TABLE 8.2 Example 2—Variability in IRB Approval of a Multicenter Research Protocol That Includes Children


Full Approval

Modified Approval




≥18 yrs only

Greater than minimal risk without direct benefit; not approvable for children



≥18 yrs only

Pediatric approval under 45 CFR 46.406 only after review of safety data from studies with adults




Approved under 45 CFR 46.406, but blood draws must be <5% of total blood volume




Minor increase over minimal risk; both parents must sign (under 45 CFR 46.406)




Minor increase over minimal risk; information gained would contribute to generalizable knowledge



≥18 yrs onlya

Board deferred approval of the participation of pediatric patients (ages 6 to 17 years) until more information about the effects of the study drug on children becomes available.




Greater than minimal risk but direct benefit (under 45 CFR 46.405); both parents must provide permission

aThe IRB application was withdrawn because the pediatric cohort was filled.

SOURCE: Ramsey (2003).

for bone age be deleted for HIV-negative controls (as a condition for waiver of parental permission).

In addition to being frustrating and sometimes costly, inconsistency in IRB judgments may raise ethical concerns. For example, when different IRBs reach different conclusions about research risks or potential benefits and place different conditions on studies, might some children be exposed to higher than acceptable levels of risk? Alternatively, might some children be denied participation in potentially beneficial research?

To some extent, the variability in IRB judgments reflects the uncertainties inherent in (and the reason for) much clinical research. It may also reflect, as discussed in Chapter 2 and 4, the limited data on the less-than-

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