# Exposure-response modelling with a pre-set target exposure before any dose is chosen

Source: https://onco.cc/ideas/idea-tr1-exposure-response-before-dose-selection/  
OnCo record `idea-tr1-exposure-response-before-dose-selection` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Instead of picking the dose by how much patients can tolerate, measure drug levels in blood and relate them to both benefit and harm across patients, then choose the dose that hits the sweet spot.

## Summary

Registrational packages include population PK and exposure-response analyses for efficacy and the main toxicities, with the target exposure range declared before phase 3 and the chosen dose justified against it; sparse PK sampling in all trial participants makes this feasible. Regulators publish the exposure-response basis for the label dose.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Programmes with pre-specified exposure-response dose selection will select doses below MTD more often and will require fewer post-marketing dose changes than programmes without.
- Rationale: Exposure-response is standard in most therapeutic areas; oncology has lagged because of the MTD tradition. Many approved oncology drugs have label doses on the flat part of the efficacy curve and the steep part of the toxicity curve.
- Proposed test: Audit new oncology approvals for the presence and use of exposure-response analysis in dose justification and compare subsequent dose-related label changes.
- Maturity: being-tested-at-scale
- Actor: regulator

## Sources

- FDA Oncology Center of Excellence: Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus

## Connected records

- terms: [Pharmacokinetics (PK), half-life and exposure](https://onco.cc/terms/pharmacokinetics/), [Pivotal (registrational) trial](https://onco.cc/terms/pivotal-trial/), [Regulators beyond the FDA (EMA/CHMP, MHRA, PMDA, NMPA, TGA)](https://onco.cc/terms/regulatory-agencies/)
- bottlenecks: [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- key papers: [FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high](https://onco.cc/key-papers/paper-drug-dosing-conundrum-nejm-2021/)

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