Loading
Cancer drugs are usually tested at the highest dose patients can stand, and that dose sticks for life. Comparing two or more doses head-to-head before the big trial would find doses that work as well with fewer side effects.
Following FDA's Project Optimus, sponsors run randomised parallel-dose cohorts (typically two or three doses spanning the exposure-response range) in phase 2 with efficacy, tolerability and PK endpoints, before selecting the dose for registrational trials. Precedent: the post-approval randomised comparison of sotorasib 960 mg versus 240 mg, which found similar efficacy. The proposal makes randomised dose comparison the expectation, with regulators declining to accept single-dose pivotal trials for targeted agents without it.
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Sotorasib, Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on, Wrong doses.
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Sotorasib, Wrong doses, Toxicity and quality of life are undervalued.
Shares Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on, Wrong doses, Toxicity and quality of life are undervalued.
Shares Wrong doses, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors.
Shares Wrong doses, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors.
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Wrong doses, Toxicity and quality of life are undervalued.
Shares Wrong doses, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors.
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Wrong doses.
Every source this page cites, grouped by who published it. Grouping is read from the web address, not assigned by hand.
A source that has moved or gone is reported by the weekly link check. /audit/