2. Selection of Doses for Proof of Concept (PoC) Studies
As a rule, PoC is tested at the maximum tolerated doses (MTD), or maximal administered
dose if MTD was not defined. This is to minimise false negative results, and to provide best test of
hypothesis, as well as to maximise
pharmacodynamics (PD) effect(s). The evaluation of several
dose levels to assess
dose response is preferred, but is not required. The assessment of
dose response allows researchers to establish a minimum effective and optimal
dose, to mitigate the
risk of the MTD not being tolerated. Gathering these further data strengthens the weight of evidence, and guides
dose selection for subsequent studies, however it increases the time required to complete phase II studies, and thus the cost.