Randomised lower-dose trials for approved drugs with quality of life as the primary endpoint
Many cancer drugs are approved at the highest dose patients could stand, not the best dose. Run trials that test lower doses on approved drugs and measure how patients feel.
Maximum tolerated dose remains the default for oral targeted agents and many antibody-drug conjugates; discontinuation for toxicity is common (abemaciclib, lenvatinib, cabozantinib, sotorasib). FDA Project Optimus addresses new drugs, not the existing catalogue. The proposal is a funded programme of post-marketing randomised non-inferiority trials of reduced or adaptive doses with patient-reported tolerability as primary and progression-free survival as a non-inferiority secondary, with regulators committed to label updates.
- Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
Pages like this
not linked directly; found by shared links- IdeaRandomise at least two doses in phase 2 before any pivotal trial
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.
- IdeaMake pre-approval dose optimisation an ICH standard so it is done once worldwide
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Sotorasib, Wrong doses.
- IdeaExposure-response modelling with a pre-set target exposure before any dose is chosen
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Wrong doses.
- IdeaStart low and step up: individualised titration of oral cancer drugs, randomised
Shares Abemaciclib, Wrong doses, Toxicity and quality of life are undervalued.
- IdeaDose adjustments driven by patients' own symptom reports, tested against clinician judgement
Shares Wrong doses, Toxicity and quality of life are undervalued.
- IdeaReal-world dose intensity and toxicity monitoring to revise labelled doses
Shares Wrong doses, Toxicity and quality of life are undervalued.
- IdeaDefine tolerability endpoints as rigorously as efficacy endpoints
Shares Wrong doses, Toxicity and quality of life are undervalued.
- IdeaAnalyse and dose by sex: women get more toxicity from many cancer drugs at the same dose
Shares Wrong doses, Toxicity and quality of life are undervalued.