Section 3: Special Issues

3.1 Assessing the Need for Increased Monitoring, Interim Continuing Review, and Verification from Sources Other than the PI

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for determining the need for: 1) IRB review more often than annually, 2) increased monitoring, and 3) verification from sources other than the PI that no material changes have occurred since previous IRB review.


2.0 Policy

It is the policy of the Organization that that all non-exempt research will be assessed at both initial and continuing review in accordance with the requirements set forth by HHS regulations at 45 CFR 46.103(b)(4), FDA regulations at 21 CFR 56.108(a)(2), and all applicable state and local laws.


3.0 Increased Monitoring and/or Interim Continuing Review


4.0 Verification from Sources Other than the Investigator


DOCUMENT HISTORY:

 Written: 1/8/2016 (Approved: 1/8/2016) - original author not recorded

 Revised: 1/2/2018 - revision not documented

3.2 Data and Safety Monitoring

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for data and safety monitoring for non-exempt research.


2.0 Policy

It is the policy of the Organization that all non-exempt research must have an appropriate plan for data and safety monitoring in consideration of the nature and risk level of the research. The Data and Safety Monitoring Plan (DSMP) may or may not include a formal Data and Safety Monitoring Board (DSMB).


3.0 Data and Safety Monitoring Plan (DSMP)


4.0 Data Safety Monitoring Board (DSMB)


5.0 Review of the DSMP by the IRB


6.0 Review of DSMB Reports by the IRB


DOCUMENT HISTORY:

 Written: 4/4/2016 (Approved: 4/4/2016) - original author not recorded

 Revised: 2/2/2018 - revision not documented

 Revised 12/22/2022 – Clarified expected contents of DSMP; other revisions to eliminate duplicate text and for clarity. {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Board notified - 12/29/2022

3.3 Privacy Interests and Confidentiality of Research Data

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for 1) protection of privacy interests of research subjects, and 2) maintenance of confidentiality of data. For the purposes of this policy “subjects” and “participants” are synonymous, and includes those persons participating in a data registry or biobank.


2.0 Policy

It is the policy of the Organization that:


3.0 Definitions


4.0 Protection of Privacy


5.0. Protection of Confidentiality


DOCUMENT HISTORY:

 Written: 1/28/2016 (Approved: 1/28/2016) - original author not recorded

 Revised: 2/2/2018 - revision not documented

 Revised – 9/22/2022 - Stylistic changes, and changes for clarity; clarified privacy requirements regarding informed consent process; clarified applicability of CoC and consent form language during interruption in or termination of NIH funding; added acknowledgement of CoCs issued by agencies other than NIH. {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Board Notified: 11/29/2022

 Revised 1/21/2024 – added definition of “identifiable sensitive information” (section 3.5); elaborated on types of research which are automatically issued a CoC by NIH (section 5.2) {Approved Russell McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

3.4 Use of Protected Health Information in Research

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for ensuring the appropriate protections for use of Protected Health Information (PHI) in research.


2.0 Policy


3.0 Definitions


4.0 Use or Disclosure of PHI for Research

The Privacy Rule permits the Organization to use or disclose PHI for research only under certain circumstances and conditions as described below:


5.0 Procedures


DOCUMENT HISTORY:

 Written: 1/28/2016 (Approved: 1/28/2016) - original author not recorded

 Revised: 4/9/2018 - revision not documented

3.5 Subject Recruitment Through Advertisements

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for recruitment of subjects through advertisements. For the purpose of this policy, “advertisements” refer to printed advertisements (including bulletins, newsletters, posters, fliers, and magazine or newspaper ads); radio and television advertisements; and electronic advertisements (including social media or other on-line venue).

Note: Invitations to participate directed to specific persons are covered by [HRPP policy 3.6](https://guides.unmc.edu/books/hrpp-policies-and-procedures/page/36-subject-recruitment-through-direct-invitation) (Subject Recruitment Through Direct Invitation).

Note: References in this policy to information provided to, or decisions made by, potential subjects also means information provided to, or decisions made by, parents, guardians or legally authorized representatives (LARs) as appropriate.


2.0 Policy

It is the policy of the Organization that


3.0 General Requirements and Prohibitions


4.0 Printed Advertisement


5.0 Radio and Television Advertisements


6.0 Electronic Advertisements (including social media or other on-line venue)


7.0 Submission and Review of Advertisements


DOCUMENT HISTORY:  Written: 4/14/2016 (Approved: 4/14/2016) - original author not recorded

 Revised: 6/28/2018 - revision not documented

 Revised 9/9/2022 – Clarified that advertisements related to research for which the Organization is relying on another IRB as the IRB of record, must be adhere to this policy; however, the ORA will not routinely review such advertising unless requested to do so by the investigator or the reviewing IRB. {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised 9/15/2022 – removed requirement that printed advertisements be prepared within RSS (functionality not yet implemented). {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised 10/12/2022 - emphasized what information “must” be included vs “may” be included, in advertisements {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Board Notified: 11/29/2022

 Revised: 12/1/2022 - typo corrected in 7.0 (Robert Lewis - IRB Assoc)

 Revised: 3/29/2023 - typos corrected in Section 2.0 and section numbering corrected 2.1-2.4 (Robert Lewis - IRB Assoc)

 Revised (10/10/2024) – modified so that ORA will review all advertisements, including those used when the Organization relies on another IRB; specified format of IRB number to be included in written advertisements; clarified advertisements must include a description of “reasonably foreseeable” risks; revised to require layout of the advertisements conform to the Organization’s requirements regarding the use of logos and brands “whenever possible” (section 4.4); clarified requirements regarding availability and value of compensation in advertisements (section 3.2.6); deleted requirement that IRB approval letter cite the approved version of the advertisement (section 7.1.3); stylistic changes. {Approved Russell McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised 12/11/2024 – deleted “address” from sections 4.2.1 and 6.1.1. {Approved Russell McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

3.6 Subject Recruitment Through Direct Invitation

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for subject recruitment through direct invitations to participate. Subject recruitment through advertisements is described in HRPP policy 3.5.


2.0 Policy

It is the policy of the Organization that


3.0 Definitions


4.0 General Prohibitions


5.0 Invitations to Patients


6.0 Invitations to Prospective Subjects who are not Patients

This section applies to prospective subjects who may be eligible for participation in research but who are not primarily eligible because they have a disease or condition being diagnosed or treated at UNMC/Nebraska Medicine (including hospital and/or clinics), Bellevue Medical Center, or Children’s Nebraska (including Children’s Physicians Clinics). They may be patients or former patients, but that is not the primary reason they may be eligible.

Note: Examples of this subject population would be public or private school students; college, trade or professional school students (e.g., UNO freshman, enrollees at a particular trade school, UNMC School of Medicine students); cultural, ethnic or religious groups (e.g., Sudanese immigrants, members of a particular church); trades or professions (e.g., farmers, physicians, prison guards).


DOCUMENT HISTORY:

 Written: 8/23/2018 (Approved: 8/23/2018) - original author not recorded

 Revised 9/25/2024: Revised definition of “Opt-In” (section 3.1); deleted definition of Honest Broker since not used in policy; clarified how distribution list obtained, processed and used (sections 4.1.1 and 4.3); clarified and simplified method of contact of potential patient subjects thru OneChart Patient Portal or Children’s Connect (section 4.6); provided regulatory reference for TCPA (sections 4.7.5 and 5.3.3); specified that phone calls must originate from a UNMC/NM, CN or UNO telephone number, unless specifically approved by the IRB (section 4.7.2 and 5.3.2). {Approved Chris Kratochvil (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 Revised 3/5/2025 - Reformatted and revised to make requirements consistent for all routes of contact with potential subjects; clarified information that must, may, and may not appear in recruitment materials; specified IRB number format; stylistic changes. {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

3.7 Finder’s Fees and Recruitment Bonuses

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements related to finder’s fees and recruitment bonuses.


2.0 Policy

HHS regulations at 45 CFR 46.116 and FDA regulations at 21 CFR 56.116 require minimization of the possibility of coercion or undue influence. It is the view of the Organization that payment of finder’s fees or recruitment bonuses to investigators or to any representative of the Organization may create the perception that subjects or potential subjects could be unduly influenced or coerced to participate (or continue participation). Therefore, it is the policy of the Organization that such payments are not permitted.


3.0 Definitions


4.0 Finder’s Fees


5.0 Recruitment Bonuses


DOCUMENT HISTORY:

 Written: 12/28/2015 (Approved: 12/28/2015) - original author not recorded

 Revised: 1/26/2018 - revision not documented

3.8 Research Subject Compensation and Reimbursement

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements and limitations regarding compensation and reimbursement of research subjects.


2.0 Policy

It is the policy of the Organization that


3.0. Definitions


4.0. General Principles


5.0 Specific Requirements for Compensation


6.0. Requirements for Reimbursement


POLICY AMENDED: Revised June 25, 2021 Separated policies and requirements for compensation (payment) from reimbursement, and reorganized policy accordingly; included definitions of above; explicitly stated that investigators should attempt to minimize financial sacrifice on the part of subjects and, as possible and appropriate, offer equitable reimbursement for costs; explicitly stated that compensation for minimal risk research may represent a reasonable incentive for participation (previously implied since no restriction placed on payment for minimal risk research); added prohibition that reimbursement for travel associated expenses may not be contingent on distance; specified preferred mechanism for compensation and reimbursement; allowed for direct payment to adolescents (and older children with justification).


DOCUMENT HISTORY:

 Written: 12/28/2015 (Approved: 12/28/2015) - original author not recorded

 Revised: 5/10/2017 - revision not documented

 Revised: 1/26/2018 - revision not documented

 Revised: 3/8/2019 - revision not documented

 Revised: 8/31/2021 - Separated policies and requirements for compensation (payment) from reimbursement, and reorganized policy accordingly; included definitions of above; explicitly stated that investigators should attempt to minimize financial sacrifice on the part of subjects and, as possible and appropriate, offer equitable reimbursement for costs; explicitly stated that compensation for minimal risk research may represent a reasonable incentive for participation (previously implied since no restriction placed on payment for minimal risk research); added prohibition that reimbursement for travel associated expenses may not be contingent on distance; specified preferred mechanism for compensation and reimbursement; allowed for direct payment to adolescents (and older children with justification).

 Revised: 6/5/2023 - Revised section 5.2 to allow the IRB has the authority to review the level of compensation and, in appropriate circumstances, limit or increase the total value; revised section 5.7 to delete preferred method of payment (preferred method will be decided by B&F; revised section 5.7 to allow, within acceptable payment mechanisms, the IRB or expedited reviewer may require a particular method in order to minimize risks or provide equitable compensation.

 Revised: 8/12/2023 - Clarified that section 6.4 refers to an “arbitrary distance threshold”; minor grammatical changes. {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

 7/3/2024 – increased hourly compensation from $20/hour to $25/hour (section 5.1); clarified that “research interventions” included, but were not limited to, the example provided in section 5.2; deleted requirement for individual IRB Executive Chair/designee approval of use of a lottery (or raffle) as a mechanism to provide compensation to subjects for participation in minimal risk research; minor stylistic changes. {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

3.9 Contraception Requirements

1.0 Purpose

The purpose of this policy and procedure is to describe the contraception requirements for subjects participating in research.


2.0 Policy

It is the policy of the Organization that subjects must utilize appropriate contraception methods while participating in research with potential for reproductive toxicity.


3.0 Categories based on FDA Pregnancy and Lactation Labeling Rule (PLLR)


4.0 Definitions of the FDA Use-In-Pregnancy Categories


5.0 Procedure


ADDENDUM #1

ICF Pregnancy Risk Statements

Category A or Group 1 drugs:

PREGNANCY RISKS It is possible that the medicines used in this study could injure a fetus [OR an unborn child] if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions

Category B or Group 2 or Group 3 drugs when contraception is NOT required:

PREGNANCY RISKS It is possible that the medicines used in this study could injure a fetus [OR an unborn child] if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.

Category B or Group 2 or Group 3 drugs when contraception IS required:

PREGNANCY RISKS It is possible that the medicines used in this study could injure a fetus [OR an unborn child] if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.

You may want to discuss this with others before you agree to take part in this study. If you wish, we will arrange for a doctor, nurse, or counselor who is not part of this study to discuss the potential risks and benefits with you and anyone else you want to have present.

Because of the potential risks, you, or your partner, must not become pregnant while you are participating in this study. Women must have a negative pregnancy test before entering the study [and before each treatment – as appropriate].

If you are sexually active and can get pregnant, or can get your partner pregnant, you must use ONE appropriate method of birth control every time you have sex, or you must not have sex.

You can get additional information about methods to avoid pregnancy by calling the UNMC Research Subject Advocate’s Office at (402) 559-6941.

You will need to continue to use birth control to avoid pregnancy for X months after finishing the research.

By signing this and being in the study, you are agreeing to not get pregnant while you are on the study and for X months after. Should you become pregnant while on this study, you should immediately notify the study personnel. The investigator will assist you in finding appropriate medical care. The investigator also may ask to be allowed to continue getting information about your pregnancy. You can refuse to provide this information.

Category C or Group 4 drugs:

PREGNANCY RISKS It is possible that the medicines used in this study could injure a fetus [OR an unborn child] if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.

You may want to discuss this with others before you agree to take part in this study. If you wish, we will arrange for a doctor, nurse, or counselor who is not part of this study to discuss the potential risks and benefits with you and anyone else you want to have present.

Because of the potential risks, you, or your partner, must not become pregnant while you are participating in this study. Women must have a negative pregnancy test before entering the study [and before each treatment – as appropriate].

If you are sexually active and can get pregnant, or can get your partner pregnant, you must use ONE [or TWO] appropriate method(s) of birth control every time you have sex, or you must not have sex.

Because of the possible risk to the fetus [OR an unborn child], methods of natural family planning are not, by themselves, reliable enough to avoid pregnancy.

You can get additional information about methods to avoid pregnancy by calling the UNMC Research Subject Advocate’s Office at (402) 559-6941.

You will need to continue to use birth control to avoid pregnancy for X months after finishing the research.

By signing this and being in the study, you are agreeing to not get pregnant while you are on the study and for X months after. Should you become pregnant while on this study, you should immediately notify the study personnel. The investigator will assist you in finding appropriate medical care. The investigator also may ask to be allowed to continue getting information about your pregnancy. You can refuse to provide this information.

Category D or Group 5 Drugs:

PREGNANCY RISKS It is possible that the medicines used in this study could injure a fetus [OR an unborn child] if you, or your partner, become pregnant while taking them. You have already been told what is known about this possibility, and you are encouraged to ask further questions.

You may want to discuss this with others before you agree to take part in this study. If you wish, we will arrange for a doctor, nurse, or counselor who is not part of this study to discuss the potential risks and benefits with you and anyone else you want to have present.

Because of the potential risks, you, or your partner, must not become pregnant while you are participating in this study. Women must have a negative pregnancy test before entering the study [and before each treatment – as appropriate].

If you are sexually active and can get pregnant, or can get your partner pregnant, you must use TWO appropriate methods of birth control every time you have sex, or you must not have sex.

Because of the possible risks to a fetus [OR an unborn child], methods of natural family planning are not, by themselves, sufficiently reliable to avoid pregnancy.

You can get additional information about methods to avoid pregnancy by calling the UNMC Research Subject Advocate’s Office at (402) 559-6941.

You will need to continue to use birth control to avoid pregnancy for X months after finishing the research.

By signing this and being in the study, you are agreeing to not get pregnant while you are on the study and for X months after. Should you become pregnant while on this study, you should immediately notify the study personnel. The investigator will assist you in finding appropriate medical care. The investigator also may ask to be allowed to continue getting information about your pregnancy. You can refuse to provide this information.

Category X Drugs:

Since studies of the drug in humans, or investigational or post-marketing data, have demonstrated fetal risk, contraception is required and the language must be at least as protective as Category D language above. If the sponsor or FDA require inclusion of specific language relating to fetal risk, monitoring for pregnancy and prevention of pregnancy in the ICF, it may be included, and redundant category D language deleted.


DOCUMENT HISTORY:

 Written: 12/28/2015 (Approved: 12/28/2015) - original author not recorded

 Revised: 11/21/2017 - revision not documented

3.10 Pregnancy Testing

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for determining how and when pregnancy testing should be performed on subjects who are of childbearing potential enrolled in protocols that describe pregnancy as an exclusion criterion.


2.0 Policy

It is the policy of the Organization that when women of childbearing potential are enrolled in protocols which include a pregnancy exclusion criterion, the protocol must have procedures in place for either pregnancy testing or self-reporting depending on the teratogenic risk.


3.0 Definition


4.0 Procedures


DOCUMENT HISTORY:

 Written: 12/28/2015 (Approved: 12/28/2015) - original author not recorded

 Revised: 1/8/2018 - revision not documented

3.11 Collecting Data from Pregnant Partners of Research Subjects

1.0 Purpose

The purpose of this policy is to describe the Organization’s requirements for obtaining informed consent, and collecting data from pregnant partners of research subjects and from their infants.


2.0 Policy


3.0 General Considerations


4.0 IRB Review



DOCUMENT HISTORY:

 Written: 1/12/2018 (Approved: 1/12/2018) - original author not recorded

 Revised: 9/9/2019 - revision not documented

3.12 Ethical Access

1.0 Purpose

The purpose of this policy is to define ethical access and to describe the Organization’s requirements to protect the privacy of potential subjects in the context of recruitment for participation in research, or for identification of potential subjects for review of medical records.


2.0 Policy

It is the policy of the Organization that


3.0 Ethical Access for Recruitment of Subjects

For the purposes of this policy, the recruitment of subjects requires two distinct activities, each of which must respect the privacy of potential subjects: (1) obtainment of information about the potential subject which leads the investigator to believe or conclude that the person is eligible for the research, and (2) subsequent approach to the person to explain the research and obtain their consent to participate.


4.0 Ethical Access for Review of Medical Records


5.0 Investigator Responsibilities


6.0 IRB Responsibilities


DOCUMENT HISTORY:

 Written: 4/16/2018 (Approved: 4/16/2018) - original author not recorded

 Revised: 11/20/2018 - revision not documented

 Revised: 2/18/2019 - revision not documented

 Revised 3/5/2025 - Specified criteria for waiver of ethical access (section 3.1.1.3); removed citations to pre-2018 Common Rule; formatting and stylistic changes {Approved Rusty McCulloh (Institutional Official), Bruce Gordon (Assistant Vice Chancellor for Regulatory Affairs, Executive Chair)}

3.13 Use of Placebo or Wash-Out of Effective Therapy in Clinical Trials

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for IRB review and approval of clinical trials that utilize placebos or wash-out of effective therapy.


2.0 Policy


3.0 Definition


4.0 Ethical Justification


5.0 Study Design Considerations



DOCUMENT HISTORY:

 Written: 1/12/2016 (Approved: 1/12/2016) - original author not recorded

 Revised: 2/7/2018 - revisions not documented

3.14 Phase I and First-in-Human Studies

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for IRB review and approval of Phase I and First in Human Studies.


2.0 Policy


3.0 Definitions


4.0 General Principles


5.0 IRB Review



7.0 Phase I Studies in Children


8.0 Phase I Studies in Decisionally Impaired Persons


DOCUMENT HISTORY:

 Written: 2/5/2018 (Approved: 2/5/2018) - original author not recorded

3.15 Managing Radiographic Incidental Findings in Human Subjects Research

1.0 Purpose

The purpose of this policy and procedure is to describe the Organization’s requirements for disclosure, or nondisclosure, of radiographic incidental findings that may affect the management of a subject’s current or future health or welfare.


2.0 Policy


3.0 Definitions


4.0 Procedures


5.0 Model CF Language


6.0 IRB Review


DOCUMENT HISTORY:

 Written: 2/28/2018 (Approved: 2/28/2018) - original author not recorded