Conducting clinical trials in challenging environments
Steven Kern
Gates Foundation
The recent Ebola crisis in West Africa incited an accelerated effort to bring new therapeutics, diagnostics, and vaccines to the region in hopes of mitigating the tremendous lethal impact of the outbreak. For therapeutics, both new entities that had not been tested in humans and drugs that had been used or approved for other indications that showed some experimental impact against Ebola virus, were accelerated forward for clinical trials. A challenge to this process was estimating effective doses to trial in the unfolding epidemic with these agents. For the new agents, evaluations in nonhuman primates provided the best estimate for scaling to effective human doses based on allometric principles. For the agents repurposed from other indications, combining human pharmacokinetic information in other disease populations, with in vitro assay data or in vivo data from experiments in murine models provided the only guidance for dosing. Pulling together the appropriate evidence to justify evaluating a compound in the midst of this crises presented challenges based on the information gaps that existed. Additionally, conducting a clinical evaluation in an environment where physical case report forms and traditional means of gathering supportive data for post trial analysis was non-existent creates an extreme situation where making the best inferences and decisions with limited data must occur. This is an area where pharmacometric analysis can provide structured process for best estimated effective dose to assess in a trial where likely only one trial attempt at assessment can be made.
