# Seamless phase 2/3 with pre-registered go rules as the default for new agents

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

## TL;DR

Instead of stopping after the mid-sized trial, waiting a year, then starting the big one, run them as one study with a clear pre-agreed rule for continuing. This saves a year or more per drug.

## Summary

Adaptive seamless designs where the phase 2 portion (dose or population selection) rolls into the phase 3 portion without a pause, with a pre-registered decision rule, an independent committee applying it, and appropriate statistical control of type I error. The idea is to make this the expected design for agents with a plausible registrational path, with regulators offering fast-track review of the adaptation plan.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Programmes using seamless 2/3 designs will reach primary phase 3 read-out at least 12 months sooner than matched programmes with separate phases, without a higher rate of failed phase 3s.
- Rationale: Operational pauses between phases account for a sizeable share of development time. Seamless designs have supported approvals in several cancers; the remaining barrier is habit and the need for early commitment to the confirmatory endpoint.
- Proposed test: Compare development timelines (first-in-human to pivotal read-out) for seamless versus sequential programmes in the same drug class, using registry start and completion dates.
- Maturity: being-tested-at-scale
- 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: [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [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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