Policies and Procedures

Background
Policies and Procedures Manual
Specific Policies and Procedures

Background

The IRB is charged with the responsibility for review and surveillance of all research involving human subjects carried out in the BSD and UCMC. Review and surveillance are conducted to assure the protection of the rights and welfare of all research subjects. The ethical principles which guide the IRB are consistent with the Declaration of Helsinki of the World Health Organization and the Belmont Report. The IRB policies and procedures also comply with the rules and regulations of: the Federal Policy for the Protection of Human Subjects (56 FR 28003; often referred to as the "Common Rule"), the Department of Health and Human Services (DHHS) Regulations (45 CFR Part 46), the regulations of the Food and Drug Administration (FDA) (21 CFR Parts 50 and 56), and the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule (45CFR Parts 160 and 164).

Links to the full text of these regulations:

45CFR46

DHHS regulations, posted on the website of the Office for Human Research Protections (OHRP)

http://www.hhs.gov/ohrp/humansubjects/index.html

21CFR50, 56, 312 (drugs), 812 (devices)

FDA regulations (agency of DHHS) apply to clinical investigations of products under its jurisdiction, such as drugs, biological products, and medical devices

www.fda.gov

45CFR160, 164

HIPAA Privacy Rule

http://www.hhs.gov/ocr/privacy/hipaa/administrative/privacyrule/index.html

 

Belmont Report

http://www.hhs.gov/ohrp/policy/belmont.html

 

Declaration of Helsinki

http://history.nih.gov/research/downloads/helsinki.pdf

 

Policies and Procedures Manual

The BSD/UCMC IRB has adopted a Policies and Procedures Manual to formalize Committee policies. This manual should be used as a reference point for investigators seeking more information about IRB processes.
This manual was last updated February 23, 2018 (available March 21, 2018).

Downloadable Version:

Policies and Procedures Manual

 

Specific Policies and Procedures

* Unanticipated Problem Reporting Policy

* Policy on Reviewing the Schedule of Events

* Policy on the Dispensing of Pharmaceuticals Used in Approved Protocols

* IRB Policy: Statements Regarding Research-Related Injury

* IRB Policy and Implementation Instructions for Obtaining Consent in Instances When the Subject is Unable to Provide Consent (Proxy/ Surrogate Consent)

* Policy on Enrolling Non-English Speaking Subjects

 

Unanticipated Problem Reporting (effective July 1, 2009)

Investigators are required to promptly report to the IRB all unanticipated problems involving risks to human subjects or others under Title 21 of the Code of Federal Regulations (21 CFR) part 56 (Institutional Review Boards), part 312 (Investigational New Drug Application), and part 812 (Investigational Device Exemptions). Sponsors and investigators should differentiate those unanticipated problems that must be reported to the IRB and those that do not. The University of Chicago policy is consistent with guidance set forth by OHRP (presented January 15, 2007) and the FDA (presented January 14, 2009) when determining what related events require review by the Institutional Review Board.

http://www.hhs.gov/ohrp
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126572.pdf


Unanticipated problems involving risks to subjects or others refer to a problem, event or information item that is not expected, given the nature of the research procedures and the subject population being studied; and which suggests that the research places subjects or others at a greater risk of harm or discomfort related to the research than was previously known. The IRB considers unanticipated problems, in general, to include any incident, experience, or outcome that meets ALL of the following criteria:

  1. unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol, investigator’s brochure, drug or device product information, informed consent document, or other research materials; and (b) the characteristics of the subject population being studied, including underlying diseases, behaviors, or traits;
  2. related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
  3. suggests that the research places subjects or others at a risk of unknown harm or addition/increased frequency of harms (including physical, psychological, economic, legal, or social harm) than was previously known or recognized.

Unanticipated problems may be adverse events, protocol deviations, noncompliance or other types of problems, but MUST meet all of the criteria listed above.

When reviewing a particular incident, experience, or outcome reported as an unanticipated problem by the investigator, the IRB may determine that the incident, experience, or outcome does not meet the criteria for an unanticipated problem.

Unanticipated problems occurring in research that is federally funded may or may not require further reporting to appropriate institutional officials, the department or agency head (or designee), and OHRP. The IRB has the authority, under HHS regulations at 45 CFR 46.109(a), to require, as a condition of continued approval by the IRB, submission of more detailed information by the investigator(s), the sponsor, the coordinating center, or DSMB/DMC about any unanticipated problem occurring in a research protocol.

It is the responsibility of the investigator to ensure that written notification of unanticipated problems is submitted to the IRB.  The investigator must complete an “Unanticipated Problem” report formwith his/her original signature (or electronic signature in AURA) and attach any additional information necessary in evaluating the report (such as laboratory or autopsy reports). All other events or adverse events that do not meet reporting criteria can be submitted as a summary at the time of continuing review. All events that do not meet the IRB reporting criteria and are not submitted as a summary at the time of continuing review will be returned to the Principal Investigator.

In reviewing the unanticipated problem, in order to ensure adequate protection of the welfare of subjects, the IRB will consider whether the event impacts the risk/benefit ratio and may need to reconsider approval of the study, require modifications to the study, or revise the continuing review timetable. Furthermore, the IRB may suspend or request further changes to an individual study due to safety concerns.

The IRB maintains submitted unanticipated problem reports in the protocol file or electronic file; notification of review of these reports is sent to the PI.

All Internal and External Unanticipated Problems must be reported to the IRB within 10 working days of investigator’s knowledge of the event. (Includes adverse events, protocol deviations, non-compliance, and other events that meet reporting criteria) For Internal Fatal/Life-Threatening Unanticipated Problems, the PI should notify the IRB Chair by phone immediately and consider voluntarily halting subject enrollment.

Unanticipated changes and protocol deviations are also considered “Unanticipated Problems.” It is the expectation of the IRB that all approved protocol procedures are being followed without alteration unless the IRB has been informed of a protocol change or deviation.

REPORTING UNANTICIPATED CHANGES TO THE PROTOCOL

The federal regulations require the IRB to review and approve proposed changes to research studies prior to initiation of these changes, except when changes are “necessary to eliminate apparent immediate hazards to the subject” [45 CFR 46.103(b)(4)(iii)]. The majority of proposed changes are reviewed through submission of amendments. Any changes that are made to eliminate apparent immediate hazards to a subject should be reported within 10 working days of the occurrence using the “Unanticipated Problem” report form to the IRB and an amendment should be submitted for the next deadline to change the protocol to eliminate future hazards of this type, as appropriate.

In the event that such a change is implemented to eliminate immediate hazards to a subject, enrollment of new subjects should be halted until the IRB has had an opportunity to consider such changes.  The reviewer may also recommend that the subjects on the study be provided specific information about the change and the cause of the change.

REPORTING DEVIATIONS/NONCOMPLIANCE

An IRB is asked to ensure prompt reporting of serious or continuing noncompliance with regulations or noncompliance with the IRB’s own requirements/determinations [45 CFR 46.103(b)(5)].  Deviations from the approved protocol, i.e., changes made without prior IRB approval, fall into this category of noncompliance. Deviations must be reported to the IRB along with a description of the effect of the deviation on subject safety and a description of how similar events will be avoided in the future.

A protocol deviation occurs when the study departs from the IRB-approved protocol in any way without the investigator first obtaining IRB approval.

Deviations range in seriousness according to how the changes may impact subject safety, the degree of noncompliance with federal and state regulations, and the degree of foreknowledge of the event. Anticipated changes to a protocol should always be reported prior to the event occurrence unless an immediate change is necessary to protect subject safety.

Repeated deviations of the same type may be an indication that an amendment is needed to permanently change study criteria.

A major deviation is one that may impact subject safety or alter the risk/benefit ratio, compromise the integrity of the study data, and/or affect subjects’ willingness to participate in the study. Major deviations should be reported within 10 working days of the investigator’s knowledge of the deviation. Reports should be made using the “Unanticipated Problem” report form.

A minor deviation is one that does not impact subject safety, compromise the integrity of the study data, or affect subjects’ willingness to participate in the study. Minor deviations should be summarized at the time of continuing review on the continuing review form.

 

Policy on Reviewing the Schedule of Events

In June of 2006, the Office of Clinical Research (OCR) sent a notice to all faculty concerning the review of the schedule of events. All studies (including investigator-initiated studies) involving clinical care services and supplies that are considered research-related require this distinction of services to be on file with the Office of Clinical Research. During the IRB continuing review process, investigators will be asked to submit this schedule of events to the OCR.

For more information on this policy, please review the following materials from the OCR.

OCR email notification of the policy

Schedule of Events Outline

Schedule of Events Policy

PowerPoint presentation on the Schedule of Events policy

Please feel free to call the Office of Clinical Research at 4-1238 if you have questions about the policy.


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Policy on the Dispensing of Pharmaceuticals Used in Approved Protocols

As part of its responsibility to protect the health and safety of Human Subjects, the Institutional Review Board (IRB) has joined with the Pharmacy in an effort to ensure that all investigational drugs dispensed under an approved IRB Protocol are in accordance with the most current dosing guidelines approved by the IRB and ensure that the Pharmacy receives timely notification of changes in dosing and/or the status of protocols.

Accordingly, the IRB will provide information to the Pharmacy on 1) expired and terminated studies, thereby ensuring that the Pharmacy will not dispense drugs for terminated or expired protocols, and 2) any or all amendments requesting a change in drug dosage. The IRB has modified the amendment form to allow staff to more easily identify those amendments involving changes in dosing. 

Once the dosage change is approved by the IRB, the Investigators will be responsible for forwarding a complete copy of the revised protocol to: Investigational Drug Pharmacist, Dept. of Pharmacy, MC 0010. Drugs will be dispensed by the Department of Pharmacy at the IRB-approved dosage. 

Questions should be forwarded to Millie Maleckar, IRB Director, at extension
2-6505.


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IRB Policy: Statements Regarding Research-Related Injury

For studies that involve a foreseeable risk of harm, federal regulations (45 CFR 46.116) require that the consent process include “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.” As the wording in consent forms is intended to inform subjects about studies, not to limit liability, the University of Chicago Biological Sciences Division IRB has set the following policy to ensure that all compensation for injury statements meet both Federal and Institutional standards.  

A.        COMMERCIAL SPONSOR STATEMENTS

It is the policy of the University of Chicago and the Medical Center that commercial sponsors of clinical research at the Medical Center must agree to pay for treatment of injuries that are the direct result of the administration of a study drug or device, or any study procedure required to be performed in the study.  This obligation of commercial sponsors is limited to research protocols designed or supplied by the commercial sponsor.  The University and the Medical Center’s obligations for treatment of research injuries, as expressed in the language below and in Medical Center’s Policy on Research-Related Injuries, will be secondary to the commercial sponsor’s obligations under the clinical trial or other sponsored research agreement.  University Research Administration is responsible for implementation of this requirement in commercially-sponsored research agreements. 

The obligations of commercial sponsors to subjects who suffer a research-related injury must be expressed in the “What Are the Costs” section of the written consent form using the following language, which should immediately precede the applicable statement concerning the Medical Center’s obligations discussed in Part B., below:

The sponsor of the study, [insert sponsor name], has agreed to pay for the care of certain injuries directly resulting from this research.  If you think that you have suffered a research-related injury, you must contact [insert PI/study doctor name] right away.  The study doctor can help you obtain more information about the sponsor’s agreement to pay for research-related injuries.

Exceptions to this consent form language may be considered by the IRB, in consultation with legal counsel, on a case by case basis if requested by the commercial sponsor, but are not looked on favorably, and must satisfy the requirements of the Medical Center’s Policy on Research-Related Injuries.

B.         UNIVERSITY/MEDICAL CENTER STATEMENTS

One of the following University of Chicago BSD/ University of Chicago Hospitals statements must be included (without any modifications) in the “What Are the Costs” section of the written consent form, immediately following the commercial sponsor statement describe in A., above (if applicable).  The appropriate statement should be chosen based upon the subject population being recruited.  The IRB recognizes that for studies that recruit both individuals with a disorder and condition and healthy controls, the use of both statements may be required. However, a separate consent form should be drafted for each of the populations with the appropriate costs statement included.

1.         For studies with therapeutic intent for the subject (including Phase I and II trials):

If you suffer an unanticipated injury as a direct result of this research and require emergency medical treatment, the University of Chicago Medical Center will provide such treatment at the University of Chicago Medical Center at no cost to you.  You must notify ___________ [insert PI/study doctor name] as promptly as possible after your injury in order to receive this care.  An injury is “unanticipated” if it is not one of the known effects of a study drug, medical device or procedure, and is not the result of your disease or condition. The costs of any non-emergency care for such an injury will be billed to you, your insurance [or the study sponsor*] in the ordinary manner.  If you think that you have suffered a research-related injury, you must let ____________ [insert PI/study doctor name] know right away.

2.         For studies involving healthy volunteers:

If you suffer an unanticipated injury as a direct result of this research and require emergency medical treatment, the University of Chicago Medical Center will provide such treatment at the University of Chicago Medical Center at no cost to you.  Costs of related non-emergency care for an unanticipated research injury will be covered if that care is provided at the University of Chicago Medical Center.  You must notify ___________[insert PI/study doctor name] as promptly as possible after your injury in order to receive this care.  An injury is “unanticipated” if it is not one of the known effects of a study drug, medical device or procedure.  If you think that you have suffered a research-related injury, you must let __________ [insert PI/study doctor name] know right away.


*(Include only if study is commercially sponsored and the sponsor designed or supplied the protocol.)

 

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IRB Policy and Implementation Instructions for Obtaining Consent in Instances When the Subject is Unable to Provide Consent (Proxy/Surrogate Consent)

Introduction: Researchers at The University of Chicago and elsewhere have been vexed by the problem of conducting studies in situations where the patient is unable to consent to participation in a research project. Such situations include many protocols in the Intensive Care Unit, the Emergency Department, the Psychiatry Department, and those involving patients with dementia. Recent changes in both federal regulations and state laws have partially remedied this situation. Researchers working in such areas now have new options for proceeding with protocols, even if the patient is unable to consent. Amendments to the Health Care Surrogate Act and the Medical Patient Rights Act provide a legal basis in the State of Illinois for the use of proxy consent in research (see Appendix for legal background).

Proxy consent should involve all the same considerations that informed consent from a competent patient involves. It also involves identifying the proper surrogate and ensuring that the research decision reflects the wishes of the subject, if known or, if not known, the best interests of the subject. In addition, the IRB will be concerned about whether the research could be accomplished in situations involving the consent of a competent patient, and will consider whether the intervention is likely to offer therapeutic benefit to the subject of the study. The IRB will always view these considerations as paramount. 

Implementation:
The University of Chicago believes in the importance of the informed consent process and believes that subjects should be given every opportunity to provide their consent. Understanding, however, that medical circumstances may preclude a subject from participating in the consent process, the University of Chicago and University of Chicago Medical Center IRBs will implement the following procedures to consider requests for surrogate consent in keeping with the Medical Patient Right Act and the Health Care Surrogate Act.
 

A. Protocol Submission and Review
1. Researchers wishing to utilize surrogate consent will be asked to provide additional information regarding this population in addition to completing the IRB Protocol Submission Form in full. 
2. The IRB will utilize the prioritized listing of surrogates in the Health Care Surrogate Act in evaluating protocols requesting to use surrogate consent. The priority order specified by the Act is as follows:

a) subject's guardian;
b) subject's spouse;
c) any adult son or daughter of the subject;
d) either parent of the subject;
e) any adult brother or sister of the subject;
f) any adult grandchild of the subject;
g) a close friend of the subject; and
h) the subject's guardian of the estate. 

3. In determining whether to approve the use of surrogate consent in a particular protocol, the IRB will consider such factors as whether the research could be done without using surrogate consent or whether the proposed intervention offers direct benefit to the subjects of the research.

B. Procedures For Surrogate Consent

1. The attending physician must determine that the subject lacks decisional capacity.

2. An attempt should be made to determine whether there is an operable and unrevoked living will, durable power of attorney for health care, or declaration for mental health treatment ("Advance Directive") which is applicable to the subject's decision about whether to participate in the research. Surrogate consent should be invoked only in cases when, after reasonable inquiry, no Advance Directive applies or, despite efforts to contact the person authorized in an Advance Directive, that person is unavailable. 

3. The researcher must attempt to identify a surrogate of the highest priority. (Note: If there is more than one surrogate of the highest priority and there is a disagreement between them, majority rules. If there is disagreement and no majority, consult with the Ethics Consult Service or the Office of Medical Legal Affairs.) 

4.The University of Chicago/UCMC Health Care Surrogate Act Certification Concerning Research must be used in all instances of surrogate consent. The certification shall be placed in the subject's medical record and a copy attached to the research consent form or, if written consent is not required, kept with the subject research records. 

5. The consent process with the surrogate should include a discussion with the attending physician and an inquiry into the extent to which the surrogate is able to speak for the subject. Following the requirements of the Health Care Surrogate Act, this discussion should emphasize the surrogate's ability to make a decision that would conform as closely as possible to what the subject would have done or intended under the circumstances. The surrogate should take into account evidence that includes the subject's personal, philosophical, religious, and moral beliefs and ethical values relative to the purpose of life, sickness, medical procedures, suffering and death.

6. In circumstances in which the subject's wishes are unknown after reasonable efforts to discern them, the decision shall be made on the basis of the subject's best interests as determined by the surrogate decision maker. In determining the subject's best interests, the surrogate shall weigh the burdens and benefits of the proposed research and shall take into account any other information, including the views of family and friends, that the surrogate decision maker believes the patient would have considered if able to act for herself or himself. 

7. The surrogate should express his/her decision to the researcher in the presence of an adult witness (at least 18 years of age). 

8. The University of Chicago/UCMC Hospitals Health Care Surrogate Act Certification Concerning Research attached to the consent form should document the surrogate decision making process described in points 5, 6 and 7. 

9. The subject should be made aware of the research and the identity of the surrogate as soon as feasible. If the subject objects and the surrogate is not a court-appointed guardian, the subject should be withdrawn from the research. 

10. The surrogate will have the same rights as the subject to receive information on the research, to withdraw consent for further participation, etc.

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(Appendix)
Legal Background:

Informed consent is one of the fundamental principles of research with human subjects. It has traditionally been recognized that proxy consent by someone other than the subject is not the same as the subject's own consent. The federal regulations require that informed consent be provided by the subject or the subject's legally authorized representative, except 1) in cases where the IRB has altered or waived some of the requirements for informed consent and the research presents no more than minimal risk or 2) in cases which meet the criteria for waiver of consent in emergency situations (45 CFR 46 and 21 CFR 50). It is State law that defines who can act as a subject's "legally authorized representative" to make treatment and /or research-related decisions on the subject's behalf.

The State of Illinois has two pieces of legislation which provide family members or others with legal authority to provide consent in situations where the patient is unable to provide consent. The Medical Patient Rights Act indicates that consent to participate in a research program or experimental procedure may be given by "the patient or, if the patient is unable to consent, the patient's guardian, spouse, parent, or authorized agent." It should also be noted that on June 27, 1997, the State of Illinois amended the Medical Patient Rights Act to align state law with the recently enacted federal (DHHS and FDA) regulations on the waiver of consent in emergency situations. 

The Health Care Surrogate Act also provides authority for a surrogate decision maker to act on behalf of patients (minor or adult) who lack decisional capacity. This statute initially applied only in situations concerning withdrawal of life sustaining treatment. Recent amendments to the statute extend the surrogate's authority to general medical treatment decisions, which can include research-related decisions.

For the purposes of this law, relevant surrogates in order of priority are as follows:

1) patient's guardian of the person;
2) patient's spouse;
3) any adult son or daughter of the patients;
4) either parent of the patient;
5) any adult brother or sister of the patient;
6) any adult grandchild of the patient;
7) a close friend of the patient;
8) the patient's guardian of the estate. 

For copies of The Medical Patient Rights Act and The Health Care Surrogate Act, please contact the Office of Medical Legal Affairs. 

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Policy on Enrolling Non-English Speaking Subjects

For research in which investigators expect to enroll non-English speaking subjects, a consent form translated into the native language of the subjects to be enrolled must be provided to the IRB with the original submission or, if this study population is being added, with the amendment. A certified translator should perform the translation and proof of certification should be provided to the IRB along with the translated consent form. 

Any recruitment materials (flyers, radio advertisements, etc.) that have been translated should also be provided to the IRB. In addition, investigators should translate all study materials that will be distributed to non-English-speaking subjects, such as surveys or questionnaires, and submit these to the IRB when the translated consent is submitted. 

The translated documents must be approved by the IRB before non-English speaking subjects can be enrolled into the study. 

Note that the exclusion criteria in certain protocols may specifically exclude non-English-speaking subjects from participating. Check your full written protocol for inclusion/ exclusion criteria before enrolling non-English speaking subjects.  

What if investigators encounter a potential subject who is Non-English-speaking, but do not already have a translated consent?

In some cases, a non-English speaker may be eligible for a study for which there is no translated consent document, and for which the study investigators could not have foreseen enrollment of a potential subject who speaks that language. In this case, investigators may choose to enroll the potential subject using a "short form" consent that has been translated into the subject's native language. 

The consent process must involve a translator who can verbally translate the information in the full written informed consent into the subject's native language. This translator must sign the full written informed consent as well as the short form consent to document that he or she participated in the consent process and that the subject has been fully informed regarding the study. A witness to the translation must also sign the consent form; the translator may him/herself function as the witness. 

If PHI will be used and/or disclosed as part of the research, the subject
should also sign a HIPAA authorization for this use/disclosure written in a
language understandable to the subject. Please contact the HIPAA Program Office or see their website for more information on translated HIPAA authorization forms: http://hipaa.bsd.uchicago.edu
A general authorization in Spanish for use/disclosure of PHI is available on that website.

Like the translated full written consent document, the IRB must approve the translated short form consent prior to its use. However, expedited review of an amendment to approve a translated short form consent is possible if the IRB has previously approved both the protocol in question and the protocol's full English-language informed consent document. 

The IRB has approved a short form consent document and has had this consent translated into several languages. Several translations have also been provided by the Cancer Clinical Trials Office (CCTO) (thanks to the CCTO for allowing the IRB office to share these). For the languages listed below, please contact the IRB for a copy of the translated document when submitting an amendment to use the short form consent.

For any language not listed below, the investigator is responsible for obtaining a certified translation.  The English language short form is available below for download:

Short form consent (English)

Available from the IRB office:

Spanish
 
Arabic
Bosnian-Serbian
Bulgarian
Cantonese
Greek
Hebrew
Hindi
Korean
Macedonian
Mandarin
Polish
Portuguese
Romanian
Russian


 

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