The new article highlights the key points related to study procedures in pediatric clinical investigations, and also provides a summary of the key points addressed in the guidance. 

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 the ethical considerations for clinical investigations with children involved. The document outlines the most important aspects that are different from the studies with adult participants involved and explains the way they should be treated. The document itself 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 framework, as well as recommendations to be considered to ensure compliance thereto. The authority also mentions that an alternative approach could be applied, provided such an approach is in line with the existing regulatory framework and has been agreed with the authority in advance. 

As explained by the FDA, in the context of a clinical investigation, procedures that are carried out as part of routine clinical care of a child generally are considered to offer a clinical benefit and do not require evaluation as a research intervention under the regulation, however, procedures that are carried out solely for research purposes and do not offer the prospect of direct benefit must meet the minimal risk criteria or no more than a minor increase over minimal risk criteria to be included in a clinical investigation unless referred for review under 21 CFR 50.54.

The authority also states that a party responsible for a clinical investigation involving children should always consider the harm that could potentially be caused to a child as a result of an intervention taking place in the course of a study. The scope of such a risk assessment should cover any risk that exceeds the ones associated with the procedures that are necessary for the due course of clinical care the child reasonably requires. In case of several interventions are required, the risks associated thereto should be considered both jointly and separately.


Procedural Sedation in Pediatric Clinical Investigations

 According to the guidance, the procedures taking place in the course of a clinical investigation of healthcare products involving children may require sedation, so the risks associated thereto should be subject to a rigorous assessment. In this respect, the following recommendations are to be considered: 

  • Procedures should be performed at a high-volume center with a dedicated pediatric sedation service;
  • There should be rigorous scientific justification for the need for non-therapeutic procedures;
  • The approach to procedural sedation and risk minimization procedures should be described in the protocol;
  • Children with chronic conditions that may place them at higher risk from procedural sedation should be carefully evaluated and potentially excluded from the protocol;
  • Should any complication occur as a result of sedation related to a non-therapeutic procedure, such a procedure should be terminated, since in this situation the risk exceeds the acceptable minimal level;
  • In case a procedure to be conducted usually requires sedation for this patient population, the same approach should be followed to ensure proper results are achieved;
  • The information about the intervention to take place, as well as the details regarding sedation to be applied should be duly communicated to parents when obtaining parental permission. 

The authority further encourages study sponsors to follow the above recommendations to ensure the risks associated with the study are within the acceptable level. The same points would also be considered by an institutional review board when assessing the risks study participants will be exposed to. As it was mentioned before, cumulative risk will be considered as well, together with the individual risks associated with each of the procedures. Should it be determined that risks associated with the intervention constitute a minor increase over minimal risk, but at the same time such an intervention is vitally important in the course of a study for its goals to be achieved, an additional review will be performed. 

Policy Overview 

In summary, the present FDA guidance describes in detail the approach to be applied concerning clinical investigations involving children. The document provides an overview of the existing regulatory framework and also highlights the key points to be considered in this regard including, inter alia, the following ones:

  • The principle of scientific necessity requires all the procedures conducted in the course of an investigation to be justified in terms of additional clinical data to be collected, provided such data is vitally important to assess the safety and effectiveness of the device, and cannot be collected in any other way.
  • The way interventions could be divided into categories based on the risks associated thereto.
  • The concept of the prospect of direct benefit and the way it should be applied.
  • The approach for the assessment of risk associated with the procedures to take place in the course of a study.
  • The way study sponsors should communicate important information about the study and obtain permission from parents/guardians of a child involved; as well as the aspects related to child assent. 
  • The scope of data required to support conducting pediatric clinical investigations.
  • The main design considerations for clinical investigations involving children. 

The authority also mentions that in case of any doubts, study sponsors are encouraged to get in touch to discuss the main points related to the study before it will be commenced. 



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