This monthly feature presents a variety of questions from clinical trial professionals with answers from WCG Clinical’s expert staff. This issue features advice from Quality Assurance Advisor Yvonne Higgins and Lindsay Abraham, regulatory lead for IRB chairs at WCG’s Western IRB.

Question: When the signature of a parent or legal guardian is required for pediatric research, what is expected in terms of the documentation collected by the investigator to prove that the person accompanying the child and signing the consent is the parent or a parent with sole custody or is a legal guardian? Are legal documents required in all cases where two parents are not accompanying the child? And even then, is legal proof required?

Answer: The requirements for permission of parents or guardians and for documentation of consent are intended by the IRB and federal regulations as an additional safeguard and protection for children and not as an obstruction for researchers. As there is no federal regulatory requirement to provide proof of a parent’s or guardians’ legal authority to consent, IRBs are unlikely to set a requirement. This is consistent with respect to confirming the identity of individuals presenting themselves for inclusion in research. Sponsors or sites may impose their own requirements.

The WCG informed consent template does include the following statements below the signature lines indicating parental permission. Some sponsors choose to include this as a check box “attestation” in the parental permission/consent form.

1st signature line: Signature of adult subject capable of consent, child subject’s parent, or individual authorized under state or local law to consent to the child subject’s general medical care.

2nd signature line: When the IRB requires permission of both parents, the signature line for the second parent includes the statement that the signature is required unless this subject is an adult, the second parent is deceased, unknown, incompetent, or not reasonably available, or the parent providing consent has sole legal responsibility for the care and custody of the child.

The approach to documentation of legal authority to consent may depend on both the research setting and on state law. State laws may vary widely. Investigators should be familiar with state or local law requirements that may be more stringent. When the research is done in a clinical care setting, the practice may already have policies in place that guide the practice of pediatric medicine. At a minimum, the clinician would have established some knowledge of the relationship between the parent and the child, and when in doubt, would have asked for additional information or documentation.

Note that federal regulations require that when research poses greater than minimal risks with no potential benefit to subjects, both parents must give their permission “unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care of the child.”

While there is no regulatory definition for “not reasonably available,” and no federal guidance on how to make the determination, the Secretary’s Advisory Committee on Human Research Protections (SACHRP) concludes that it is “ultimately the responsibility of the investigator to adequately assess, document and decide whether a parent is not reasonably available given the specific facts and circumstances of each situation, including the level of that second parent’s participation in the life of the child.”

In this case, the investigator could include a note to the study file documenting the assessment and decision to allow one parent’s permission to enroll in a study.

To read SACHRP’s recommendations on parental permission, click here: https://bit.ly/2Zf2xwf.

Question: Is it mandatory to update the consent form during a yearly Investigator Brochure update (when the safety updates were already shared with sites via “Dear Investigator” letters), or can the updates wait until the next protocol amendment that requires a consent form update?

Answer: The answer to this question largely depends on what new information is contained within the Investigator’s Brochure update. When the new information is significant, such as new risk or safety information, then the start of the answer to this question is found in 21 CFR 50.25(b)(5), which states that “significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject.”

The question is when, and how. These aspects were addressed by the Secretary’s Advisory Committee on Human Research Protections (SACHRP) in their recently published recommendation titled “New Information Provided to Previously Enrolled Research Subjects.” In this recommendation, SACHRP notes that consent is an ongoing process and that “in some research studies, circumstances arise in which new information becomes available that needs to be shared with subjects as part of this ongoing consent process.”

As noted in the SACHRP recommendation, there is no regulatory requirement that states that the new information must be added to the consent form and the subjects must thereafter reconsent to participation in the research. However, when the information is significant, it must be communicated to subjects, which can be done in several different ways. It may be by providing the information verbally to subjects and documenting the discussion in the research record or by the use of a consent form addendum. However, modification to the existing consent form and reconsent of subjects is often a best practice.

A few key points to consider when determining when and how to provide significant new information to research subjects include:

• Subjects should be provided significant new information as soon as possible;
• The significant new information should also be provided to new subjects that enroll in the research if the study is still open to enrollment;
• It is appropriate to document, by a research record note or consent form (including addendum), that the subjects received the information and thereafter still agree to participation in the research.

Given these points, when there is significant new information that has been provided to investigators via a “Dear Investigator” letter, the most prudent time to provide information to subjects is when the letter is received rather than waiting until the Investigator’s Brochure update. If the consent form has not yet been updated by the time the Investigator’s Brochure has been updated, it would be appropriate to update the consent form at that time rather than waiting until there is a protocol amendment necessitating further consent form updates.

To read SACHRP’s recommendations on providing new information to subjects, click here: https://bit.ly/2ObCM9C.