OnCo
ideasIdea

Require a randomised phase 2 before any phase 3

Many large trials are launched on the strength of a small study with no comparison group, and most of those large trials fail. Insisting on a smaller randomised comparison first would filter out weak drugs earlier.

Sponsors and regulators adopt an expectation that phase 3 in a new indication is preceded by a randomised phase 2 (or the phase 2 portion of a seamless design) with a concurrent control, rather than a single-arm response-rate study. Exceptions for very large single-arm effects in refractory settings.

Hypothesis
Programmes with a randomised phase 2 will have a phase 3 success rate at least 15 percentage points higher than programmes proceeding from single-arm phase 2, and overall development cost per approval will fall despite the added step.
Rationale
Response rates in single-arm studies are poor predictors of survival benefit, and phase 3 oncology failure rates are among the highest of any therapeutic area. Randomised phase 2 also yields early estimates for planning the phase 3.
What would test it
Compare phase 3 success rates for programmes with and without randomised phase 2 across a decade of registry data, adjusting for indication and mechanism.
Maturity
early clinical
Who has to act
industry
Cost to try
Medium ($1M to $50M)
Years to first evidence
3
Bottlenecks it attacks
  • Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
  • Failures are hidden · Negative trials, failed drugs and abandoned programmes are rarely published, so the same mistakes are repeated.

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terms

2
Objective response rate (ORR)Progression-free survival (PFS)

bottlenecks

2
Failures are hiddenTrial design, endpoints and cost