# Pre-specified crossover-adjusted survival in every trial that allows crossover

Source: https://onco.cc/ideas/idea-tr1-crossover-adjusted-survival-standard/  
OnCo record `idea-tr1-crossover-adjusted-survival-standard` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

When control-arm patients switch to the new drug after their cancer grows, the survival comparison gets muddied. Trials should plan in advance how they will correct for this, and report both raw and corrected numbers.

## Summary

Protocols permitting treatment switching pre-specify the adjustment method (rank-preserving structural failure time, inverse probability of censoring weighting, two-stage estimation), the assumptions, and sensitivity analyses, with the estimand defined under ICH E9(R1). Both intention-to-treat and adjusted OS are reported in the label and in HTA submissions. Health technology agencies already require this ad hoc; the idea is to make it a registration requirement.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Mandatory pre-specified adjustment will reduce the frequency of OS results that are uninterpretable because of crossover, and will produce more consistent HTA decisions across countries for the same drug.
- Rationale: Crossover is ethically necessary but currently destroys the OS signal in many trials, feeding disputes about value. Methods exist and are used inconsistently, often chosen after seeing the data.
- Proposed test: Audit recent oncology approvals with crossover for whether adjusted OS was pre-specified; then require it and re-audit after three years for interpretability and HTA discordance.
- Maturity: early-clinical
- Actor: regulator

## 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

- institutions: [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/)
- terms: [Hazard ratio (HR)](https://onco.cc/terms/hazard-ratio/), [Overall survival (OS)](https://onco.cc/terms/os/)
- 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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