Clinical Evaluation of Therapeutic Vaccines for HIV Seropositives: Approaches to the Design of Efficacy Trials

identified and come into widespread use, patients in this trial who
wished to take the new therapy would be permitted to do so, probably
causing the event rate being observed in the trial to decrease. The
data monitoring committee might, in such a situation, recommend either
entering more patients or lengthening the followup period. The latter
approach might appear more feasible in that context then it does now,
since the appearance of an effective new therapy would likely diminish
the urgency of answering the vaccine question.
This problem is of least concern in the group with greatest potential to
benefit from vaccines--those with higher levels of CD4 counts--because
these individuals are also the least apt to be taking other treatments.
o How long should it take to prepare the detailed design and establish the
required infrastructure?
We believe that a small committee with the relevant experience and
expertise could come to agreement about the details of the trial design
in a few months. This committee should include individuals with indepth understanding of the science, with experience in treating HIVinfected patients in -different settings, and with experience in
designing and conducting large, simple trials. It should include
clinical and statistical expertise, and should include representation
from HIV high risk communities, pharmaceutical companies and the FDA.
The process of setting up the infrastructure will take longer. With
respect to the latter, if new contracts would have to be established, it
might take as long as a year before one could be at the point of
entering patients. If the infrastructure could be developed via
existing contracts, the time could probably be cut in half.
VI. RELATIVE MERITS OF THE TWO APPROACHES
Each of these two approaches has its advantages and disadvantages; their
relative merits might differ depending on the particular features of the new
agent or regimen under study. In the context of therapeutic vaccines, some
advantages of each approach are listed below:
Advantages of the Traditional Approach
o Large trials possibly exceeding capability of existing mechanisms
do not have to be initiated unless Phase II data are positive. If
the first few vaccine products prove incapable of affecting immune
and viral markers, the approach could be discarded without ever
having to do a large-scale trial.
o Agents with minimal biological activity would be identified sooner,
after being administered to fewer patients.

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