[Letter to Quentin N. Burdick from Kay Holcombe]

OCT- 15- 1. 1 FRMI-I FIA L E ISLAT I E AFFA I R TO 9023 9564 -

Page 2 - The Honorable Quentin N. Burdick
characteristics of HIV, it seems likely that vaccinated
subjects in an HIV vaccine efficacy study would need to be
followed for at least two years.
With regard to your second question concerning how many
different human efficacy trials could be run in the
United States, more than one controlled pivotal efficacy study
could be conducted concurrently in the United States.
Likewise, more than one vaccine could be evaluated. However,
at the time when one vaccine is proved to be effective, placebo
controlled trials would be discontinued. Subsequent trials
would need to be head-to-head comparison trials, i.e., the
effective vaccine versus the investigational vaccine.
Comparison trials, for example to prove equivalence, require
more resources to conduct because larger sample sizes are
required.
N inf ctetd members of high risk groups, i.e., where 30-50% of
subjects are already infected and the practices that lead to
infection are continuing to occur in that specific group, are
often good subjects for an efficacy trial. For example,
homosexual males not practicing safe sex might be good subjects
for a vaccine efficacy trial, obviously, persons already
infected would not be subjects of prophylactic vaccine efficacy
trials.
Concerning your question on running tests on groups which may
be at higher risk in the future, clinical trials of AIDS
vaccines should be designed with anticipation of the future
spread of the virus. Populations with a high prevalence of
infection currently may prove to have a low frequency of new
infections in the future, and vice versa. These dynamics
should be taken into account.
You also asked about testing vaccines outside the United State
as an alternative to limiting efficacy testing to primates.
With regard to our position on human efficacy studies conducted
overseas, available data suggest that certain foreign sites
would be appropriate for pivotal AIDS vaccine efficacy studies,
especially to evaluate prevention of heterosexual transmission
of HIV infection. It is quite likely that pivotal efficacy
studies for an AIDS vaccine will be conducted outside the
United States. FDA has previously accepted data to support
licensure from foreign studies for a number of vaccine and
therapeutic products.
FDA would accept such foreign data from we ll-conductetwel -
LmQnISoreQd trials as the definitive AIDS vaccine efficacy data
to support licensure, if the studies addressed conditions of
virus spread relevant to the United States. There would also