# SMART designs to test treatment strategies, not just single drugs

Source: https://onco.cc/ideas/idea-tr1-smart-designs-for-adaptive-strategies/  
OnCo record `idea-tr1-smart-designs-for-adaptive-strategies` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Real treatment is a series of decisions: start with this, switch to that if it fails. Sequential multiple-assignment randomised trials test whole strategies by randomising patients again at each decision point.

## Summary

SMART designs re-randomise participants at pre-specified decision points (e.g., at first progression or at ctDNA rise) to compare adaptive treatment strategies, estimating the best dynamic regime rather than the best single drug. Used in behavioural science and some leukaemia trials, rarely in solid tumours. Combined with a platform structure, this can address resistance-driven sequencing.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: SMART trials will identify treatment strategies that improve OS over the best single-decision comparison in at least one common solid tumour setting within five years.
- Rationale: Sequencing and switching decisions drive outcomes as much as the choice of first drug; single-decision RCTs cannot evaluate them, and observational sequencing data are confounded.
- Proposed test: Run one SMART in metastatic colorectal or prostate cancer comparing switching rules (radiographic vs ctDNA-triggered) and second-line choices, with OS as the primary endpoint.
- Maturity: speculative
- Actor: research

## 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

- roadmaps: [Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch](https://onco.cc/roadmaps/prostate-roadmap/)
- ideas: [Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer](https://onco.cc/ideas/idea-prostate-randomise-the-sequence-not-only-the-drugs/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [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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