Change in Subject's Status

Children who turn 18 years of age during a study are now adults and they must re-consent to continue their participation.

• If the study procedures are limited to data analysis, re-consent is not required;
• If any study procedures remain which were required to have informed consent by the IRB, the 18 year old must consented in order to continue participating in the study. The procedures requiring re-consent could include but are not limited to the following:
  • Study visits
  • Continuation of study intervention
  • Study monitoring procedures
  • Collection of data from medical records
  • Use of individually identifiable specimens or data under future use provisions of the informed consent form.

Does this mean that subjects must be re-consented to use data or specimens in a registry or repository?

Yes. If the investigator remains in contact with the subject and data continues to be collected, the subject must re-consent. If there is no ongoing contact, the data and/or specimens should be de-identified by deleting all links between the Master List containing individually identifiable data and the data/specimens.

For a more complete discussion see the Summary of the NIH Conference on The Ethical Use of Pediatric Biospecimens in Research.

Children may be incapable of providing assent because they are too young or the research is too complex. When the IRB has required assent for subjects who are old enough or mature enough to provide it, the investigator is obligated to reassess the subject's capabilities throughout the study.

• When the child reaches an age, maturity and intellectual capacity to provide meaningful assent, then they must be granted the opportunity to assent or dissent from continued participation.

• If the IRB has [*waived the requirement for assent*] for some or all children, then the investigator is still obligated to provide information to the child, appropriate to their level of understanding, throughout the research even if they are not obligated to obtain assent.

Can a child who is now old enough to assent refuse to continue to their participation?

Yes. Respect for children as autonomous persons mandates that the child be permitted to withdraw their voluntary participation in research at any time even if it has a negative impact on the research.

Pregnant women and their fetuses are considered special classes of vulnerable subjects and there are additional protections and requirements for their participation in research. These protections are provided in 45 CFR 46 Subpart B: Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research.

CHOP's FWA requires that the IRB apply the Subpart B protections for all research involving pregnant women and the fetus. IRB SOP 502: Research Involving Pregnant Women, the Fetus and Neonates details the CHOP IRB's policies regarding research covered by Subpart B.

In addition, girls who become pregnant are no longer considered children in the State of Pennsylvania since they may consent for their own treatment.

When children become wards of the state, their continued participation in the research may require the IRB to make additional determinations. See Section V.B of IRB SOP 406: Children in Research for more information about wards of the state and their participation in research.

Can a pregnant woman take part in a survey involving questionnaires?

No. Pregnant women may take part in research only when the IRB has approved the research under Subpart B.

What if it isn't obvious that the woman is pregnant, do we still need to ask?

Most studies that involve interventions or procedures will be required to include questions about possible pregnancy and/or pregnancy tests.

However, if the study involves a simple questionnaire and and it is not obvious that the prospective participant is pregnant, the IRB may, under these circumstances to require the investigator to add this question when it is not appropriate to the research in question.

What do I need to do if a girl becomes pregnant during a study?

There are a number of changes that might be required. The IRB should be contacted as soon as possible to discuss the possible required changes.

1. The event must be reported as an unanticipated problem to the IRB, unless it is included as an anticipated event in the study protocol (e.g., a study about fertility);

2. If the IRB has not approved the participation of pregnant women, the study intervention should be stopped immediately;

3. If there are no study interventions, the investigator may amend the study and request that the study be approved under Subpart B.

4. If there are any interventions or procedures which could negatively impact fetal development, the subject should be followed until delivery an beyond to ensure that there are no serious adverse events sustained by the fetus (birth defects).

Prisoners are considered to be vulnerable in the research context and may only take part in very limited types of research. The regulatory requirements are enumerated in 45 CFR 46 Subpart C: Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects defines the requirements for all research involving prisoners and in the CHOP IRB SOP 503: Research Involving Prisoners.

For the IRB to even consider whether or not prisoners may take part in research, a prisoner representative must attend the IRB meeting. Since the CHOP IRB does not routinely have a prisoner representative at its meetings, an amendment must be submitted requesting continuation of a subject who becomes incarcerated during the study.

What do I need to if a participant becomes incarcerated during a study?

The investigator should immediately contact the IRB to discuss the appropriate next steps and the event must be reported as an unanticipated problem to the IRB.

• If the IRB has not approved the participation of prisoners, and the investigator believes that it is in the best interest of the subject to continue on an investigational intervention, they may request continued participation. The IRB may grant this request until the study can be amended and approved under Subpart C.

• If the study does not involve any interventions, the subject may remain in the study as long as they will not undergo any study procedures until after release from incarceration;

• The investigator may need to end the subjects participation.

The IRB must provide approval if the investigator wants to continue data collection following a subject withdrawal from an interventional study. If approved, the investigator may ask the subject/family withdrawing from the study whether they wish to provide continued follow-up and further data collection subsequent to their withdrawal from the interventional portion of the study. The discussion with the participant distinguishes between study-related interventions and continued follow-up of associated clinical outcome information, such as medical course or laboratory results obtained through non-invasive chart review, and address the maintenance of privacy and confidentiality of the participant's information. The researcher must obtain the participant's consent for this limited participation in the study (assuming such a situation was not described in the original consent document). The IRB must approve the consent document.

If a participant withdraws from the interventional portion of a study and does not consent to continued follow-up of associated clinical outcome information, the researcher must not access for purposes related to the study the participant's medical record or other confidential records requiring the participant's consent. However, a researcher may review study data related to the participant collected prior to the participant's withdrawal from the study, and may consult public records, such as those establishing survival status.