English

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

Methodology 2020-12-25 v2 Quantitative Methods Applications

Abstract

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.

Keywords

Cite

@article{arxiv.2012.05301,
  title  = {What Were They Thinking? Pharmacologic priors implicit in a choice of 3+3 dose-escalation design},
  author = {David C. Norris},
  journal= {arXiv preprint arXiv:2012.05301},
  year   = {2020}
}

Comments

5 pages, 3 figures, 1 table, 13 references with added hyperlinks. Version 2 restores to the exhibit on page 2 a DCG clause which v1 had mistakenly cropped; additionally, footnote 6 is expanded and a few minor typographical or grammatical improvements are made