ideasIdea
SMART designs to test treatment strategies, not just single drugs
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.
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.
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.
What would test it
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
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.