The new article provides additional details regarding the parental/guardian permission to be obtained before commencing an investigation, and also regarding the supporting data a study sponsor shall provide.
The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to ethical considerations for clinical investigations for medical devices involving children. The document describes in detail the regulatory approach to be applied for clinical trials where the involvement of children is vitally important to ensure all the safety- and performance-related matters are duly addressed. In particular, the authority emphasizes the specific nature of such studies and highlights the key points to be considered in this respect. It is important to mention that the guidance document is non-binding in its legal nature, nor is intended to introduce new rules or impose new obligations, but rather to provide additional clarifications regarding the existing regulatory requirements, as well as recommendations to be followed by medical device manufacturers and study sponsors to ensure compliance thereto. The authority also mentions that an alternative approach could be applied, provided such an approach is in line with the respective legislation and has been agreed with the authority in advance.
The scope of the guidance covers, inter alia, the aspects related to the parental/guardian permission to be obtained before the study will be commenced. In this respect, the regulation states the following:
- A clinical investigator must obtain permission from the parent(s) or guardian(s) when a child is enrolled in a clinical investigation (21 CFR 50.55(e));
- The parental/guardian permission form must address the required elements of consent, as well as appropriate additional elements (21 CFR 50.25) to allow the parent(s) or guardian to make an informed decision.
The authority also mentions that before the commencement of a study, all the parties involved, including parents, guardians, and assenting children should be able to ask questions related to the participation in the investigation and receive additional information in the course of a study upon request.
As further explained by the FDA, assent means a child has provided an affirmative agreement to participate in a clinical investigation; mere failure to object should not be construed as assent (21 CFR 50.3(n)). Thus, according to the existing regulatory requirements, a study sponsor shall duly take all the steps necessary to ensure assent unless it cannot be provided. Under the general rule, it is presumed that children over 7 years old can provide assent, however, the decision will depend on numerous factors and should be taken on a case-by-case basis.
At the same time, it is important to mention that the legal nature of an assent to be provided by a child concerning participation in a trial is slightly different from the informed consent to be provided by an adult participating in an ordinary investigation. In particular, an institutional review board (IRB) may determine that a study can be commenced even without an assent obtained in case of the child is reasonably incapable to provide such an assent, or if participation in an investigation considers a prospect of direct benefit, and is important in terms of health protection. Furthermore, it is also stated that in certain cases, the capability determination made by the IRB could be waived. Such an approach could be applied provided the below criteria are met:
- The clinical investigation involves no more than minimal risk to the subjects;
- The waiver will not adversely affect the rights and welfare of the subjects;
- The clinical investigation could not practicably be carried out without the waiver; and
- Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
Under the general rule, an institutional review board is entitled to determine whether in each specific case assent is required, and in which way it should be obtained.
The document also highlights the key points related to the data required to support conducting pediatric clinical investigations. According to the guidance, a wide range of sources of information could be used when deciding on the design of a study, including information from nonclinical studies, bench testing, and literature review. The said information could be used to assess the risks and benefits associated with the study to be conducted with the children involved. In certain cases, adult data could be used as well, however, the authority mentions that early inclusion of children in medical product development or the initiation of clinical trials directly in children may be appropriate. At the same time, it is not always feasible to use adult data – for instance, in case the study in question is related to a disease that is common only for children, or has a more severe pediatric form. In such cases, the early involvement of children will be reasonable and justified.
The scope of additional data to be collected before the commencement of a trial depends on the quality and reliability of the data already available. The authority also mentions that in the case of clinical studies related to medical devices, the simulation could be conducted to collect additional data.
In summary, the present FDA guidance provides additional clarifications regarding the regulatory framework for clinical investigations involving children. The document explains the way consent should be obtained from parents or guardians and also outlines the scope of data supporting an investigation.
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