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What Were They Thinking? Pharmacologic priors implicit in a choice of 3+3 dose-escalation design

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arxiv 2012.05301 v2 pith:JANLBFF7 submitted 2020-12-09 stat.ME q-bio.QMstat.AP

classification stat.MEq-bio.QMstat.AP
keywords trialdesignbeliefsdesignsdose-escalationexpectationsimplicitpharmacologic
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If explicit, formal consideration of clinical pharmacology at all informs the design and conduct of modern oncology dose-finding trials, the designs themselves hardly attest to this. Yet in conducting a trial, investigators affirm that they hold reasonable expectations of participant safety - expectations that necessarily depend on beliefs about how certain pharmacologic parameters are distributed in the study population. Thus, these beliefs are implicit in a trial's presumed conformance to a community standard of safety, and may therefore to some extent be reverse-engineered from trial designs. For one popular form of dose-escalation trial design, I demonstrate here how this may be done.

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Cited by 1 Pith paper

Reviewed papers in the Pith corpus that reference this work. Sorted by Pith novelty score. Full citation record

  1. Dose-Escalation Trial Protocols that Extend Naturally to Admit Titration

    math.CT 2025-07 conditional novelty 7.0 of 10

    A categorical preorder on trial tallies reveals a new monotonicity flaw in the 3+3 dose-escalation design and yields right Kan and Galois extensions that support titration.

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