OnCo
ideasIdea

Exposure-response modelling with a pre-set target exposure before any dose is chosen

Instead of picking the dose by how much patients can tolerate, measure drug levels in blood and relate them to both benefit and harm across patients, then choose the dose that hits the sweet spot.

Registrational packages include population PK and exposure-response analyses for efficacy and key toxicities, with the target exposure range declared before phase 3 and the chosen dose justified against it; sparse PK sampling in all trial participants makes this feasible. Regulators publish the exposure-response basis for the label dose.

Hypothesis
Programmes with pre-specified exposure-response dose selection will select doses below MTD more often and will require fewer post-marketing dose changes than programmes without.
Rationale
Exposure-response is standard in most therapeutic areas; oncology has lagged because of the MTD tradition. Many approved oncology drugs have label doses on the flat part of the efficacy curve and the steep part of the toxicity curve.
What would test it
Audit new oncology approvals for the presence and use of exposure-response analysis in dose justification and compare subsequent dose-related label changes.
Maturity
being tested at scale
Who has to act
regulator
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks
  • Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.

Key papers

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Connected

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