This section of the Investigator Manual covers research responsibilities after approval, changes of protocol, continuing review and reportable event requirements, reporting clinically relevant information, and communicable disease testing.

Researcher Responsibilities After IRB Approval

In addition to the requirements described elsewhere in this manual and in the Toolkit library, you are responsible for the following after you receive IRB approval:

  1. Do not start human research activities until you have the final IRB approval letter.
  2. Do not start human research activities until you have obtained all other required institutional approvals, including approvals of departments or divisions that require approval prior to commencing research that involves their resources.
  3. Ensure that there are adequate resources to carry out the research safely. This includes, but is not limited to, sufficient investigator time, appropriately qualified research team members, equipment, and space.
    1. Delegate responsibility to the research staff in accordance with the staff’s training and qualifications.
    2. Assure that all procedures associated with the research are performed, with the appropriate levelof supervision, only by individuals who are licensed or otherwise qualified to perform them.
    3. Monitor the research study and perform quality management activities to ensure the protection of subjects and the quality of the research data.
  4. Obtain the legally effective informed consent from human subjects or their representatives, using only the currently approved informed consent documents, and provide a copy to the subject, if applicable.
    1. Ensure that only IRB-approved investigators obtain informed consent from potential subjects.
  5. If unavailable to conduct this research personally, as when on sabbatical leave or vacation, arrange for another IRB-approved investigator on this study to assume direct responsibility, or notify the IRB of alternate arrangements
  6. Maintain accurate and complete research records, including but not limited to, entire copies of signed informed consent and authorization documents (original, wet-ink version is required when study is FDA regulated), and retain these records according to IRB policy and the applicable regulatory retention terms.
  7. Fully inform the IRB of all locations in which human subjects will be recruited for this project and obtain and maintain current IRB approvals/letters of agreement when applicable
  8. Update study personnel; see “How to Update Personnel” section above. [Add Link]
  9. Personally conduct or supervise the human research. Recognize that the investigator is accountable for the failures of any study team member.
    1. Conduct the human research in accordance with the relevant current protocol as approved
      by the IRB, and in accordance with applicable federal regulations and local laws.
    2. When required by the IRB ensure that consent or permission is obtained in accordance withthe relevant current protocol as approved by the IRB.
    3. Do not modify the study or project without prior IRB review and approval unless necessary to eliminate apparent immediate hazards to subject.
    4. Protect the rights, safety, and welfare of subjects involved in the research.
  10. Submit to the IRB:
    1. Proposed modifications to the approved research, as described in this manual. (See “How to Submit a Change” and “Change Requirements”)
    2. If required, a continuing review application asrequested in the approval letter. (See “Continuing Review Requirements”)
  11. Report any of the information items listed in “Reportable Event Requirements.”
  12. Submit an updated disclosure of financial interests within thirty days of discovering or acquiring (e.g., through purchase, marriage, or inheritance) a new financial interest.
  13. Do not accept or provide payments to professionals in exchange for referrals of potential subjects (“finder’s fees.”)
  14. Do not accept payments designed to accelerate recruitment that were tied to the rate or timingof enrollment (“bonus payments.”)
  15. See additional requirements of various federal agencies in this manual’s appendices. These represent additional requirements and do no override the baseline requirements of this section.
  16. If the IRB directs or your study is selected for an onsite post-approval review, cooperate with post-approval monitoring staff to complete the onsite review.
  17. If the study is a clinical trial and supported by a Common Rule agency, one IRB-approved version of a consent form that has been used to enroll participants must be posted on a public federal website designated for posting such consent forms. The form must be posted after recruitment closes, and no later than 60 days after the last study visit. Please contact the study sponsor with any questions.

Continuing Reviews

If your study requires continuing review, you must submit your continuing review no later than 45 days prior to the last day of approval to allow sufficient time for IRB review. When completing the continuing review form, if your study enrolls subjects, you will be required to specify enrollment totals. Enrollment is defined as eligible, appropriately informed individuals agreeing to participate in a study who have provided informed consent and initiated study procedures. Alternatively, your protocol can define enrollment as is appropriate for the study. In both cases, enrollment totals should be reported consistently from year to year. For data and/or specimen only protocols, this number should reflect the total number of data and/or specimens accessed for research purposes. This number should not exceed the total number of subjects requested in the approved protocol. If you wish to request additional subjects, you should submit a change for review.

If the approval of human research expires because you have failed to submit the continuing review application or you submitted the continuing review application without enough time for IRB review prior to expiration, all human research procedures related to the protocol or study under review must cease, including recruitment, advertisement, screening, enrollment, consent, interventions, interactions, and collection or analysis of private identifiable information.

If current subjects will be harmed by stopping human research procedures that are available outside the human research context, provide these on a clinical basis as needed to protect current subjects. If current subjects will be harmed by stopping human research procedures that are not available outside the human research context, immediately contact the IRB office and provide a written list of the currently enrolled subjects and why they will be harmed by stopping human research procedures. If current subjects will be harmed by stopping human research procedures that are not available outside the human research context, these should continue as necessary for subject safety. Any ongoing procedures that were not able to safely stop should be summarized in the continuing review application.

If the IRB reviewed your continuing review application, but requires modifications to secure approval, you should submit those modifications in a timely fashion so they can be reviewed before study approval lapses.

For more information, see How to Submit a Continuing Review, FDA Regulations and IRB Review, and HRP 314-WORKSHEET-Critera for Approval.

Reporting Clinically Relevant Information to Participants

Research teams should identify in their IRB applications any clinically relevant results that could be produced by study tests or procedures. Clinically relevant information may arise because of radiological examinations conducted for research purposes, physical examinations or physiologic tests, test results from samples collected from subject, or the analysis of cognitive or behavioral assessments completed by subjects. Examples include:

  • MRIs of the head may identify serious medical concerns, such as brain tumors, that might not be identified if the subject had not taken part in the research
  • Genetic testing may identify actual or potential conditions that may affect the health of the individual participating in the research (and their relatives) or a reproductive decision
  • Validated psychological screening tests may identify potential suicidality or severe depression
  • Laboratory tests that reveal severe anemia or suggest diabetes

In addition to identifying the possibility of clinically relevant results that may be discovered, you should describe whether you intend to disclose the results to subjects. The IRB would not expect (and in some cases will not allow) the dissemination of information to subjects generated from tests or procedures that are considered experimental or have not been clinically validated. This is because the clinical relevance of the results in such cases may be unclear and can create inadvertent anxiety or confusion for the participant without providing potential benefit. In addition, the IRB generally does not allow the release of laboratory analyses to subjects unless they are performed by a CLIA-approved entity. Finally, the IRB would expect that any results released to subjects from research tests should be actionable.

If the results will be disclosed to participants, the research team will be asked to identify who assesses whether the information should be reported to subjects, provide a timeframe for reporting the results to subjects (results should be reported in a timely manner, e.g. within 30 days), and describe the process for informing subjects of these results and whether other resources are in place to assist with the explaining the results and their consequences to research subjects (e.g., a genetic counselor, referral to a physician). If the study team plans to release results directly to a subject’s health care provider, this should be with the subject’s permission and a qualified member of the research team should call the health care provider to contextualize the results and highlight any that may require follow-up. Results generally may not be released, particularly if the study is covered by a Certificate of Confidentiality, to someone other than the participant (e.g., participant’s spouse or family after participant loses capacity or after death) absent participant consent.

If the IRB has not previously approved the disclosure of clinically relevant findings to subjects and a special circumstance arises for a single subject, research teams may submit a reportable event to request disclosure. The following information should be included in the new information report:

  • Description of the incidental finding (e.g., abnormal result of laboratory test or MRI), when it was discovered and who discovered it
  • Rationale for disclosing the incidental finding (i.e., why the subject may benefit from knowing this information)
  • Process for informing the subject of the incidental finding (i.e., who is going to disclose the finding, how, and who should the subject contact regarding questions)
    • Statement clarifying whether this is expected to occur again or if this is an isolated incident (if not an isolated incident, a change of protocol is required)

“Souvenir” Radiology Images

Study teams may give study participants an image from a research radiology scan as a souvenir of their participation if the following conditions are met:

  • No more than three views are provided;
  • The image is labeled “Research image not for diagnostic use”

Communicable Disease (Including HIV)

If you plan on collecting information about or testing participants for communicable disease status, additional considerations apply. The IRB generally defines a communicable disease as:

  • Health conditions that must be reported to health authorities under state and/or federal law, such as hepatitis, tuberculosis, or syphilis.
  • Health conditions that may require health care providers to use contact precautions, such as gown and gloves or isolation, when interacting with an affected individual.

Your protocol or application should address why such information must be collected for your study as well as whether any test results will be disclosed to participants and what impact, if any, such testing will have on their clinical care. The informed consent document must include language informing potential participants about such testing and its impact on their clinical care.

For HIV testing, additional requirements apply, including those mandated by state law.

  • Informed consent: Participants must be informed the research includes HIV testing or use of HIV test results and the associated risks, unless the criteria for the IRB to waive informed consent are met. If results will be placed in the participant’s medical record, they must be informed of this as well. Under Wisconsin law, the informed consent process for HIV testing must also include a written or oral explanation or description of:
    • HIV infection
    • HIV test results
    • Requirements for reporting to the State epidemiologist
    • Treatment options for a person who has a positive HIV test result; and
    • Services provided by AIDS service organizations and other community-based organizations.
    • Study teams can use the UW Health’s Health Facts, “HIV and AIDs” to satisfy these state law requirements.
  • Reporting HIV test results: If a participant tests positive for HIV/AIDS, a report must be made to the state epidemiologist. If identifiable specimens are provided to the University of Wisconsin Hospital and Clinics (UWHC) laboratory or the Wisconsin State Laboratory of Hygiene (WSLH), the UWHC laboratory or WSLH will make required reports to the state epidemiologist. If only coded specimens are provided to the UWHC laboratory or WSLH, you are responsible for making all required reports.
  • Maintaining records: State law requires that a record be maintained of the following:
    • Whether the person or their authorized representative consented to or declined the HIV test;
    • Any authorization for disclosure of HIV test results that the person or their authorized representative has made;
    • Results of an HIV test administered to the person.
    • Additionally, for purposes of verifying compliance with Wisconsin reporting laws, the study team should maintain records of any report made to local health departments or the state epidemiologist; such forms may be de-identified to protect subjects’ privacy.
  • Use of test results from the medical record: HIV test results are confidential but may be revealed without the subject’s authorization for research purposes if:
    • The researcher is affiliated with a health care provider,
    • The study has permission for the research,
    • The researcher provides written assurance to the person releasing the HIV test results that:
      • Use of the information requested is only for the purposes under which it is provided to the researcher;
      • The information will not be released to a person not connected with the study and;
      • The final research product will not reveal information that may identify the subject unless the researcher has obtained consent for disclosure from the subject.