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USFDA Guideline for : Clinical Investigations of Medical Products Involving Children

USFDA Guideline on September 23, 2022, the US Food and Drug Administration issued a preliminary guidance concerning the ethical aspects of involving and safeguarding children in clinical trials. This guidance is expected to undergo finalization in the near future.

Clinical studies involving children are crucial for gathering data on the safety and efficacy of medical products such as drugs, biological items, and medical devices. These investigations aim to safeguard children from potential risks associated with using medical products that might be unsafe or ineffective. Given that children cannot provide consent themselves, they are considered a vulnerable population and are provided with additional protections when participating in such studies. These safeguards are fundamental for the initiation and execution of pediatric investigations within medical product development programs. This guidance outlines the FDA\’s current perspective on ethical considerations for conducting clinical studies involving medical products in children.

It\’s important to note that FDA guidance documents typically do not establish legally binding responsibilities. Instead, they represent the Agency\’s current viewpoints on a subject and should be treated as recommendations unless specific regulatory or statutory requirements are referenced. When the term \”should\” is used in FDA guidance, it indicates a suggestion or recommendation rather than a mandatory requirement.

Medical Products, which encompass Drugs, Biological Products, and Medical Devices, are addressed collectively in this preliminary guidance. Its objective is to offer support to industry stakeholders, sponsors, and institutional review boards (IRBs) in the context of enrolling children in clinical trials.

Given the vulnerability of children and their inability to provide consent independently, any clinical study involving minors necessitates additional protective measures. The FDA, as outlined in this guidance, emphasizes ethical considerations in the execution of therapeutic trials involving children.

In accordance with regulatory guidelines outlined in 21 CFR parts 50 and 56, institutional review boards (IRBs) must adhere to specific protocols. When evaluating clinical investigations involving FDA-regulated medical products targeted at enrolling children, additional measures for safeguarding children are delineated in 21 CFR part 50, subpart D.

Data to Support Conducting Pediatric Clinical research USFDA Guideline

Various sources of information can inform the planning of pediatric clinical investigations. These include insights from nonclinical studies, bench testing, modeling, and simulation (particularly for devices), as well as existing literature. By evaluating the potential risks and benefits, these data help determine the suitability of conducting trials involving children.

In certain scenarios, gathering adult data prior to commencing pediatric trials may not be obligatory, depending on the quality and relevance of available information. Nonetheless, if pertinent adult data exist, they can guide the design of trials involving pediatric subjects, in accordance with the Principle of Scientific Necessity (refer to section III.A). There\’s also merit in involving children early in the development of medical products or initiating trials directly in this demographic when appropriate.

There are instances where conducting studies in adults may not be ethical or feasible. Take, for instance, rare diseases with high pediatric mortality rates, where there might be a scarcity of affected adults or their condition may be less severe, making their experiences less applicable to the more critical pediatric cases.

Considerations for Designing Clinical Investigations Involving Children USFDA Guideline

When planning clinical investigations involving children, it is imperative to optimize the acquisition of information while minimizing the number of participants. The risks associated with pediatric clinical investigations can vary depending on the specific subgroup of pediatric patients. Several factors should be taken into account during the design phase and risk assessment process:

• • Age and level of physiological development of the child.

• • Characteristics and progression of the medical condition targeted for treatment.

• • Severity of the condition in the child at the time of the study.

• • Presence of any additional complicating medical conditions.

• • Previous evidence of the safety and efficacy of the drug or device in older age groups, or anticipated based on prior clinical or preclinical studies.

• • Expected duration of drug or device usage and its potential impact on the child\’s physical growth, developmental milestones, as well as behavioral and psychosocial aspects.

In pediatric clinical investigations USFDA Guideline

Procedures undertaken as part of standard clinical care for a child are generally regarded as beneficial and do not necessitate evaluation as a research intervention according to regulations. However, procedures conducted solely for research purposes, lacking the prospect of direct benefit, must adhere to minimal risk criteria (21 CFR 50.51) or entail no more than a slight increase over minimal risk criteria (21 CFR 50.53) to be included in a clinical investigation, unless subject to review under 21 CFR 50.54 (refer to section III.F).

Assessment of risk should encompass potential harm, invasiveness, and frequency of planned procedures. For instance, single procedures like lumbar punctures or muscle biopsies are often considered to present a minor increase over minimal risk in many cases.

Conversely, extensive organ biopsies such as liver or kidney biopsies, conducted solely for research, typically exceed a minor increase over minimal risk and should not be performed on children unless it constitutes part of their routine clinical care for their condition. Additionally, when evaluating procedural risk, factors such as the necessity of sedation not related to the child\’s clinical care (non-therapeutic procedural sedation, see section IV.C.1) or the use of contrast agents should be taken into account.

For example, while a single MRI without contrast might be deemed minimal risk, the inclusion of contrast or sedation is likely to elevate the risk to at least a minor increase over minimal risk, depending on the specific type of contrast and sedation\’s associated risks.

For further insights into these guidelines, please refer to the provided LINK for details on the document \”Ethical Considerations for Clinical Investigations of Medical Products Involving Children.