Special and Vulnerable Populations

• Pregnant Women and Fetuses (45 CFR 46 Subpart B)
  • Lack of adequate research involving potential risks that could be imposed to both the fetus and woman. These risks could be while pregnant or long term risks.
• Prisoners (45 CFR 46 Subpart C)
  • Prisoners are at an increased risk of coercion into participation in a clinical trial and researchers must ensure that their participation is Prisoners who are competent have the fundamental right to decide whether or not to participate in research. Investigators must ensure that prisoner participation will not affect their parole status in any way.
• Children (45 CFR 46 Subpart D)
  • By definition, children are unable to provide informed consent to participate in research, although they may be able to give their assent. If children are able to give assent, investigators must provide information about the investigation in a way that matches the child’s level of comprehension.

The classification of a participant into a vulnerable population should not be an exclusion criteria in terms of study enrollment. The study team shall make plans to correctly enroll these individuals and work with their IRB of record. Legislation is in place as a safeguard. This ensures that enrollment of these participants into research studies are done so in a legal manner while providing adequate protection to these populations.

In addition to adhering to standard IRB approved guidelines for obtaining informed consent, there are some additional elements investigators should be aware of when obtaining informed consent. The investigator should go through the informed consent form in its entirety and ensure that approval is obtained. The enrollment note should still be completed as a way of documenting the informed consent, but may need to include possible modifications that need to be made in order to comply with the appropriate subpart. If applicable, the investigator should also check if the IRB has additional requirements regarding a third party/non-biased witness involved in the consent.

Prior to beginning the procedure, informed consent must be obtained. However, for children parental consent will be required and if appropriate assent as well. Assent is defined as a child’s affirmative agreement to participate in the research study. Federal guidelines do not set a specific age where assent is possible as it can vary based on the research being done. The investigator must relay information about the research procedure as well as possible risks and benefits in a way compatible with the child’s comprehension and ability to understand. The IRB (Institutional Review Board) determines whether assent can be obtained based on the age, maturity, and psychological state of the children involved (21 CFR 50.55–https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50/subpart-D/section-50.55).

If the child turns 18 during the course of the study, the informed consent must be completed in order to reaffirm their willingness to continue their participation in the study.

For research involving children, the following approval criteria must be satisfied:

• The research must not involve greater than minimal risk to the
• If the research involves more than minimal risk it must offer a direct benefit or contribute to the well being of the child.
• If the research presents a minor increase over minimal risk but does not provide direct benefit or contribute to the well-being of the child, the research can only be approved if it meets the following sub-criteria:
  • The risk is measured as a minor increase
  • The intervention or protocol is appropriate regarding the subject’s
  • The intervention or protocol is likely to yield important, generalizable knowledge about the disorder or disease.

The HHS (U.S. Department of Health and Human Services) defines a prisoner “as an individual involuntarily confined or detained in a penal institution. The term intends to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provides alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment , trial, or sentencing.” (45 CFR 46.303(c)–https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-C/section-46. 303#p-46.303(c)).

For research involving prisoners, the following approval criteria must be satisfied:

• The research under review must fall under one of the following categories under 45 CFR 306(a)(2)–https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-C/section-46.306#p-46.306(a)(2)
• Any incentives such as food or medical care given to the subject n as a result of their participation in the research should not interfere with their ability to weigh the risks of the research.
• The potential risk must be commensurate with risks that would be encountered by non-prisoners.
• The information must be presented in a language comprehensible to the
• The procedure for participant selection must be fair to all
• There must be a clear assurance that the state parole boards will not take a prisoner’s participation into research when determining parole.

Additional criteria used to classify a prisoner include:

• Individuals that are detained in a residential facility for court-ordered substance abuse as an alternative to criminal prosecution or incarceration.
• Individuals that have psychiatric illnesses that have been committed voluntarily to an institution as an alternative to criminal prosecution or incarceration.
• Parolees that are detained at a treatment center as a condition of

The following criteria do not classify individuals as prisoners; however, they are commonly misinterpreted.

• Individuals that are receiving non–residential and court ordered substance abuse treatment that are living in the community.
• Individuals that have been voluntarily committed to an institution for psychiatric illness
• Individuals that have been civilly committed to non-penal institutions for psychiatric illness treatment because their conditions make them a danger to themselves.
• Probationers or individuals wearing monitoring

If a research participant becomes a prisoner during the course of the clinical investigation, the investigator must notify the IRB immediately and suspend any research interventions with the subject. If the investigator asserts that the participant should still be enrolled in the study for their own personal best interest, the subject can continue to participate until the 45 CFR part 46 Subpart C (https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-C) has been satisfied. The investigator must still notify the IRB for re-assessment of the study.

For research involving pregnant women and fetuses, the following approval criteria must be satisfied:

• Preclinical studies on pregnant animals and clinical studies on nonpregnant women have been conducted and provide data to assess the level of risk on a pregnant human
• If there is any risk to the fetus from the intervention, the study can continue if there is direct benefit to the woman or fetus.
• Any risk is least possible for achieving the full objectives of the
• The individual is fully informed regarding the potential of both current and future risks to the fetus or neonate.