# Require a randomised phase 2 before any phase 3

Source: https://onco.cc/ideas/idea-tr1-randomised-phase-2-before-phase-3/  
OnCo record `idea-tr1-randomised-phase-2-before-phase-3` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Phase 3 trials are often launched on a small single-arm response-rate study with no comparison group, and most then fail. Requiring a randomised phase 2 with a concurrent control first, with exceptions only for large effects in refractory settings, would filter out weak drugs earlier.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: industry

## Sources

- Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017): https://doi.org/10.1136/bmj.j4530

## Connected records

- terms: [Objective response rate (ORR)](https://onco.cc/terms/orr/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13](https://onco.cc/key-papers/paper-davis-bmj/)

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