Medical research in infants and children in the eighties: analysis of rejected protocols.

We reviewed the 351 protocols dealing with research in infants and children in our institute between July 1982 and August 1988 to identify ethical issues that complicate the execution of pediatric research. Of the 16 rejected protocols (4.5%) 12 were drug studies, three dealt with the nature or course of disease states and one was in the area of behavioral sciences. Drug studies were significantly more likely to be rejected than all other studies. The most common reason for rejection (n = 10) were major scientific flaws that, according to the Committee, would result in inability of the study to answer the questions posed by the researchers. In nine cases the Committee judged a study to be physically invasive without a direct benefit to the involved infant/child. In three cases, the Committee rejected a study because patients with serious medical conditions might be randomized to receive placebo and not a drug that, based on current knowledge from adults, would possibly improve their condition. In three protocols, current antimicrobial therapy covered all pathogens causing the infection and the proposed new therapy could not improve the prognosis further but only be equal or inferior. Researchers who had more than one protocol rejected had significantly more protocols submitted (7.17 +/- 1.35) than those who had only one rejection (1.86 +/- 0.36, p less than 0.0005) or than the 10 researchers with the highest number of studies without a single rejection (4.2 +/- 0.4, p less than 0.05). These numbers suggest that scientists who perform more research are more likely to stand at the front line of unresolved ethical issues.