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- Operations Manual - Roles and Responsibilities of Investigators and Research Staff
Operations Manual - Part 6
Eligibility requirements for conducting human subjects research vary depending on the role of the researcher. Research personnel must be appropriately qualified by training and/or experience to perform their research responsibilities.
The Principal Investigator (PI) bears ultimate responsibility for all activities associated with the conduct of a research project, including compliance with federal, state and local laws, institutional policies and ethical principles. The PI remains ultimately responsible even when some aspects of the research are delegated to other members of the study team.
Graduate students/trainees are permitted to serve in the role of PI, but must have a faculty advisor who shares in the student’s responsibility for the conduct of the research. Undergraduate students/trainees may be permitted to serve in the role of PI on minimal risk studies only and must have a faculty advisor who shares in the student’s responsibility for the conduct of the research.
Co-Investigators (Co-Is) are a subset of Key Personnel who have special responsibilities on research projects. Co-Is are obligated to ensure that the project is designed and conducted in compliance with applicable laws and regulations and institutional policy governing the conduct of human subjects research. The Co-I must be qualified by training and experience to conduct his or her responsibilities on the research project.
Each Co-I must explicitly acknowledge to the Institutional Review Board (IRB) their participation as a Co-Investigator on the study and will be asked to acknowledge their addition to or deletion from any existing IRB-approved study. Co-Is will be notified of, but will not be required to acknowledge, submissions from the PI to the IRB, such as amendments, adverse event reports, scheduled continuation reviews, and terminations, and any related communications regarding such submissions.
"Subinvestigator" is a term specific to FDA-regulated studies. It identifies study team members who make critical clinical trial-related procedures and/or to make important trial-related decisions. Generally, these are also study Co-Is but may also include study team members with critical and important trial-related roles.
All research conducted by students/trainees, including postdoctoral fellows, must include a Faculty Advisor (FA) as a member of the study team. In addition to the expectation that the FA provide active mentorship to the student during the conduct of the research, the FA shares responsibility with the student/trainee researcher for the ethical conduct of the research and is institutionally accountable for the study.
Other Key Personnel include individuals who contribute to the scientific development or execution of a study in a substantive, measurable way. Typically, these individuals have doctoral or other professional degrees, although individuals at the masters or baccalaureate level are sometimes considered Key Personnel depending on their involvement in a project. Research fellows, residents, associates and consultants may be Key Personnel.
Supervision by faculty members is required for any research performed by students/trainees in any role, to ensure the proper conduct of research and protection of subject rights and welfare.
Table 8 provides information about permissible roles for U-M faculty, students/trainees and staff on IRB applications. Exceptions to these requirements are at the discretion of the Vice President for Research (VPR) or designee.
Table 8: Who May Serve as Principal Investigator, Co-Investigator/Subinvestigator, or Faculty Advisor/Mentor on IRB Applications
|Current Status||PI||Co-I / Subinvestigator||Faculty Advisor / Mentor||Additional Requirement(s)|
Active Emeritus Faculty
|Yes||Yes||No||Application must include Faculty Advisor/Mentor|
|Other qualified individuals||No||Yes||No||Permission of the IRB|
II. ROLES AND RESPONSIBILITIES OF INVESTIGATORS AND RESEARCH STAFF FOR THE PROTECTION OF HUMAN SUBJECTS
The PI has primary responsibility for protecting the rights and welfare of human subjects in research. Details about the HRPP general requirements for protecting human research subjects are provided in Part 7 of this Operations Manual (OM). The PI’s primary responsibilities also include the following:
PIs must personally perform or delegate to qualified co-investigators or research staff all of the necessary tasks to carry out their studies. Even when specific tasks are delegated, the PI remains ultimately responsible for proper conduct of the study and fulfillment of all associated obligations.
The PI must provide members of the research team with sufficient oversight, training and information to facilitate appropriate safety procedures and protocol adherence. In addition, the IRB must be informed if a PI is no longer able to fulfill his or her duties for any reason including, but not limited to, traveling for a prolonged period of time.
The PI and any Co-I, key personnel, and other research staff (together referred to as “researchers” or the “research team”) are expected to be knowledgeable about and comply with the requirements of each of the following:
- The Common Rule and other federal research laws and regulations;
- Applicable state law;
- The University’s Federalwide Assurance;
- Institutional policies and procedures for the protection of human subjects and reporting and managing conflicts of interest;
- The terms and conditions of any research agreements (with government or private sponsors); and
- The basic ethical principles that guide human subjects research.
Some of the laws and regulations that most directly and routinely impact the conduct of human subjects research studies are described in Part 11 of this OM. Institutional policies and procedures include this OM, as well as policies and procedures maintained by the academic units to which researchers and research staff are appointed, IRB policies and procedures, and the policies and procedures of other research review units with relevant oversight responsibilities, such as the Investigational Drug Service and the Radiation Safety Committee.
PIs must ensure that adequate resources (facilities, equipment, supplies, and personnel) exist to:
- Conduct the research (e.g., through internal or external funding for staff, facilities and equipment);
- Protect subjects; and
- Ensure the integrity of the research.
Researchers responsible for multi-site research should evaluate the resources available at each site where the research will be conducted.
Researchers must complete educational training as required by the University, the relevant IRB, and other review units prior to initiating research, and should not undertake responsibility for human subjects studies unless they understand these requirements and are willing to be held accountable for complying with the relevant standards and protecting the rights and welfare of research participants. For additional information on training for human research refer to Part 13 of this OM.
Researchers may contact the Institutional Official (IO), the Deputy Institutional Official (DIO), or the General Counsel to obtain answers to questions, express concerns or convey suggestions regarding the human research protection program.
Following are descriptions of some of a researcher’s central obligations when conducting studies involving human subjects. They are intended only as a general guide and do not contain a comprehensive description of all of researcher responsibilities.
Federal regulations, institutional policy, and guiding ethical standards require that human subjects research be designed to minimize risks to participants. Minimizing risks and protecting human research subjects take precedence over the goals and other requirements of any research endeavor.
One of the ethical justifications for research involving human subjects is the social value of advancing scientific understanding and promoting human welfare. However, the value of research depends upon the integrity of study results. If a research study is so methodologically flawed that little or no reliable information will result, it is unethical to put subjects at risk or even to inconvenience them through participation in such a study.
To minimize risks to subjects and protect subjects rights and welfare:
- Researchers are expected to design protocols that comply, at a minimum, with applicable regulatory and institutional policy requirements, as well as the principles of the Belmont Report (i.e., respect for persons, beneficence, justice);
- The research must be reasonably expected to answer its proposed question; and
- The knowledge reasonably expected to result from the research must be sufficiently important to justify the undertaking.
All research procedures must be consistent with sound research design. For example:
- Recruitment and enrollment plans should promote equitable subject selection (i.e., subjects should equitably bear the burdens and enjoy the benefits of participation in research);
- Whenever appropriate, researchers should use procedures already being performed on subjects for diagnostic and treatment purposes;
- When appropriate, research plans should make adequate provision for (a) monitoring subjects to promptly detect any adverse events and (b) reviewing data collected to ensure subject safety;
- Research plans must contain adequate provisions to protect the privacy of subjects and confidentiality of data collected;
- If some or all of the participants in a study are likely to be vulnerable to coercion or undue influence (e.g., children, prisoners, pregnant women, mentally disabled individuals, or economically or educationally disadvantaged people), the research plan should provide for additional safeguards, as appropriate, to protect their rights and welfare.
Informed consent must be obtained from and documented for each prospective research subject (or the subject’s legally authorized representative) before the subject begins to participate in the research (including any related eligibility testing not conducted solely for clinical purposes), unless the appropriate IRB has approved a waiver or alteration of consent, or waiver of documentation, as described in Part 3 of this OM.
Informed consent is not a single event or document, but an ongoing process that takes place between the investigator (or other key personnel, as appropriate) and the research subject. Informed consent requires full disclosure of the nature of the research and the subject’s participation, adequate understanding on the part of the subject (or the subject’s legally authorized representative), and the subject’s voluntary decision to participate.
The PI is responsible for ensuring that each potential subject understands the nature of the research and participation in the project and gives his or her informed consent to participate. Although the PI may delegate responsibility for part or all of the consent process to co-investigators or research staff, the PI remains responsible for ensuring each subject has been properly consented.
The Office of Human Research Protections (OHRP) outlines the key information (elements of informed consent) that must be conveyed to subjects as part of the informed consent document and process (45 CFR 46.116). The informed consent process and informed consent document must contain at least the basic elements as listed below:
i. A statement that the study involves research
This includes explaining the purposes of the research and any procedures that the subject will undergo and specifying which procedures are experimental (e.g., a new drug, extra tests, non-standard methods of management such as randomizing the subject to a treatment or placebo arm). The statement must describe how much time the subject can expect to devote to the study (e.g., how long will study visits or research-related procedures take, what is the total expected length of participation after enrollment).
ii. A description of any reasonably foreseeable risks
This includes any reasonably foreseeable risks, discomforts, inconveniences, and harms associated with the research activities. These risks should not be understated nor glossed over. If additional risks are identified during the course of the research project, the IRB must be informed. In such cases, the IRB may require revisions to the consent process and document(s), and may require subjects previously consented to be re-contacted and informed about the new risks. The IRB must approve any protocol or consent revisions and any proposed communication to subjects about these revisions.
iii. A description of any benefits to the subject
Subjects must be provided with information about any benefits that may reasonably be expected from the research, either to them individually or to society at large. If there is no reasonable expectation of direct benefit, the subject must be informed. Payments for participation may never be listed as benefits of the research.
iv. A disclosure of appropriate alternative treatment
To ensure subjects can make an informed choice about participation in the research, appropriate alternatives to participation that might be advantageous to subjects must be described, where applicable. For example, in a drug study, the medications being studied may be available outside the research study from a physician without the need to participate in the research. Investigators should be reasonably specific in describing the nature and type of available alternatives.
v. A statement describing the protections to privacy and confidentiality
Subjects must be told the extent, if any, to which individual privacy and confidentiality of research records that may identify them will be maintained, and who will have access to those records. For example, sponsors, funding agencies, regulatory agencies, and IRBs and other institutional officials may review research records. If a study involves the collection, use, or disclosure of protected health information, it will be regulated not only by the Common Rule but also by privacy regulations promulgated under the Health Insurance Portability and Accountability Act of 1996 (HIPAA) as well as special policies and standards required by the covered entity (e.g., health care provider, health plan, or clearinghouse) where the information originated.
vi. For research involving more than minimal risk, a statement addressing research related injury
For research involving more than minimal risk, the consent process must provide an explanation as to whether any compensation or treatment will be provided to an injured subject (injury in this context refers both to physical injuries and to less tangible injuries, such as injury to reputation or legal rights). If so, the compensation and treatment should be described, or the subject should be told where to find additional information. In no event may the consent process or the documentation of consent include exculpatory language (e.g., requiring subjects to give up legal rights to which they otherwise would be entitled, such as the right to sue in case of an adverse response to a study intervention).
vii. An explanation of whom to contact for questions or concerns
Subjects must be informed about whom to contact for answers to pertinent questions or concerns about the research or their rights as research subjects, as well as whom to contact in the event of a research-related injury, if injuries are foreseeable. Specifically, they should be told how to contact the researchers and whom they can contact if they cannot reach or do not want to speak with the researchers. They also should be told how to lodge a complaint (e.g., by contacting the IRB office or the VPR or, in the case of a privacy concern, the Privacy Official). Subjects may file an anonymous complaint using the University’s Compliance Hotline.
viii. A statement that participation is voluntary
Subjects must be specifically informed that participation in a project is on a voluntary basis; that they may discontinue participation at any time; and that no penalty will be imposed, and no rights to which they would otherwise be entitled be waived as a result of refusal to participate in the research or later withdrawing from the research.
- The consent form must be approved in advance by the IRB.
- In some cases, the IRB may approve a waiver or alteration of consent, or waiver of documentation, as described in Part 3 of this OM. A waiver of documentation means that the potential participant is provided all of the information required for informed consent but is not asked to sign a consent form.
- Verbal and written information must be conveyed in language that is understandable to the subject or the subject’s legally authorized representative.
- Investigators must ensure that consent is sought only under circumstances that minimize the possibility of coercion or undue influence. For example, subjects must be given a sufficient opportunity to determine whether or not to participate in the study. It is therefore desirable to allow some time between initial discussion of the opportunity to participate in the research and the final decision, as recorded in the consent document.
- Each subject (or a subject’s legally authorized representative) must be provided with a copy of the consent document at the time of consent, unless the IRB specifically has waived this requirement. This need not be a signed copy.
In limited circumstances, (e.g., for illiterate or non-English speaking subjects), the IRB may approve use of a “short form” consent process. This method of consent is typically used in clinical settings. In the “short form” consent process, the required elements of informed consent normally presented in writing are presented orally to the subject or subject’s legally authorized representative.
Requirements for using “short form” consent:
- The IRB must approve a written summary of what is to be said to the subject or representative;
- A witness must be present at the oral presentation;
- The witness must sign both the short form and a copy of the summary;
- The person obtaining consent must sign a copy of the summary;
- Copies of both the short form and the summary must be provided to the subject or representative.
Signed consents must be retained for:
- At least three (3) years after completion of the research (six (6) years if protected health information will be used or disclosed in connection with the study in accordance with HIPAA requirements); or
- Longer if required by institutional policy or applicable sponsor agreements or regulations.
Investigators conducting research in health care settings are encouraged to retain original duplicates of informed consent documents in both the research record and the regular medical record to ensure compliance with the health care organization’s and research documentation requirements. Depending on the circumstances of the study, they may also be required to maintain documentation of HIPAA-compliant authorization.
An IRB must review and approve all research activities that meet the definition of human subjects research before they are initiated, unless an IRB has determined that the activities are exempt from IRB oversight (see Part 4 of this OM for additional details). Prior IRB approval is also required for pre-research activities such as access to databases containing private information and screening data for possible recruitment and enrollment. IRB approval for exemption is necessary, but not sufficient in such cases; the PI must also comply with other policies, at the University or otherwise, governing access to such database. For example, access to a University of Michigan database would typically require permission of the University data steward as well as the creation of a Memorandum of Understanding setting forth the terms and conditions applicable to use of that database for approved research purposes.
For non-exempt research, the IRB is also responsible for review and approval of continuing review, progress reports, change of protocol, adverse event reporting, Other Reportable Information or Occurrence (ORIO) reporting, monitoring and record keeping. Researchers must at all times cooperate with the IRB in fulfilling its responsibilities.
(a) PI Obligations Before IRB Approval
i. IRB Submissions
The PI is responsible for the content of all submissions (e.g., initial review, continuing review, adverse event reporting, ORIO reporting, progress reports) to the IRB and other review units and for ensuring that those documents are submitted in a timely manner, as required by the IRB or other review unit. The PI must include on the IRB application all key personnel who contribute to the scientific development or execution of a study in a substantive, measurable way.
ii. Responding to IRB Requests for Information
To assist the IRB in fulfilling its responsibilities, researchers must provide all information requested by the IRB in a timely fashion.
(b) PI Obligations After IRB Approval
i. Adhering to Approved Protocol
Researchers must conduct research as specified in the IRB-approved protocol and must comply with all IRB determinations, including directives to terminate participation in designated research activities.
ii. Changes to Research
Any proposed changes in the research must be submitted to the IRB via an amendment application and approved in advance by the IRB unless necessary to eliminate apparent immediate hazards to subjects. Similar requirements apply for other review units (e.g., Investigational Drug Service, Radiation Safety Committee, etc.) responsible for oversight of research activities. Investigators must promptly report to the IRB any additional risks that are identified during the course of the research project.
iii. Continuing Review
PIs are responsible for monitoring their approval periods and submitting a continuing review application in a timely manner so as to permit the IRB to review and issue an approval prior to expiration of the study.
iv. Lapse of IRB Approval
If IRB approval for a study lapses for any reason, even if the investigator submitted an application for review in a timely manner and promptly responded to any requests for clarifications or changes, the research must stop until the IRB issues its formal approval or determines that it is in the best interest of individual subjects to continue participating in the research interventions or interactions.
v. Reporting to the IRB
Investigators must promptly report to the IRB any of the following:
- Unanticipated problems involving risks to subjects or others, such as an adverse event or exposure of a member of the research team to a harmful substance;
- Potential noncompliance with applicable laws or regulations or IRB requirements, whether by investigators, research staff, or others, even if the noncompliance was unintentional or was discovered in the course of quality assurance or quality improvement activities;
- Disapprovals, suspensions, or terminations of the project by any University or non-University review units or agencies (e.g., the Investigational Drug Service (IDS) or Institutional Biosafety Committee (IBC), or the IRB at another performance site, or a regulatory agency such as the National Institutes of Health (NIH), Food and Drug Administration (FDA), or National Science Foundation (NSF).
vi. Audits and Inspections
Investigators and research staff are expected to cooperate with:
- Internal evaluations, inspections, and audits performed by authorized internal oversight authorities, including the IRBs, the Office of Human Research Compliance Review (OHRCR) and the Office of University Audits;
- External reviews (e.g., by industry sponsors or government agencies such as the FDA or NIH Office of Research Integrity). Any external investigation, inspection, or other external review and its outcome must be reported to the IRB responsible for the research in question. Researchers should consult with their administrators, the IRBs, as appropriate, the University of Michigan Office of Research (UMOR), and/or the Office of the Vice President and General Counsel for assistance and representation.
Financial conflicts of interest relating to human subjects research must be disclosed. Such conflicts of interest are not inherently wrong, and as long as they are disclosed and appropriately managed or resolved, they do not distort and can benefit the research process. A conflict of interest may arise when a faculty or staff member has a relationship with an outside organization that puts the faculty or staff member in a position to influence the university's decisions in ways that could lead directly or indirectly to financial gain for the faculty or staff member or his or her family, or give improper advantage to others to the detriment of the University.
The University and individual academic units have established mechanisms to identify and manage potential conflicts, including annual disclosure requirements, research and sponsored project application questions, and informal communications. For detailed information about the University’s conflict of interest and commitment policies, see the Conflict of Interest Policies website.
An investigator who believes he or she or other members of the research team may have a conflict that has not otherwise been disclosed should consult with the appropriate conflict of interest committee for guidance to determine whether the conflict is reportable and, if so, how it might be managed (see Part 9 of this OM for additional information).
Certain clinical studies involving human subjects must be registered on and have results posted in ClinicalTrials.gov. For a full description of ClinicalTrials.gov requirements see Part 11 of this OM.
When conducting research involving FDA-regulated products, researchers must comply with all applicable FDA regulations and fulfill all investigator responsibilities or all sponsor-investigator responsibilities, as applicable. Refer to Part 8 of this OM for a description of the circumstances under which human subjects research studies become subject to FDA regulations.
Investigators have additional responsibilities when studies are required to follow guidelines of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP). Guidance on ICH-GCP is included in Part 11 of this OM.