Make clonal clearance, not tumour shrinkage, a trial endpoint
A drug that shrinks a tumour by half but leaves the resistant sub-population untouched will fail. Trials should measure whether every sub-population is cleared, not just overall size.
Response criteria (RECIST) measure bulk diameter; ctDNA endpoints measure total variant allele fraction. Neither captures whether all subclones are suppressed. A clonal clearance endpoint, defined as undetectable plasma signal for every baseline-identified subclone at a fixed timepoint, could be validated as a surrogate and used in early-phase trials to distinguish drugs that shrink from drugs that eradicate.
- Tumour heterogeneity and clonal evolution · A tumour is many tumours. Treatments that kill most cells leave the rest to grow back, changed.
- 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.
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not linked directly; found by shared links- IdeaKill combination arms early using circulating tumour DNA, before waiting for scans
Shares RECIST, Circulating tumour DNA (ctDNA), Progression-free survival (PFS), Trial design, endpoints and cost.
- IdeaUse a blood test at six weeks to decide whether to keep going
Shares RECIST, Circulating tumour DNA (ctDNA), Progression-free survival (PFS), Trial design, endpoints and cost.
- IdeaTrack clones in blood with methylation patterns instead of mutations
Shares Tumour heterogeneity and clonal evolution, Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
- IdeaValidate real-world progression endpoints so pragmatic trials can use them
Shares RECIST, Progression-free survival (PFS), Trial design, endpoints and cost.
- IdeaPublish the disagreement between trial doctors and independent reviewers for every trial
Shares RECIST, Progression-free survival (PFS), Trial design, endpoints and cost.
- TermProgressive disease and radiographic progression
Shares RECIST, Circulating tumour DNA (ctDNA), Progression-free survival (PFS).
- IdeaAI-assisted central imaging reads to cut endpoint cost and variability
Shares RECIST, Progression-free survival (PFS), Trial design, endpoints and cost.
- IdeactDNA-guided dose holidays for lung cancer targeted therapy
Shares Tumour heterogeneity and clonal evolution, Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).