SOP 500 Reviews Requiring Special Consideration (SC)
501 Vulnerable Populations
Not every human being is capable of self-determination. The capacity for self-determination matures during an individual's life, and some individuals lose this capacity wholly or in part because of illness, mental disability, or circumstances that severely restrict liberty. Some persons are in need of extensive protection, even to the point of excluding them from activities that may harm them. Other persons require little protection beyond making sure they undertake activities freely and with awareness of possible adverse consequence. Indeed, some types of research may, in and of themselves, create a vulnerable group – that is, the subjects lose their autonomy or are exposed to unknown risks. The extent of protection afforded should depend upon the risk of harm and the likelihood of benefit. The judgment that any individual lacks autonomy should be periodically reevaluated and will vary in different situations.
Potentially vulnerable groups may include:
- Pregnant women and fetuses
- Other vulnerable groups
1.1.1 If an investigator indicates in the study submission that prisoners will participate in the research, or that subjects may reasonably be expected to be incarcerated at some time point during the study, the following additional requirements will apply to IRB review of the project:
A. Local regulations: In addition to meeting federal regulations, the project must comply with local and state requirements for inclusion of prisoners as subjects.
B. IRB composition: A majority of IRB members will have no association with the prison(s) involved; and at least one member shall be a prisoner advocate with appropriate background and experience to serve in that capacity.
C. Additional duties where prisoners are involved: The IRB may review research involving prisoners only if it finds that the following conditions are met:
- The research falls into one of the following categories:
i. The research under review involves solely research on the practices both innovative and accepted, which has the intent and reasonable probability of improving the health and well being of the subjects. In cases where prisoners may not benefit from the research because they are assigned to a control group in a manner consistent with the protocol approved by IRB, the FDA has published notice in the Federal Register of its intent to approve such research.
ii. Research on conditions particularly affecting prisoners as a class (e.g., vaccine trials on hepatitis) provided that the Secretary, HHS, or designee has published notice in the Federal Register of its intent to approve such research.
- Any possible advantages accruing to the prisoner through participation in the research, when compared to the general living conditions, medical care, quality of food, amenities, and opportunity for earnings in prison, are not of such a magnitude that the prisoner's ability to weigh the risks and benefits of the research 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-prison volunteers.
- Selection procedures within the prison are fair to all prisoners and immune from arbitrary intervention by prison authority or prisoners. Unless the Investigator provides the IRB justification in writing for following some other procedures, control subjects must be selected randomly from the group of eligible prisoners for the research project.
- Any information given to subjects is presented in language that is appropriate for the subject population.
- Adequate assurance exists that parole board(s) 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 clinical investigation will have no effect on his/her parole.
- Where there is need for follow-up examination or care of subjects after the end of their participation in the research, adequate provision has been made for such examination or care, taking into account the varying lengths of prisoner sentences, and for informing subjects of this fact.
1.1.2 When Subjects Become Prisoners During a Research Protocol
This policy applies whenever any human subject in a research protocol becomes a prisoner at any time during the protocol, e.g., after the research has commenced. This is necessary because it is unlikely that review of the research and the consent document contemplated the constraints imposed by the possible future incarceration of the subject.
- If a subject becomes a prisoner after enrollment in research, the Principal Investigator is responsible for reporting this situation in writing to the IRB immediately.
- At the earliest opportunity after receiving the Investigator’s notice or otherwise becoming aware of the prisoner status of a subject, the IRB should review the protocol again with a prisoner representative as a member of the IRB. The IRB should take special consideration of the conditions of being a prisoner.
- Upon this review, the IRB can either (a) approve the involvement of the prisoner-subject in the research in accordance with this policy or (b) determine that this subject must be withdrawn from the research.
- Additionally, the IRB should confirm that, when appropriate, the informed consent process includes information regarding when subsequent incarceration may result in termination of the subject’s participation by the Investigator without regard to the subject’s consent.
Research in children requires that the IRB carefully consider consent, beneficence, and justice.
The determination of risk (possible harms) and possible benefit to the child is at the core of the concept of beneficence when considering research in a pediatric population.
Therefore, the IRB must consider the degree of risk and discomfort involved in the research in relation to the direct benefits it offers to the child before it can determine whether or not the IRB has the authority to approve the study.
1.2.1 Determination of risk:
When reviewing research conducted on children, risk is defined in terms of minimal and greater than minimal risk, and may only be approved by the IRB as follows:
|Risk determination||Benefit assessment||IRB action|
|Minimal||With or without direct benefit||Approvable|
|Greater than minimal risk*||Potential benefit to child||Approvable|
|Greater than minimal risk||No direct benefit to individual offers general knowledge about the child’s condition or disorder||Approvable case-by-case*|
|Greater than minimal risk||No direct benefit to child offers potential to, “understand, prevent, or alleviate a serious problem affecting the health and welfare of subjects”||Not approvable**|
* Risk may not be more than a minor increase over minimal risk, consent of both parents required under normal circumstances.
** Approval to proceed with this category of research must be made by the Secretary of the HHS with input from selected experts, and following opportunity for public review and comment.
1.2.2 Children may be subjects of research only if informed consent is obtained from the parents or legal guardian. Children over the age of 7 must agree to participate in the research and provide written assent and separate assent forms should be provided based on reasonable age ranges for comprehension i.e., 7-10, 11-15, 16-18 years of age.
1.3 Pregnant Women and Fetuses
1.3.1 Pregnant women or fetuses prior to delivery may be involved in research if all of the following conditions are met:
A. Where scientifically appropriate, preclinical studies, including studies on pregnant animals, and clinical studies, including studies on nonpregnant women, have been conducted and provide data for assessing potential risks to pregnant women and fetuses;
B. The risk to the fetus is not greater than minimal, or any risk to the fetus, which is greater than minimal, is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus;
C. Any risk is the least possible for achieving the objectives of the research;
D. The woman's consent or the consent of her legally authorized representative is obtained in accord with the informed consent provisions of subpart A of 45 CFR 46, unless altered or waived in accord with Sec. 46.101(i) or Sec. 46.116(c) or (d);
E. The woman or her legally authorized representative, as appropriate, is fully informed regarding the reasonably foreseeable impact of the research on the fetus or resultant child;
F. For children as defined in 45 CFR 46.402(a) who are pregnant, assent and permission are obtained in accord with the provisions of 45 CFR 46 subpart D;
1.3.2 Research involving, after delivery, the placenta, the dead fetus, or fetal material.
- Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any applicable federal, state, or local laws and regulations regarding such activities.
- If information associated with material described in paragraph (a) of this section is recorded for research purposes in a manner that living individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research subjects and all pertinent regulations apply.
1.4 Other Vulnerable Groups
Although federal regulations list vulnerable groups, other vulnerable groups may include mentally impaired persons, employees of the Sponsor or Investigator, terminally ill patients, and the very elderly. The IRB will determine special protections for these groups on a case-by-case basis, taking into account the risks and benefits and other protections afforded by institutional policies and state and federal law.
Cognitively Impaired Subjects:
Studies involving subjects who are decisionally-impaired may take place over extended periods. The IRB should consider whether periodic re-consenting of individuals should be required to ensure that a subject’s continued involvement is voluntary. The IRB may require that Investigators re-consent subjects after taking into account the study’s anticipated length and the condition of the individuals to be included (e.g., subjects with progressive neurological disorders). Additionally, the IRB should consider whether, and when, it should require a reassessment of decision-making capacity.
These policies and procedures apply to all research submitted to the IRB.
3. APPLICABLE REGULATIONS AND GUIDELINES
The Belmont Report
45 CFR 46.111, 46.116
45 CFR 46: Subparts B, C, D
21 CFR 56.111
OHRP IRB Guidebook
4. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
502 Deception and Incomplete Disclosure in Research
Deception and incomplete disclosure can be valuable research methodologies. In social and behavioral research especially, deception and/or incomplete disclosure are often necessary to avoid study bias or test a hypothesis that requires subjects’ misdirection; however, their use presents special challenges to ensure that research is conducted ethically.
The use of deception and/or incomplete disclosure can interfere with the ability of subjects to make fully informed decisions about whether or not to participate in research, and thus research employing these methods requires special consideration by the IRB. In addition to determining if study procedures interfere with subjects’ ability to provide informed consent, and if there is sufficient justification for the use of such measures, the IRB will also evaluate if a debriefing process is necessary, and if so, if it has been adequately developed.
Deception involves an investigator providing false information to subjects or intentionally misleading them about some aspect of the research.
Incomplete disclosure occurs when an investigator intentionally withholds material information about the specific purpose or nature of the research.
For research involving deception or incomplete disclosure
- The study must not present more than minimal risk to the subjects.
- The investigator must demonstrate that the deception/incomplete disclosure is necessary to meet the aims of the research.
- When practical and deemed appropriate, during the informed consent process, subjects should be told that some information is being withheld and will be provided at a specified time.
- Unless impractical or inappropriate, investigators should debrief subjects regarding the deception and/or incomplete disclosure. The debriefing should occur as early as possible, without interfering with the research. The debriefing should take place as early as possible, preferably at the conclusion of the subject’s participation but no later than the conclusion of the research.
- The research must meet the criteria for a modification of the required elements of informed consent.
The policies and procedures apply to all human subjects research involving deception or incomplete disclosure conducted by BYU investigators.
3. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.111
4. REFERENCES TO OTHER APPLICABLE SOPs
503 International/Translational Research
All research proposals that are conducted outside the United States and target non-military, non-U.S. research subjects for enrollment must meet certain criteria before study-related procedures can be initiated. Internet research that may incidentally enroll non-U.S. research subjects are not subject to this policy.
These policies and procedures apply to all BYU staff and IRB members and to research submitted to the IRB. Procedures normally followed outside the United States for research involving human subjects may differ from those set forth in federal and BYU policies. These may result from differences in language, culture, society, history, social norms, or laws. Both the U.S. and host country standards for protecting human participants must be respected during the IRB’s review and approval process and the conduct of the research.
BYU investigators should take special consideration of relevant international and national laws, policies, customs, and other local factors, such as privacy laws, the availability of national health insurance, philosophically different legal systems, and social policies that may make U.S. research forms and procedures inappropriate.
While the BYU IRB does not seek to impose standards for written informed consent documentation that contradict the laws, policies, or customs of other nations, BYU does not relax the standards for ethical conduct of research for a meaningful consent process. In its review process, the BYU IRB makes a reasonable effort to see that the informed consent process is meaningful in terms of local cultural standards and comports with international standards of ethical research.
Investigators should pay special attention to both international and local laws, standards, customs, and to cultural, political, and religious norms in preparing written consent documents or proposing alternative consent processes. Requests to review and waive some standard elements of the consent process or document may be considered by the IRB. Research proposals for which a waiver of written consent may be reasonable should include an explanation of international or local laws, standards, customs, or religious or cultural norms, or other conditions requiring the waiver. The BYU IRB recognizes that cultural, political, or religious norms in some locations may be ethically or morally problematic. In these cases, investigators are responsible to provide explanation of how they will protect the dignity and welfare of all human subjects who participate in the research.
Local Review and Procedures
If a project meets the definition of human subjects research, investigators are required to submit a research application to the BYU IRB and must receive approval prior to conducting the research. In addition to the initial review of these studies, the BYU IRB must also conduct continuing review, review modifications, review complaints, and reportable events, and perform post-approval monitoring.
Before research is conducted at an international site, the investigator is responsible to determine whether the country has laws or guidance related to the protection of human subjects, or laws that otherwise prohibit or restrict the research.
If local IRB or ethical group approval is not reasonably available, the BYU IRB may require that the study is reviewed by an IRB member, consultant, or legal counsel with appropriate knowledge, experience, or expertise in the relevant laws, standards, or customs, or cultural, political, or religious norms, of the location where the research will be conducted. The investigator is expected to provide names of such individuals. The BYU IRB may also seek additional information or answers to questions from the investigators themselves. The BYU IRB has final determination as to which consultant, if any, is selected to provide a review. Even with the best efforts of all involved, clear, definitive statements of local laws and customs as they relate to proposed research projects are sometimes non-existent. In these cases, the BYU IRB seeks to reasonably weigh all available evidence regarding ethical standards in the United States and in the research location.
The policies and procedures apply to all BYU human subjects research conducted full or in part outside of the United States and targeting non-U.S. research subjects
4. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.101(h)
71 Fed Reg 10511 (July 7, 2006)
5. REFERENCES TO OTHER APPLICABLE SOPs
- If required by local laws governing research in the location, IRB approval from an authorized local ethical board or group must be obtained before research begins. In addition, the investigator is responsible for compliance with any relevant local laws.
- Where no local board or group similar to an IRB exists, investigators should use reasonable efforts to rely on local experts or community leaders, if available, to provide explanation as to why local review is not available and consultation about local expectations or guidelines for research involving human subjects. In these cases, the goal is for local community leaders or experts, if reasonably available, to attest to the host country’s standards for human participant protection and to the protocol’s conformity to those standards. When research is conducted in collaboration with local institutions, the IRB may require investigators to provide a letter of cooperation from those institutions.
- Examples of local reviews may include, but are not limited to, the following: Ethics committees; Drug approval agencies; Local ministries; Local governances; Local universities or scholars affiliated with local universities; NGOs, especially those that are familiar with research standards or practices in the location; or Local schools.
- Local IRB approval or other letters of support (as applicable) shall be submitted to the BYU IRB upon receipt. Upon request from the BYU IRB or the BYU Office of the General Counsel, the investigator shall provide reasonable assurances that the research complies with relevant local laws. Research must not commence until all necessary approvals have been obtained.