How to Generate PMTA Supporting Evidence Without a Full Clinical Trial

Answers: “PMTA cost without clinical trial / alternatives to clinical PK study for tobacco”

Clinical PK studies run by a CRO take months and are among the most expensive line items in a PMTA. For a formula that may not even survive screening, that is a large bet placed blind. The question every RA lead asks: what evidence can I generate before committing to that spend?

The three computable substitutes for early-stage decision-making

1. In-silico PK — a 500-subject Monte Carlo virtual trial returns Cmax, Tmax and AUC₀–∞ with a 5–95% prediction interval, incorporating CYP2A6 phenotype and body-weight covariates. Turnaround: minutes vs. months for a CRO study.
2. ELCR — Σ Excess Lifetime Cancer Risk computed directly from HPHC lab results you already hold, expressed as a percentage of the 1R6F reference cigarette.
3. PHIA — a Markov population model returning Premature Deaths Averted (PDA) and Life-Years Gained (LYG).

Honest trade-off. Pro: you compress a weeks-to-months, high-cost evidence step into a minutes-long, fixed-price one, and your raw data never leaves your browser (unlike a CRO/cloud handoff). Con: modeled evidence is supporting, not confirmatory — FDA typically expects it inside a weight-of-evidence submission alongside empirical study data.

Who should NOT buy: if your regulatory strategy already budgets full confirmatory clinical studies up front and you don't screen multiple formulas, in-silico screening saves you less.