Investigator responsibilities for conducting human subject research at Aurora Health Care
Aurora Health Care is guided by the ethical principles regarding research involving human subjects as set forth in the report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (the "Belmont Report"). The three basic principles that govern the protection of human subjects in biomedical and behavioral research as set forth in the Belmont Report, and adhered to by Aurora Health Care, are:
- Respect for persons: recognition of the personal dignity and autonomy of individuals and special protection of those persons with diminished autonomy;
- Beneficence: obligation to protect persons from harm by maximizing anticipated benefits and minimizing possible risks of harm; and
- Justice: fairness in the distribution of research benefits and burdens.
These principles are designed to protect the rights and welfare of human subjects and are the basic tenets underlying the Aurora Institutional Review Board (IRB) policies and operations.
Before any research project involving human subjects (including involvement of humans in one or more of the categories of research exempted or waived under the federal regulations), human biological material or identifiable protected health information can begin, it must be reviewed and approved by the Aurora IRB, an administrative body established to protect the rights and welfare of human research subjects.
The Research Subject Protect Program (RSPP) is responsible for the operational support, initial and ongoing training, and general management of the Aurora IRB. The RSPP/Aurora IRB is responsible for the oversight of all human subject research conducted at Aurora Health Care facilities, or by Aurora Health Care physicians, staff, or employees.
The Investigator is charged with the responsibility for the conduct of the research study and is the ultimate protector of the subject's rights and safety. It is the investigator's responsibility to keep the Aurora IRB informed of all activities involving the research study for the duration of the study. An investigator is responsible for the accurate documentation, investigation, and follow-up of all possible study-related adverse events. Investigators are also responsible for informing governmental agencies (FDA or other federal funding agency, e.g. Department of Health and Human Services, National Institutes of Health, etc.) and other sponsors of any unanticipated or serious adverse events, as appropriate.
The following may not be applicable to all research studies conducted at Aurora Health Care. Please contact the RSPP office at (414) 219-7744 if you have further questions about your responsibilities related to conducting human subject research at Aurora Health Care.
What is research?
"Research" is defined as "a systematic investigation... designed to develop and contribute to generalizable knowledge." [45 CFR 46.102(d)].
Who is a "human subject"?
A "human subject" is defined broadly by federal regulation as, "a living individual" about whom an investigator (whether professional or student) conducting research obtains:
- Data through intervention or interaction with the individual; or
- Identifiable private information [45 CFR 46.102(f)].
Note: FDA regulations define "human subject" as "an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient." [21 CFR 50.1(g)].
Aurora IRB Review of Human Subject Research
An investigator has the obligation to bring any activity that may involve:
- Humans as research subjects;
- Protected health information (patient medical records) owned by Aurora Health Care; or
- Any activity in which Aurora Health Care is considered "engaged" in research to the attention of the RSPP office to determine if further action is required. The Aurora IRB may also review research studies submitted by non-Aurora facilities or investigators, provided the investigator has agreed to the oversight of the Aurora RSPP, as indicated on the submission.
The Aurora IRB is the sole body designated to make human subject research determinations at Aurora Health Care. For some categories of research, it is difficult to discern whether the proposed activities qualify as human subject research. If an Investigator would like the Aurora IRB to make a Human Subject Research determination relative to their proposed activities, they may complete the Request for Determination of Human Subject Research form located on the Aurora Web site. An Aurora IRB Chair will review the information to determine whether the Investigator may conduct the proposed project as Non Human Subject or Non-Research, OR whether the study must be submitted to the Aurora IRB as Human Subject Research. If the Chair determines that the project is Human Subject Research, the Investigator will be required to submit their project on the appropriate Aurora IRB submission form (either full submission [301-A] or exempt submission [302-A]), and have the research activities reviewed and approved by the Aurora IRB before the research can begin.
If you have a question about whether your project meets the definition of Human Subject Research, contact the RSPP/IRB office at (414) 219-7744 or email us.
A qualified clinician, who will be responsible for all study-related health care decisions, must be listed as an investigator or sub-investigator on all research proposals submitted for review by the IRB. The investigator must ensure that he/she has the necessary qualifications and clinical privileges to perform the procedures and therapies involved in the research study. If the investigator's medical staff privileges become suspended or revoked, he/she must immediately report such suspension to the RSPP Manager or Aurora IRB Chair.
If the research involves medical treatment or intervention, a qualified clinician must provide for referrals for needed healthcare during the research and for needed follow-up after the research has ended, as necessary.
Any physician conducting Human Subject Research at any Aurora Metro region facility will be required to complete an application for Research Privileging. The application will be completed when the physician is due to renew his/her Aurora Health Care medical staff privileging appointment.
This request for Research Privileging will be reviewed and approved as an "additional" privilege by the Aurora Health Care Metro Inc. Board of Directors ("Metro Board"). The Research Privilege, administered by the Aurora IRB, is valid for two years from the date of the Metro Board's approval, at which time it will need to be renewed.
If any services provided to a research subject are delivered at an Aurora Health Care facility and a bill for those services will be submitted to a third-party payor, the investigator should contact Aurora's Research Medicare Billing Analyst at Aurora's Medical Audit Office prior to IRB submission to initiate all required and appropriate billing procedures.
Medical malpractice insurance
The Aurora IRB will recommend that the investigator should contact his/her medical practice carrier to provide notice that he/she is conducting a particular research study. This notification will allow the investigator to determine prospectively whether he/she will be covered under his/her policy. In addition, all investigators must participate in the Wisconsin Patient Compensation Fund if they are conducting research at an Aurora Facility.
Informed consent is a person's documented, voluntary agreement to participate in research. Informed consent is the cornerstone for research involving human subjects. Subjects need to understand why the research is being pursued, what procedures and time commitments are involved, and the potential risks and benefits.
It is the responsibility of the investigator to ensure that informed consent is obtained by personnel who are knowledgeable about the study and who are able to adequately respond to questions from the study subject. The investigator (or the individual to whom the investigator delegates this responsibility) must obtain informed consent/authorization from each research subject, or their legally authorized representative, prior to his or her enrollment into the research study, unless the Aurora IRB waives the requirement for informed consent and/or authorization. The subject's consent to participate must be documented by their signature on an Aurora IRB-approved informed consent document, unless the Aurora IRB otherwise waives or alters the requirement for obtaining documentation of informed consent.
If the research study involves a medical treatment or intervention in which consent is normally obtained in the clinical setting, and the medical records will be maintained at an Aurora facility, Wisconsin state law (Wis. Stat. 448.30) requires that a physician [who is the principal investigator or a sub-investigator in the study] inform the patient [subject] about the availability of all alternate, viable medical modes of treatment and about the benefits and risks of these treatments. It is the Aurora RSPP's position that any attempt to discharge this responsibility to another individual (e.g., a non-physician study coordinator) would constitute a breach of the physician's duty to provide informed consent under state law. However it is ultimately the principal investigator's decision.
The investigator must use the most current IRB-approved version of the informed consent document at the time of subject enrollment. Approval and expiration dates are indicated on the consent document. Consent documents are valid only during the dates indicated; and the investigator may use the document only during the period for which they are valid. Investigators must follow Aurora Health Care guidelines for obtaining and documenting informed consent/authorization (IRB Policies IC 701 and HI 1201).
Informed consent is an ongoing process, which requires the investigator to keep the subject apprised of issues that arise which may affect their willingness to continue participation. The subject's continued willingness to participate should be verified and documented in the subject's medical record and/or research record each time there is contact with the subject.
The IRB must be informed of the failure of an investigator to obtain written informed consent/authorization from the research subject or his/her legally authorized representative prior to beginning any research-related activities. The investigator must notify the IRB in accordance with IRB Policy RR 403, as applicable.
Recruitment for potential study subjects
Recruitment materials to be viewed by potential research subjects (advertisements, letters to potential subjects, internet postings, and any other materials for subject recruitment) require prospective IRB review and approval prior to use, distribution or posting.
Materials should be submitted to the IRB in "camera ready" format.
Recruitment information designed for radio or television use should be submitted for IRB review and approval prior to taping to ensure the appropriateness of the text. However, a final taped (audio or video) version will be required before final approval will be issued.
If you are conducting more than one research study for which a subject may be eligible, the IRB will request additional information (via the submission form) regarding the selection criteria used to determine the most appropriate study for a subject's participation.
Problems that require prompt reporting to the IRB
Investigators are to promptly report any problems discovered or encountered during the conduct of the research to the IRB as soon as possible, but in no case more than 10 working days after discovery. These problems include:
- adverse events that are, in the opinion of the investigator, both unexpected and related or probably related to the research (see Policy RR 403 for definitions of "unexpected" and "related")
- unanticipated adverse device effects that relates to the rights, safety, or welfare of subjects
- new information that indicates a change to the risks or potential
benefits of the research, examples include:
- change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol
- interim analyses
- new publications
- sponsor imposed suspension of research
- subject or research staff complaints related to risk
(see Policy 403 for other examples or call the RSPP office if in doubt if your new information is reportable)
- Injuries to subjects or others
- change to the protocol done without prior IRB review to eliminate an apparent immediate hazard to a subject
- protocol violations that indicate that subjects or others were harmed, or that indicate subjects or others might be at increased risk of harm
All problems must be reported on the appropriate Aurora IRB form (Modification form [403-C]. Adverse Event Reporting form [403-A or 403-B], Significant New Finding form [403-F] or Significant Violation form [403-G]). The IRB Chair will review all submitted reports and determine whether they are 1) unexpected and (2) indicates that subjects or others are at increased risk of harm. If both points are met, the problem is considered an Unanticipated Problem Involving Risks To Subjects Or Others. Unanticipated Problem Involving Risks To Subjects Or Others are taken to the IRB for further review. Unanticipated Problem Involving Risks To Subjects Or Others are reported to external agencies and appropriate institutional officials per Policy RR 408.
Changes in approved research
Changes in approved research, and in the current IRB-approved informed consent document, may not be initiated without prospective IRB review and approval, except where necessary to eliminate apparent immediate hazards to human subjects. Reportable changes include the addition or deletion of investigators or sub-investigators. Investigators must submit requests for all changes (including those designed to improve the protection of subjects participating in the research) to the Aurora IRB, in writing, using the Aurora IRB modification form available on the IRB's website (see IRB Policy RR 403 for additional guidance). Minor changes that do not significantly increase risk to the subject may be reviewed by the expedited review process.
Violations (a deviation from the conduct of a research study as reviewed and approved by the IRB) and protocol exceptions (a planned single deviation from the research study reviewed and approved by the IRB and pre-approved by the sponsor) must be reported to the IRB per the guidelines outlined in IRB Policy RR 403).
Research Administrative Hold, suspension or termination
The IRB may ask an Investigator to place some or all research activities related to a currently approved protocol on an Administrative Hold (a temporary or permanent stop to research activities) until additional information can be obtained, in order to determine if: 1) a change in the risk-benefit profile has occurred, or 2) potential areas of non-compliance exist. (See Aurora Policy RR 403 for more information on Administrative Holds.)
All currently approved research that is not being conducted in accordance with the policies of the Aurora IRB, federal, state, and local requirements, or has been associated with unexpected serious harm to subjects may be subject to suspension or termination of IRB approval. The IRB may determine that currently approved research be suspended or terminated for the following reasons, including but not limited to:
- Serious and continuing non-compliance with federal, state or local regulations, or IRB policy
- Failure to respond to an IRB request for more information relative to an Administrative Hold
- Failure to submit a closure report after multiple attempts
- Failure to obtain IRB-approved informed consent
- Change in the risk-benefit ratio of the research, that is, the study has been associated with unexpected serious harm to subjects
For more information on suspension or termination of IRB approval see IRB Policy RR 403.
Periodic reports/final reports
The length of time IRB approval is given for a research protocol will be no more than one year, and may be less depending on the level of risk involved with the research. Investigators are requested to provide a periodic progress report regarding their investigation 90 days prior to the end of the approval period, in accordance with IRB Policy RR 404. There is no grace period extending the conduct of the research beyond the expiration date of IRB approval. Extensions beyond the expiration date will not be granted. If the Aurora IRB does not re-approve the research by the specified expiration date, subject accrual must be suspended pending re-approval of the research by the Aurora IRB.
If a study is suspended or terminated by the Sponsor for any reason whatsoever, the investigator shall immediately notify the IRB of the Sponsor's action and the basis for such action.
Upon study completion, a final report must be filed with the RSPP within 14 calendar days in accordance with IRB Policy RR 405.
Response to requests for information from the Aurora IRB
Prompt compliance/response to all RSPP/Aurora IRB requests for information regarding a research study (including consent forms, adverse reaction reports, progress reports, etc.) are required to assist the Aurora IRB in the review of research.
Maintenance of study records
For FDA-regulated studies
Investigators are required to follow record retention procedures outlined in federal regulations 21 CFR 312.60(c) (investigational drugs) and 21 CFR 812.140(d) (investigational devices) for the conduct of their research study. At a minimum, investigators must maintain research records for at least three (3) years after completion of the research. All records must be accessible for inspection and copying by authorized representatives of the IRB and the federal department or agency supporting the research, if any. Beyond three (3) years, requirements for record retention vary with the type of research conducted and provisions of the investigator's funding source. It is the investigator's responsibility to clearly understand the retention requirements of their sponsor.
Maintenance of records for non-FDA studies
The IRB recommends that investigators who conduct research that does not involve the use of investigational articles regulated by the FDA should maintain his/her records for a period of 10 years from the date of the last research intervention for an adult subject, or for a period of 20 years from the date of the last research intervention, or until a particular minor subject reaches 21, whichever time period is longer.
Responsibilities of sponsor-investigators who conduct research studies involving investigational drugs or investigational devices
Sponsor-investigators are responsible for complying with all requirements applicable to sponsors and investigators conducting a research study involving an investigational drug or investigational device in accordance with 21 CFR 312 and 21 CFR 812. The IRB may require a sponsor-investigator to provide adequate assurances that proper monitoring of the research study will occur or to form an independent data monitoring committee.
Training and education.
All investigators and sub-investigators will be required to complete appropriate training for protecting the rights and safety of human subjects before Aurora IRB approval will be granted.
It is also the responsibility of the principal investigator to ensure that the members of his/her research team are properly trained and aware of all scientific, protocol, human subject, privacy, and ethical matters related to the conduct of the research.
Online training is available using the NIH Human Participant Protections Education for Research Teams located at http://cme.cancer.gov/c01/. Other human subject protection training courses used to satisfy this requirement will be considered by the Manager of the RSPP on a case-by-case basis. Please contact the RSPP office at (414) 219-7744 for more information about on-going training and education for investigators and research teams in the protection of human subjects.
Conflict of interest
The protection of human subjects requires objectivity in communicating risks, selecting subjects, ensuring informed consent, and collecting, analyzing and reporting data. Therefore, the IRB will consider conflict of interest (COI) issues in its review of research proposals.
All investigators must submit form GA 104-A (Research Staff COI Statement) along with their Submission Application to the IRB declaring whether they, or any other person responsible for the design, conduct, or reporting of the research, has an economic interest in, or acts as an officer or a director of any outside entity whose financial interests would reasonably appear to be affected by the research, in accordance with IRB Policy GA 104. For research studies conducted under the jurisdiction of the FDA, the investigator must also disclose to the sponsor information regarding the investigator's financial interest in the outcome of the study, which may include: a payment arrangement (e.g., a royalty); a proprietary interest in the product (e.g., a patent); or an equity interest in the sponsor of the study. The sponsor will be responsible for disclosing the information to the FDA as required by the federal regulations. It is the investigator's obligation to also report such conflicts to the Aurora Research Integrity Committee through the Aurora RSPP.
Failure to adhere to IRB Policies and Procedures
Investigators who fail to abide by the Aurora IRB Policies and Procedures, as well as other applicable federal, state and local laws and regulations governing the conduct of human subject research, shall be investigated for such noncompliance in accordance with IRB Policy CO 601. Furthermore, the Signatory Official may recommend corrective action to the applicable medical staff(s) of which the investigator is a member.
Observation of consent process and/or the conduct of research
As warranted, the IRB may direct a member of the IRB, RSPP office, or the Research and Quality Compliance Specialist to observe the consent process and/or the conduct of research. That individual will report back to the IRB any issues that require attention.
If you have any questions, concerns, complaints, or comments about the IRB process or the IRB office, do not hesitate to contact us at (414) 219-7744 or email us.