University of Washington
Human Subjects Manual

VI. Special Research Subject Populations

Research with minors - Research with pregnant women and fetuses - Research with prisoners
Research with subjects who are not competent to provide consent - Research involving subjects with reproductive potential
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1. Research with minors

   Research involving persons below the legal age of consent is important for the health and well-being of all children, and may be conducted by faculty, staff, and students of the UW provided the Human Subjects Review Committee (and where applicable, those of its affiliated institutions where such research will be performed), has determined that:
   

   1. studies, where appropriate, have been conducted first on animals, adult humans, then on older children, before involving infants;
   2. risks are minimized by using the safest procedures consistent with sound research design; and
   3. adequate provisions are made to protect the privacy of subjects and their families, and to maintain confidentiality of data.
   
   
   1. Permission of Children and Parents or Guardians
      
      
      1. Adequate provisions must be made for soliciting and documenting the assent of children prior to their involvement as research subjects.

         "Assent" in this context means the child's affirmative agreement to participate, not merely the absence of his or her objection, after adequate explanation. This differs from the term "consent," which indicates voluntary participation by a person of legal age and competency who is able to exercise free power of choice based on complete information. Assent must be obtained from any child who might reasonably be expected to comprehend the nature of his or her involvement in the research, regardless of age but at least by seven years. Research protocols should include forms for documentation of assent of subject children. Simplified written forms are recommended for children of seven years and over, and forms documenting oral assent for those under seven years or otherwise incapable of utilizing written forms.

         The only exceptions to this requirement for assent of the child are: a) when the subject is incapable of comprehension or communication of understanding and assent or b) when the research intervention holds out a clear prospect of direct benefit that is important to the health or well-being of the child and is available only in the context of the research. In these cases, assent should not be offered. Under all other circumstances, a child's objection to participation in research shall be binding.

      2. Permission of the parent or legally appointed guardians must be documented. Permission of one parent is sufficient only when one or more of the following conditions apply:
         
         1. the risk of physical or psychological damage is minimal -- minimal risk is defined here as not exceeding that normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy children;
         2. where the intervention holds out the prospect of direct benefit for the individual subjects or represents a monitoring procedure required for the well-being of the subjects;
         3. one parent is deceased, unknown, incompetent, or not reasonably available, or the child has a guardian or belongs to a single parent family, where only one person has legal responsibility for the care, custody, and financial support of the child.
         
         
      3. When parents of research subjects are under the legal age of consent, their consent alone may be considered sufficient where they are "emancipated minors," i.e., where they are maintaining their own residence and exercising primary economic and social control of their own and the child's life. When the parents of the child are dependent upon others for support, then consent of those exercising ultimate economic and social control of the child's life must also be obtained.
         
         
      4. When the research involves the diagnosis or treatment of diseases related to reproductive health, minor subjects aged fourteen and older and subject to the laws of the state of Washington may consent to their involvement in the research without the permission of their parents.
         
         
      5. The Human Subjects Review Committee may waive the requirement for consent of parents or guardians when a research protocol is designed for conditions where such permission is not a reasonable requirement, provided an appropriate mechanism for protecting the subjects is substituted. Examples might include some research involving abused or neglected children, or high school and college students engaged as subjects in classroom projects involving minimal risk. One alternative which may be used under these circumstances is the appointment of a social worker, physician, nurse, school authority, or other individual to act as surrogate parent. A person so appointed would be expected to participate not only in the process of solicitation of the child's assent, but also in the conduct of the research, in order to provide reassurance for the subject and to intervene or support the child's desire to withdraw if participation becomes too stressful.
      
      
   2. Degree of Risk Involved
      
      
      1. Research on children which involves more than a minimal risk (as defined in section VII..P) may be conducted when it holds out the clear prospect of direct benefit to the individual subjects, or contributes to their well-being. The degree of risk involved under these circumstances must be justified by the anticipated benefit to the subjects, and the relation of anticipated benefit to such risk is at least as favorable to the subjects as that presented by available alternative approaches.
         
         
      2. Research on children involving more than minimal risk, which does not hold out the prospect of direct benefit for the individual subjects, may be conducted when the degree of risk represents a minor increase over minimal risk and when one of the following circumstances apply: 1) the degree of risk involved is reasonably commensurate with that ordinarily experienced by the subjects by virtue of being treated for their specific disorder or condition; 2) the anticipated knowledge is likely to be of substantial benefit to another family member, or is likely to yield generalized knowledge about the subject's disorder or condition which is of vital importance for understanding or ameliorating that disorder or condition in others.
         
         
      3. Research that cannot be approved under the guidelines of the preceding paragraphs because of the substantial increase in degree of risk or for other reasons may be conducted only after: 1) the Human Subjects Review Committee has determined that such research presents an opportunity to understand, prevent, or ameliorate a serious problem affecting the health or welfare of children; and 2) the Secretary of the DHHS or his or her designate, after consultation with a panel of experts in pertinent disciplines, has reached a similar conclusion; and 3) that the proposed research will be conducted in accordance with basic ethical principles, with adequate provisions for soliciting the assent of children and the permission of their parents or guardians.
         
      
      
   3. Special Custodial Circumstances
      
      
      1. Children who are wards of the State should not be involved in research involving more risk than that normally encountered in the lives of healthy children, unless 1) such research is related to their social status as orphans, abandoned children, or the like, or to their medical status, such as blind or mentally retarded; or 2) the research is conducted in a group setting, such as a school, wherein the majority of subjects are not wards of the State. Under either of these circumstances an advocate for each child must be appointed, with an opportunity to intercede that would normally be provided by parents. One individual may serve as advocate for more than one child, but no advocate may be used who is an employee of the institution responsible for the research.
         
         
      2. When children reside in treatment facilities, in foster homes, or other custodial circumstances where they are in the care of persons with the right to act in loco parentis, and when the parents are not available, an advocate shall be appointed for each child. Permission for participation in research under these circumstances must be granted by any individual acting in loco parentis, in addition to the advocate. Conditions governing assent of the child shall be the same as for other children as outlined above.
         
   
   
2. Research with pregnant women and fetuses
   
   

   No research activity involving pregnant women as subjects may be conducted unless:
   

   1. appropriate studies on animals and non-pregnant individuals have been completed;
   2. except where the purpose of the activity is to meet the health needs of the mother or the particular fetus, the risk to the fetus is minimal and, in all cases, is the least possible risk for achieving the objectives of the activity;
   3. individuals engaged in the activity will have no part in:
      
      1. any decisions as to the timing, method, and procedures used to terminate the pregnancy, and
      2. determining the viability of the fetus at the termination of the pregnancy;
         and
   4. no procedural changes which may cause greater than minimal risk to the fetus or the pregnant woman will be introduced into the procedure for terminating the pregnancy solely in the interest of the activity. No inducements, monetary or otherwise, may be offered to terminate pregnancy for purposes of the activity.

   Research on pregnant women may be conducted only if the woman and the prospective father are legally competent and have given their informed consent after having been fully informed regarding possible impact on the fetus. The father's informed consent need not be secured if:
   

   1. the purpose of the activity is to meet the health needs of the mother;
   2. his identity or whereabouts cannot reasonably be ascertained;
   3. he is not reasonably available; or
   4. the pregnancy resulted from rape.

   Research on fetuses in utero may be conducted if:
   

   1. the purpose of the activity is to meet the health needs of the particular fetus and the fetus will be placed at risk only to the minimum extent necessary to meet such needs, or
   2. the risk to the fetus imposed by the research is minimal and the purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means.

   If a fetus ex utero has been found to be viable, it may not be involved as a subject unless:
   

   1. there will be no added risk to the fetus resulting from the activity, and the purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means, or
   2. the purpose of the activity is to enhance the possibility of survival of the particular fetus to the point of viability.

   A nonviable fetus may be involved as a subject in an activity covered by this subpart if:
   

   1. vital functions of the fetus will not be artificially maintained,
   2. experimental activities which of themselves would terminate the heartbeat or respiration of the fetus will not be employed, and
   3. the purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means.

3. Research with prisoners

   Research involving prisoner subjects always requires Human Subjects Review Committee review, unless all of the information to be used by investigators is within the public domain. Research with prisoners that involves more than minimal risk has essentially been prohibited by Federal regulations.

   Research involving prisoners is limited to the following areas:
   

   1. study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects;
   2. study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the subjects.

   Research may also be conducted on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis, which is much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults). The Human Subjects Review Committee will refer such applications to the Secretary of the Department of Health and Human Services. The study may proceed only after the Secretary has consulted with appropriate experts including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of his intent to approve such research; or

   Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the subjects may also be conducted. If the study requires the assignment of prisoners to control groups that may not benefit from the research, the Human Subjects Review Committee will refer the application to the Secretary of the Department of Health and Human Services. The study may proceed only after the Secretary has consulted with appropriate experts, including experts in penology, medicine, and ethics, and published notice, in the Federal Register, of the intent to approve such research.

   Any possible advantages accruing to the prisoner through his or her participation in the research, when compared to the general living conditions, medical care, quality of food, amenities and opportunity for earnings in the prison, may not be 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 should be commensurate with risks that would be accepted by non-prisoner volunteers.

   Procedures for the selection of subjects within the prison must be fair to all prisoners and immune from arbitrary intervention by prison authorities or prisoners. Unless the principal investigator provides to the Human subjects Review Committee justification in writing for following some other procedures, control subjects must be selected randomly from the group of available prisoners who meet the characteristics needed for that particular research project.

   The information about the study must be presented in language that is understandable to the subject population.

   Adequate assurance must exist 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.

   Where the Human Subjects Review Committee finds there may be a need for follow-up examination or care of participants after the end of their participation, adequate provision must be made for such examination or care, taking into account the varying lengths of individual prisoners' sentences, and for informing participants of this fact.

   When the Human Subjects Review Committees review applications proposing to include prisoners as subjects, a prisoner advocate will be present for the deliberation.

4. Research with subjects who are not competent to provide consent
   

   When legal incompetents (other than children) and adults unable to give informed consent are to be used as subjects in diagnostic or therapeutic research, the legally responsible adult must sign the consent form giving approval for participation in the activity. Consent by the subject may be desirable, as well, but usually is optional. When neither diagnostic nor therapeutic procedures are involved, the legally incompetent's refusal to participate in non-therapeutic research is binding.

   When there is a question about the competency of an adult who has not been declared legally incompetent, a subject advocate should participate in the consent process. The subject advocate should be able to attest to the subject's apparent understanding of the research or to the probable consent of the subject if he or she were competent. In this latter situation, the anticipated benefit to the subject should clearly outweigh the risks, if they are greater than minimal. Further, if there are any indications that he or she does not wish to participate, then the individual should be excluded from the study.

   The subject advocate should be fully informed about the research and be a party, where possible, to the oral explanation given to the subject. The role of the subject advocate carries with it a shared responsibility for the welfare of the subject. Because of this responsibility, it may be desirable to involve the subject advocate, insofar as practicable, throughout the duration of the procedures or treatment.

   The importance of the subject advocate increases with the risk to the subject. However, the subject advocate is intended as a protection and not as an obstacle in life-threatening situations where there are no alternative forms of treatment. Not all critically ill patients are "incompetent"; therefore an individual who has not been declared legally incompetent may choose to waive the right to a subject advocate by initialing the consent form where the subject advocate would otherwise sign. An investigator will want to consider such waivers very carefully.

5. Research involving subjects with reproductive potential

   It is important to conduct research to be able to detect the effects of gender, where relevant. Therefore, researchers should include equitable numbers of men and women as research subjects. Subjects with reproductive potential (women of childbearing potential and fertile men) should not be excluded from research unless the health of the subject or the integrity of the research would be placed at risk. The decision to enroll subjects of reproductive potential in studies should be made after evaluating the risks demonstrated in studies with appropriate animal subjects, the probably risks to humans, the nature of the disease under study, and the potential benefits of the study results.

   Researchers must counsel subjects of reproductive age to use an active method of contraception or abstinence for as long as there is risk to a fetus. This use may extend beyond the termination of the study, in some cases. Female subjects of reproductive age should have a pregnancy test performed before beginning the study. Researchers may also perform pregnancy testing at intervals throughout the study depending on the nature of exposure to the intervention that poses risk to the fetus. When adolescents are involved in studies as subjects, researchers must take particular care to preserve the confidentiality of information about sexual activity and contraception use when discussing these issues with the adolescents' parents.

   Consent forms used for studies in which there is potential risk to subjects of reproductive age should explain these risks in lay language and should also explain the need for use of contraception.

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   Section VII. Special Topics