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N-of-1 and rapid platform trials

Building a trial around one patient, or letting one trial swap drugs in and out as evidence accumulates.

Bespoke antisense drugs have been made for single patients with rare neurological disease under an FDA pathway, and the same logic is being applied to private neoantigen and splice-targeting therapies in cancer. Adaptive platform trials such as I-SPY 2 in breast cancer graduate or drop arms on interim Bayesian analysis, which is the scalable version of the same idea. The obstacles are manufacturing, cost, and how to learn anything generalisable from a single case.

Generic schematic · not to scale · placeholder for the drug discovery front
Guide RNA library · Knockout → dependency

How it works

Either an intervention is designed for one person's mutation, or a master protocol keeps a shared control arm while arms enter and leave, so each new question costs less.

Strengths
  • Reaches patients whose subgroup will never be studied
  • Platform designs reuse the control arm
  • Faster answers from fewer patients
Limitations
  • Extreme cost per patient for true N-of-1
  • Interpretation without randomisation is fragile
  • Regulatory and reimbursement paths unclear

Latest papers

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Latest papers · live from Europe PMC
Open in Europe PMC

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