# Make pre-approval dose optimisation an ICH standard so it is done once worldwide

Source: https://onco.cc/ideas/idea-reg-global-dose-optimisation-guideline/  
OnCo record `idea-reg-global-dose-optimisation-guideline` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The FDA now asks companies to find the right dose of a cancer drug before approval. If every regulator asked the same way, companies would do it once and doses would match worldwide.

## Summary

FDA's Project Optimus (guidance finalised 2024) expects randomised dose comparison before approval for oncology drugs; other regulators have not formally adopted it, so sponsors face different expectations and may launch different doses in different regions. The proposal is an ICH efficacy guideline codifying dose-optimisation expectations for oncology (randomised comparison of at least two doses, exposure-response, tolerability endpoints) so that one programme serves all regions and approved doses converge.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: After adoption, the proportion of new oncology approvals with different approved doses in different regions falls to near zero, and the rate of post-approval dose reductions in labels falls by half.
- Rationale: Historical maximum-tolerated-dose development left many targeted drugs approved at doses later shown to be excessive (sotorasib and several kinase inhibitors). Divergent regional expectations multiply cost and delay adoption of the better dose.
- Proposed test: ICH concept paper and expert working group; track regional dose divergence and label dose changes for products developed under the guideline against the prior five-year cohort.
- Maturity: early-clinical
- Actor: regulator

## Sources

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

## Connected records

- drugs: [Sotorasib](https://onco.cc/drugs/sotorasib/)
- bottlenecks: [Regulatory divergence between regions](https://onco.cc/bottlenecks/b-regulatory-fragmentation/), [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/)
- roadmaps: [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)

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