Key 1 – Adhere to translational science principles
To design a robust clinical trial for an anti-infection drug, we usually
need to know three sets of information: a) the disease symptomatology
and progression; b) the underlying mechanism of disease periods, i.e.,
dynamics of viral load and immune response; and c) host-virus-drug
interactions. We must have clear objective definitions of disease
progression and improvement. Objectively, this may be reflected by viral
load and host immune response. Viral load can be quantified through
RT-PCR while immune response can be tracked through inflammatory markers
and antibody production. By studying drug PK and PD, maybe indirectly
from previous programs, we can optimize the dosage regimen (dosage,
dosing interval and treatment duration) to maximize the cure rate,
reduce toxicity and avoid drug resistance. The information obtained is
critical in understanding trial results, as drugs will have different
effects depending on disease progression. For example, a drug may be
falsely dismissed as ineffective if it is given too late in the disease
course. We must go beyond standard clinical evaluations and leverage
basic science measures to enrich trial outcomes.