ideasIdea

Randomise the next line of treatment before the first one fails

Trials usually study one treatment at a time, so nobody knows the best order. Deciding the next step in advance, by lottery, answers the sequencing question at little extra cost.

Sequencing questions are almost never answered because patients leave the trial at progression. A pre-randomised design assigns the second-line option at the time of first-line enrolment, keeps patients within the protocol at progression, and collects the progression biopsy. Total sample size increases modestly, but the design yields a real strategy comparison rather than isolated line-by-line results.

Hypothesis

Strategy-randomised sequencing trials detect clinically meaningful differences in overall survival between drug orders that line-by-line trials cannot detect, in at least one common setting.

Rationale

Overall survival depends on the whole sequence, not the first agent; oncology has repeatedly discovered that ordering matters (for example in metastatic colorectal and prostate cancer) only through retrospective analysis.

What would test it

Add pre-randomised second-line assignment to two ongoing first-line trials and compare information gained per patient with a matched conventional design.

Maturity

speculative

Who has to act

research

Cost to try

Medium ($1M to $50M)

Years to first evidence

Bottlenecks it attacks

Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
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.

Connected

4top

Pages like this

not linked directly; found by shared links

terms

ADC sequencing Overall survival (OS)

bottlenecks

Acquired resistance to every therapy Trial design, endpoints and cost