precautionary-package: Safety Diagnostics for Dose-Escalation Trial Designs

Description Author(s) References


Enhances various R packages that support the design and simulation of phase 1 dose-escalation trials, adding diagnostics to examine the safety characteristics of these designs in light of expected inter-individual variation in pharmacokinetics and pharmacodynamics.


David C. Norris (


  1. Norris DC. Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials. F1000Research. 2017;6:112. doi: 10.12688/f1000research.10624.3.

  2. Norris DC. Costing ‘the’ MTD. bioRxiv. August 2017:150821. doi: 10.1101/150821.

  3. Norris DC. Precautionary Coherence Unravels Dose Escalation Designs. bioRxiv. December 2017:240846. doi: 10.1101/240846.

  4. Norris DC. One-size-fits-all dosing in oncology wastes money, innovation and lives. Drug Discov Today. 2018;23(1):4-6. doi: 10.1016/j.drudis.2017.11.008.

  5. Norris DC. Costing ‘the’ MTD ... in 2-D. bioRxiv. July 2018:370817. doi: 10.1101/370817.

  6. Norris DC. Ethical Review and Methodologic Innovation in Phase 1 Cancer Trials. JAMA Pediatrics. 2019;173(6):609 doi: 10.1001/jamapediatrics.2019.0811.

  7. Norris DC. Comment on Wages et al., Coherence principles in interval-based dose finding. Pharmaceutical Statistics 2019, DOI: 10.1002/pst.1974. Pharmaceutical Statistics. March 2020. doi: 10.1002/pst.2016.

  8. Norris DC. Retrospective analysis of a fatal dose-finding trial. arXiv:2004.12755 [stat.ME]. April 2020.

  9. Norris DC. What Were They Thinking? Pharmacologic priors implicit in a choice of 3+3 dose-escalation design. arXiv:2012.05301 [stat.ME]. December 2020.

precautionary documentation built on Jan. 15, 2021, 3:36 p.m.