Getting the dose right - The dose selected for a phase 3 program was selected by the client's chief scientist, despite commentary from FDA that the dose was wrong. Two expensive phase 3 trials failed. My analyses revealed that the dose was 2-fold too small. A new trial with the larger dose produced the exact balance between efficacy and safety.
Getting the dose right - An entire clinical program used weight-based dosing. A pharmacokinetic analysis, commissioned shortly before NDA submission, revealed that exposure did not vary as a function of weight. A high incidence of non-trivial adverse events in heavier subjects (with no increase in efficacy) supported non-weight-based dosing. Pharmacodynamic analyses led to improved dosing regimens.
Getting the dose right - Pharmacokinetic results from two phase 1 PK studies in healthy non-US subjects were weight-normalized. These results were used in a phase 2 study in the US and plasma concentrations were 2-fold larger than predicted. The unexpected results led to a 2-year suspension in development. My analyses reveals that weight-based dosing was not appropriate and that the higher concentrations in the US study could be explained by weight-based dosing.
Antibody development - Simulations of a clinical trial for an antibody revealed that the proposed trial was likely to fail. The company ignored these recommendations; the trial failed as predicted. The company asked that I propose a new dosing regimen, simulate this regimen, and use this information to convince regulatory authorities to permit trials to resume.
Real-time analyses - An early-stage company needed rapid analyses from a first-in-man trial to permit selection of dosing regimens for subsequent trials (a decision was needed in < 5 days). In 3 days, I provided preliminary NONMEM analyses, simulated dosing regimens for the second trial, recommended improved sampling regimens.
Diligence - A pharma company in-licensed a novel delivery system: mean data available during diligence suggested that the desired delivery profile would be easy to achieve. My analyses revealed that no subject had an acceptable release profile; mean data were misleading. The company decided that additional phase I data was needed before further development.