The IRB has and follows written policies and procedures for identifying and analyzing risks and identifying measures to minimize such risks. The analysis of risk includes a determination that the risks to participants are reasonable in relation to the potential benefits to participants and to society. (AAHRPP Element II.3.A)

Definitions

Risk in the context of human subject research refers to the combination of the probability and magnitude of some future harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary independently and result in risks that range from "high" to "low" depending on whether they are more (or less) likely to occur, and whether the potential harm is more (or less) serious.

Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. [45 CFR 46.102(i); FDA 21 CFR 56.102(i)]. For example, the risk of drawing a small amount of blood from a healthy individual for research purposes is no greater than the risk of doing so as part of routine physical examination.

Other definitions of risk or greater than minimal risk: Regulations, funding agency requirements or guidances applicable to specific situations or populations (e.g., prisoners, children) may refer to different definitions, including definitions of minimal risk. See Other Federal Agencies - Additional Requirements [GUI-42].

 9.1     Steps to Minimizing Risk

Section revised: 7/15/2015  

The IRB has and follows written policies and procedures for identifying and analyzing risks and identifying measures to minimize such risks. The analysis of risk includes a determination that the risks to participants are reasonable in relation to the potential benefits to participants and to society. (AAHRPP Element II.3.A)

These policies and procedures are based on: Common Rule 45 CFR 46.111(a) (1),(2); FDA 21 CFR 56.111(a)(1),(2); VHA Handbook 1200.05.

When reviewing the protocol application submitted by the Protocol Director (PD), the IRB analyzes levels of risk, ensures risks are minimized, and ensures risks are reasonable relative to anticipated benefits, before approving the proposed research.  (See Chapter 14.3.)

Identifying Potential Risks (PD Input)

The PD must describe in the Protocol Application:

      Potential risks to participants, including a scientific estimate of their frequency, severity, and reversibility.

      The statistical incidence of complication and the mortality rate of the proposed procedure, if known.

      The planned procedures for protecting against or minimizing potential risks, including risks to confidentiality.  Two plans are necessary:

                                 i.         One to ensure necessary medical or professional intervention in the event of harm to participants

                                ii.         One to ensure the safety of participants and the validity and integrity of research data.  Data and safety monitoring must be commensurate with risks and the size and complexity of the trials. (See Chapter 9.2 below).

When proposing changes to the research, PDs must submit a Modification form describing the proposed changes and explaining their impact on the level of risk and potential benefits.

Analyzing Levels of Risk (PD Input)

When PDs submit a new Protocol Application, Modification Form, or a Continuing Review Form, they must indicate the level of risk as being:

      Low – including, but not limited to, any minimal risk that does not fit under expedited categories 1-7 (e.g., innocuous procedures such as phlebotomy, urine or stool collection, no therapeutic agent, or safe therapeutic agent such as the use of an FDA approved drug or device)

      Medium – e.g., therapy with chemotherapy, antibodies, or a non-FDA approved potentially toxic drug, invasive procedures such as organ biopsies or catheter procedures, and some studies using biological agents

      High – e.g., novel therapeutic procedures, first-in-humans drug or device studies, some studies using biological agents or recombinant DNA vector studies

Ensuring Risks Are Minimized (IRB Determination)

The breadth of scientific disciplines represented by the IRB membership (see Chapter 6) allows for a critical assessment of research protocols. The IRB considers the overall level of risk to participants in evaluating the proposed research in accordance with the conditions outlined in 45 CFR 46.111(a)(1-7), 21 CFR 56.111(a)(1-7) and the ethical principles outlined in the Belmont Report.  Furthermore, the IRB may consult with additional experts as needed.  [45 CFR 46.111(a)(1)(i),  21 CFR 56.111 (a)(1)(i)]

Before approving a research protocol, the IRB must determine that risks are minimized as follows by:

      Ensuring that the proposed research has a sound research design

-       [45 CFR 46.111(a)(1)(i) , 21 CFR 56.111.(a)(1)(i)]

      The research does not expose subjects to unnecessary risks

-       [45 CFR 46.111(a)(1)(i) , 21 CFR 56.111.(a)(1)(i)] and

      Whenever appropriate, utilizing procedures that are already being performed on the subjects for diagnostic or treatment purposes

-       [45 CFR 46.111(a)(1)(ii), 21 CFR 56.111.(a)(1)(ii)].

 

The IRB examines the research plan, including research design and methodology, to determine that there are no inherent flaws that would place research participants at unnecessary risk.  This includes the risk that research lacking in statistical power may not lead to meaningful results.  Appropriate safeguards can also minimize risk to participants, for example: having an adequate data monitoring plan, or protecting confidentiality by using coded data.  If risks are not adequately minimized, the protocol will not be approved as written. See guidance Evaluating Sound Study Design.

The IRB also considers the professional qualifications and resources (including time, equipment, support services) of the research team to protect participants and minimize potential harm.  Research personnel must have received appropriate training, and clinicians involved in the research must maintain appropriate professional credentials and licensing privileges. 

See Chapter 14.5 and Chapter 15.1.

Potential Risks v. Anticipated Benefits (PD Input)

The Protocol Application requires that the PD describe the potential benefit(s) that may be gained by participants, and how the knowledge gained may benefit the participants, future participants or society. The PD must explain how these potential benefits to the participant or society outweigh the risks inherent in the research.

Potential Risks v. Anticipated Benefits (IRB Determination)

The IRB determines whether the risks of the research are reasonable in relation to the anticipated benefits (if any) to research participants and the importance of the knowledge that may reasonably be expected to result. [45 CFR 46.111(a)(2), 21 CFR 56.111(a)(2), 38 CFR 16.111(a)(2)]

The IRB bases its risk/benefit analysis on the information provided by the PD and by the expertise of its members and consultants who utilize the most current information about the risks and benefits of the interventions involved in the research. 

The IRB considers only those risks that result from the research, and does not consider long-range effects (e.g., public policy implications) of applying the knowledge gained in the research.  The IRB does not consider those risks and benefits that participants would receive even if not participating the research.  [45 CFR 46.111(a)(2) and 21 CFR 56.111(a)(2)]

 

 

 

9.2      Data Monitoring Plan

Section revised: 7/15/2015

The IRB has and follows written policies and procedures for reviewing the plans for data and safety monitoring, when applicable, and determines that the data and safety monitoring plan provides adequate protection for participants.  (AAHRPP Element II.3.B)

To approve research, the IRB must determine that, where appropriate, the research plan makes adequate provisions for monitoring the data to ensure the safety of research participants. (45 CFR 46.111(a)(6), 21 CFR 56.111(a)(6), 38 CFR 16.111(a)(6))

Many studies (e.g., if more than minimal risk) need a Data and Safety Monitoring (DSM) Plan:

      The DSM Plan must be commensurate with the level of risk, size and complexity of the study.

      The DSM Plan might need to include a DSMB or DMC (a data safety monitoring board, or committee – the terms are generally used interchangeably): for example, a DSMB or DMC may be required as part of the monitoring plan by NIH, FDA, other sponsors, or the IRB.

PDs are required to describe a Data Monitoring Plan, if applicable, on the Protocol Application.

See:

      Guidance Data and Safety Monitoring [GUI-P20] - for detailed information on what a data monitoring plan might address, when a data monitoring plan is required , and when a data monitoring board or committee is required.

      Data Safety Monitoring Plans, and Data Monitoring Committees - Decision Chart [GUI-P21]

      Chapter 15.4  - discusses PD responsibilities

      VA requirements VHA Handbook 1200.05, paragraph 29

      Data Monitoring Committees - FDA March 2006 Guidance for Clinical Trial Sponsors

      Data Monitoring Plans and Data Monitoring Committees – NIH and NCI policies:

-       NIH: Policy for Data and Safety Monitoring

-       NIH: Further Guidance On Data And Safety Monitoring For Phase I And Phase II Trials 

-       NCI: Data and Safety Monitoring Guidelines: Essential Elements  

 

Additional Requirements

Additional requirements might apply, depending on the source of support/funding (e.g., Department of Defense, Department of the Navy): see Other Federal Agencies - Additional Requirements [GUI-42].

IRB Review of the Data Monitoring Plan

The IRB primary reviewer reviews the proposed Data Monitoring Plan, and the administration and composition of the monitoring entity, when applicable. If additional expertise is needed, the IRB will seek input from persons with appropriate knowledge.

Continuing Review; Timeframe for Reporting Data Monitoring Findings to the IRB

It is not the role of the IRB to perform data monitoring, but to ensure that appropriate monitoring is taking place, and to review reports from the monitoring entity.

The IRB must ensure that the conditions satisfied in order for initial IRB approval of the research are still satisfied at continuing review. These include, but are not limited to, determinations by the IRB regarding risks, potential benefits, informed consent, and safeguards for participants.  Thus, the PD must include in the continuing review application the outcomes of data and safety monitoring including a summary of adverse events, any unanticipated problems, and any new information pertaining to the research - either from the research itself or from other sources, which have occurred since the previous IRB review. The amount of detail required depends on the type of research being conducted.  In many cases, an appropriate summary would be a simple brief statement that there have been no unanticipated problems and that adverse events have occurred at the expected frequency and level of severity as documented in the research protocol, the informed consent document, and any investigator brochure.

In addition, periodic (usually annual) reports from the monitoring entity are submitted by the PD to the IRB at continuing review. (When a monitoring entity is used, the IRB conducting continuing review of the research may choose to rely on a current statement from the monitoring entity indicating that it has and will continue to review study-wide adverse events, interim findings, and any recent literature that may be relevant to the research.)  

Whether the method of monitoring is by PD oversight or from the establishment of a DSMB, the IRB can tailor a specific timeframe for future reporting of data monitoring findings to the IRB.  The IRB can set the date of continuing review for the protocol as being less then the maximum of a year, if they determine that interim reporting of data monitoring information will serve to better protect participants.  Alternatively, the IRB can request a report after a specific number of participants are enrolled or after a serious adverse event has been reported.

9.3      Risks to Vulnerable Populations

Section revised: 12/07/2015

The IRB has and follows written policies and procedures for determining the risks to prospective participants who are vulnerable to coercion or undue influence and ensuring that additional protections are provided as required by applicable laws, regulations, codes, and guidance. (AAHRPP Element II.4.A)

The IRB is cognizant of the vulnerable nature of many participants. Food and Drug Administration (FDA) regulations and the Common Rule require IRBs to give special consideration to protecting the welfare of vulnerable participants.

In order to approve research involving vulnerable populations, the IRB must determine, where appropriate, that additional safeguards have been included to protect the rights and welfare of participants who are likely to be vulnerable to coercion or undue influence, such as:

      Children (45 CFR 46 Subpart D; 21 CFR 50 Subpart D),

      Prisoners (45 CFR 46 Subpart C),

      Pregnant women, human fetuses, or neonates (45 CFR 46 Subpart B),

      Persons with mental disabilities, or

      Economically or educationally disadvantaged persons

Additional Requirements

Additional requirements might apply, depending on the source of support/funding (e.g., Department of Defense, Department of the Navy, and the Environmental Protection Agency): See Other Federal Agencies - Additional Requirements [GUI-42].

The IRB includes among its members persons who are knowledgeable about and experienced in working with vulnerable participants.  (45 CFR 46.107(a); 21 CFR 56.107(a)).  When a research study involves a vulnerable population not otherwise covered by these policies, the IRB takes steps to evaluate whether additional safeguards have been included in the research to protect the rights and welfare of participants.  

See also Chapter 12.2 for consent procedures for vulnerable populations.

Considerations in Reviewing Research involving Vulnerable Participants

The IRB considers the following elements of the research plan when reviewing research involving vulnerable participants:

      Strategic issues that involve inclusion and exclusion criteria for selecting and recruiting participants; informed consent and willingness to volunteer; coercion and undue influence; and confidentiality of data.

      Group characteristics, such as economic, social, physical, and environmental conditions, to ensure that the research incorporates additional safeguards for vulnerable participants.

      Participant selection to prevent over-selection or exclusion of certain participants based on perceived limitations or complexities associated with those participants.  For example, it is not appropriate to target prisoners as research participants merely because they are a readily available captive population.

      Application of state or local laws that bear on the decision-making abilities of potentially vulnerable populations.  State statutes (as discussed in Chapter 12) often address issues related to competency to consent for research, emancipated minors, legally authorized representatives, the age of majority for research consent, and the waiver of parental permission for research.

      Procedures for assessing and ensuring participants capacity, understanding, and informed consent or assent.  When weighing the decision whether to approve or disapprove research involving vulnerable participants, the IRB verifies that such procedures are a part of the research plan.  In certain instances, it may be possible for investigators to enhance understanding for potentially vulnerable participants.  Examples include requiring someone not involved in the research to obtain the consent, the inclusion of a consent monitor, a participant advocate, interpreter for hearing-impaired participants, translation of informed consent forms into languages the participants understand, and reading the consent form to participants slowly and ensuring their understanding paragraph by paragraph.

      Need for additional safeguards to protect potentially vulnerable populations.  For example, the IRB may require that the investigator submit each signed informed consent form to the IRB, that someone from the IRB oversee the consent process, or that a waiting period be established between initial contact and enrollment to allow time for family discussion and questions. 

For information on the recruitment of vulnerable populations see:

      Observation of the Consenting Process

      Guidance Recruitment

      Human Subjects Research  website

      Chapter 14.4.

 

Children

Children: Under the regulations, children are persons who have not attained the legal age for consent to treatments or procedures involved in the research under the applicable jurisdiction in which the research will be conducted.

The IRB follows the requirements of the DHHS regulations at 45 CFR 46, Subpart D and FDA regulations at 21 CFR Part 50, Subpart D in reviewing protocols involving children.  The IRB makes the findings and determinations required by the DHHS and FDA regulations related to the risks before allowing research involving children to proceed. 

See guidances:

      Additional Protections for Inclusion of Children in Research (OHRP)

      Additional Safeguards for Children in Clinical Investigations (FDA)

      Parental Permission

      Chapter 12.2 for consent requirements for research involving children participants.

 

VA Research Involving Children

Research involving children must not be conducted by VA investigators while on official duty or at VA or approved off-site facilities unless permission has been granted by the Local Medical Center Director. If the permission is granted, the research must be in accordance with applicable Federal regulations pertaining to children as research subjects (see 45 CFR Part 46, Subpart D 46.401 – 46.409). See VHA Handbook 1200.05.

 

Prisoners

Prisoner: Any individual involuntarily confined or detained in a penal institution.  This includes individuals:

      sentenced to such an institution under a criminal or civil statute,

      detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution,

      detained pending arraignment, trial, or sentencing.

DHHS details special protections for research involving prisoners, who due to their incarceration may have a limited ability to make truly voluntary and un-coerced decisions about whether or not to participate as participants in research.

[45 CFR 46, Subpart C].   The IRB will apply the standards of Subpart C to all prisoner research, whether or not DHHS-supported.

 

DHHS-supported research: The IRB must certify to the Secretary (of DHHS), via the Office for Human Research Protections (OHRP) that it has reviewed and approved the research under 45 CFR 46.305; additionally, the Secretary (through OHRP) must determine that the proposed research falls within permissible categories [45 CFR 46.306(a)(2)].

If biomedical or behavioral research is conducted or supported by DHHS, approval must be obtained from the Secretary of DHHS (through OHRP) before commencing research.

Note: OHRP discourages expedited review of any research involving prisoners as participants.

Non-DHHS-supported research:  Certification to OHRP is not required; the IRB substitutes a comparable risk assessment measure in place of the review and approval by the Secretary of DHHS.

Refer to guidance Involvement of Prisoners in Research for:

      Special requirements regarding IRB composition and additional duties

      Categories of permissible research

      Other requirements pertaining to DHHS-supported research

      IRB required findings.

In order to consider research involving prisoners, the IRBs must:

      Ensure a majority of its members are not otherwise associated with the prison(s) involved in the research, and

      Include a prisoner or a prisoner advocate, who can adequately represent the interests of the prisoners, unless the research has already been reviewed by an IRB that included a prisoner advocate.

 

When a previously enrolled research subject becomes a prisoner and the relevant research protocol was not reviewed and approved by the IRB (under 45 CFR 46, Subpart C) the PD should promptly notify the IRB of this event through the IRB Report Form.  The PD should state that all research interactions and interventions with, and obtaining identifiable private information about, the now-incarcerated prisoner-participant will cease until the requirements of Subpart C have been satisfied with respect to the relevant protocol, unless the PD asserts that it is in the best interests of the participant to remain in the research study while incarcerated, in which case the IRB Chair may determine that the participant may continue to participate in the research until the requirements of Subpart C are satisfied. Upon receipt of notification that a previously enrolled research participant has become a prisoner, the IRB should promptly re-review the protocol in accordance with the requirements of Subpart C if the PD wishes to have the prisoner participant continue to participate in the research.


Research Involving Prisoners in California

If the research involves prisoners in a California facility, the IRB must comply with the additional limitations and requirements in California Penal Code Sections 3501 - 3523.  Those provisions limit the types of biomedical research that may be conducted and place additional requirements on other types of research. Guidance Research Involving Prisoners – California Penal Code: Section 3501 – 3523  is referred to when the IRB reviews a protocol involving prisoners in California facilities.

DHHS Conducted or Supported Epidemiologic Research Involving Prisoners as Subjects

Under certain conditions DHHS conducted or supported epidemiologic research may be approvable by the Secretary of DHHS, as outlined in the Federal Register Vol 68 No.119, June 20, 2003.

VA Research Involving Prisoners

Research involving prisoners must not be conducted by VA investigators while on official duty, or at VA-approved off-site facilities unless a waiver has been granted by the Chief Research and Development Officer (CRADO). If the waiver is granted, the research must be in accordance with applicable Federal regulations pertaining to prisoners as research subjects (45 CFR Part 46, Subpart C 46.301 – 46.306).

See VHA Handbook 1200.05 or the VA research website for requirements for requesting a waiver.

 

Decisionally Impaired Participants

The IRB reviews the risk-benefit analysis including the possibilities of coercion and undue influence, and must determine whether such participants should be recruited and whether support mechanisms, such as surrogate consent, are appropriate.  See Chapter 12.2 for more information on the consent process, and criteria for including decisionally impaired participants in research.

Pregnant Women, Human Fetuses, and Neonates

The Department of Health and Human Services (DHHS) details special protections for research involving pregnant women, human fetuses, and neonates.  [45 CFR 46, Subpart B.] 

Under these regulations, the IRB is required to document specific findings to minimize the potential for risk or harm to the fetus, and additional attention must be given to the conditions for obtaining informed consent, in accordance with the guidance Research Involving Pregnant Women, Fetuses, and Neonates.

In general, Subpart B requires that research involving pregnant women, human fetuses, and neonates should involve the least possible risk.  Persons engaged in the research may have no part in the timing, method, or procedures used to terminate the pregnancy, or to determine the viability of the fetus.  No inducements may be offered to terminate a pregnancy.

Four separate conditions, each with their own requirements and IRB determinations, apply to research with pregnant women, human fetuses, and neonates:

            1.         Research Involving Pregnant Women.  No pregnant women may be involved as a participant in research unless either of the following conditions applies:  The purpose of the activity is to meet the health needs of the mother, and the fetus is placed at risk only to the minimum extent necessary to meet such needs; OR the risk to the fetus is minimal.  The mother and the father must be legally competent and provide consent, unless the purpose of the research is to meet the health needs of the mother, or the father is not reasonably available, or the pregnancy resulted from rape.

            2.         Research Directed at Human Fetuses.  The IRB must find that:  the purpose of the research is to meet the health needs of the individual fetus and shall be conducted in a way that will minimize risk; OR the research will pose no more than minimal risk to the fetus, and the purpose of the activity is to ascertain important biomedical knowledge that is unobtainable by other means.  These activities are permitted only if the mother and father are legally competent and have given their informed consent, unless the father is not reasonably available or the pregnancy resulted from rape.

            3.         Research Involving Neonates.  For research involving neonates, the IRB must distinguish between viable and non-viable neonates.  Viable is defined in the regulations as being able to survive to the point of independently maintaining a heartbeat and respiration, given the benefit of available medical therapy.  If the neonate is viable, it is considered a child and may be involved in research to the extent permissible under 45 CFR 46, Subpart D, which is discussed later in this chapter.

      A non-viable neonate may not be involved in research unless all of the following conditions apply:  The vital functions of the neonate are not artificially maintained; experimental activities that would of themselves terminate the heartbeat or respiration are not employed; AND the purpose of the research is development of important biomedical knowledge that cannot be obtained by other means.  Research involving a non-viable neonate is permitted only when both parents have given their informed consent, unless one parent is not reasonably available or the pregnancy resulted from rape or incest.  In the case of non-viable neonates consent by a parents legally authorized representative is not allowed. 

      A neonate of uncertain viability may not be involved in research unless one of the following conditions applies:  There is no added risk to the neonate and the purpose of the research is to obtain important biological knowledge that cannot be obtained by other means; OR the purpose of the activity is to enhance the probability of survival of the individual neonate.  Research involving a neonate of uncertain viability is permitted only if either parent or the parents legally authorized representative gives their permission. 

Non-pregnant women of reproductive potential

Unilateral exclusion of non-pregnant women of reproductive potential from research is not permitted by the IRB.  Exclusion requires compelling scientific justification.  Where such justification exists, it may also be appropriate to exclude men of reproductive potential.

 

VA Research – special requirements

      Pregnant Women: See VHA Handbook 1200.05 for specific requirements.

      Fetuses: Research in which the subject is a fetus, in-utero or ex-utero (including human fetal tissue) must not be conducted by VA investigators while on official duty, or at VA facilities, or at approved off-site facilities.

      In Vitro Fertilization: Research related to in vitro fertilization must not be conducted by VA investigators while on official duty, or at VA facilities, or at approved off-site facilities.

Other Potentially Vulnerable Participants

The context of the research is an important consideration for the IRB when reviewing research that involves other potentially vulnerable participants such as research involving homeless persons, members of particular minority groups, or the economically or educationally disadvantaged.  Research involving significant follow-up procedures or offering significant monetary compensation may unduly influence certain types of participants and the IRB takes such considerations into account.  Nevertheless, research involving these participants is socially important for understanding and eventually improving adverse health and general well-being in these populations.

Employees and Students

Employees, lab personnel, students, and trainees at STANFORD and other facilities under the purview of the IRB are considered vulnerable participants, in particular because of the risk of coercion and undue influence.  The IRB has the same standards for approving research involving these groups as other vulnerable participants.

9.4      Suspension or Termination of IRB approval

Section revised: 3/13/13  

The IRB has and follows written policies and procedures for suspending or terminating IRB approval of research, if warranted, and for reporting these actions, when appropriate.  (AAHRPP Element II.2.G)

Definitions

Suspension:  Temporary withdrawal of IRB approval for some or all research procedures in a protocol or the permanent withdrawal of IRB approval of part of a protocol. Continuing review of the research is still required.  A sponsor-imposed suspension alone does not constitute such a suspension, as it is not an action by the IRB to withdraw approval of a previously approved protocol.  Similarly, an action by the Protocol Director (PD) that halts or materially changes some or all of the PDs protocol as previously approved by the IRB does not constitute such a suspension (but may need to be submitted to the IRB as a protocol modification).

Termination:  Permanent withdrawal of IRB approval of a previously approved protocol. Continuing review of the research is still required.

Suspension or Termination by the Convened IRB

The IRBs have the authority (45 CFR 46.113; 21 CFR 56.113) to suspend or terminate a previously approved protocol (i.e., both from the approval of this policy by the Vice Provost and Dean of Research and through the charge to IRB Chairs and members at the time of their appointment.) 

The IRB may act to suspend or terminate a protocol for any of the following reasons including but not limited to:

      Not conducting research in accordance with IRB requirements

      Unexpected serious harm to subjects.

The IRB Chair shall:

      Notify the PD in writing of it the IRB decision to suspend or terminate its approval along with a statement of the reasons for the IRB action and any terms and conditions of any suspension.

      Report the decision to suspend or terminate to the Vice Provost and Dean of Research and others in accordance with the procedure set forth in Chapter 3.9.

The PD shall be provided with an opportunity to respond in person or in writing to the IRB on a suspension or termination.

If the IRB action in relation to the suspension or termination involves the withdrawal or modification of participation of current participants from the research, the IRB shall direct the PD to contact the participants to:

      Make such notification with an explanation, after its review and approval by the IRB

      Describe any monitoring and follow-up for safety reasons that will be conducted

      Provide contact information for the PD and the IRB where the participant may report any adverse events or unanticipated problems.

 

Suspension or Termination by an Authorized Individual

The following STANFORD officials are authorized to suspend or terminate IRB approval pending review by the IRB responsible for continuing review of the protocol: the Vice Provost and Dean of Research, the Chair of the IRB responsible for continuing review of the protocol, the Director of Research Compliance, and any other STANFORD official who is authorized to take such action by virtue of his or her office or of a policy or procedure of the relevant STANFORD organization.  The STANFORD official who makes a suspension of a protocol shall immediately:

      Notify the PD: (i) to halt the portion of the IRB approved protocol that poses immediate, material risk to participant health and welfare, (ii) of the reasons for the suspension or termination, and (iii) of the opportunity to respond in person or in writing to the official and IRB on the suspension or termination

      Report the suspension or termination and its basis to the IRB.

The IRB staff shall:

      Report the suspension or termination as a suspension or termination of IRB approval to the Vice Provost and Dean of Research and others in accordance with the procedure set forth in Chapter 3.9

      Immediately initiate the appropriate procedure for review of the basis for the suspension or termination (e.g., the procedure for reviewing possible non-compliance or a possible unanticipated problem. See Chapter 3.9, 3.10). 

If the halt in some or all of the protocol involves the withdrawal from the research or modification of participation of current participants, the official or IRB shall direct the PD to contact the participants to:

      Make such notification with an explanation, after its review and approval by the IRB

      Describe any monitoring and follow-up for safety reasons that will be conducted

      Provide contact information for the PD and the IRB where the participant may report any adverse events or unanticipated problems.

 

Protection of Participants Who May Be Affected by the IRB Action

If the suspension or termination will affect participants in the protocol (e.g., requires withdrawal of participants), the IRB shall utilize a process that takes into account the impact on their health and safety.  This should occur before the suspension or termination, when it is feasible and delay will not jeopardize their health and safety.  Examples include:

      Requiring the PD to submit proposed procedures for any withdrawal of participants

      Allowing participants to continue (e.g., treatment with an investigational drug) if the IRB determines that it is in their best interests

      Requiring submittal for review and approval of the IRB or its designee of all communications by the PD to participants about the IRB action

      Designating an investigator other than the PD to be responsible for carrying out the IRB decision

      Requiring the appointment of a new PD or transferring responsibility for participants to another investigator

      Requiring the PD to carry out follow-up or monitoring of participants appropriate to the circumstances (e.g., for any adverse impact on participants after suspension or termination)

      Requiring special reporting (e.g., adverse events or outcomes) concerning participants by the PD.

 

VA Research

Once notified of the suspension, the investigator must immediately submit to the IRB Chair, a list of research subjects for whom suspension of the research would cause harm. The IRB Chair, with appropriate consultation with the VA Chief of Staff, determines if the subject may continue in the research. See VHA Handbook 1200.5 for additional procedures and reporting requirements for suspension or termination of IRB approval for VA research.