# Emulate combination trials from real-world data to triage which ones to run

Source: https://onco.cc/ideas/idea-tr2-rwe-combination-emulation/  
OnCo record `idea-tr2-rwe-combination-emulation` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Combinations used off-label in over 200 patients in clinico-genomic databases can be analysed by target trial emulation. Emulations cannot replace trials, but they can rule out the pairs with no signal and flag those with large effects before money is spent on randomised studies.

## Summary

Target trial emulation with clinico-genomic databases can estimate effects of combinations that are used in practice but never randomised. Emulations cannot replace trials but can deprioritise pairs with no signal and flag those with large effects. The proposal is a standing programme that emulates every combination used in over 200 patients in the database and publishes ranked results with pre-registered protocols.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Combinations flagged as futile in pre-registered emulations will subsequently fail randomised testing in at least 80% of cases, allowing trialists to redirect resources.
- Rationale: Target trial emulation reproduced the results of several oncology trials when confounding was addressable; its false negatives are rarer than its false positives, which suits a triage role.
- Proposed test: Pre-register emulations for ten combinations with pending randomised readouts and score concordance when trials report.
- Maturity: early-clinical
- Actor: data

## Sources

- Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017): https://doi.org/10.1016/j.cell.2017.11.009

## Connected records

- companies: [Foundation Medicine (Roche)](https://onco.cc/companies/foundation-medicine/), [Tempus AI](https://onco.cc/companies/tempus/)
- collections: [AACR Project GENIE](https://onco.cc/collections/genie/)
- terms: [Real-world evidence](https://onco.cc/terms/real-world-evidence/)
- bottlenecks: [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/), [Weak real-world evidence and registries](https://onco.cc/bottlenecks/b-real-world-evidence/)
- key papers: [Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy](https://onco.cc/key-papers/paper-palmer-cell/)

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