Stanford University Office of the Dean of Research
Human Research Protection Program (HRPP)
DOMAIN II: RESEARCH COMPLIANCE OFFICE, INCLUDING IRBs
Chapter 9: Risks to Research Participants
The IRB staff and the IRBs systematically evaluate risks to participants and potential benefits as part of the initial review and ongoing review of research. (AAHRPP Standard II-4)
Risk in the context of a human research participant is when any individual who may be exposed to the possibility of injury, including physical, psychological, or social injury, as a consequence of participation as a participant in any research, development, or related activity which departs from the application of those accepted methods necessary to meet his or her needs, or which increases the ordinary risks of daily life. Potential risks in such research include but are not limited to:
· Use of an investigational device
· Use of an investigational drug
· Use of commercially available drugs, reagents or chemicals
· Radioisotopes/radiation producing machines
· Recombinant DNA/biohazardous agents
· Psychological, social, legal or economic well-being.
Minimal risk means that the probability and magnitude of harm or discomfort in the research are not greater in and of themselves than those encountered in daily life or during the performance of routine physical or psychological examinations or tests. (45 CFR 46.102)
9.2 Measuring and Minimizing Risk
The IRBs have the following written policies and procedures for identifying and analyzing potential sources of risk and measures to minimize risk, including physical, psychological, social, legal, or economic risks. (AAHRPP Element II.4.A)
These policies and procedures are based on Common Rule and Food and Drug (FDA) regulations which delineate specific criteria for the approval of research. After the Protocol Director (PD) submits a completed protocol application, the IRBs must analyze levels of risk, ensure risks are minimized, and ensure risks are reasonable relative to anticipated benefits, before approving the proposed research.
See Chapter 14.3.
Identifying and Planning Protection against Risks (PD Input)
The process of identifying risk begins with the New Protocol Application Forms for Regular or Expedited Review. The PD is asked to describe the potential risks to research participants, including a scientific estimate of the frequency, severity, and reversibility. In addition, PDs must report the statistical incidence of complication and the mortality rate of the proposed procedures on the New Protocol Application, if these data are known.
Then the PD must describe the planned procedures for protecting against or minimizing potential risks, including risks to confidentiality. Two plans are necessary:
· One to ensure necessary medical or professional intervention in the event of harm to participants
· One to ensure the safety of participants and the validity and integrity of research data. Monitoring must be commensurate with risks and the size and complexity of the trials.
The risk section of the New Protocol Application also requires that the PD describe the potential benefit(s) to be gained by participants or by the acquisition of important medical knowledge which may benefit future participants. Finally the PD must explain how the potential research benefits to the participant or community outweigh the risks inherent in the research.
IRB procedures require PDs to submit a Revision Application (Documents F.1.g. and F.1.h.) if the research procedures are modified. This form asks if the modification in procedure changes the level of risk to participants. The PD must explain the risk level and benefits on the Revision Application.
Analyzing Levels of Risk (PD Input)
When the PD submits a New Protocol Application, he/she must evaluate the level of risk as being:
· Low (innocuous procedures, e.g., phlebotomy; no therapeutic agent)
· Medium (“safe” therapeutic agent)
· High, which can be further categorized as:
a. Therapy with chemotherapy, antibodies, or a potentially toxic drug
b. Risky procedures (e.g., insulin clamp, organ biopsy)
c. Vulnerable participants (e.g., children, prisoners, pregnant women, economically and educationally disadvantaged, decisionally impaired, and homeless people).
Educational materials delineating these levels of risk are included in the human research educational program that all PD and key staff involved in the research must successfully complete. PDs must indicate the level of risk involved with the proposed research on the initial, continuing, regular, and expedited protocol review forms. IRB staff is available to answer PDs’ questions regarding risk levels as they complete these forms.
9.3 Analyzing Levels of Risk and Ensuring Risks Are Minimized (IRB Determination)
The IRBs consider the overall level of risk to participants in evaluating 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. Before approving a research protocol, the IRB must determine that risks are minimized by:
· Ensuring that the proposed research has a sound research design [45 CFR 46.111(a)(1)(i) and 21 CFR 56.111.(a)(1)(i)]
· Does not expose subjects to unnecessary risks [45 CFR 46.111(a)(1)(i) and 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) and 21 CFR 56.111.(a)(1)(ii)].
The IRB examines the research plan, including research design and methodology, to determine that there are no obvious flaws that would place research participants at unnecessary risk. This includes the risk that the research is so poorly designed or is so lacking in statistical power that meaningful results cannot be obtained. The IRB refers to the following guidance and checklists to document that these concerns are adequately addressed in the protocol: Guidance for Sound Study Design in Clinical Trials (Document F.4.z.); Guidance for Sound Study Design in Non-clinical Research (Document F.4.aa.); Protocol Checklist (D.2.f.iii.); and Presenter Checklist (Document F.5.b.). If the risks are not adequately minimized, the protocol may not be approved as written.
The IRBs are comprised of members with backgrounds in a wide representation of scientific disciplines (Electronic Section E). While the IRB members with scientific backgrounds provide a critical assessment of the research, scientific merit, and feasibility, the IRB consults with additional experts when aspects of research design seem to pose a significant concern. [45 CFR 46.111(a)(1)(i) and 21 CFR 56.111 (a)(1)(i)]
The IRB also considers the professional qualifications and resources (including time, equipment, support services) of the research team to protect and minimize potential harm to participants. The IRB will ensure that clinicians involved in the research maintain appropriate professional credentials and licensing privileges. See Chapter 14.5: Human Resources Protection Resources, and Chapter 15.1: Qualification of Protocol Directors and Research Staff.
Ensuring Risks are Reasonable Relative to Anticipated Benefits (IRB Determination) (45 CFR 46.111(a)(2))
The IRBs analyze research risks to determine if risks to participants are reasonable in relation to potential benefits to participants and to society. (AAHRPP Element II.4.A) After the IRB staff reviews the protocol application for completeness, the IRB staff assigns the protocol to an IRB. The IRB Chair and the designated IRB staff assign a primary reviewer to each protocol. The reviewer is responsible for reviewing the application in detail and preparing summary comments that will be presented to the full IRB. An important part of the primary reviewer’s role is to carefully consider the potential risks and benefits of the proposed research. If necessary, the primary reviewer may request additional information from the PD to help clarify any questions regarding the application.
In order to approve research, the IRB reviews the information provided by the PD on the New Protocol Application and determines if 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.
The IRB develops its risk/benefit analysis by evaluating the most current information about the risks and benefits of the interventions involved in the research, in addition to information about the reliability of this information. 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. [45 CFR 46.111(a)(2) and 21 CFR 56.111(a)(2)]
The IRBs review the plan for data and safety monitoring in research protocols, when applicable, and determine that the plan provides adequate protection for participants. (AAHRPP Element II.4.B) See guidance Data Monitoring Plans.
The IRB requires a Data Monitoring Plan for protocols involving:
· A phase III clinical intervention have a monitoring entity that consists of a data safety monitoring board (DSMB), a data safety monitoring committee (DSMC), or an equivalent reviewing body
· Blinded studies, multiple sites, vulnerable research participants, or high-risk interventions or new, unfamiliar interventions not otherwise categorized as a phase III clinical trial, with a case-by-case determination by the primary reviewer(s) as to the need for a DSMB or alternative
· More than minimal risk.
Examples of a Monitoring Entity are:
· Industry sponsored data monitoring committee (DMC)
· DSMB or a DSMC
· NIH sponsored cooperative group
· Monitoring committee formed by sponsor other than NIH
· Medical monitor
· Independent physician
PDs are required to describe their Data Monitoring Plan, if applicable, on the New Protocol Application. The Data Monitoring Plan must be commensurate with the level of risk, size and complexity of the study. PDs are instructed to consult the guidance Data Monitoring Plans. See also Chapter 15.4.
To approve research, the IRBs must determine that, where appropriate, the research plan makes adequate provisions for monitoring the data to ensure the safety of research participants. As part of the primary reviewer’s assessment of the protocol application, he or she carefully reviews the proposed Data Monitoring Plan, and the administration and composition of the monitoring entity, when applicable. The reviewer ensures that the Data Monitoring Plan includes the appropriate elements, and that reporting is addressed as specified in the guidance Events and Information that Require Prompt Reporting to the IRB.
If the primary reviewer does not have adequate expertise to assess the Data Monitoring Plan or the monitoring entity (if one is specified in the plan), the reviewer is encouraged to consult with individuals with appropriate clinical, scientific or biostatistical expertise.
When a monitoring entity is used, the IRB conducting continuing review of the research may rely on a current statement from the monitoring entity indicating that it has and will continue to review study-wide AEs, interim findings, and any recent literature that may be relevant to the research. Whether the method of monitoring is by the minimum (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 back to the IRB after a specific number of participants are enrolled or after a serious adverse event has been reported.
9.5 Risks to Vulnerable Populations
The IRB staff and the IRBs have the following written policies and procedures for determining the risks to vulnerable populations as defined in applicable federal regulations, and specifically for determining the required risk categories in protocols involving children and prisoners. (AAHRPP Element II.4.C)
The IRBs must be cognizant of the vulnerable nature of many participants. In order to approve research, the IRB must determine that, where appropriate, 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), 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.
When an IRB finds that it regularly reviews research involving such vulnerable participants, the IRB includes among its members persons who are knowledgeable about and experienced in working with these vulnerable participants. (45 CFR 46.107(a))
Food and Drug Administration (FDA) regulations and the Common Rule require IRBs to give special consideration to protecting the welfare of particularly vulnerable participants, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons. Because veterans have a history of obeying orders and making sacrifices, and because some veterans may not have access to other health care, some might consider veterans a potentially vulnerable population.
The IRB is also required to ensure that it has adequate representation on the Board to consider specific kinds of research involving these vulnerable populations in a satisfactory manner.
Elements to Consider in Reviewing Research involving Vulnerable Participants
The IRBs pay special attention to the following elements of the research plan when reviewing research involving vulnerable participants.
1. The IRBs consider 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.
2. The IRBs carefully consider group characteristics, such as economic, social, physical, and environmental conditions, to ensure that the research incorporates additional safeguards for vulnerable participants.
3. Investigators are not permitted to over-select or exclude certain groups based on perceived limitations or complexities associated with those groups. For example, it is not appropriate to target prisoners as research participants merely because they are a readily available “captive” population.
4. The IRBs must be knowledgeable about applicable 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.
5. Just as in providing medical care, research studies that plan to involve any potentially vulnerable populations must have adequate procedures in place 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 IRBs look to see that such procedures are a part of the research plan. In certain instances, it may be possible for researchers 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.
6. The IRBs may require additional safeguards to protect potentially vulnerable populations. For instance, the IRBs may require that the investigator submit each signed informed consent form to the IRB, that someone from the IRB oversee the consent process (see Observation of the Consenting Process, Document C.4.f.ii.), or that a waiting period be established between initial contact and enrollment to allow time for family discussion and questions. See also Guidance on Recruitment (Document F.4.u.) and Chapter 14.4: Recruitment.
Pregnant Women, Human Fetuses, and Neonates involved in Research
The Department of Health and Human Services (DHHS) regulations at 45 CFR Part 46, Subpart B detail special protections for research involving pregnant women, human fetuses, or neonates. Under these regulations, the IRBs are 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 provided in the pink laminated sheet “Research Involving Pregnant Women, Fetuses, and Neonates” (Document D.5.g.).
On the other hand, unilateral exclusion of non-pregnant women of reproductive potential from research is not permitted by an IRB. Exclusion requires compelling scientific justification. Where such justification exists, it may also be appropriate to exclude men of reproductive potential.
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 matters relating to the termination of 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 as outlined below and in Document D.5.g., Laminated Sheet on Research Involving Pregnant Women or Fetuses:
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 IRBs 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 IRBs 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 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 Part 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.
· 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 non-viable neonate or a neonate of undetermined viability is 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.
Research Involving Prisoners
DHHS regulations at 45 CFR 46, Subpart C detail 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. A prisoner is defined as any individual involuntarily confined or detained in a penal institution. OHRP discourages expedited review of any research involving prisoners as participants. During its review, the IRB may consult the Laminated Sheet entitled Guidance on the Involvement of Prisoners in Research (Document D.5.i.).
In order to consider research involving prisoners, the IRBs must:
· Have a majority of its members not otherwise associated with the prison
· 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.
Permitted Research Categories: Under DHHS regulations, prisoners may only participate in the following categories of research:
· Studies (involving no more than minimal risk or inconvenience) of the possible causes, effects, and processes of incarceration and criminal behavior
· Studies (involving no more than minimal risk or inconvenience) of prisons as institutional structures or of prisoners as incarcerated persons
· Research on particular conditions affecting prisoners as a class (providing the Secretary of HHS has consulted with appropriate experts and published the intent to support such research in the Federal Register)
· Research involving practices that have the intent and reasonable probability of benefiting the prisoner participant. If the research involves possible assignment to a control group that may not benefit from the research, the Secretary of HHS must also consult with appropriate experts and publish the intent to support the research in the Federal Register. (45 CFR 46.306)
· Research in which the sole purposes
1. Are
i. To describe the prevalence or incidence of a disease by identifying all cases, or
ii. To study potential risk factor associations for a disease
and
2. Where the institution responsible for the conduct of the research
certifies to the Office for Human Research Protections, DHHS, acting on behalf of the Secretary, that the IRB approved the research and fulfilled its duties under 45 CFR 46.305(a)(2)–(7) and determined and documented that
i. The research presents no more than minimal risk and no more than inconvenience to the prisoner-participants, and
ii. Prisoners are not a particular focus of the research. (67 FR 62432)
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.
If the research is not DHHS-funded, the IRBs substitute a comparable risk access measure in place of the referral to the Secretary of DHHS for consultation with experts.
When a previously enrolled research subject becomes a prisoner and
the relevant research protocol was not reviewed and approved by the IRB in
accordance with the requirements of DHHS regulations at 45 CFR part 46, subpart
C, the PD should promptly notify the IRB of this event through the IRB Report
Form (Document F.2.f.i. and ii.). The PD should state that all research
interactions and interventions with, and obtaining identifiable private
information about, the now-incarcerated prisoner-subject 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 subject
to remain in the research study while incarcerated, in which case the IRB Chair
may determine that the subject may continue to participate in the research
until the requirements of subpart C are satisfied. Upon receipt of notification
that a previously enrolled research subject has become a prisoner, the IRB
should promptly re-review the protocol in accordance with the requirements of
subpart C if the principal investigator wishes to have the prisoner subject
continue to participate in the research.
IRB Required Findings: The following determinations must be made by the IRB before research involving prisoners goes forward (45 CFR 46.305):
· The research under review represents one of the categories of research listed above.
· Any possible advantages accruing to the prisoner through his or her participation in the research, when compared with the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, are not of such a magnitude that his or her ability to weigh the risks of the research against the value of such advantages in the limited choice environment of the prison is impaired.
· The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers.
· Procedures for selecting participants within the prison are fair to all prisoners, and immune from arbitrary intervention by prison authorities or prisoners. Unless the PD provides to the IRB justification in writing for following some other procedures, control participants must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project.
· The information is presented in language that is understandable to the participant population.
· Adequate assurance exists that parole boards will not take into account a prisoner’s participation in the research in making decisions regarding parole, and each prisoner is clearly informed in advance that participation in the research will have no effect on his or her parole. A letter from the appropriate prison authority must be obtained to assure that participation in the research will not be used for parole decisions.
· Where the IRB finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision has been made for such examination or care, taking into account the varying lengths of individual prisoner’s sentences, and for informing participants of this fact.
If the research is DHHS-supported, the IRB must certify these findings to the Office for Human Research Protections (OHRP). Certification to OHRP is not required for research not supported by DHHS. However, the IRB will apply the standards of Subpart C to all prisoner research.
Research Involving Prisoners in California
If the research involves prisoners in a California facility, the IRBs 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. The IRBs comply with those limitations and requirements by consulting the IRBs’ “Guidance on California Requirements Regarding Research Involving Prisoners – Penal Code Section 3501 – 3523” in Document F.4.n. when reviewing a protocol involving prisoners in California facilities.
Research Involving Children
The IRBs follow 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. 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 IRBs make the findings and determinations required by the DHHS and FDA regulations related to the risks before allowing research involving children to proceed. The IRBs refer to guidance provided by the Laminated Sheets on Additional Protections for Inclusion of Children in Research (Common Rule) and Additional Safeguards for Children in Clinical Investigations (FDA) (Documents D.5.a. and D.5.h.). Proposed research must fall within one of four risk-benefit categories.
|
Risk Categories for Research involving Children |
Implications |
|
Greater than Minimal Risk But Presenting the Prospect of Direct Benefit |
· Anticipated benefit justifies the risk · Anticipated benefit is at least as favorable as that of alternative approaches |
|
Greater than Minimal Risk and No Prospect of Direct Benefit But Likely to Yield Generalizable Knowledge About the Participant’s Disorder or Condition |
· Only a minor increase over minimal risk · Likely to yield generalizable knowledge about the child’s disorder or condition that is of vital importance for the understanding or amelioration of the disorder or condition · The intervention or procedure presents experiences to the child that are reasonably commensurate with those in the child’s actual or expected medical, dental, or expected medical, dental, psychological, social, or educational situations
|
|
Research Not Otherwise Approvable Which Presents an Opportunity to Understand, Prevent, or Alleviate a Serious Problem Affecting the Health or Welfare of Children |
· IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children · The HHS Secretary or the Commissioner of Food and Drugs approves, after consultation with a panel of experts in pertinent disciplines (e.g., science, medicine, education, ethics, law) and following publication in the Federal Register and public comment |
A more detailed discussion of the requirements and legal principles relating to parental permission, assent of children, and consent of emancipated and self-sufficient minors are described in the guidance Additional Protections for Inclusion of Children (<18 years) in Research (Document D.5.a.), which is provided to investigators who include children in their research and to IRB staff and members who review those protocols, and in the guidance Parental Permission. Additionally, checklists Soliciting or Waiving the Assent of Children (Document F.4.kk.), and Soliciting or Waiving the Permission of Parents or Guardians (Document F.4.ll.), are used by IRB staff and members to confirm that requirements are met.
Research Involving Decisionally Impaired Participants
Decisionally impaired persons are individuals who have a diminished capacity for judgment and reasoning due to a psychiatric, organic, developmental, or other disorder that affects cognitive or emotional functions. Other individuals, who may be considered decisionally impaired, with limited decision-making ability, are individuals under the influence of or dependent on drugs or alcohol, those suffering from degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps. The policies and procedures for involving such participants in research are discussed in Chapter 12.8.
Research Involving Other Potentially Vulnerable Adult Participants
Employees, lab personnel, students, and trainees at STANFORD and other facilities under the auspices of the IRBs should also be considered vulnerable participants. Thus, the IRBs have the same standards for approving research involving these groups as other vulnerable participants.
The context of the research is an important consideration for IRBs to have in mind when reviewing research that involves other potentially vulnerable participants. Research involving homeless persons, members of particular minority groups, or the economically or educationally disadvantaged pose significant challenges. Research involving significant follow-up procedures or offering significant monetary compensation may unduly influence certain types of participants, and the IRBs take 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.
9.6 Suspension or Termination of IRB approval
The IRB has the following written policies and procedures for suspending or terminating a previously approved protocol if warranted by findings in the continuing review or monitoring process. (AAHRPP Element II.4.D)
Suspension means a temporary withdrawal of IRB approval of some or all of a protocol or the permanent withdrawal of IRB approval of part of a protocol. With a suspension of IRB approval, 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 that halts or materially changes some or all of the PD’s protocol as previously approved by the IRB does not constitute such a suspension (but may need to be submitted to the IRB as a revision to the protocol).
Termination means a permanent withdrawal of IRB approval of a previously approved protocol. With a termination of IRB approval, continuing review of the research is still required.
Procedure for Suspension by an Authorized Individual
The following STANFORD officials are authorized to suspend IRB approval pending review by the IRB responsible for continuing review of the protocol: the Vice Provost and Dean of Research and Graduate Policy, the Associate 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 an 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, and (iii) of the opportunity to respond in person or in writing to the official and IRB on the suspension
· immediately report the suspension and its basis to the IRB.
The IRB staff shall:
· report the suspension as a “suspension of IRB approval” to the Vice Provost and Dean of Research and Graduate Policy and others in accordance with the procedure set forth in Chapter 3.9.l
· immediately initiate the appropriate procedure for review of the basis for the suspension (e.g., the procedure for reviewing possible non-compliance under Chapter 3.9 or a possible unanticipated problem under Chapter 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.
Procedure For Suspension Or Termination By the Convened IRB
The IRBs have the authority to suspend or terminate (i.e., both from the approval of this policy by the Vice Provost and Dean of Research and Graduate Policy and through his charge to IRB Chairs and members at the time of their appointment (see IRB Charge in Documents D.4.a. and D.4.g.)).
The IRBs may act to suspend or terminate under the following procedures and for any of the following reasons but are not limited to them:
· Not conducting research in accordance with the IRBs’ requirements
· Unexpected serious harm to subjects.
The IRB chair shall:
· notify the PD in writing of it’s the IRB’s decision to suspend or termination its approval along with a statement of the reasons for it’s the IRB’s actions and any terms and conditions of any suspension.
· report its decision to suspend or terminate to the Vice Provost and Dean of Research and Graduate Policy and others in accordance with the procedure set forth in Chapter 3.9.l.
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.
9.6.1 Protection of Participants Who May Be Affected by the IRB’s Action
If the suspension or termination will affect participants in the protocol (e.g., requires withdrawal of participants), the IRBs 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’s 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.