DTAT – Dose Titration Algorithm Tuning

The DEDUCTION Project

explainers

The DEDUCTION Project is the latest—and possibly conclusive—development within the DTAT research programme. This post explains its origins, motivation and current outlook.

How large must a dose-optimization trial be?

explainers

This is a lay explanation for my paper accepted for publication in a CPT: Pharmacometrics & Systems Pharmacology special themed issue on Dose Optimization in Oncology

Notes on therapeutic index in oncology dose finding

tweetorials

Announcing an important update to the EscRisk app, with provisional efforts to trace the therapeutic index idea within the oncology dose-finding literature…

Complete Path Enumeration (CPE)

tweetorials

This demonstrates the feasibility of a programme I’ve set forth, for the ‘exact’ simulation of ANY dose-escalation design.

Influenced by @MarkusTriska‘s exacting perspective…

What Were They Thinking?

tweetorials

This thread introduces a Dec 2020 paper I posted on arXiv, containing several important elements including the advent of what I have since termed complete path enumeration (C…

Retrospective on a Fatal Dose-Finding Trial

tweetorials

This thread introduces an April 2020 paper I posted on arXiv, introducing a therapeutic index concept has become crucial to several later developments.

An Article of Impeachment

tweetorials

This tweetorial explains a Dec 2019 preprint I posted on OSF. See also this short video.

Debut of R package ‘precautionary’

tweetorials

This thread marked the debut of R package precautionary. The historical origins documented here remain of interest, despite major (and ongoing, mid-2021) improvements that…

DIA IDSWG KOL Lecture

Many thanks to the DIA Innovative Designs Scientific Working Group (IDSWG — formerly ADSWG, A = Adaptive) for their kind invitation to give a KOL Lecture today. Special…

FDA OCE response on dose individualization

journal

Here is the text of FDA’s April 20, 2020 response to a query submitted on my behalf Jan 22 by the office of Congresswoman Rep. Pramila Jayapal. (Advance to page 2 of this…

Therapeutic Synergism and the Statistician

short-videos

This very short (2:20) video surveys the core argument of this working paper, which shows how 1-size-fits-all dosefinding ruins therapeutic synergism.

Comment on Wages et al., Coherence principles in interval-based dose finding

under-review

UPDATE: (Mar 30) Yesterday, PST published my letter online. Wages, Iasonos, O’Quigley & Conaway thus far appear to have offered no reply despite ample time to do so.

On the MTD heuristic and the TLA shell-game

*TLA = Three-Letter Acronym

Missed opportunities at Phase 1 Manchester

journal

“Phase 1: Where Science Becomes Medicine” was the apt title of last week’s conference in Manchester England, devoted to phase 1 trials in oncology. The ‘Science’ and ‘Medicin…

‘Interventional pharmacoeconomics’ debases drugs and pharmacology alike

unfit_to_print

A Letter to the Editor of JAMA Oncology, desk-rejected July 15, 2019:

Publications

This site is devoted to the lay outreach component of my research programme in dose individualization for cancer treatments. At the core of this research lies a…

Precautionary Coherence for IRBs

short-videos

This very short (2:20) video introduces the Precautionary Coherence principle for IRB (Institutional Review Board) audiences. You can find a more detailed exposition of the…

DTAT for Pharma Investors

short-videos

Pharma investors’ tolerance for 1-size-fits-all dose finding continues to astonish me. In this short video, I put the case for making early-phase trial methodology an issue…

Into the Mind of the
#OneSizeFitsAllogist

longer-videos

I have on my bookshelf a 300-page book devoted entirely to 1-size-fits-all dose finding—a practice that any sensible layperson sees immediately as utterly wrongheaded. When…

Clinicians must regain control over phase 1 cancer combination-therapy trials

explainers

This is a lay explainer for my bioRxiv preprint Costing ‘the’ MTD … in 2-D.

One-size-fits-all dosing of cancer treatment drugs: How much does it cost society?

explainers

This is a lay explainer for my bioRxiv preprint Costing ‘the’ MTD.

On the elementary nature of Precautionary Coherence

dialogues

The following hypothetical dialogue illustrates the elementary nature of the ‘precautionary coherence’ (PC) argument that I have detailed elsewhere. This dialogue occurs…

A new concept may help us at last abandon one-size-fits-all dosing of cancer treatment drugs

explainers

This is a lay explainer for my F1000Research paper, Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

Dose-finding realism that resonates with clinicians

unfit_to_print

A Letter to the Editor of Clinical Cancer Research, desk-rejected Oct 19, 2018:

Dose escalation belies the therapeutic intent of phase I trials

unfit_to_print

Adapted from the text of a ‘Comments and Controversies’ piece rejected by the Journal of Clinical Oncology in April 2018