the individual subject;
(b) the risk is justified by the anticipated benefit; and
(c) the relation of the anticipated benefit to the risk is at least as favorable to the subjects as that presented by available alternative approaches.

3. Research that involves more than minimal risk to children if:

(a) the risk represents a minor increase over minimal risk;
(b) the intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social or educational situations; and,
(c) the research is likely to yield generalizable knowledge about the subjects’ disorder or condition which is of vital importance for the understanding or amelioration of the subjects’ disorder or condition.

4. Research that the IRB believes does not meet the previous categories, 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, must be reviewed by HHS.

Definitions

For purposes of this policy the following definitions are used, consistent with federal and state regulations:

1. "Children" are persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.
2. "Assent" means a child's affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent. The assent procedure should reflect a reasonable effort to enable the child to understand what their participation in research would involve.
3. "Permission" means the agreement of parent(s) or guardian to the participation of their child or ward in research. In general, permission should be obtained from both parents before a child is enrolled in research. However, the IRB may find that the permission of one parent is sufficient on an individual or group basis for research when risks are minimal or the research will directly benefit the child. The requirement of obtaining parental or guardian permission can be waived in special circumstances.
4. "Guardian" means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care.

Research Involving Pregnant Women & Fetuses :

Pregnant Women and Fetuses are considered protected populations, and research must provide the additional protections listed here.

With regard to research involving the participation of pregnant women as research subjects, the following requirements must be met:

1. Preclinical studies, including studies on pregnant animals and clinical studies, including studies on non-pregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;
2. The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus; or, if there is no such prospect of benefit, the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means;
3. Any risk is the least possible for achieving the objectives of the research;
4. If the research holds out the prospect of direct benefit to the pregnant woman, the prospect of a direct benefit both to the pregnant woman and the fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means, her consent is obtained in accord with informed consent provisions;
5. If the research holds out the prospect of direct benefit solely to the fetus, then the consent of the pregnant woman and the father is obtained in accord with informed consent provisions, except that the father's consent need not be obtained if he is unable to consent because of unavailability, incompetence, or temporary incapacity or the pregnancy resulted from rape or incest.
6. Each individual providing consent is fully informed regarding the reasonably foreseeable impact of the research on the fetus or neonate;
7. For children who are pregnant, assent and permission are obtained in accord with federal regulations regarding children in research;
8. No inducements, monetary or otherwise, will be offered to terminate a pregnancy;
9. Individuals engaged in the research will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy;
10. Individuals engaged in the research will have no part in determining the viability of a neonate.

Review of Projects Involving Fetuses or Fetal Tissue

Research conducted by UCSC investigators that is funded by federal agencies other than the VA must comply with provisions of the NIH Revitalization Act of 1993 (Public Law 103-43) with respect to use of fetal tissue. The VA prohibits research involving a fetus, in-utero or ex-utero (including human fetal tissue) or in vitro fertilization by VA investigators.

Applicable Regulations: The NIH Revitalization Act of 1993 (Public Law 103-43), Section 498B of the Public Health Service Act (42 U.S.C. 298g-2)

Surrogate Consent

No person who has the capacity for consent may be enrolled in a study without his or her informed consent.

IRB review of projects involving surrogate consent (as evidenced by a “legally authorized representative” signature line in the consent document) shall conform to the requirements of California law AB2328 that specifies the requirements for and procedures related to the surrogate consent process.

The decisional capacity of a potential research subject should be evaluated when there are reasons to believe that the subject may not be capable of making voluntary and informed decisions about research participation.

For research protocols that involve subjects with mental disorders that may affect decision-making capacity, the IRB may determine that capacity assessments are necessary, unless the investigator can justify why such assessments would be unnecessary for a particular group. The requirement for an independent evaluator becomes increasingly justified as the risks to subjects increase.

For research that poses greater than minimal risk, the IRB should generally require investigators to use an appropriate means of determining the potential participant’s capacity to consent. The Decisional Capacity Taskforce guidelines present several alternative approaches for meeting this requirement. Even in research involving only minimal risk, the IRB may still require that the study include a capacity assessment if there are reasons to believe that potential subjects’ capacity may be impaired. It is not necessary to require a formal capacity assessment by an independent professional for all potential research subjects with mental disorders.

For research protocols involving subjects who have fluctuating or limited decision-making capacity the IRB should ensure that investigators establish and maintain ongoing communication with involved caregivers. Periodic re-consent should be considered in some cases. Third party consent monitors may be used during the recruitment and consenting process, or waiting periods may be required to allow more time for the subject to consider the information that has been presented.

It is often possible for investigators and others to enable persons with some decisional impairments to make voluntary and informed decisions to consent or refuse participation in research. Potential measures include repetitive teaching, group sessions, audiovisual presentations, and oral or written recall tests. Other measure might include follow-up questions to assess subject understanding, videotaping or audio-taping of consent interviews, second opinions, use of independent consent observers, or involvement and/or concurrent consent of a trusted family member or friend in the disclosure and decision-making process.

Determination of decisional capacity

Decisional capacity in the research context has been interpreted by the American Psychiatric Association as requiring:

1) ability to evidence a choice;
2) ability to understand relevant information;
3) ability to appreciate the situation and its likely consequences; and
4) ability to manipulate information rationally.

A range of professionals and methods may be utilized to assess capacity. In general the consent assessor should be a researcher or consultant familiar with dementias and qualified to assess and monitor capacity and consent in such subjects on an ongoing basis. The IRB will consider the qualifications of the proposed individual(s) and whether he or she is sufficiently independent of the research team and/or institution.

The protocol should describe who will conduct the assessment, the method by which prospective subjects’ decisional capacity will be evaluated, and the criteria for identifying incapable subjects. Less formal procedures to assess potential subjects’ capacity may be permitted if a formal assessment is not feasible. Less formal procedures could include the ways professionals often make judgments about capacity in routine interactions.

California law AB2328, codified as California Health & Safety Code Section 24178 became effective January 1, 2003 and clarifies who may serve as a research subject’s “legally authorized representative.” The IRB review of a new or revised application that proposes to have the option of consent by surrogates will address the project’s compliance with the provisions of state law as noted below.

Surrogate consent may be considered only in research studies relating to the cognitive impairment, lack of capacity, or serious or life-threatening diseases and conditions of research subject. The investigator shall include in the IRB application/modification form a protocol-specific plan for the sequence of steps that will be employed to acquire and document surrogate consent provided by a legally authorized representative. These steps include the following:

1. Whenever possible, investigators will attempt to obtain informed consent directly from the subject.
2. If the potential research subject is obtunded, unconscious or otherwise obviously lacking in decision-making capacity, the investigator shall: a) Document that observation in the research record and in the subject’s medical record; b) Proceed with the steps listed below under Identifying Persons to Provide Surrogate Consent
3. If the potential research subject has questionable capacity to consent but is not unresponsive, the investigator shall: a) Consistent with the standard consent process, describe the research to the subject;
   b) Perform and document an assessment of the participant’s decisional-capacity relevant to the information provided about the research study; c) If lack of decisional capacity is evident, the investigator shall inform the potential research subject of the investigator’s intent to obtain surrogate consent; d) If the subject expresses resistance or dissent to participation or to the use of surrogate consent by word or gesture, the subject shall be excluded from the research study. e) If no resistance or dissent is expressed by the potential research subject, the investigator shall document this fact, and document that the description of the research project was communicated to the subject by placing a note in the medical record and in the research record.
   f) Proceed with the steps listed below under Identifying and Informing Persons providing Surrogate Consent

Identifying Persons to Provide Surrogate Consent

In a non-emergency room environment, surrogate consent may be obtained from any of the following potential surrogates who has reasonable knowledge of the subject, in the following descending order of priority:

1. The person's agent designated by an advance health care directive.
2. The conservator or guardian of the person having the authority to make health care decisions for the person.
3. The spouse of the person.
4. The domestic partner of the person as defined in Section 297 of the Family Code
5. An adult son or daughter of the person.
6. A custodial parent of the person.
7. Any adult brother or sister of the person.
8. Any adult grandchild of the person.
9. An available adult relative with the closest degree of kinship to the person.

In non-emergency room research settings, no surrogate consent may be utilized if there is a disagreement whether to consent among the members of the highest available priority class of surrogates, (e.g., where two members of persons in the highest of categories (5) – (7) disagree and there is no person in categories (1) – (4) available.

In non-emergency room research settings only, the investigator is responsible for ensuring that the surrogate:

1. Has reasonable knowledge of the subject;
2. Is familiar with the subject’s degree of impairment;
3. Is willing to serve as the substitute decision-maker;
4. Understands the risks, potential benefits, procedures and available alternatives to research participation;
5. Makes their decisions based on the subject’s known preferences, and where the subject’s preferences are unknown, makes decisions based upon the surrogate’s judgment of what the subject’s preferences would be if different from their own.

In an emergency room setting, the order of priority does not apply, nor does the surrogate have to show reasonable knowledge of the subject. Surrogate consent may be obtained from a surrogate decision maker who is any of the following:

1. The person's agent designated by an advance health care directive.
2. The conservator or guardian of the person having the authority to make health care decisions for the person.
3. The spouse of the person.
4. The domestic partner of the person as defined in Section 297 of the Family Code.
5. An adult son or daughter of the person.
6. A custodial parent of the person.
7. Any adult brother or sister of the person.
8. In emergency room research settings, no surrogate consent may be utilized if there is a disagreement whether to consent among any available surrogates.

Obtaining Consent from the Surrogate

1. Investigators shall describe to potential surrogates the nature of ongoing decisions during the study regarding the subject’s participation, decision to participate in certain procedures, changes to the study, etc., in order to ensure that the surrogate will be willing to undertake these on-going responsibilities.
2. The surrogate shall complete the “Self-Certification of Surrogate Decision Makers for Participation in Research” form as an attachment to the informed consent document for the research study, and be given a copy of this form along with a copy of the consent to keep. In addition, the researcher must keep the signed form in the research records along with the signed consent. The “Self-Certification of Surrogate Decision Makers for Participation in Research” form verifies the willingness of the person to serve as a surrogate, details the relationship of the surrogate to the subject and the surrogate’s qualifications demonstrating “reasonable knowledge” of the research subject. (Note: Section 3 of the “Self-Certification of Surrogate Decision Makers for Participation in Research” form is required only for surrogate consent in non-emergency room environment settings).
3. Potential surrogates must be advised that if a higher-ranking surrogate is identified at any time, the investigator will defer to the higher-ranking surrogate’s decision regarding the subject’s participation in the research.
4. For non-emergency room environment research only, if the potential surrogate identifies a person of a higher degree of surrogacy, the investigator is responsible to contact such individuals to determine if they want to serve as surrogate.
5. Surrogates are prohibited from receiving any financial compensation for providing consent. This does not prohibit the surrogate from being reimbursed for expenses the surrogate may incur related to the surrogate’s participation in the research.
6. Assessment of the decision-making capacity of the surrogate should be implemented only when the investigator has reason to believe that the surrogate’s decision-making capacity may be impaired.

NOTE: Surrogate consent to participate in research under California Health & Safety Code section 24178 is not permitted for persons in a State of California mental health facility inpatient psychiatric ward, or persons on psychiatric hold. This is more restrictive than the standard under previously existing law whereby an incapacitated adult with a conservator or guardian could be enrolled onto a study being conducted in an inpatient psychiatric unit because conservators and guardians were considered legally-authorized representatives.

Re-consenting of Research Subjects

Consenting is an ongoing process. All applicable criteria that would trigger re-consenting a subject in any study shall apply to subjects whose consent has been provided by a surrogate. In addition:

• A subject who regains the cognitive ability to consent must be re-consented using standard consenting procedures.
• In the event a subject has been initially consented by a surrogate, and a surrogate of higher priority subsequently notifies the investigator of that relationship to the subject, the investigator must defer to the higher priority surrogate’s decision regarding whether the subject will continue to participate or to withdraw from the study.
• Investigators shall describe to potential surrogates the nature of ongoing decisions during the study regarding the subject’s participation, decision to participate in certain procedures, changes to the study, etc., in order to ensure that the surrogate will be willing to undertake these on-going responsibilities.
• In the event that the surrogate dies, the subject must be re-consented subsequently upon any event that would otherwise trigger re-consenting the subject.

Research in a Foreign Country

The political or social climate in a foreign country may be such that normal methods for protecting the confidentiality of research data and the identity of subjects are not adequate. Researchers should address this problem in their protocols. Except under unusual circumstances, the procedures to be employed should not be less stringent than those required by the UCSC IRB for research in this country, even if those customary in the foreign country are less restrictive.

Medical Research

Medical Research Subject's Bill of Rights: Under California law only, any person asked to take part in a "medical experiment," or any person asked to consent to another person's participation, must be given a copy of the "bill of rights" in a language in which the person is fluent.
"Medical experiment" is defined in law as:

(a) The severance, penetration, or damaging of the tissues of a human subject, and the use of a drug or device as defined under California law, use of electromagnetic radiation, heat, or cold, or use of a biological substance or organism, in or upon a human subject, in the practice or research of medicine in a manner not reasonably related to maintaining or improving the health of the subject or otherwise directly benefiting the subject; or
(b) Withholding medical treatment from a human subject for any purpose other than maintenance or improvement of the health of the subject; or
(c) The investigational use of a drug or device licensed by the Federal Food and Drug Administration (FDA) or the California Department of Health Services; there are additional FDA requirements for consent forms:
(1) A statement of risk(s) must be clearly stated. (2) A statement of alternative treatments must be clearly stated. (3) A statement that the U.S. Food and Drug Administration may also inspect the research records.

In preparing protocols for research covered by this law, the UCSC IRB requests that researchers, (a) indicate their intention to distribute the bill of rights to their prospective subjects, and (b) add the following notice to their proposed written consent forms: "I acknowledge receiving and reading the Medical Research Subject's Bill of Rights," or words to that effect.

Radiation: The Radiation Safety Committee must approve the use of radioactive materials, lasers, etc., before a human subjects protocol is submitted to the UCSC IRB.
Drawing Blood: If routine blood draws are involved in the research, the consent form should describe the amounts in lay terms, e.g., teaspoons. The form should describe the risks of the procedure as "temporary discomfort, bruising, or discoloration, and rarely an infection," or words to that effect.
AIDS: Under California law, people asked to be subjects of AIDS research are entitled to receive a written description of certain of their rights. The UCSC IRB has prepared a short description for use by researchers and will send it to those who submit research protocols involving AIDS research studies.