OnCo
ideasIdea

No accelerated approval for a combination without proof each part contributes

Regulators should refuse to approve a two-drug combination unless there is evidence that both drugs are doing something, so patients are not exposed to useless extra toxicity and cost.

Several combinations (for example anti-TIGIT plus PD-L1, IDO inhibitor plus PD-1) reached phase 3 without randomised evidence of the added agent's contribution and failed. FDA guidance on co-development already asks for contribution-of-components data but allows exceptions. Making a randomised contribution assessment (or a factorial design) a firm condition of accelerated approval for combinations would redirect development effort towards combinations with evidence of synergy.

Hypothesis
Combination phase 3 failure rates fall by at least a third within five years of a firm contribution-of-components requirement, as measured against the preceding five years.
Rationale
The TIGIT and IDO programmes together consumed thousands of patients and billions of dollars with single-arm or non-randomised phase 2 evidence. Randomised phase 2 with a contribution arm would have flagged the lack of effect.
What would test it
Audit the last decade of combination phase 3 failures for whether a contribution-of-components study existed; model the effect of a requirement; implement via guidance and track.
Maturity
early clinical
Who has to act
regulator
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks

Connected

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