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U.S. Department of Health and Human Services

Advisory Committees

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Questions for PES Consideration: Exploratory IND Studies in the Pediatric Population

Pediatric Ethics Subcommittee of the
Pediatric Advisory Committee Meeting

Wednesday, May 11, 2011
Bethesda North Marriott Hotel,
5701 Marinelli Rd,
Bethesda, Maryland, 20852

  1. The administration of some drug and biological products may present more than a minor increase over minimal risk.  Accordingly, a clinical investigation to study that drug must offer the enrolled child a sufficient prospect of direct benefit to justify that risk (21 CFR 50.52). Under these circumstances, a study of drug metabolism may use, for example, a population pharmacokinetic approach as part of a trial designed to offer the prospect of direct benefit. In some circumstances, could the use of a sub-therapeutic dose of such a drug or biological product reduce the risk to no more than a minor increase over minimal risk, thereby allowing an exploratory IND study in children with the relevant disorder or condition (21 CFR 50.53)? What, if any, are the circumstances under which this approach may be appropriate? What data would be necessary in order to make this risk assessment?
  2. The administration of a single dose of some drug and biological products may present only a minor increase over minimal risk, based on adequate data in support of this assessment. Under these circumstances, a single dose pharmacokinetic (and perhaps pharmacodynamic) study can be performed in children with the relevant disorder or condition (21 CFR 50.53). Could the use of a sub-therapeutic dose of such a drug or biological product reduce the risk to no more than minimal risk, thereby allowing an exploratory IND study in children without the relevant disorder or condition (21 CFR 50.51)? What, if any, are the circumstances under which this approach may be appropriate? What data would be necessary in order to make this risk assessment?
  3. There are other issues beyond the assessment of risk that may enter into the judgment about the ethical acceptability of a given clinical investigation, such as the scientific merit of the protocol, the social value of the research, the skill and experience of the investigators, or the potential for exploitation of economically disadvantaged populations. Please discuss how these, and other relevant ethical considerations, should factor into a decision to allow an exploratory IND trial to proceed. In your discussion, please clarify any differences in these considerations between a population of children with a disorder or condition and a population of normal, healthy children.
  4. There is well documented variability and deficiencies in the system of IRB review of clinical trials. In light of the discussion of the above questions, how can we assure that children would be adequately protected if we allowed for the broader inclusion of children in exploratory IND trials?