Factorial dose finding for drug combinations instead of full dose of everything
When two cancer drugs are combined, each is usually given at its full single-agent dose, which often proves too toxic. Testing a grid of dose pairs would find combinations that work with tolerable side effects.
Combination phase 1/2 studies use model-based two-agent dose-finding (partial-order CRM, BOIN-COMB) or factorial randomised designs to explore dose pairs, with efficacy and tolerability read-outs at each pair, rather than fixing one agent at its label dose and escalating the other. Regulators expect a justification for each agent's dose in combination labels.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
- Too many combinations to test · There are thousands of possible drug pairs and sequences. Trials can test a few dozen a year.
Pages like this
not linked directly; found by shared links- IdeaRetire the 3+3: model-based dose finding that counts late and chronic side effects
Shares Wrong doses, Small-molecule kinase inhibitors, Immune checkpoint inhibitors.
- IdeaDose adjustments driven by patients' own symptom reports, tested against clinician judgement
- IdeaPublicly funded dose-reduction trials of expensive approved drugs
Shares Wrong doses, Small-molecule kinase inhibitors, Immune checkpoint inhibitors.
- IdeaFind the lowest effective doses of both drugs in a combination, not the highest tolerated
Shares Too many combinations to test, Wrong doses, Immune checkpoint inhibitors.
- IdeaMechanistic computer models to pick combination doses before dosing patients
Shares Too many combinations to test, Wrong doses.
- IdeaAnalyse and dose by sex: women get more toxicity from many cancer drugs at the same dose
- IdeaRestore weight-based dosing and vial sharing for immunotherapy in the label
Shares Wrong doses, Immune checkpoint inhibitors.
- IdeaUse food effects to cut the dose and cost of oral drugs that absorb better with meals