Frequently Asked Questions
|Adverse Events||Spanish Speaking Subjects|
|Approval||IRB Approval Expires|
|Exemption||Research Subject becomes a Prisoner|
|Electronic Signatures||Key Study Personnel|
|Informed Consent||Other Questions|
- It is the responsibility of the UTHSC IRB, not the investigator, to determine whether research activities qualify for Exemption.
- Enrollment occurs when the consent form is signed, not when the subject is randomized. Therefore, an estimate of screened failures should be incorporated into the target enrollment number submitted to the IRB. Also, the number of subjects who signed the consent form, not just those subjects who were randomized, should be included on the renewal application under the number of subjects accrued.
- The principal investigator or collaborating investigator must sign the consent form within 72 hours of the subject's entry into the study.
- At the time of expiration of IRB approval, all study activities, including recruitment, consent, data collection and data analysis must stop. If you wish to continue any activities that are directly related to subject safety, please contact the IRB office to request permission to continue those activities until IRB approval is reinstated.
- Remember to use the most current version of the consent form template and the UTHSC IRB approved standard language whenever you submit a new or amended consent form. Consent form templates are updated/revised by the IRB often. You can find the most current versions on the UTHSC IRB website, and there is a link to the consent form page from within the "Help" button in iMedRIS. Please do not use old templates that you may have saved on your computer.
- An adverse event (AE) must be reported to the IRB if it is (a) unexpected; (b) serious; and (c) possibly, probably, or clearly related to the research intervention.
- A protocol deviation must be reported to the IRB if it (a) has harmed or has posed a significant risk of substantive harm to the individual research subject; or (b) has compromised the scientific integrity of the data collected for the study; or (c) appears to result from the wiling or knowing misconduct on the part of an investigator or study staff; or (d) appears to involve some other serious or continuing noncompliance with federal, state, or local research regulations.
- When a local investigator receives a protocol waiver from a study sponsor, or the principal investigator of an investigator-initiated study proposes to enroll a subject who does not meet the approved inclusion/exclusion criteria, the details of the proposed waiver, subject identification, and all supporting documentation must be submitted to the UTHSC IRB for review and approval prior to implementation of the protocol waiver.
- If your project/study includes pediatric subjects, remember the following:
- Add the Assent Discussion page as the last page of your consent form if the study population includes subjects 8-13 years of age.
- Add the signature line for the assent of the minor for subjects 14-17 years of age.
- Add a line for the signature of the Legally Authorized Representative (LAR) for studies that include subjects <= 17 years of age.
Q: What are adverse events or other unanticipated problems, and how are they categorized?
A: An adverse event is an untoward medical occurrence that may present itself during the course of a research study. An unanticipated adverse event is a medical occurrence whose nature, severity or frequency is not consistent with existing information regarding the risk profile of the study procedure or test article. For pharmaceutical studies this usually reflects inconsistency with the information contained in the current investigator brochure. A serious adverse event is a medical occurrence that results in death, is life threatening, requires in-patient hospitalization, creates persistent or significant disability or incapacity, or results in a congenital anomaly or birth defect. An important medical event that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse event when, based upon appropriate medical judgment, it may require medical or surgical intervention to prevent one of the outcomes noted above. Unanticipated problems other than adverse events include occurrences such as (but not limited to) accidental overdoses of study medications, deviations from study inclusion/exclusion criteria, or failure to follow criteria for subject withdrawal.
Q: What classifications are used for the relation of the adverse event to the study intervention?
A: An adverse event may be related to the study intervention if it may reasonably be regarded as possibly, probably, or clearly caused by the intervention. Alternatively the relationship of adverse events to study interventions may be characterized as either "unrelated" or as "unlikely related."
Q: What is the UTHSC IRB policy regarding reporting of adverse events?
A: All adverse events must be reported if the event meets the definition for an unanticipated serious event and is also possibly, probably, or clearly related to the intervention. All deaths, regardless of cause or anticipation, must be reported within 24 hours of such occurrence. All other adverse events must be reported within 5 working days from the date of the occurrence. The relationship of the adverse event to the research intervention must be determined by the investigator.
Q: I'm planning a human subjects research project at a hospital where I have privileges but which is not affiliated with UT's IRB. The hospital IRB has approved the protocol. Am I required to submit to UT's IRB?
A: There are a few points that need to be considered: First, if the individual asking the question is UT faculty, he/she will need to also submit his/her research application to the UTHSC IRB. In addition, if the individual asking the question will be conducting research at The Regional Medical Center at Memphis (the Med), or UT Medical Group, Inc., or Methodist Healthcare-Memphis Hospitals or one of its affiliated entities he/she will need to also submit his/her research application to the UTHSC IRB. However, another point that needs to be considered when determining whether or not an application needs to be submitted to the UTHSC IRB is which hospital IRB has already approved the study. For example, if St. Jude Children's Research Hospital has approved the study, the individual may invoke the cooperative agreement with St. Jude IRB, and St. Jude will forward a copy of the application and approval to the UTHSC IRB for review. If, however, the hospital IRB that has already approved the application is Baptist Memorial Hospital or the VA Medical Center, then the research project will also need to be submitted to the UTHSC IRB, using the appropriate UTHSC IRB forms, for review and approval.
Q: I am interested in conducting a research study using a commercially available drug for the approved purpose. Does the UTHSC IRB need to review this research before my study is initiated?
A: Yes. All clinical investigations (which means any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration (FDA), or is not subject to requirements for prior submission to the FDA, but the results of which are intended to be submitted later to, or held for inspection by, the FDA as part of an application for a research or marketing permit) require UTHSC IRB review and approval.
Q: I am planning a research project using purchased human cell lines in an animal model. Do I need IRB approval?
A: Yes, Cell research involving human subjects or information, or products derived from human subjects must be submitted to the
IRB for approval.
Q: If I'm using human cell lines purchased from a commercial vendor, why must I obtain IRB approval to have them declared exempt from human subjects protection regulations?
A: Federal regulations protecting human subjects research (i.e., 45 CFR Part 46) clearly state that the use of cell lines purchased from commercial vendors such as the American Type Culture Collection is not considered to be human subjects research. Neither is research that involves cells from a donor whose identity cannot be readily ascertained by the investigator (http://grants.nih.gov/grants/policy/hs/faqs_specimens.htm#Q1). However, the Office of Human Research Protections (OHRP) states that investigators not be given the authority to make an independent determination that human subjects research is exempt but should consult with the appropriate institutional authority to help make that determination. University policy has assigned that authority to the Chair of the IRB. Investigators should contact the IRB office for help in completing the single page form used in establishing that cell lines are exempt from consideration as human subjects research.
Q: What do I need to know about humanitarian use devices and IRB approval?
A: First, a few definitions:
- HUD-Humanitarian Use Device is the device corollary to an orphan drug. The device must be indicated for use in a disease or condition that affects fewer than 4,000 US patients per year.
- HDE- Humanitarian Device Exemption is the application that must be submitted to the FDA in order to get approval to get an HUD designation.
- PMA - Pre-Market Approval is the corollary to an New Drug Application.
An FDA-approved HDE is not a research protocol; it is an approval for treatment/diagnostic use of the device. It essentially allows a sponsor to market the "orphan" device without the usual clinical trials to prove its effectiveness.
Q: Why is the IRB involved in overseeing a treatment/diagnostic device?
A: Because of the unique situation in which an untested device is being used, the FDA regulations require the added protection that the HUD can only be used if the facility's IRB has approved the use. (21 CFR 814.124) In its most recent guidance on the topic, the FDA now recommends that the IRB conduct a full board review at its initial consideration, though expedited review may be appropriate for continuing review.
Q: Is informed consent required?
A: Although not required by the FDA regulations, written informed consent is highly advisable, including a statement that the device is unproven.
Q: What else should the IRB require?
A: Although not required by the FDA regulations, IRB review should include sufficient information to support the use of the HUD such as generic and trade name, six-digit HDE number from the FDA, date of HUD designation, description of the device, contraindications, warnings or precautions, adverse effects on health, alternative practices/procedures, summary of studies using the device, and marketing history
Q: Must each use be approved?
A: No. The IRB may decide if a blanket approval or a case-by-case approval is more appropriate.
Q: May patients be charged for an HUD?
A: Yes. FDA regulations allow patients to be charged so long as the amount charged does not exceed the costs of research and development, fabrication or distribution. If the amount is $250 or more, the HDE must include verification from a CPA or other appropriate individual that the amount charged does not exceed the allowed costs.
For more how-to information on HUDs and HDEs, see http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm110194.htm
From: Institutional Review Board Management and Function, Bankert Amdur
Q: When does the study of medical records that contain patient identifiers qualify for exempt status?
A: The federal regulations set two conditions for assigning exempt status for this sort of study. First, all the records must be in existence prior to initiation of the study. The application for exempt status should specify the inclusive dates of the records to be reviewed under the description of the subject population. Second, the investigator must record the data from the medical record in a manner that subjects cannot be directly or indirectly identified. In satisfying this condition, it is permissible retain linkage between individual medical records and entries on a data collection sheet, provided that this linkage is destroyed once the data abstraction is complete. The intention to follow this procedure should be clearly stated in the section of the exempt application on study procedures.
Q: My research project has been declared exempt by the IRB, and I have a letter that I need to include with a grant application indicating the exemption number. Can I mark "no" to the human subjects question and still include my exemption letter?
A: No. If you are conducting research that has been declared exempt, you must mark "yes" to the human subjects question on the NIH grant application package, then include UT's FWA# and the IRB exemption # and approval date.
Q: Can an electronic signature instead of a handwritten signature be used to document informed consent?
A: Yes, a written consent, which may be an electronic version, must be given to and signed by the subjects or the subjects' legally authorized representatives, unless the IRB waives the requirement to obtain informed consent [45 CFR 46.116(d)] or the IRB waives the requirement to obtain a signed consent form [45 CFR 46.117(c)]. In addition, some form of the informed consent document must be made available to the subjects or the subjects’ legally authorized representatives in a format that they can retain. For example, subjects or the subjects’ legally authorized representatives may be provided a hard copy of the signed consent form. Further, a secure system that provides encrypted identifiable signatures must be used when obtaining electronic or digital signatures.
Q: Who is considered key study personnel (KSP) according to UTHSC?
A: For the purpose of completing section 3.0 of the IRB electronic application, the designation “key study personnel” includes all persons who will have a significant role in the design or conduct of the research, and includes at a minimum all principal investigators and co-investigators, any individuals who are individually named on a grant or contract application, persons who are listed on an FDA form 1572, research coordinators, persons who supervise those who obtain informed consent, individuals who obtain informed consent, and those who are named as contact persons in the informed consent documents or recruitment materials for research.
Q: What do the signatures on the research informed consent document mean?
- Subject - The subject's signature indicates that the person has voluntarily decided to participate in the study, and to the best of his/her ability, understands the meaning and requirements of the study.
- Legally Authorized Representative - Tennessee state law does not address the issue of clinical research participation for a subject either too young or incapacitated to make informed decisions for themselves. Therefore, we look to policies and procedures for health care decision-making for incompetent patients for guidance. Surrogate consent is authorized utilizing the "legally authorized representative" with following hierarchy: conservator, guardian, attorney in fact, spouse, adult child, parent, adult siblings, other adult relative of the patient, or any other adult who has exhibited special care and concern for the patient, who is familiar with the patient's personal values, who is reasonably available, and who is willing to serve. UTHSC policy requires the signature of the legally authorized representative when a subject is less than 8 years old, or the subject cannot make decisions for themselves at that time. In addition, a line to document the relationship between the subject and the legally authorized representative is required on the informed consent document.
- Person Obtaining Consent - The signature of the person obtaining consent indicates that the study has been explained in detail including, but not limited to the contents of the informed consent, purpose of the study, visits and procedures involved, risks and benefits, alternative treatments, confidentiality, the right to withdraw from the study at any time, treatments provided, arms of the study and randomization. The subject has had sufficient time to read the informed consent document, ask questions, and thoroughly consider their option to participate or not.
- Principal Investigator - The signature of the principal investigator attests that, to the best of his/her knowledge, the informed consent process has been properly conducted, and that the person who conducted the informed consent interview is knowledgeable about the study, and is authorized by the principal investigator to conduct the interview. UTHSC policy requires the principal investigator sign the informed consent document within 72 hours.
- Assent - UTHSC policy requires that each child aged 8 or older provide assent, provided that the investigator's determines that the child is capable of assent by evaluating the child's level of maturity, psychological and emotional capacity, as well as the nature of the study.
Q: I would like to enroll Spanish-speaking subjects in my IRB approved research study. As one of the members of my research staff speaks Spanish, may I have him/her verbally translate the English consent form for the Spanish-speaking subjects when they come in for a visit?
A: No. Federal Regulations (45 CFR 46.116) require that information that is given to the subject or the representative shall be in a language understandable to the subject or the representative. As such, you will need to submit to the UTHSC IRB office a Form 2 (Application for Revision) to change your application to indicate that you will be recruiting Spanish-speaking subjects. In addition, you will need to submit a copy of the consent form translated in Spanish with a signed copy of the Translator's Declaration that can be found on the UTHSC IRB website at www.uthsc.edu/research/irb. The Translator's Declaration states that the Spanish consent form is a true and accurate translation of the English consent form. You may begin enrolling Spanish-speaking subjects once you have received IRB approval.
Q: What should I do if IRB approval of my research study expires?
A: According to federal regulations, if IRB approval of a specific study expires before continuing review and approval occur, investigators must stop all research activities involving human subjects related to that study (45 CFR 46.103(b)), except where they judge that it is in the best interests of already enrolled subjects to continue to participate. When investigators make this judgment, they must promptly notify the IRB (45 CFR 46.103(b)(5)). When the IRB reviews the investigator's decision, it may decide whether it is in the best interests of already enrolled subjects to continue to participate in the research by considering the best interests of subjects either one at a time or as a group. If an IRB determines that it is not in the best interests of already enrolled subjects to continue to participate, investigators must stop all human subjects research activities, including intervening or interacting with subjects, or obtaining or analyzing identifiable private information about human subjects (45 CFR 46.103(b)). Investigators may resume the human subjects research activity once continuing review and approval by the IRB has occurred.
Q: Does the IRB need to review a newspaper advertisement for my research study?
A: Yes. FDA requires that an Institutional Review Board (IRB) review and have authority to approve, require modifications in, or disapprove all research activities covered by the IRB regulations [21 CFR 56.109(a)]. An IRB is required to ensure that appropriate safeguards exist to protect the rights and welfare of research subjects [21 CFR 56.107(a) and 56.111]. In fulfilling these responsibilities, an IRB is expected to review all the research documents and activities that bear directly on the rights and welfare of the subjects of proposed research, including the methods and material that investigators propose to use to recruit subjects.
FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection process. Advertisements and other recruitment materials must receive approval by the IRB prior to the use of such materials. Advertisements and other recruitment materials refer to but are not limited to: materials to be published in local newspapers, broadcast on television or radio networks, placed on the internet, or posted or distributed in pamphlets, posters, signs, brochures, announcements, or promotional materials; descriptions of financial rewards, enrollment fees, and payment to subjects for participation; and any other plans, procedures or materials designed to solicit the participation of subjects in research.
Should you decide to revise any advertisements or recruitment materials that have already been approved by the IRB or the venue in which the materials will be used, these revised materials must receive prior approval of the IRB.
Q: Can subjects be recruited via email?
A: Yes. However, it is important to state, in your protocol, how the email addresses were obtained (e.g., you will be using the University listserv, or the PI is a professor and has email addresses of his students in a distribution list, or the potential subjects have agreed to be contacted for research by signing up for a registry online).
TIP: When contacting subjects directly (via mailed letter or email message), the introductory paragraph should include a general statement regarding how the investigator obtained the subjects' contact information (e.g., "We are contacting members of the XXX Association regarding..." or "You are receiving this questionnaire because you are a patient of the investigator, Dr. John Doe").
Q: What should an investigator do if a subject becomes a prisoner after enrollment in research?
A: The investigator should report this situation to the IRB immediately.
Q: What should be done when a subject becomes a prisoner after enrollment in a study that was not reviewed and approved by the IRB in accordance with the requirements of subpart C: Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects?
A: When a previously enrolled research subject becomes a prisoner and the relevant research protocol was NOT reviewed and approved by the IRB in accordance with the requirements of HHS regulations at 45 CFR part 46, subpart C, the principal investigator should promptly notify the IRB of this event. All research interactions and interventions with, and obtaining identifiable private information about, the now-incarcerated prisoner-subject must cease until the requirements of subpart C have been satisfied with respect to the relevant protocol.
NOTE: OHRP has allowed one important exception. In special circumstances in which the principal investigator asserts that it is in the best interests of the subject to remain in the research study while incarcerated, the IRB Chairperson may determine that the subject may continue to participate in the research until the requirements of subpart C are satisfied.
Upon receipt of notification that a previously enrolled research subject has become a prisoner, the IRB will promptly re-review the protocol in accordance with the requirements of subpart C if the principal investigator wishes to have the prisoner subject continue to participate in the research.
Q: Is an adolescent (e.g., age 14) detained in a juvenile detention facility a prisoner?
A: "Prisoner" is defined by HHS regulations at 45 CFR part 46.303(c) as "any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing." Therefore, an adolescent detained in a juvenile detention facility is classified a prisoner according to the Federal Regulation.
Q: When may a principal investigator delegate study tasks?
A: The principal investigator may delegate many study tasks to site staff - provided that they are qualified to perform the tasks and it is within the scope of their professional licensure if the task requires a license. Such determinations must be based on FDA requirements, as well as local laws and regulations. For example, the principal investigator may delegate performance of physical exams to a nurse practitioner, advanced practice nurse, or PA. Most state Nurse Practice Acts do not permit an RN without an advances practice certification to perform physical exams (not to be confused with physical assessments, which RNs routinely perform). In the same manner, a principal investigator may delegate administration of an intravenous study drug to an RN, but not to a medical assistant. Likewise, the informed consent of subjects should be obtained by staff who are qualified by education and background to adequately explain the details of the study.
However, there are some tasks that the principal investigator cannot delegate. For example, the principal investigator or another study physician is responsible for determining if a subject must be withdrawn from a study due to an adverse event. In all cases, the principal investigator has final responsibility for the general conduct of the study at his or her site including, but not limited to, ensuring that all study-related processes and procedures are conducted in accord with the protocol and in compliance with local IRB policy and federal regulations for the protection of human subjects.
Q: In documenting a patient's eligibility for a study, must the investigator obtain the prospective subject's previous medical records, or are history forms completed at the start of a study considered adequate?
A: Some studies are so complex, and have so many complicated inclusion/exclusion criteria, that a review of previous medical records is a necessity. A well-written clinical summary prepared by the subject's primary physician, along with relevant lab reports and related documents, will usually suffice. Photocopies of prior medical records are not required. In more straightforward studies that have few inclusion/exclusion criteria, the completion of a history form alone may be adequate (i.e., without the need to obtain prior medical records). The caveat here is that the history taker must be clinically knowledgeable in order to ask the appropriate questions and adequately probe the study candidate for additional information when needed.
UTHSC IRB office
Memphis, TN 38163
Phone: (901) 448-4824
Fax: (901) 448-5103