Guidance details review process for pediatric research not approvable by an IRB

The US Food and Drug Administration (FDA) last week issued draft guidance offering insights to sponsors and institutional review boards (IRBs) on the process for referring research involving children in cases where such research would not normally be approvable by an IRB. In such cases, an IRB may refer the study to FDA or the Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP).

Conducting pediatric clinical trials is a sensitive matter, and researchers and regulators must be even more cautious when they are involved in clinical trials or other regulated human subjects research. Typically, if a trial puts a patient at any significant risk, an IRB must oversee the study to ensure the interests of patients are addressed.

Regulations found in 45 CFR part 46, subpart D, and 21 CFR part 50, subpart D, which are collectively referred to as “subpart D,” govern all human subjects research overseen by HHS and FDA, respectively. These regulations ensure that research does not involve greater than minimal risk, or in cases where there are greater than minimal risk there is the “prospect of direct benefit to the individual subjects” or for the research to “yield generalizable knowledge about the subjects’ disease or condition.”

If a proposed study involving children does not meet these requirements, FDA explains that the research may proceed if an IRB “finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health and welfare of children,” and the FDA commissioner or HHS secretary consults with experts on the matter and gives opportunity for public comment and determines that the study either satisfies subpart D requirements, or that the study meets several additional conditions. Those conditions include that the research “presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;” will be conducted according to sound ethical principles; and features adequate provisions for soliciting the assent of children and permission from their parents or guardians.

The criteria for this review process are established under 21 CFR 50.54 and 45 CFR 46.407, and IRBs may seek a referral from FDA or OHRP under these regulations.

“An IRB may refer research involving children as subjects to FDA and/or OHRP for review [under regulation], as applicable,” the guidance states. “Regardless of the agency to which the referral is submitted, both FDA and OHRP intend to consult with each other on any referrals received [under their respective regulations] to ensure the appropriate agency has been notified and to determine whether a joint review (i.e., a review by both FDA and OHRP) is needed.”

The draft guidance lays out the process for determining whether FDA, OHRP, or both have jurisdiction over a particular study, the referral review and acceptance processes, recommendations for preparing for a Pediatric Advisory Committee (PAC) and Pediatric Ethics Subcommittee (PES) meeting or an OHRP Expert Panel Meeting, and information regarding the final determination issued by either agency.

The guidance also explains the process differences in the case of a joint FDA and OHRP review, as well as additional information pertaining to multisite research and an abbreviated review process for studies that are similar to research considered in past PAC/PES or expert panel meetings.

Historically, children have been underrepresented in clinical trials due to the sensitive ethical considerations of including them in research. Due to this conundrum, many medical products lack adequate pediatric labeling or instructions for use. However, in recent decades there has been a push to include pediatric patients in more clinical research and to promote the approval of products intended for use in children.

In recent months, FDA has published several guidances addressing conduct and ethical considerations for pediatric trials.

In September, the agency published a guidance on extrapolating adult data in pediatric populations for clinical trials, and another on ethical and physiological issues sponsors should consider when planning to run clinical pharmacology studies for pediatric products.

In October, FDA published a guidance detailing how sponsors can measure pediatric growth consistently in clinical trials for drugs used to treat both rare and common diseases.

FDA

Guidance details review process for pediatric research not approvable by an IRB

Related topics

Recommended content

Welcome to the new RAPS Digital Experience