AZT: Pediatric Study Changed After Worse Monotherapy Survival


A government study of treatment for children with symptomatic
HIV infection was stopped early after those treated with AZT
alone showed worse survival than those in at least one of the
comparison treatment groups.

ACTG 152 compared AZT alone, ddI alone, and the combination
of AZT plus ddI, for treating children from three months to
18 years old who had little or no prior anti-HIV treatment.
The trial was double blind, meaning that neither the patients
nor the doctors treating them knew who was in which group.
But for ethical reasons, a special committee called the DSMB
(Data Safety Monitoring Board) periodically unblinds such
studies in secret, so that in case there is a major
difference between the treatment arms, the study can be
stopped or revised so that patients are not left on the worse
treatment. In this case, the DSMB recommended that the AZT-
only arm be discontinued, but that the other two arms
continue because the survival difference between them is not
great enough to meet the statistical test required for
stopping that part of the study. Because the study is
continuing, the DSMB will not say which of the other two arms
looks better at this time, since doing so could bias the
results and seriously harm the study. Unless a DSMB stops or
changes a study, it says nothing. ACTG 152 will reach its
scheduled end later in 1995, at which time all the data will
be available to be analyzed.

Comment

This result -- a difference large enough to stop the trial
early -- was unexpected. We may not be able to know what it
means until the study stops later this year. There are many
possibilities. One is that those assigned to the combination
treatment did better than those assigned to a single
treatment alone -- and that the survival difference was
unexpectedly great because HIV disease can progress faster in
children than in adults.

We hope to learn more at the ACTG meeting next week. A major
question, which may need to wait until the end of the study,
is the effect of age differences in this result. Children
three months old may react differently to treatment than
those 17 years old -- even if Congress lumped them together
when it mandated "pediatric" trials at the expense of adult
research. Age-related analysis will be important for
developing treatment recommendations for children of
different ages, for understanding what this result may say
about treatment of adults, and for guidance about when and
how adult data can reliably be used to guide treatment for
children.