Dose reduction studies: how much of the treatment effect is lost?

A recent FDA report called Project Optimus states that "poorly characterized dose and schedule may lead to selection of a dose that provides more toxicity without additional efficacy, severe toxicities that require a high rate of dose reductions, intolerable toxicities that lead to premature discontinuation and missed opportunity for continued benefit from the drug, and potentially persistent or irreversible toxicities that limit the options for receiving benefit of subsequent therapies". The FDA found that 15% of all oncology drugs approved from 2010 to 2022 required a post-marketing requirement to investigate alternative dosing and improve the risk:benefit profile of the drug. One of the headings of Project Optimus relates to the impact of a reduced dose on outcome. That is our focus in this presentation. We consider a completed Phase 3 trial and ask the question: how much of the treatment effect is sacrificed by a dose reduction?