Invasive Placebos, Patient Burdens, and Community Advocacy

The “Additional Safeguards for Children in FDA-Regulated Clinical Investigations,” 21 CFR 50 subpart D, places limits on the risk to which a child can be exposed in a study. Absent a prospect of direct clinical benefit, institutional review boards (IRBs) cannot approve an intervention or procedure that exceeds “a minor increase over minimal risk.” If there is an ethical justification for the study to proceed, the IRB may refer the protocol for review by a federal panel under 21 CFR 50.54. A study allowing use of a totally implantable central venous access device (TICVAD) to provide placebo was referred for federal panel review; the committee voted unanimously in favor of a TICVAD. A determination by the Food and Drug Administration commissioner was issued within 10 weeks of the initial referral, an unprecedented time line. The Duchenne Muscular Dystrophy community was instrumental in initiating the referral and informing the panel’s decision.