Frequently asked questions

Institutional Review Board

• How soon before the meeting should packets be submitted?
  Protocols submitted the 1st through the 15th of each month will be submitted to IRB #1. Protocols submitted the 16th through the end of each month will be submitted to IRB #2.
• When and where does the IRB meet?
  Meetings are held the first and third Wednesdays of the each month in Suite 440, Room 110, Children's Corporate Center.

Submission information

• What forms do you need to submit for a new protocol to the IRB and where do you get them?
  Forms for full committee, expedited and exempt review are located on IRBNet.org. You must complete the Registration Wizard first before proceeding with your submission. If you are a first-time user, you must register under Children's Hospital of Wisconsin. For IRBNet training, contact Gwen Miner at (414) 337-7133.

Collaborative Institutional Training Initiative course in the Protection of Human Subjects

To comply with the terms of our Federal-wide Assurance, any person participating in research on human subjects must have training in the Protection of Human Subjects. The approved training program is the Collaborative IRB Training Initiative. Children's Research Institute and Children's Hospital IRB require completion of this program for all personnel working with human subjects. 

Once initial certification is obtained, the CITI Refresher Course must be completed every two years. New users must register on the CITI Web site. Follow the red registration link and use the "all others" drop down menu to register under The Medical College of Wisconsin. Once you have completed the registration you can log in to CITI and complete the training. Please record your login information. 

You will need your user name and password in the future to complete the required refresher courses. The CITI program requires refresher training every two years. You will start to receive monthly reminders about six months before the two-year anniversary of your original CITI training completion.

Accessing CITI for the refresher course

Go to www.citiprogram.org, enter your user name and password. If you do not remember the user name and password you used the first time you entered the CITI site, but do know what e-mail address you had the first time you registered, you can open the option that says "forgot your user name" and submit your e-mail address. CITI will e-mail your user name. You will need to repeat this process for your password. If you also do not remember the e-mail address you used to register the first time, you will need to contact CITI directly to have them reset it. At the bottom of the CITI registration page there is a link "contact us." On it you will find a phone number, (305) 243-7970, and an e-mail address you can use to make an inquiry for help. Once logged in to the CITI site, find the "refresher" course link.

Your refresher course completion will be tracked electronically. Please keep a copy of your refresher certificate to confirm your training status.

Scientific ethics

All research personnel handling, recording, generating, analyzing or publishing scientific data must complete a brief training in Scientific Ethics every two years. All personnel requiring this training will need to sign a Children's Research Institute Code of Scientific Ethics. Children's Research Institute requires all persons working with scientific data to be trained every two years in Scientific Ethics. To accomplish this training, we have selected a reading entitled Ethics and Scientific Publication (Advances in Physiology Education, 29:59-74, 2005).

Shipping hazardous material

Federal law requires specific training for any person shipping biological or hazardous materials or supervising the process of shipping biological or hazardous materials. This training can be completed by reserving a copy of the Saf-T-Pak CD-ROM from Greg Anderson. This training must be completed every two years. In the event that the Saf-T-Pak software is not available from Children's Research Institute, Medical College employees have the option of getting a copy from the Medical College Safety Office.

Review process

• Do advertisements, recruitment materials, participant information sheets and newsletters need to be approved by the IRB?
  Yes. Any information that will be provided to potential participants or enrolled participants must be reviewed and approved by the IRB and Children's Hospital Public Relations prior to its use. IRB will evaluate the materials for accuracy and impartiality.
  
• How does the IRB review process of new protocols that do not fall in the expedited or exempt review categories work?
  Protocols are distributed to members two weeks before each meeting. The IRB utilizes a primary reviewer system. Three members of the board review the full protocol along with the summary, consent, assent and HIPAA forms. All other members review the summary, consent, assent and HIPAA forms only. The full application is presented at each meeting for questions and review. Principal investigators are invited to attend the meeting at which their protocol is discussed to answer questions and clarify the project. Correspondence regarding the board's decisions usually are sent to investigators within three to five working days after the meeting.
  
• What is meant by "expedited" review?
  Expedited review does not mean the review process will go faster. It means that full committee review at a convened meeting may not be required. To qualify for an expedited review, a project must involve no more than minimal risk to participants. Federal regulations allow the IRB to expedite the review of categories of research as described in 45 CFR 46.110 and 21 CFR 56.110. The chair or designee will review projects submitted for expedited review. The Office for Human Research Protections decision chart is a helpful tool in the assessment of the applicable review type. If the reviewer (chair or designee) does not approve the application for expedited review, it will need to go to the full committee.
  
• What is exempt review and who determines when it applies?
  The chair or designee of the IRB determines which projects qualify for exempt review. Such research must fall within one of the federally-defined categories (45 CFR 46.101(b)). These categories reflect minimal risk to participants and usually they involve collection of anonymous data or data that are publicly available. 
  
• Your project was not approved by the HRRB, now what do you do?
  In the letter of notification, the IRB provided you with reasons why the project was not approved. You may address these concerns in writing and request that the board evaluate the protocol again.
  
• What is the guidance regarding clinical trial Web sites?
  Web sites, along with print and broadcast advertisements, commonly are used by investigators and institutions to recruit research subjects. In some cases, the information provided on these Web sites may constitute the earliest components of the informed consent process. In May 2002, the HHS Office of Inspector General issued a report, Clinical Trial Web sites: A Promising Tool to Foster Informed Consent. The OIG report recommended that Office of Human Research Protection:
  • Provide further guidance to IRBs on clinical trial Web sites.
  • Clarify that risk and benefit information in trial listings is subject to IRB review and approval.
  • Require IRB review of any prescreening used for specific trials.

  Guidance
  One method of recruiting subjects is through advertisements (such as posted notices and newspaper or magazine advertisements, Web sites). OHRP consistently has interpreted HHS regulations to provide IRB authority and responsibility for review of study recruitment material, including advertisements. Although Web sites use a different medium than traditional print or broadcast advertisements, the requirements are the same.

• When is IRB review of clinical trial Web sites required?
  When information posted on a clinical trial Web site goes beyond directory listings with basic descriptive information. Such information is considered part of the informed consent process and therefore requires IRB review and approval. Basic descriptive information includes:
  • Study title.
  • Purpose of the study.
  • Protocol summary.
  • Basic eligibility criteria.
  • Study site location(s).
  • How to contact the study site for further information.

  Information exceeding such basic listing information includes descriptions of clinical trial risks and potential benefits or solicitation of identifiable information.

• What points should IRBs consider when reviewing clinical trial Web sites, if appropriate?
  As with the review of all recruitment materials, IRBs should pay particular attention to the risk and potential benefit of information to ensure it is presented in a balanced and fair manner. The information presented should not mislead, for example, by promising benefits or implying a benefit beyond that potentially provided by the research.

  IRBs reviewing clinical trial Web sites also should assess the types of incentives, if any, being offered to prospective subjects. Monetary and nonmonetary incentives (such as access to services or programs) can create undue influence on a potential subject's decision about research participation. IRBs must ensure that the clinical trial Web site makes clear that participation in a trial is voluntary and that incentives for participation do not compromise a prospective subject's assessment of the risks or affect his or her choices.

  Some clinical trial Web sites ask viewers to answer questions regarding eligibility for a specific clinical trial. If identifiable private information is collected via the clinical trial Web site, the IRB should review plans for protecting the confidentiality of that information. The IRB should ensure that the Web site clearly explains how identifiable private information might be used.

  Informed consent must be obtained for the collection of any information about the respondent unless the IRB has determined that the informed consent requirement can be waived. There only are two circumstances under which the regulations give IRBs authority to waive the requirements for obtaining informed consent. The first IRB waiver authority is applicable only to research activities designed to study certain aspects of state or local public benefit or service programs. The conditions under which this waiver may be authorized by an IRB are detailed at 45 CFR 46.116(c). The second IRB waiver authority is described in the HHS regulations at 45 CFR 46.116(d) as follows:

  An IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent set forth in this section, or waive the requirements to obtain informed consent provided the IRB finds and documents that:

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

  (Note that research involving children as subjects requires parental permission and child assent unless waived (46.408).)

• When is IRB review of clinical trial Web sites not required?
  Clinical trial Web sites that provide only directory listings with basic descriptive information about clinical trials in general (as listed above) do not need to be reviewed by an IRB. Examples of clinical trial listing services that do not need IRB review and approval include the National Institutes of Health's ClinicalTrials.gov Web site, the NIH National Cancer Institute's cancer clinical trials listing (Physician Data Query) and the government-sponsored AIDS Clinical Trials Information Service.

• All we're doing is reviewing charts for information that will be analyzed and may be submitted for publication. Do we still need IRB review?  Yes. Institutional policies and federal regulations mandate that retrospective chart review receive IRB review before any data is collected. Such studies usually are expedited by the IRB.

Review of case reports 

A case report is the retrospective review of a single patient's clinical course and usually includes a literature review related to the noteworthy aspect of the case. It is the account of "an interesting person with an interesting issue or problem." A case report may provide clues in identifying a new disease or adverse health effect from an exposure. It is most likely to be used when the disease is uncommon and caused exclusively or primarily by a single kind of exposure. A case report has no hypothesis, data analysis or generalized. Children's Hospital administration has decided that if you are doing a review of one case report and there are no identifiers being used, then it is not considered research and does not require IRB submission. If you are looking at more than one case report on the same person or subject, it is considered research.

A case study is a qualitative research method. It is the in-depth analysis, empirical inquiry or investigation of a person or group in a natural, uncontrolled setting. This research method is done from the participants' perspective and studies how they make meaning of the world, not how researchers manipulate it. Qualitative researchers study things in their natural settings, attempting to make sense of, or to interpret, phenomena in terms of the meanings people bring to them.

A case study includes multiple data sources, such as interviews, documents, archival records, direct observations and physical artifacts. Analysis is through description, themes and assertions. Researchers from many disciplines (such as social/behavioral, educational or epidemiological) use this method to build upon, produce new and dispute current theory. A case study requires IRB submission.

A case series is a group of two or more case reports. A case series requires IRB submission.

Consent/assent

• When can consent/assent be waived?
  The IRB may determine that obtaining and/or documenting informed parental consent and child assent may not be necessary under the regulations 45. CFR 46.116(d) and 117(c)(1) and (2) respectively and state laws. In general, the project may not involve more than minimal risk. Waiving or altering the informed consent process will not adversely affect the rights and welfare of the participants. Obtaining consent would somehow alter the research or jeopardize confidentiality of participants, and pertinent information about the research may be made available to the participants after the study.

• When should assent be obtained?
  The American Academy of Pediatrics has stated that a child with the cognitive age of 7 is capable of assenting to research. The IRB adopted this as its guideline. Children ages 7 to 13 should sign a separate assent form. In circumstances where there is a disparity between cognitive age and chronological age, the investigator should document his or her rationale for obtaining or not obtaining child assent.

• What do you do with the signed consent, assent and HIPAA Forms?
  Copies of the forms should be given to participant and parent, placed in the medical record. The researcher should keep the original.

HIPAA

The hospital has no reason to believe that any reasonably anticipated recipient of the information could use it alone, or in combination with other information, to identify an individual.

For further information, you may access the NIH booklet "Protecting Personal Health Information in Research: Understanding the HIPAA Privacy Rule." 

Other questions

• How do you consent/assent when the parent of a child is a minor and not emancipated?
  Under the Food and Drug Administration's interim rule on "Additional Safeguards for Children in Clinical Investigations of FDA-regulated Products," the term "children" is defined to mean "persons who have not attained the legal age for consent to treatments or procedures involved in clinical investigations, under the applicable law of the jurisdiction in which the clinical investigation will be conducted." One of the responsibilities of the IRB under the interim regulations is to "determine that the permission of each child's parent or guardian is granted." "Parent" is defined as a child's "biological or adoptive parent." Thus, the general rule is that the minor's parent or guardian must consent. The question is: When, if ever, is a minor able to consent to treatment under Wisconsin law?
  
  Under Wisconsin law, "child" is defined as a person who is less than 18 years old. Only one general exception to this rule under Wisconsin law was found, and that is related to the emancipation of married minors. Under the guardianship law, except for minors found to be incompetent, a minor is no longer a proper subject for guardianship once he or she is married. Under Wisconsin law, a marriage license may be issued to a person between the ages of 16 and 18 with the written consent of the person's parents or guardian. Under Wisconsin law, a minor who lawfully is married would be considered emancipated and a parent or guardian would not be required to sign a consent to treatment or to participation in research. Since the marriage itself is the emancipating act, subsequent divorce or death of the minor's spouse would not negate the widowed or divorced minor's ability to consent to medical treatment.
  
  Federal law regarding the recruitment of military personnel allows enrollment of applicants 17 years of age with the written consent of the parent or legal guardian. The Veteran Affairs regulations that govern informed consent do not expressively acknowledge minors enrolled in the military as emancipated.
  
  There are some Wisconsin statues that govern specific medical procedures that grant minors broader consent rights. For example, the statute governing parental consent required prior to abortion defines an emancipated minor as "a minor who is or has been married; a minor who has previously given birth; or a minor who has been freed from the care, custody and control of her parents, with little likelihood of returning to the care, custody and control prior to marriage or researching the age of majority." A minor child, 14 or older, may consent to HIV testing. Minors 12 or older many consent to preventative or treatment services for the abuse of alcohol or other drugs on an outpatient basis, and a minor of any age may consent to testing or treatment for sexually-transmitted infections. If a research study involved only treatment covered by one of these exceptions, it would appear to be appropriate to consider accepting the minor's consent to the research study. It certainly would be appropriate to get the minor's assent to accompany parental consent.
  
  While we generally recognize a minor mother as having the authority to consent to non-research treatment for her child, there is no specific statutory authority acknowledging her right to do so. Therefore, the FDA regulations would appear to allow enrollment of the child of a minor parent in a research study only where both the minor parent and the minor's parent or legal guardian (the grandparents) consent.

• Can children who are in foster care or court custody participate in research?
  OHRP does not have any formal guidance on foster children. As noted in 45 CFR 46.409(b), the IRB shall require appointment of an advocate for each child who is a ward. The advocate shall be an individual who has the background and experience to act, and agrees to act in the best interests of the child. The IRB can place the responsibility of identifying and appointing a foster child advocate on the investigator. The information should be included in the protocol in sufficient detail, including the advocates ongoing involvement with the foster child(ren), that the IRB can make a determination if the plan is adequate to ensure protection of these participants.

• What is the difference between a protocol deviation, a protocol violation and a protocol exception?

Protocol deviation
Any alteration/modification to the IRB-approved protocol. The protocol includes the detailed protocol, protocol summary, consent form, recruitment materials, questionnaires and any other information relating to the research study.
Protocol exception
Any temporary protocol deviation that is approved by the IRB prior to its initiation, such as enrollment of a subject who does not meet the eligibility criteria. Note: Any permanent change to the protocol constitutes an amendment that must be submitted to the IRB for approval prior to initiation.
Protocol violation
Any protocol deviation that is not approved by the IRB prior to its initiation or implementation.

Major violation
A violation that may impact subject safety, affect the integrity of study data and/or affect the subject's willingness to participate in the study.
Minor violation
A violation that does not impact subject safety, compromise the integrity of study data and/or affect the subject's willingness to participate in the study.