Comment Now! Ethical Considerations in Pediatric Studies Draft Guidance

09/27/2022

Photo by Ben White on Unsplash

The US Food and Drug Administration (FDA) released a draft guidance “Ethical Considerations for Clinical Investigations of Medical Products Involving Children” in September 2022. The draft guidance clarifies the ethical principles for the conduct of pediatric clinical trials, including that children are a vulnerable population so additional safeguards are needed to ensure their safety. The safety of pediatric participants is covered under the FDA regulations 21 CFR part 50, subpart D, Additional Safeguards for Children in Clinical Investigations, and 45 CFR part 46, subpart D, Additional Protections for Children Involved as Subjects in Research.

Background

When children are a target population to receive an investigational product, pediatric clinical trials are necessary to understand if it is safe and effective, including if there are differences between age groups. Outcomes from adult clinical trials are often not directly translatable to pediatric populations because of differences in the way they absorb, distribute, metabolize, and excrete drugs and in their response to a device. Clinical trials generate the information needed to understand the correct dosing for the different age groups and the age range that is appropriate for administration.

 

Summary of Draft Guidance

The draft guidance identifies the following key ethical principles under the aforementioned regulations.

  • Principle of scientific necessity includes:

    • Equitable participant selection, and

    • Justice - for example, if children are needed to participate or if adults are sufficient

  • Risk categories without a prospect of direct benefit are:

    • Minimal risk, or

    • Minor increase over minimal risk

  • Prospect of direct benefit:

    • Does not rely on the confirmation of effectiveness in adult clinical trials before consideration

    • Is based on data: evidence of clinical benefit in adults, nonclinical/animal studies, modeling, or effect on a surrogate endpoint

    • Relies on an IRB decision that the risk is justified by the benefit, and it is at least as beneficial as alternative treatments

    • Also relies on the IRB assessing safety data from adult or nonclinical/animal studies, or from children using the drug for a different indication

  • Component analysis of the risk to the participant is used to determine if a clinical trial offers a prospect of direct benefit. If it does not, the risk threshold is minor increase over minimal risk.

  • The IRB may approve a clinical trial under certain circumstances when there is more than a minor increase over minimal risk. (Potential for review per 21 CFR 50.54)

  • Parent or guardian permission and child assent are both required unless the

    • Assent is waived by the IRB

    • IRB determines that the children are incapable of assenting

    • Prospect of direct benefit is great, and the benefit is only available in the clinical trial

The following are considerations for design of pediatric clinical trials per the regulations.

  • Data to support conducting pediatric clinical investigations

  • Design considerations for clinical investigations

  • Study procedures in pediatric clinical investigations

After the decision that children are needed to participate in a clinical trial, the minimization of risk is the next consideration (e.g., study procedures that follow clinical care to reduce risk exposure). Study design considerations should include collecting only the essential data to minimize study procedures. Component analysis involves considering the impact of study design to the risk level, such as if a placebo arm withholds available treatment, or if study procedures surpass the minor increase over minimal risk threshold.

 

Comment on the draft guidance now through Dec 27, 2022 HERE.

 

Special Considerations in Pediatric Trials recorded webinar available for purchase HERE. It answers these and more questions:

  • Which regulations are applicable in pediatric clinical research?

  • What are the physiological and developmental differences between children and adults?

  • How do you manage unique study procedure issues in pediatric populations?

  • What is the difference between informed consent, permission, and assenting?

  • How do you manage the most common enrollment issues in pediatric studies?

Clarified in ICH E8(R1), the General Considerations for Clinical Studies Guideline, study design should incorporate a patient centered approach with a consultation of stakeholders who are knowledgeable about living with the condition. 

  • Want to learn more? The interactive eLearning course is available for purchase HERE.

  • Read our blog HERE for more information.

 

- The Clinical Pathways Team

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