IRB

The U.S. Department of Health and Human Services defines research as "a systematic investigation designed to develop or contribute to generalizable knowledge." An activity may be considered research even if it is part of a non-research program.

Research is sometimes confused with other areas of study, such as Quality Improvement and Evidence Based Practice projects (see below). Both of these study types involve systematic investigations, but that on its own does not mean that a study is research. Additionally, the results of these study types will often be disseminated to people who could benefit from them. However, the difference is that the primary aim of the study must be to develop or contribute to generalizable knowledge. The differences between the types of studies may be subtle, and they will sometimes overlap.

Research at Riverside has to go through the Riverside IRB if it involves human subjects. A "human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) Data through intervention with the individual, or (2) Identifiable private information."

This means that even if researchers obtain information about the research subjects through their medical records or another database, the research must be approved by the IRB if that information is identifiable. If using an existing database, please see the New Research section to determine if your research may be eligible for Exempted Review by the IRB.

Quality Improvement Studies (QI) are activities with the "goal of improving the performance of institutional practice in relationship to an established standard." As described in the section "What qualifies as research?" QI studies differ from research in that their primary aim is to create institution-specific knowledge.

QI studies do not require IRB approval, but it is recommended that potential QI investigators contact the Research Office to make sure that their studies are not research.

Evidence Based Practice (EBP) is when an investigator uses the results of previous studies to implement the measures of the study. This may involve some form of data collection to determine whether the results of the original study are replicated. However, as opposed to research, the goal is not to develop or contribute to generalizable knowledge, but instead to put that evidence into practice.

Data collection and analysis for EBP does not require IRB approve. However, it is recommended that investigators contact the Research Office to make sure that their studies are not research.

Riverside encourages continuing education and professional development for nurses, including supporting research, QI, and EBP studies by Riverside's nursing staff. In particular, the Magnet Office works with nurses to develop their research. While IRB review may also be required, nurse investigators should first contact the Magnet Office at (815) 936-8908 for more information.

IRB forms

IRB New Study checklist

To determine whether your study requires IRB approval, or what kind, please see the Riverside Guide to Human Subjects Research.

Full board review means that your study is reviewed at a meeting of the IRB. These meetings are normally scheduled for the third Wednesday of every month. Submissions are required by the Monday two weeks prior. Submissions must include the Application for IRB Review, along with all supporting documentation.

Expedited review means that your study may not have to wait for the full IRB to convene. Instead, it is reviewed by the IRB Chair or other IRB members designated by the Chair. The reviewer may approve your study, require modifications for approval, or propose that it be sent to the full IRB for disapproval.

Eligibility criteria:

• Your study must present no more than minimal risk to the participants, relative to the daily life of a normal, healthy person.
• Expedited review cannot be used where identification of the subjects or their responses would reasonably place them at risk of civil or criminal 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.
• See the attached list of General and Adjunct categories for expedited review eligibility criteria.

If your study may be eligible for expedited review, complete and submit the IRB Expedited Review form for approval, along with the Application for IRB Review and supporting documentation.

Exempt review means that your study may not require the approval of Riverside's IRB, either because it does not constitute "research" in the technical sense, or because it is not covered by human subject research regulations. The Office of Human Research Protection (part of Health and Human Services) recommends that someone other than a research investigator on the study decide whether that study is exempt from IRB review. To submit your study for exemption, please submit the IRB Exemption form for approval, along with the Application for IRB Review and supporting documentation.

IRB Exemption form

Quality Improvement studies and Evidence Based Practice studies that do not fall under the category of research do not require IRB approval, though they may require the permissions of other departments before moving forward. However, some QI and EBP studies may fall into the area of research as well, in which case they require IRB approval. If you have questions about whether your project qualifies as research, please contact the Research Office.

If your study involves human subjects, you may need to fill out an IRB Exemption form.

Nursing students conducting possible quality improvement or EBP studies should contact the Magnet Office for more information.

Full board review means that your study is reviewed at a meeting of the IRB. These meetings are normally scheduled for the third Wednesday of every month. Submissions are required by the Monday two weeks prior. Submissions must include the Application for IRB Review, along with all supporting documentation.

Expedited review means that your study may not have to wait for the full IRB to convene. Instead, it is reviewed by the IRB Chair or other IRB members designated by the Chair. The reviewer may approve your study, require modifications for approval, or propose that it be sent to the full IRB for disapproval.

Eligibility criteria:

• Your study must present no more than minimal risk to the participants, relative to the daily life of a normal, healthy person.
• Expedited review cannot be used where identification of the subjects or their responses would reasonably place them at risk of civil or criminal 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.
• See the attached list of General and Adjunct categories for expedited review eligibility criteria.

If your study may be eligible for expedited review, complete and submit the IRB Expedited Review form for approval, along with the Application for IRB Review and supporting documentation.

Exempt review means that your study may not require the approval of Riverside's IRB, either because it does not constitute "research" in the technical sense, or because it is not covered by human subject research regulations. The Office of Human Research Protection (part of Health and Human Services) recommends that someone other than a research investigator on the study decide whether that study is exempt from IRB review. To submit your study for exemption, please submit the IRB Exemption form for approval, along with the Application for IRB Review and supporting documentation.

IRB Exemption form

Quality Improvement studies and Evidence Based Practice studies that do not fall under the category of research do not require IRB approval, though they may require the permissions of other departments before moving forward. However, some QI and EBP studies may fall into the area of research as well, in which case they require IRB approval. If you have questions about whether your project qualifies as research, please contact the Research Office.

If your study involves human subjects, you may need to fill out an IRB Exemption form.

Nursing students conducting possible quality improvement or EBP studies should contact the Magnet Office for more information.

In order to be eligible as a Principal Investigator, you must be either a member of Riverside Medical Staff or a Medical Center employee.

Students, interns, or post-doctoral researchers may serve as Principal Investigator under the supervision of a member of Riverside Medical Staff or a Medical Center employee providing Study Oversight (see Study Oversight Form below).

Investigator Agreement

Study Oversight Form (if applicable)

All individuals serving as investigators on studies, in any capacity, must complete CITI training. CITI trains investigators on principals of ethical research.

Once all investigators have completed their training, their certificates should be included with the IRB application.

Instructions on CITI training

In order to be eligible as a Principal Investigator, you must be either a member of Riverside Medical Staff or a Medical Center employee.

Students, interns, or post-doctoral researchers may serve as Principal Investigator under the supervision of a member of Riverside Medical Staff or a Medical Center employee providing Study Oversight (see Study Oversight Form below).

Investigator Agreement

Study Oversight Form (if applicable)

All individuals serving as investigators on studies, in any capacity, must complete CITI training. CITI trains investigators on principals of ethical research.

Once all investigators have completed their training, their certificates should be included with the IRB application.

Instructions on CITI training

• Protocol 
  
   
  • Your study protocol should be a comprehensive description of the study’s background, hypothesis, risks, benefits, procedures, duration, and ethical considerations. This protocol should be included with your IRB application.
  • For more information on writing your protocol, refer to the protocol templates provided for Clinical Protocols, Chart Review Protocols, and Survey and Observational Research Protocols.
• Data tracking form / Data monitoring information 
  
   
  • Include a copy of whatever you are using to track participant data, such that the IRB can evaluate the aspects of the study that are being recorded.
  • Describe plans for monitoring the data collected to ensure the safety of the subjects.
• Investigator brochure (unapproved drugs) 
  
   
  • If your study involves the testing of drugs that have not been approved by the FDA, you should have a copy of the investigator brochure from the trial sponsor. The investigator brochure describes relevant scientific information about the product such as formulation, nonclinical studies, effects in humans, and guidance for the investigator.
• Package insert (approved drugs) 
  
   
  • If your study involves testing drugs that have been approved by the FDA, include the package insert (also known as the prescription drug information) with your application.
• Device Brochure 
  
   
  • The device labeling/brochure should inform patients and their caregivers about safe and effective use of the device. Your study should include device information available for both patients and physicians.
• Grant Application 
  
   
  • If study funding is from a grant, include the grant application and other documentation in your application.

Other hospital approval processes may require additional supporting documentation.

If the research involves acquiring physiological data from human subjects through equipment, or using equipment to stimulate human subjects, the investigators must attach additional data about the equipment itself to the IRB application.

This requirement applies where the subject of the research is that equipment or data acquisition itself. For example, if the subject of the research is conducting EKGs, this requirement would apply. However, if the human subjects receive EKGs as part of standard care in the course of the study, this reporting requirement would not apply.

Where the research involves equipment for stimulation and physiological data acquisition, attach Research Equipment Form – Appendix A to the IRB Application.

If the research involves the use of any drugs, chemical or biological agents, or devices, the study is subject to FDA regulations. Investigators planning on using any of these must attach additional data about the agents or devices to the IRB application.

Drugs that are used incidental to the research (such as pain medication incidental to use of an experimental surgical device) do not need to be listed so long as they are standard of care.

Attach Drugs, Agents, and Devices Form – Appendix B to the IRB Application, making sure to list all drugs, agents, and devices that are being researched.

If the research involves collecting, analyzing, or banking human cells, tissues, fluids, or any other human biological samples, whether taken for this research or for possible future research, investigators must attach additional data with the IRB application.

Attach Biological Materials Form – Appendix C to the IRB Application.

If the research involves acquiring physiological data from human subjects through equipment, or using equipment to stimulate human subjects, the investigators must attach additional data about the equipment itself to the IRB application.

This requirement applies where the subject of the research is that equipment or data acquisition itself. For example, if the subject of the research is conducting EKGs, this requirement would apply. However, if the human subjects receive EKGs as part of standard care in the course of the study, this reporting requirement would not apply.

Where the research involves equipment for stimulation and physiological data acquisition, attach Research Equipment Form – Appendix A to the IRB Application.

If the research involves the use of any drugs, chemical or biological agents, or devices, the study is subject to FDA regulations. Investigators planning on using any of these must attach additional data about the agents or devices to the IRB application.

Drugs that are used incidental to the research (such as pain medication incidental to use of an experimental surgical device) do not need to be listed so long as they are standard of care.

Attach Drugs, Agents, and Devices Form – Appendix B to the IRB Application, making sure to list all drugs, agents, and devices that are being researched.

If the research involves collecting, analyzing, or banking human cells, tissues, fluids, or any other human biological samples, whether taken for this research or for possible future research, investigators must attach additional data with the IRB application.

Attach Biological Materials Form – Appendix C to the IRB Application.

Include with your application copies of all materials that will be used to recruit study participants, such as brochures, emails, videos, flyers, website designs, posters, telephone scripts, etc.

Be sure to describe your recruiting process in detail in your Application for IRB Review.

If you have any questions about what is acceptable recruiting practice, please refer to the.

A HIPAA Authorization form is required if your study uses the protected health information of any individual. The Authorization must be specific to the activities in your study. To ensure that your form has all of the required elements, refer to the HIPAA authorization form template.

HIPAA Officer contact information: If you believe that there has been a breach of PHI, please contact Karen Block at 815-935-7256, ext. 4850.

If your study requires the use of PHI, but obtaining patient authorization is not practicable, you may apply for a waiver of authorization. The rights and welfare of the participant cannot be adversely affected by the study, and the PHI cannot be shared with individual identifiers still attached.

Application for Waiver of Authorization

Your study may qualify for a partial waiver of authorization by requesting access to PHI for the sole purpose of previewing the medical records of prospective research participants. This PHI may not leave Riverside Medical Center.

Application for Partial Waiver of Authorization

In order to disclose PHI to another entity without patient authorization, you will require a Data Use Agreement with that entity. Execution of a Data Use Agreement allows Riverside to share a Limited Data Set with that entity for the purposes of research.

A Limited Data Set is comprised of PHI that may include city, state, ZIP code, elements of date, and other numbers, characteristics, or codes that are not "direct identifiers." The Limited Data Set may not include the sixteen "direct identifiers" designated by the HIPAA Privacy Rule.

"Direct identifiers" include:

• Names
• Postal address information, other than town or city, state, and ZIP code
• Telephone numbers
• Fax numbers
• Email addresses
• Social security numbers
• Medical record numbers
• Health plan beneficiary numbers
• Account numbers
• Certificate/license numbers
• Vehicle identifiers and serial numbers, including license plate numbers
• Device identifiers and serial numbers
• Web universal resource locators (URLs)
• Internet protocol (IP) address numbers
• Biometric identifiers, including fingerprints and voiceprints
• Full-face photographic images and any comparable images

Data Use Agreement form.

If your research involves the use of PHI that has all unique identifiers removed (also known as a “De-identified Data Set”), your data set is not subject to the HIPAA Privacy Rule. Instead of a Waiver of Authorization form or a Data Use Agreement, you will need to fill out a HIPAA De-identification Certification form.

Refer to the HIPAA De-identification Certification form for a list of direct identifiers.

If your study requires the use of PHI, but obtaining patient authorization is not practicable, you may apply for a waiver of authorization. The rights and welfare of the participant cannot be adversely affected by the study, and the PHI cannot be shared with individual identifiers still attached.

Application for Waiver of Authorization

Your study may qualify for a partial waiver of authorization by requesting access to PHI for the sole purpose of previewing the medical records of prospective research participants. This PHI may not leave Riverside Medical Center.

Application for Partial Waiver of Authorization

In order to disclose PHI to another entity without patient authorization, you will require a Data Use Agreement with that entity. Execution of a Data Use Agreement allows Riverside to share a Limited Data Set with that entity for the purposes of research.

A Limited Data Set is comprised of PHI that may include city, state, ZIP code, elements of date, and other numbers, characteristics, or codes that are not "direct identifiers." The Limited Data Set may not include the sixteen "direct identifiers" designated by the HIPAA Privacy Rule.

"Direct identifiers" include:

• Names
• Postal address information, other than town or city, state, and ZIP code
• Telephone numbers
• Fax numbers
• Email addresses
• Social security numbers
• Medical record numbers
• Health plan beneficiary numbers
• Account numbers
• Certificate/license numbers
• Vehicle identifiers and serial numbers, including license plate numbers
• Device identifiers and serial numbers
• Web universal resource locators (URLs)
• Internet protocol (IP) address numbers
• Biometric identifiers, including fingerprints and voiceprints
• Full-face photographic images and any comparable images

Data Use Agreement form.

If your research involves the use of PHI that has all unique identifiers removed (also known as a “De-identified Data Set”), your data set is not subject to the HIPAA Privacy Rule. Instead of a Waiver of Authorization form or a Data Use Agreement, you will need to fill out a HIPAA De-identification Certification form.

Refer to the HIPAA De-identification Certification form for a list of direct identifiers.

One of the most important principles of ethical human subject research is that the research subject consents to participate and is informed of that to which he or she is consenting. If you are working with a study sponsor, the sponsor may already have an informed consent document drafted to submit to the IRB. If not, you will need to draft a document that informs subjects of the subject of the research, their right to refuse to participate, and other details.

To help in drafting an Informed Consent, refer to the Riverside Informed Consent template.

Before participation in any research.

This includes prior to screening (i.e., finding eligible study subjects)

• If you cannot obtain consent prior to screening patients for your study, you may apply for a partial waiver of authorization that enables researchers to screen applicants before approaching them for HIPAA authorization and informed consent forms.
• To apply for a Partial Waiver of Authorization, see the applicable section under "HIPAA Authorizations" above.

The IRB will only consider waiving documentation of informed consent where there is minimal risk to the subject, or where the consent document is the only record of the individual participant and its disclosure could put the subject at risk. In these cases, consent may be obtained orally.

For the IRB to consider waiving informed consent for your study, the following requirements must be met:

• The research must involve no more than minimal risk to the subjects.
• Waiving or altering the informed consent will not adversely affect the rights and welfare of the subjects.
• The research could not be practicably carried out without the waiver or alteration
• Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

If your study complies with these requirements, you will need to apply for a Waiver of Informed Consent with the IRB.

Consent is not just a document, it is a process. This process involves:

• Telling the potential subject about the study in which he or she might wish to participate.
• Giving the potential subject a consent form to read.
• Asking whether he or she has any questions.
• Asking him or her to sign the consent form.

Be sure that the privacy of the potential subject is preserved during the process of consent as well as after. Even a spouse may create considerable pressure for a potential participant that would otherwise not be there even if the potential subject later consulted with the spouse.

The potential subject may need time to consider participation, or to consult with his or her primary physician in the case of a clinical trial.

For information on required language and a useful template, please refer to our Informed Consent Template.

• Note that this is only a template; keep in mind best practices and your knowledge of human research ethics when drafting your informed consent document. Make sure that it is easy to read, consistent, and directed to the potential participant.
• The FDA provides more guidance on its requirements for consent forms here.
• Federal Policy prohibits language that is made to waive or appears to waive any legal right. This means that your informed consent document should not include language that exculpates you from legal liability, but may include language that informs potential participants of existing legal rights, for instance, that they will not share in profits from the research.

Witness signatures on Informed Consent forms. Witness signatures are not required for a standard Informed Consent Form. They are required if a short form consent form is used and approved by the IRB, and if the potential subject is illiterate.

The signature of the subject (or his or her legally authorized representative) must be dated. In some cases, it may be useful to include the time of that the consent document was signed. This might include cases in which the research begins on the same date that the consent document is signed. A time stamp documents that consent was obtained prior to beginning research on that date.

Non-English speaking subjects

• The consent document should be in a language that the subject understands. 
  
   
  • If the consent interview is in English, the consent document should also be in English.
  • Similarly, if you anticipate that subjects will be interviewed and give consent in a language other than English, you must prepare an accurate, translated consent document in both languages. Consider using a consultant to ensure that the translation is correct.
  • Carefully consider whether you and other investigators will be able to effectively work with the potential subject such that his or her consent will be truly informed and legally effective.
• Illiterate English-speakers 
  
   
  • If an individual speaks and understands English or the language in which the study will be conducted, he or she may have the consent document read to him or her and “make his mark” on the document.
  • A witness must be present during the oral presentation of the consent information if the consenting individual cannot read it. Both the witness and the individual must sign the consent document and receive copies.
  • Note that the IRB will consider illiterate subjects to be vulnerable to coercion, and therefore will ensure that appropriate safeguards for their protection are in place.

Who should keep copies and how long?

• The subject must be given a copy of the consent document, preferably a photocopy of the signed and dated consent.
• Unless you have received a waiver of informed consent, you—the investigator—must keep the signed consent forms in a secure location (to be defined in the application for IRB approval) for three years after the end of the study.

A witness is not required if it is a standard informed consent with all of the DHHS elements; only required if it is a "short form" consent.

• Requiring a witness signature is not prohibited, and some investigators may choose this additional safeguard. A witness may help ensure that the informed consent process was followed, and attest to all of the required elements.
• If you choose to require a witness signature, be sure that the witness knows what he or she is observing.
• When a witness signs the consent document, the witness must also receive a copy of the consent document.

Designated surrogate.

• Informally appointed surrogate 
  
   
  • Where a patient lacks decisional capacity and has no Health Care Power of Attorney, Living Will Declaration, or Mental Health Treatment Preference Declaration, the Illinois Health Care Surrogate Act authorizes physicians to identify a surrogate decision maker based on a defined set of criteria.
  • If a surrogate has been informally appointed, research physicians should think carefully about risks and consent issues, and consult with the IRB before requesting consent in such cases.
• Formally appointed surrogate 
  
   
  • In the case of health care, a surrogate decision-maker may have been appointed by the patient through a Durable Power of Attorney for Health care, Living Will Declaration, or Mental Health Treatment Preference Declaration. Or, a surrogate decision-maker, or guardian, may have been appointed by the court for those unable to make their own legal and medical decisions.
  • If the potential research participant has a surrogate decision-maker appointed through a document such as a Durable Power of Attorney for Health Care, ensure that the document does not place a limitation on treatments provided as a part of research or on the surrogate consenting to the individual’s participation in research.
  • If the potential participant is a minor or under guardianship, the guardian must receive court authorization to consent to experimental treatment for mental health and/or developmental disabilities.

Consent for research involving children.

• Permission of the child’s parent or guardian must be obtained prior to a child participating in a study 
  
   
  • Where research involves an FDA-regulated product, subparts B and D of 21 CFR 50 apply.
  • Otherwise, the general and required elements of consent outlined in 45 CFR 46.116 apply, as does documentation according to Section 46.117.
  • Additional regulations apply to children who are wards of the state and emancipated minors.
• If the child is legally able to consent to treatment (such as in certain cases allowed to Illinois state law), HHS guidance advises that that child should also be able to consent to study participation that involves the same treatment.
• As with adults, waiver of permission may be appropriate in emergencies and life-threatening situations.
• Both parents must give their permission for a child to participate in research unless one parent is: 
  
   
  • Deceased
  • Unknown
  • Incompetent
  • Not reasonably available
  • Only one parent has legal responsibility for the care and custody of the child
• Assent: Generally speaking, a child’s assent should be required if he or she is seven years old or higher. 
  
   
  • There are no federal guidelines indicating an exact age at which assent ought to be possible.
  • The IRB has wide discretion in determining whether a child is capable of assent, and can waive the requirement for assent under some circumstances.
  • Researchers should, if possible, conduct research with children capable of assenting before those who are not.
• What is assent? 
  
   
  • According to federal guidelines, assent is "a child’s affirmative agreement to participate in research."
  • It is not enough that the child passively agrees to submit to the intervention or procedure. He or she must actively agree.
  • Assent is not a substitute for parental consent. 
    
     
    • If the IRB determines that assent is required, parental consent does not override a lack of assent. If the parents consent but the child does not assent, the child’s decision prevails.
    • Be sure to document whether you intend to seek parental consent or the minor’s assent first in your application for IRB approval. Generally, parents should be approached for consent prior to approaching the child for assent.
• The assent process 
  
   
  • The assent process should be tailored to the age and maturity of the child. For younger children, he or she may have the study explained to him or her orally and decide to consent verbally. Make a note of the child’s assent, and keep it along with the parental permission form.
  • Particularly with younger children, take care to describe what his or her study experience will be.
  • For older children, especially those age 12 and over, you should use a written assent form. This form should explain the study in language understandable to him or her.
  • If an adolescent reaches the age of majority while the research is being conducted, he or she should be given the opportunity to consent or refuse consent.

Some psychological studies involve holding withholding information about the study from participants, or deceiving participants about the study’s true purpose, in order to achieve accurate results. In such cases, the IRB will closely review the special concerns related to deception in research. These concerns will include whether the deception is necessary, and the potential risks to the participants.

The following statement, or some similar statement, must appear in every consent form/information sheet for studies involving deception:

• "Research designs often require that the full intent of the study not be explained prior to participation. Although we have described the general nature of the tasks that you will be asked to perform, the full intent of the study will not be explained to you until after the completion of the study. At that time, we will provide you with a full debriefing which will include an explanation of the hypothesis that was tested and other relevant background information pertaining to the study. You will also be given an opportunity to ask any questions you might have about the hypothesis and the procedures used in the study."

Following any such study, participants should be debriefed in detail about the deception, how it was used, and why it was necessary.

If the risk profile of your study changes during the course of the research, consent should be re-obtained from participants. This might occur when:

• New findings may relate to the willingness of the participant to continue.
• New treatments have become available.
• The study procedure has been changed or modified.

If the consent form in use changes in a way that alters the information provided, it may be appropriate to re-consent participants.

If an adolescent participant reaches the age of majority while the research is being conducted, he or she should be given the opportunity to consent or refuse consent.

If consent was obtained for research involving an individual with temporary decisional impairment, that individual should be given the opportunity to consent once the impairment has ended.

Re-consent documentation:

• If a new full consent form is given to the subject, efforts should be made to emphasize or highlight the information that has changed.
• In some cases, a consent addendum will be best. This addendum would describe what information has changed and remind the participant of his or her right to withdraw from the study.

Before participation in any research.

This includes prior to screening (i.e., finding eligible study subjects)

• If you cannot obtain consent prior to screening patients for your study, you may apply for a partial waiver of authorization that enables researchers to screen applicants before approaching them for HIPAA authorization and informed consent forms.
• To apply for a Partial Waiver of Authorization, see the applicable section under "HIPAA Authorizations" above.

The IRB will only consider waiving documentation of informed consent where there is minimal risk to the subject, or where the consent document is the only record of the individual participant and its disclosure could put the subject at risk. In these cases, consent may be obtained orally.

For the IRB to consider waiving informed consent for your study, the following requirements must be met:

• The research must involve no more than minimal risk to the subjects.
• Waiving or altering the informed consent will not adversely affect the rights and welfare of the subjects.
• The research could not be practicably carried out without the waiver or alteration
• Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

If your study complies with these requirements, you will need to apply for a Waiver of Informed Consent with the IRB.

Consent is not just a document, it is a process. This process involves:

• Telling the potential subject about the study in which he or she might wish to participate.
• Giving the potential subject a consent form to read.
• Asking whether he or she has any questions.
• Asking him or her to sign the consent form.

Be sure that the privacy of the potential subject is preserved during the process of consent as well as after. Even a spouse may create considerable pressure for a potential participant that would otherwise not be there even if the potential subject later consulted with the spouse.

The potential subject may need time to consider participation, or to consult with his or her primary physician in the case of a clinical trial.

For information on required language and a useful template, please refer to our Informed Consent Template.

• Note that this is only a template; keep in mind best practices and your knowledge of human research ethics when drafting your informed consent document. Make sure that it is easy to read, consistent, and directed to the potential participant.
• The FDA provides more guidance on its requirements for consent forms here.
• Federal Policy prohibits language that is made to waive or appears to waive any legal right. This means that your informed consent document should not include language that exculpates you from legal liability, but may include language that informs potential participants of existing legal rights, for instance, that they will not share in profits from the research.

Witness signatures on Informed Consent forms. Witness signatures are not required for a standard Informed Consent Form. They are required if a short form consent form is used and approved by the IRB, and if the potential subject is illiterate.

The signature of the subject (or his or her legally authorized representative) must be dated. In some cases, it may be useful to include the time of that the consent document was signed. This might include cases in which the research begins on the same date that the consent document is signed. A time stamp documents that consent was obtained prior to beginning research on that date.

Non-English speaking subjects

• The consent document should be in a language that the subject understands. 
  
   
  • If the consent interview is in English, the consent document should also be in English.
  • Similarly, if you anticipate that subjects will be interviewed and give consent in a language other than English, you must prepare an accurate, translated consent document in both languages. Consider using a consultant to ensure that the translation is correct.
  • Carefully consider whether you and other investigators will be able to effectively work with the potential subject such that his or her consent will be truly informed and legally effective.
• Illiterate English-speakers 
  
   
  • If an individual speaks and understands English or the language in which the study will be conducted, he or she may have the consent document read to him or her and “make his mark” on the document.
  • A witness must be present during the oral presentation of the consent information if the consenting individual cannot read it. Both the witness and the individual must sign the consent document and receive copies.
  • Note that the IRB will consider illiterate subjects to be vulnerable to coercion, and therefore will ensure that appropriate safeguards for their protection are in place.

Who should keep copies and how long?

• The subject must be given a copy of the consent document, preferably a photocopy of the signed and dated consent.
• Unless you have received a waiver of informed consent, you—the investigator—must keep the signed consent forms in a secure location (to be defined in the application for IRB approval) for three years after the end of the study.

A witness is not required if it is a standard informed consent with all of the DHHS elements; only required if it is a "short form" consent.

• Requiring a witness signature is not prohibited, and some investigators may choose this additional safeguard. A witness may help ensure that the informed consent process was followed, and attest to all of the required elements.
• If you choose to require a witness signature, be sure that the witness knows what he or she is observing.
• When a witness signs the consent document, the witness must also receive a copy of the consent document.

Designated surrogate.

• Informally appointed surrogate 
  
   
  • Where a patient lacks decisional capacity and has no Health Care Power of Attorney, Living Will Declaration, or Mental Health Treatment Preference Declaration, the Illinois Health Care Surrogate Act authorizes physicians to identify a surrogate decision maker based on a defined set of criteria.
  • If a surrogate has been informally appointed, research physicians should think carefully about risks and consent issues, and consult with the IRB before requesting consent in such cases.
• Formally appointed surrogate 
  
   
  • In the case of health care, a surrogate decision-maker may have been appointed by the patient through a Durable Power of Attorney for Health care, Living Will Declaration, or Mental Health Treatment Preference Declaration. Or, a surrogate decision-maker, or guardian, may have been appointed by the court for those unable to make their own legal and medical decisions.
  • If the potential research participant has a surrogate decision-maker appointed through a document such as a Durable Power of Attorney for Health Care, ensure that the document does not place a limitation on treatments provided as a part of research or on the surrogate consenting to the individual’s participation in research.
  • If the potential participant is a minor or under guardianship, the guardian must receive court authorization to consent to experimental treatment for mental health and/or developmental disabilities.

Consent for research involving children.

• Permission of the child’s parent or guardian must be obtained prior to a child participating in a study 
  
   
  • Where research involves an FDA-regulated product, subparts B and D of 21 CFR 50 apply.
  • Otherwise, the general and required elements of consent outlined in 45 CFR 46.116 apply, as does documentation according to Section 46.117.
  • Additional regulations apply to children who are wards of the state and emancipated minors.
• If the child is legally able to consent to treatment (such as in certain cases allowed to Illinois state law), HHS guidance advises that that child should also be able to consent to study participation that involves the same treatment.
• As with adults, waiver of permission may be appropriate in emergencies and life-threatening situations.
• Both parents must give their permission for a child to participate in research unless one parent is: 
  
   
  • Deceased
  • Unknown
  • Incompetent
  • Not reasonably available
  • Only one parent has legal responsibility for the care and custody of the child
• Assent: Generally speaking, a child’s assent should be required if he or she is seven years old or higher. 
  
   
  • There are no federal guidelines indicating an exact age at which assent ought to be possible.
  • The IRB has wide discretion in determining whether a child is capable of assent, and can waive the requirement for assent under some circumstances.
  • Researchers should, if possible, conduct research with children capable of assenting before those who are not.
• What is assent? 
  
   
  • According to federal guidelines, assent is "a child’s affirmative agreement to participate in research."
  • It is not enough that the child passively agrees to submit to the intervention or procedure. He or she must actively agree.
  • Assent is not a substitute for parental consent. 
    
     
    • If the IRB determines that assent is required, parental consent does not override a lack of assent. If the parents consent but the child does not assent, the child’s decision prevails.
    • Be sure to document whether you intend to seek parental consent or the minor’s assent first in your application for IRB approval. Generally, parents should be approached for consent prior to approaching the child for assent.
• The assent process 
  
   
  • The assent process should be tailored to the age and maturity of the child. For younger children, he or she may have the study explained to him or her orally and decide to consent verbally. Make a note of the child’s assent, and keep it along with the parental permission form.
  • Particularly with younger children, take care to describe what his or her study experience will be.
  • For older children, especially those age 12 and over, you should use a written assent form. This form should explain the study in language understandable to him or her.
  • If an adolescent reaches the age of majority while the research is being conducted, he or she should be given the opportunity to consent or refuse consent.

Some psychological studies involve holding withholding information about the study from participants, or deceiving participants about the study’s true purpose, in order to achieve accurate results. In such cases, the IRB will closely review the special concerns related to deception in research. These concerns will include whether the deception is necessary, and the potential risks to the participants.

The following statement, or some similar statement, must appear in every consent form/information sheet for studies involving deception:

• "Research designs often require that the full intent of the study not be explained prior to participation. Although we have described the general nature of the tasks that you will be asked to perform, the full intent of the study will not be explained to you until after the completion of the study. At that time, we will provide you with a full debriefing which will include an explanation of the hypothesis that was tested and other relevant background information pertaining to the study. You will also be given an opportunity to ask any questions you might have about the hypothesis and the procedures used in the study."

Following any such study, participants should be debriefed in detail about the deception, how it was used, and why it was necessary.

If the risk profile of your study changes during the course of the research, consent should be re-obtained from participants. This might occur when:

• New findings may relate to the willingness of the participant to continue.
• New treatments have become available.
• The study procedure has been changed or modified.

If the consent form in use changes in a way that alters the information provided, it may be appropriate to re-consent participants.

If an adolescent participant reaches the age of majority while the research is being conducted, he or she should be given the opportunity to consent or refuse consent.

If consent was obtained for research involving an individual with temporary decisional impairment, that individual should be given the opportunity to consent once the impairment has ended.

Re-consent documentation:

• If a new full consent form is given to the subject, efforts should be made to emphasize or highlight the information that has changed.
• In some cases, a consent addendum will be best. This addendum would describe what information has changed and remind the participant of his or her right to withdraw from the study.

Research involving children must fit into one of the following three categories to be approved:

• The research must present no greater than minimal risk to children.
• If the research involves an intervention or procedure and presents greater than minimal risk, it must have the potential to directly benefit the individual child participant.
• Or, if the research involves an intervention or procedure and presents greater than minimal risk, and the research does not offer potential to directly benefit the individual child participant: 
  
   
  • The risk must only be a minor increase over minimal risk.
  • 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 "The intervention or procedure 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." (CFR §46.406)

Research involving children that involves blood draws may only be considered under expedited review if it does not exceed “the lesser of 50 mL or 3 mL per kg in an 8-week period,” and blood draws are not more frequent than two times per week.

CFR §46.305(a) requires that research involving prisoners meet the following seven requirements:

• "The research under review represents one of the categories of research permissible under §46.306(a)(2);
• "Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;
• "The risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers;
• "Procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the Board justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;
• "The information is presented in language which is understandable to the subject population;
• "Adequate assurance exists that parole boards will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and
• "Where the Board finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact."

Following IRB approval, research involving prisoners that is supported by the Department of Health and Human Services will require additional OHRP review before it can proceed.

Appropriate animal studies must have been completed prior to IRB approval of studies that involve pregnant women

• If animal studies have not been completed, there must be a clear therapeutic need or benefit to the mother or fetus.
• If animal studies of reproductive toxicology and teratology have not been completed the consent document must clearly indicate that this information is lacking.

Risk to the fetus or resultant child:

• Informed consent must include fully informing the woman possible impacts of the study to the fetus or child.
• Risk to the fetus should not be greater than minimal.
• If risk is greater than minimal, it must be caused solely by interventions or procedures that potentially directly benefit the woman or fetus.

Indicate in your protocol follow-up for the pregnant woman both before and after delivery, even if the research is terminated prior.

Fetal viability:

• Investigators or anyone engaged in the research protocol will have no part in determining the viability of a fetus.
• Investigators or anyone engaged in the research protocol will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy.
• No inducements, monetary or otherwise, may be made to terminate a pregnancy. (CFR §46.204)

Paternal consent

• The father’s consent is not required for a pregnant woman to participate if the purpose of the study is to meet the health needs of the mother;
• The father’s identity or location is unknown or cannot be reasonably determined;
• The father is not reasonably available; or
• The pregnancy resulted from rape.

Women of childbearing potential:

• If your research involves women of childbearing potential and the risk of harm to the mother or fetus, precautions should be taken to increase subject safety. 
  
   
  • Contraception and pregnancy tests may be offered
  • Informed consent should include clear information on the possibility of birth defects.
• Research with males and mutagenic compounds may be transferred to a woman when the woman is impregnated an unaware of the risk. These risks should be must be included in the protocol and consent.

Research involving children must fit into one of the following three categories to be approved:

• The research must present no greater than minimal risk to children.
• If the research involves an intervention or procedure and presents greater than minimal risk, it must have the potential to directly benefit the individual child participant.
• Or, if the research involves an intervention or procedure and presents greater than minimal risk, and the research does not offer potential to directly benefit the individual child participant: 
  
   
  • The risk must only be a minor increase over minimal risk.
  • 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 "The intervention or procedure 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." (CFR §46.406)

Research involving children that involves blood draws may only be considered under expedited review if it does not exceed “the lesser of 50 mL or 3 mL per kg in an 8-week period,” and blood draws are not more frequent than two times per week.

CFR §46.305(a) requires that research involving prisoners meet the following seven requirements:

• "The research under review represents one of the categories of research permissible under §46.306(a)(2);
• "Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired;
• "The risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers;
• "Procedures for the selection of subjects within the prison are fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the Board justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project;
• "The information is presented in language which is understandable to the subject population;
• "Adequate assurance exists that parole boards will not take into account a prisoner's participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole; and
• "Where the Board finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact."

Following IRB approval, research involving prisoners that is supported by the Department of Health and Human Services will require additional OHRP review before it can proceed.

Appropriate animal studies must have been completed prior to IRB approval of studies that involve pregnant women

• If animal studies have not been completed, there must be a clear therapeutic need or benefit to the mother or fetus.
• If animal studies of reproductive toxicology and teratology have not been completed the consent document must clearly indicate that this information is lacking.

Risk to the fetus or resultant child:

• Informed consent must include fully informing the woman possible impacts of the study to the fetus or child.
• Risk to the fetus should not be greater than minimal.
• If risk is greater than minimal, it must be caused solely by interventions or procedures that potentially directly benefit the woman or fetus.

Indicate in your protocol follow-up for the pregnant woman both before and after delivery, even if the research is terminated prior.

Fetal viability:

• Investigators or anyone engaged in the research protocol will have no part in determining the viability of a fetus.
• Investigators or anyone engaged in the research protocol will have no part in any decisions as to the timing, method, or procedures used to terminate a pregnancy.
• No inducements, monetary or otherwise, may be made to terminate a pregnancy. (CFR §46.204)

Paternal consent

• The father’s consent is not required for a pregnant woman to participate if the purpose of the study is to meet the health needs of the mother;
• The father’s identity or location is unknown or cannot be reasonably determined;
• The father is not reasonably available; or
• The pregnancy resulted from rape.

Women of childbearing potential:

• If your research involves women of childbearing potential and the risk of harm to the mother or fetus, precautions should be taken to increase subject safety. 
  
   
  • Contraception and pregnancy tests may be offered
  • Informed consent should include clear information on the possibility of birth defects.
• Research with males and mutagenic compounds may be transferred to a woman when the woman is impregnated an unaware of the risk. These risks should be must be included in the protocol and consent.

Multi-site studies are those where more than one site is used to conduct the research. In these studies, one site will be the main study site.

If a Riverside site is the main study site for a multi-site research study, and the study does not qualify for the use of a Central IRB, all study sites must complete and file Site Information forms.

The purpose of the Site Information Form is to make sure that the IRB is able to fulfill its obligation to be aware of local issues at sites, and to make sure that research will be ethically conducted at all sites.

All site investigators must also complete CITI training and submit copies of their CVs.

Central IRBs are Institutional Review Boards that act as the IRB of record for multi-site studies, coordinating with local IRBs and ensuring consistency in the protocol and human subjects’ protection procedures.

In order to use a Central IRB, the study must meet the following criteria:

• The study is to be coordinated through the Central Research Exchange (CRE);
• The Study will be conducted at multiple sites
• The study sponsor requires the use of a central IRB for participation
• The central IRB has been approved for use by the Riverside IRB; and
• A Coordination Agreement is in place between the Riverside IRB and the central IRB.

If all of these criteria are met, the Riverside Principal Investigator must send the following to the Riverside Research Office:

• Documentation of Central IRB requirement, either by CRE or sponsor (Note: Must include proposed central IRB.)
• Site list
• Protocol

Multi-site studies are those where more than one site is used to conduct the research. In these studies, one site will be the main study site.

If a Riverside site is the main study site for a multi-site research study, and the study does not qualify for the use of a Central IRB, all study sites must complete and file Site Information forms.

The purpose of the Site Information Form is to make sure that the IRB is able to fulfill its obligation to be aware of local issues at sites, and to make sure that research will be ethically conducted at all sites.

All site investigators must also complete CITI training and submit copies of their CVs.

Central IRBs are Institutional Review Boards that act as the IRB of record for multi-site studies, coordinating with local IRBs and ensuring consistency in the protocol and human subjects’ protection procedures.

In order to use a Central IRB, the study must meet the following criteria:

• The study is to be coordinated through the Central Research Exchange (CRE);
• The Study will be conducted at multiple sites
• The study sponsor requires the use of a central IRB for participation
• The central IRB has been approved for use by the Riverside IRB; and
• A Coordination Agreement is in place between the Riverside IRB and the central IRB.

If all of these criteria are met, the Riverside Principal Investigator must send the following to the Riverside Research Office:

• Documentation of Central IRB requirement, either by CRE or sponsor (Note: Must include proposed central IRB.)
• Site list
• Protocol

The fee for initial IRB review is $1500. This fee is intended to cover the cost of providing educational opportunities for investigators, coordinators, IRB members, and staff.

An additional $750 fee will be assessed for funded multi-site research where the Riverside IRB acts as the central IRB of record.

IRB fees will be waived for students and medical staff members conducting unfunded research.

Send a check made to “Riverside Medical Center,” along with an IRB Application, to: 

Lisa Zipsie 
Riverside Medical Center 
350 N. Wall Street 
Kankakee, IL 60901

All studies approved by the IRB require periodic review by the IRB on study status and regulatory compliance. This review—a "continuation review"—must occur at least annually. Unless a study is re-approved through a continuation review, its IRB approval will expire as of the date indicated on the last approved Application for IRB Review.

• If a research study’s IRB approval expires, all research must cease until the IRB re-approves the study.
• There may be no contact with subjects in the study except to cancel previously arranged appointments and to accept reports of adverse events.
• No study data may be reviewed or analyzed until the IRB re-approves the study, unless that data is completely de-identified and in aggregate form.
• If your research study’s approval has expired, please contact the Research Office for more information on how to proceed.

Applications for Continuation Review should be completed and submitted to the IRB at least two weeks prior to the next IRB meeting. It is recommended that investigators submit a draft of the application as soon as possible to the Research Office so that it can be reviewed for errors.

Include the following with your application for Continuation Review:

• Application for Continuation Review form;
• Current results or observations;
• Current informed consent form; and
• Any recent literature on the subject that has come out since IRB approval.

If your application went through expedited review when it was first approved, it may be eligible for expedited continuation review. If so, please include the Application for Expedited Review with your application.

If you wish to amend your study, please see the section on Amendment Requests, and submit the documents required for an amendment along with your application for Continuation Review.

In order for changes to be made to a study that has received IRB approval, the IRB must approve an Application for Amendment. These changes may include anything from minor changes to substantive revisions.

Examples of changes that might require IRB approval include but are not limited to the following:

• Findings that change the risk/benefit profile of the study
• Changes to study procedure
• Changes to records collected (including, for example, the protected health information that is collected from the subject)
• Changes to eligibility criteria
• Changes to the study site
• ANY changes to the consent form, including small error corrections
• Changing investigators.

Examples of changes that would not likely require IRB approval include:

• Amendment typos that do not substantively affect the meaning of what was written (unless in the informed consent form);
• Minor formatting changes to record keeping logs;
• Changes to the office staff that are not involves as investigators in the study.

Substantive changes that would change the risk profile of the study may be made without prior IRB approval only to avert immediate harm to the study subjects, where suspending the research would also result in harm. In these cases, the Research Office and IRB Chair should be notified immediately, and an Amendment Application should be submitted to the IRB as soon as possible.

Applications for Amendment should be submitted to the IRB through the Research Office at least two weeks prior to the next scheduled IRB meeting; it is recommended that investigators send a draft to the IRB as soon as possible so that any errors may be corrected prior to submission.

The following must be included with an application to amend an IRB-approved study:

• Amendment Request form
• Application for IRB Review (Redline version of original application with changes)
• Protocol with changes in redline
• Informed Consent Form in redline, if applicable
• Any other forms that have changed, including data collection forms and patient brochures

If the study was initially approved through the expedited review process, it may be eligible to go through an expedited review for the amendment process as well.

If applying for expedited review, submit the Application for Expedited Review with the complete Application for Amendment.

Once an IRB-approved research study has been completed, the investigators must apply for Study Closure. Study Closure is a process through which the study formally ends, and which also gives the IRB the opportunity to learn the final results of the human subject research it approved. In order to apply for Study Closure, investigators must submit the following to the IRB:

• Application for Study Closure form
• Study results

The Application for Study Closure should be submitted to the IRB at least two weeks prior to the next IRB meeting.

If the study does not have final study analysis completed, a preliminary summary of the research should be submitted, including the final number of subjects and study observations. For additional study analysis to be completed after Study Closure, research must be limited to data analysis in aggregated form. If preliminary study analysis is not available, the study should be submitted for continuation review.

If a research study does not comply with IRB and Riverside policies and regulations, or it is determined that the risk to the subjects outweighs the potential benefits of the study, the IRB has the right to terminate its approval of the study. This is called “Study Termination.” The IRB will send notification of Study Termination to the investigators involved.

If a study is terminated, all research activity must end immediately and preliminary study results must be sent to the IRB.

Adverse events include the following:

• Expected or unexpected harmful effects of an investigational or FDA-approved drug, biologic or device, observed in the approved project, or in other research settings similar to that of the approved project;
• A procedural error involving a human subject enrolled in the study;
• Physical or emotional harm to the subject during the execution of the experimental protocol;
• A breach of confidentiality or privacy; or
• An event occurring on the premises of the institution housing the research project, not as a direct result of the research, but in conjunction with it.

Investigators must include with their informed consent documentation a means of reaching them so that research subjects are able to report adverse events or unexpected problems.

Investigators are expected to immediately report any unanticipated problem or unanticipated adverse event to the IRB without waiting for the next Continuation Review.

• Investigators must contact the Research Office as soon as possible.
• In addition to prompt reporting to the Research Office, investigators must submit a completed Adverse Event form to the IRB, along with a copy of the current Informed Consent form, and any relevant documentation of the event such as subject medical records documenting the event.
• The IRB will determine the degree to which risks to human subjects may have changed, if there is any need to revise the consent document, and if the consent document is adequate.

Multi-site studies/sponsored studies

• Investigators working on multi-site and sponsored studies should contact their study administrator if an adverse event or UPRISO occurs, as changes at one site may have significant changes across the entire study.
• If the multi-site research is covered by an OHRP assurance, either the Riverside IRB or the main research entity must report the event to the supporting HHS agency head and the OHRP, in accordance with 45 CFR 46.103(a). This means that Riverside investigators must check the institutional agreements with the study sponsor and central monitoring entity to determine the entity responsible for reporting adverse events or reportable UPRISOs.
• Particular studies may also require reporting for events in addition to those outlined above.

As necessary, the IRB will report unanticipated problems to the supporting HHS agency head (or designee) and OHRP as required by 45 CFR 46.103(a).

Emergency use is the use of an investigational drug, biological product, or device, on a human subject in a life-threatening situation in which no standard acceptable treatment is available.

There are several different types of events in which emergency use occurs.

• The drug, biological product, or device has not yet been approved for an IND or IDE, respectively.
• A physician wants to use the article in this emergency situation in a way that has not been approved by the IND or IDE.
• The physician is not an investigator under the IND or IDE.
• Research not subject to FDA regulations, and that therefore does not require an FDA IND application or an FDA IDE.

Determine the appropriateness of emergency use without an IND/IDE. 
In order for an unapproved device to be used in one of the above circumstances, the physician must assess the potential benefit from the use of the unapproved device, and to have substantial reason to believe that benefits will exist. Additionally, all of the following must be true:

• The patient has a life-threatening condition that needs immediate treatment.
• No generally acceptable alternative treatment for the condition exists; and
• Because of the immediate need for the device, there is no time to use existing procedures to get FDA approval for the use.

Obtain the article. 
Contact the agent’s manufacturer to determine whether it will ship the agent, and, as required for drugs and biologics, request that the FDA authorize shipment of the test article in advance of the IND.

Determine whether there is time for IRB approval of the use. 
Attempt to contact the IRB prior to the use of the test article.

Obtain informed consent /certification by physician 
Obtain informed consent of the subject, or the subject’s legally authorized representative, unless both the investigator and a physician who is not otherwise participating in the clinical investigation certify all of the following in writing:

• The subject is confronted by a life-threatening situation necessitating the use of the test article;
• Informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the subject;
• Time is not sufficient to obtain consent from the subject’s legal representative; and
• No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the subject’s life.

Investigators must file an Emergency Use report with the IRB within five working days of the emergency use.

Research on human subjects that is not regulated by the FDA is subject to the Department of Health and Human Services. Under 45 CFR 46, Protection of Human Subjects, the HHS does not specifically allow for the emergency use of a test article without IRB approval.

However, non-research purposes may be permitted. The following criteria apply to the emergency use of a test article:

• The test article is to be used in a single subject by a physician licensed to practice medicine in the State of Illinois
• The subject is facing a life-threatening condition, for which there is no conventional treatment, or conventional treatments have failed
• The physician has legitimate access to a test article, and believes that there is a reasonable likelihood that it may be helpful in the life-threatening condition
• The subject to receive the test article will not be enrolled in a research study involving the test article employed
• If subsequent use of the test article is contemplated in the same subject or in others, a new application to the IRB is required in advance of that use.

If these criteria are met, the physician may use the test article on a subject without prior IRB approval. The physician must also do the following:

• Obtained written informed consent from the subject or the subject’s legal representative
• In the patient’s record, enter a description of the procedure, and attach a copy of the informed consent document
• Within five days of using the test article, submit to the IRB the following: 
  
   
  • Emergency Use form
  • A copy of the informed consent document used.

In some studies, it may be anticipated that the study will always be conducted under emergency conditions. If this is the case, the investigators should apply for a Waiver of Informed Consent when applying for IRB Review.

Investigators of an approved study are required to report protocol deviations/violations to the IRB that do not fall under the adverse event category without waiting for the regularly scheduled continuing review.

Protocol deviations/violations include:

• Inclusion/exclusion errors
• Consent process errors
• Wrong version of consent form used
• Unapproved consent form used
• Performed a procedure that is not included in the IRB approved protocol
• Failure to report an adverse event within expected timeframe
• Study visit or study procedures out of visit window, only if the principal investigator fees that the deviation meets one or more of the criteria for reporting
• Other deviations/violations that do not fall into the categories above that the investigator may fell necessary to report to the IRB for safety or ethical reasons.

It is the responsibility of all study investigators to make sure that protocol deviations/violations do not occur. If they do, the investigator who discovers the deviation/violation is responsible for immediately informing the principal investigator of the deviation/violation.

Once the principal investigator is informed of the deviation/violation, he or she must submit a Protocol Deviation/Violation form to the IRB as soon as possible.

The IRB will review the submitted deviation/violation to determine if it meets the following criteria:

• Where the rights/welfare of the subject(s) affected?
• Was the safety of the subject(s) affected?
• Was the integrity of the research data affected?
• Was the subject(s)’ willingness to continue study participation affected?

The IRB will determine if the corrective action taken by the investigators is appropriate and the deviation/violation will be filed. If it is determined that the corrective action taken by the investigators was inadequate or the same type of violation/deviation is repeatedly occurring, additional corrective action may be requested by the IRB.

A number of ethical regulations and guidelines have been established on the subject of research on human subjects. Investigators must familiarize themselves with these prior to beginning any research.

Many of these regulations and guidelines are reviewed in the CITI Training modules required by all investigators conducting research at Riverside. In addition to this training, investigators should refer to the documents themselves when formulating their research, and ask the IRB if they have any questions.

The Riverside IRB is registered as an IRB Organization (IORG) with the DHHS. As an IORG, the IRB has registered as an IRB which may review research that is subject to regulation by federal departments or agencies. The parts of the Code of Federal Regulations below provide specific guidance for researchers subject to federal regulation.

45 CFR 46 "applies to all research involving human subjects conducted, supported or otherwise subject to regulation by any federal department or agency which takes appropriate administrative action to make the policy applicable to such research."

21 CFR 50 "applies to all clinical investigations regulated by the Food and Drug Administration."

21 CFR 56 "contains the general standards for the composition operation, and responsibility of an Institutional Review Board (IRB) that reviews clinical investigations regulated by the Food and Drug Administration."

The Belmont Report was commissioned in 1974 by the Department of Health, Education, and Welfare following the National Research Act, and created in 1979. Its purpose was to identify the basic ethical principles that should underlie biomedical and behavioral research involving human subjects.

As part of its FederalWide Assurance with the OHRP, the Riverside Medical Center IRB has assured that regardless of the source of support for the research, research conducted at Riverside will adhere to the principles of the Belmont Report.

The Basic Ethical Principles identified and elaborated in the Report are:

• Respect for Persons
• Beneficence
• Justice

The Commission also identified and clarified certain Applications of the Ethical Principles within research:

• Informed Consent
• Assessment of Risk and Benefits
• Selection of Subjects

The Nuremberg Trials following World War II included the trials of twenty-three doctors who had conducted experiments on human subjects, many who argued that no established principle at the time forbid their experiments. In their trial verdict, the Council for War Crimes adopted ten points on “ethical research.” These points, along with the later Declaration of Helsinki, later became the basis for the Code of Federal Regulation’s section on human subject research.

The principles of ethical research delineated by the Nuremberg Code are as follow:

• The voluntary consent of the human subject is absolutely essential.
• The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
• The experiment should be so designed and based on the results of animal experimentation and knowledge of the natural history of the disease or other problem under study, that the anticipated results will justify the performance of the experiment.
• The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
• No experiment should be conducted, where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.
• The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
• Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.
• The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.
• During the course of the experiment, the human subject should be at liberty to bring the experiment to an end, if he has reached the physical or mental state, where continuation of the experiment seemed to him to be impossible.
• During the course of the experiment, the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him, that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

The Declaration of Helsinki is a set of guidelines on human experimentation created by the World Medical Association. The Declaration does not automatically have any force, but instead depends on legal authorities codifying the Declaration.

In 2008, after the most recent revision to the Declaration of Helsinki, the FDA decided to abandon its adherence to the Declaration, and instead require clinical trials performed under its jurisdiction to conform to the rules of Good Clinical Practice from the International Conference on Harmonization (ICH-GCP).

Although the FDA does not require adherence to the Declaration, investigators participating in international trials, or those who wish to understand the development of regulations such as 45 CFR 46, may wish to familiarize themselves with current and past versions of the Declaration of Helsinki. Note that even trials with international arms must adhere to FDA regulations when conducted in the United States.

The FDA has adopted the International Conference on Harmonization’s Good Clinical Practices guidelines as the new standards for research, replacing the Declaration of Helsinki. As opposed to the Declaration, it has been commented that the ICH-GCP is more practically oriented rather than a general statement of ethical principles.

The ICH-GCP includes guidelines for the following areas:

• General Principles
• IRBs and Ethics Committees
• Investigators
• Sponsors
• Clinical Trial Protocols and Protocols
• Investigator’s Brochures
• Essential Documents for Clinical Trials

Funding conflicts may arise when the investigator or his/her family is funded by a party that has an interest in the research, such as a product manufacturer.

The investigator might also have previously received payment by the interested party, or be attempting to obtain future funding from the interested party.

Interested parties include not only product manufacturers, but also for-profit or non-profit agencies whose mission statements would create an interest in a particular result.

Conflicts may also arise if investigators have ownership interests in interested parties, seats on their boards, or other involvement.

Subject conflicts arise when investigators have previous relationships with potential research subjects that put them in positions of authority, or that would create a conflict with the subject participating in the study.

Positions of authority that would create a conflict include, for example, subjects who are the employees or students of the investigators. Subjects must never be required to participate as a condition of employment or class participation.

Additionally, a participant who has a previous relationship with the investigator might be in a position to compromise study results. For example, if a subject in a blinded trial with a placebo arm is related to the investigator, it creates a question of whether the investigator had any control over the study arm in which the subject was placed.

Examples of when an investigator may have an interest in the subject matter or results if he or she will receive compensation for particular results, or if a relative requires treatment for the disease being studied.