SUBPART D PRESENTATIONSUBPART D PRESENTATION

Inaugural meeting of the Pediatric Ethics Inaugural meeting of the Pediatric Ethics Subcommittee (PES) of the Pediatric Subcommittee (PES) of the Pediatric Advisory Committee (PAC); part of the Advisory Committee (PAC); part of the inaugural meeting of the PACinaugural meeting of the PACPediatric Ethics SubcommitteePediatric Ethics Subcommittee– Address Subpart D referralsAddress Subpart D referrals– Address ethical issues that impact on research Address ethical issues that impact on research

affecting the pediatric populationaffecting the pediatric population

First open meeting with OHRP regarding a First open meeting with OHRP regarding a joint referral under 45 CFR 46.406 and 21 joint referral under 45 CFR 46.406 and 21 CFR 50.54 CFR 50.54

FDA involvement with Subpart D regulationsFDA involvement with Subpart D regulations

Advisory Committee RecommendationsAdvisory Committee Recommendations

November 15, 1999November 15, 1999

Children’s Health Act of 2000Children’s Health Act of 2000

Interim Final Rule Interim Final Rule

April 24, 2001April 24, 2001

1999 Advisory Committee 1999 Advisory Committee RecommendationsRecommendations

FDA should adopt the principles described FDA should adopt the principles described in 45 CFR Part 46, Subpart D: Additional in 45 CFR Part 46, Subpart D: Additional Safeguards for Children in Clinical Safeguards for Children in Clinical InvestigationsInvestigations

Recommendation endorsed by AAP and Recommendation endorsed by AAP and PhARMAPhARMA

Children’s Health Act of 2000Children’s Health Act of 2000

Requires that all HHS-funded, supported, Requires that all HHS-funded, supported, or or regulatedregulated research comply with these research comply with these additional protections for childrenadditional protections for children

Interim Final Rule (4/24/01)Interim Final Rule (4/24/01)

Adoption of Subpart D regulations by FDAAdoption of Subpart D regulations by FDA

Pediatric Advisory CommitteePediatric Advisory Committee

Best Pharmaceuticals for Children Act, Best Pharmaceuticals for Children Act, 20012001

Pediatric Research Equity Act, Pediatric Research Equity Act,

20032003

45 CFR 46.407, 21 CFR 50.5445 CFR 46.407, 21 CFR 50.54

If an IRB does not believe it can approve the If an IRB does not believe it can approve the research under 46.404/50.51, 46.405/50.52, research under 46.404/50.51, 46.405/50.52, or 46.406/50.53, the clinical investigation or 46.406/50.53, the clinical investigation may proceed only if:may proceed only if:– The IRB finds that the research presents a reasonable opportunity to The IRB finds that the research presents a reasonable opportunity to

further the understanding, prevention, or alleviation of a serious further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children problem affecting the health or welfare of children

--and----and--

45 CFR 46.407, 21 CFR 50.54 (cont.)45 CFR 46.407, 21 CFR 50.54 (cont.)

– The Secretary/Commissioner of FDA, after consultation with a The Secretary/Commissioner of FDA, after consultation with a panel of experts in pertinent disciplines (e.g., science, medicine, panel of experts in pertinent disciplines (e.g., science, medicine, education, ethics, law) and following an opportunity for public education, ethics, law) and following an opportunity for public review, and comment determines either:review, and comment determines either:

The clinical investigation in fact satisfies The clinical investigation in fact satisfies 46.404/50.51 or 46.405/50.52 or 46.406/50.53, or46.404/50.51 or 46.405/50.52 or 46.406/50.53, orThe following three conditions are met:The following three conditions are met:

1. The clinical investigation presents a 1. The clinical investigation presents a reasonable opportunity to further the understanding, prevention, reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or or alleviation of a serious problem affecting the health or welfare of childrenwelfare of children

2. The clinical investigation will be 2. The clinical investigation will be conducted in accordance with sound ethical principlesconducted in accordance with sound ethical principles

3. Adequate provisions are made for 3. Adequate provisions are made for soliciting assent and parental permissionsoliciting assent and parental permission

Possible Recommendations the PES Possible Recommendations the PES Can Make to the PACCan Make to the PAC

Recommend allowing the protocol to proceed Recommend allowing the protocol to proceed because it satisfies 46.404/50.51, 46.405/50.52, because it satisfies 46.404/50.51, 46.405/50.52, or 46.406/50.53or 46.406/50.53Recommend allowing the protocol to proceed, Recommend allowing the protocol to proceed, with modifications, because it satisfies with modifications, because it satisfies 46.404/50.51, 46.405/50.52, or 46.406/50.5346.404/50.51, 46.405/50.52, or 46.406/50.53Recommend allowing the protocol to proceed Recommend allowing the protocol to proceed because it satisfies 46.407/50.54 because it satisfies 46.407/50.54 Recommend that the protocol not be allowed to Recommend that the protocol not be allowed to proceed, providing specific reasons proceed, providing specific reasons

GOALSGOALS

TRANSPARENCYTRANSPARENCY

PUBLIC INPUTPUBLIC INPUT

EFFICIENCYEFFICIENCY

TIMELINESSTIMELINESS

CLARITYCLARITY

CONSISTENCYCONSISTENCY

EXPERT INPUT EXPERT INPUT (ethical, scientific, (ethical, scientific, legal, medical, legal, medical, educational)educational)

HARMONIZATION HARMONIZATION WITH OHRP (unified, WITH OHRP (unified, comprehensive comprehensive federal process)federal process)

HHS and FDA Regulations regarding allowing a protocol to HHS and FDA Regulations regarding allowing a protocol to proceed under 21 CFR 50.51 or 45 CFR 46.404proceed under 21 CFR 50.51 or 45 CFR 46.404

.52 .405.52 .405

.53 .406.53 .406

.54 .407.54 .407

are comparable. The differences occur after the PAC are comparable. The differences occur after the PAC makes its decision.makes its decision.

After today's’ meeting of the PES?After today's’ meeting of the PES?

1.1. Chair summarizes PES’ review and gives PES’ recommendations to PAC Chair summarizes PES’ review and gives PES’ recommendations to PAC

2.2. Recommendation of PAC submitted to FDA CommissionerRecommendation of PAC submitted to FDA Commissioner- OHRP submits finding of Commissioner to HHS SecretaryOHRP submits finding of Commissioner to HHS Secretary

3.3. Decision by HHS SecretaryDecision by HHS Secretary