The article provides an overview of the applicable regulatory requirements for ethical considerations in the context of clinical investigations of medical devices initially intended to be used for children. 

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to ethical considerations for clinical investigations of medical products involving children. Once finalized, the document will provide additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be considered to ensure compliance thereto. At the same time, it is important to mention that FDA guidance documents are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the existing legislation and has been agreed with the authority in advance. 

The present draft guidance is published for public consultations – the authority encourages industry representatives to provide their feedback and suggestions on the matter. The FDA will consider the comments received when preparing a final version of the guidance. 



The authority acknowledges the importance of clinical investigations in children as a source of data on the safety of healthcare products, including medical devices, to ensure public health protection for the risks associated with the use of healthcare products that could be unsafe or inefficient. At the same time, the applicability of the general approach for clinical trials in the case of children is limited. For instance, they cannot provide consent for participation in a clinical trial themselves, hence, additional safeguards are necessary to ensure the protection of their interests. The said safeguards are vitally important when it takes to initiating or conducting a clinical investigation with children involved. 

The authority also mentions that clinical investigations related to products subject to regulation by the FDA, but that are not medical products by their regulatory nature, are falling outside the scope of the present guidance, even though some of the considerations may be similar. As it was mentioned before, the aspects highlighted are the ones the parties responsible for healthcare products (including medical devices) should pay attention to. 

Regulatory Background 

As explained by the FDA, the ethical principles for the protection of human subjects in FDA-regulated clinical investigations are reflected in the requirements in 21 CFR parts 50 and 56; additional safeguards for children are included in 21 CFR part 50, subpart D. The said regulatory requirements are to be followed by all the parties involved including, inter alia, institutional review boards (IRBs) undertaking the review of clinical investigations related to medical devices intended to be used for children and requiring children to be involved as study subjects. Additional safeguards mentioned herein are also regulated under 45 CFR part 46, subpart D, Additional Protections for Children Involved as Subjects in Research. The authority also mentions that all clinical investigations related to healthcare products that are subject to regulation by the FDA should comply with the regulatory requirements outlined in parts 50 and 56. At the same time, in case an investigational device exemption (IDE) or an investigational new drug application (IND) is required, parties responsible for an investigation are encouraged to get in touch with the authority to discuss the investigational plan and further steps to be taken, while the protocol of the trial should be submitted to the respective division of the authority. 


Ethical Framework 

Following the requirements set forth by the applicable regulations, to be reviewed and approved, a clinical investigation requiring children to be involved as study participants should meet all the applicable regulatory requirements including, but not limited to, the following ones: 

  • 21 CFR 50.51, which refers to the minimal risk and provides that the risk children will be exposed to should not exceed the minimal one. 
  • 21 CFR 50.52, which states that in certain cases the above risk limit could be exceeded, provided there is an expected direct benefit to the study participants. 
  • 21 CFR 50.53, which states that in certain cases the above risk limit could be exceeded even if there is no benefit expected, but important clinical data is to be collected in the course of a trial. In such a case, the children should either have or be at risk for the specific disorder or condition that will be studied in the clinical investigation, while objective or empiric data should support that the condition proposed for study has the potential to negatively impact the child’s health and well-being or increase the risk of developing a health problem in the future, as well as that collection of the data will enhance understanding towards prevention, diagnosis, improvement, or treatment of the condition. 

The authority additionally emphasizes that in all cases explicit content of parents or guardians should be duly obtained. 

The aspects outlined herein above are the main ones to be taken into consideration by the parties responsible for clinical trials with children involved, and also by the institutional review boards. 

In summary, the present FDA guidance describes in detail the regulatory policy the authority intends to apply for clinical investigations for healthcare products intended to be used for children with children involved as study participants. The document highlights the key points to be considered in the context of a risk-based approach and the determination of an acceptable risk depending on the expected clinical benefit or importance of clinical data to be collected. 



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