SP-0102: Redefining the dose distribution (i.e. dose painting with/without dose escalation/dose de-escalation)

Redefining dose-limiting toxicity.

Using SAS to Assess Dose Proportionality in Dose Escalation Studies

Dose escalation studies provide a good opportunity to assess the linearity of PK parameters. This paper describes hypothesis testing and confidence interval (C.I.) methods for assessing dose proportionality based on linear regression and weighted least squares (WLS) linear regression. SAS® code is presented using an example study and AUCinf data.

Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients.

BACKGROUND AND AIMS Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients. METHODS All consecutive...

Individualized Tamoxifen Dose Escalation-Letter.

In a recent commentary (1), Hertz and Rae have put the relevance of pharmacokinetically guided dosing of tamoxifen into perspective. We appreciate this effort and fully agree that more evidence is required to refine the relationship between exposure to the active tamoxifen metabolite endoxifen and clinical outcome parameters. On the basis of the relatively long survival of adjuvantly treated br...

Dose escalation with over-dose and under-dose controls in Phase I/II clinical trials.

To save valuable time and resources in new drug development, Phase I/II clinical trials with toxicity control and drug efficacy as dual primary endpoints have become increasingly popular. Escalation with over-dose control (the EWOC) is a Bayesian adaptive Phase I clinical trial design that can accurately estimate the maximum tolerated dose (MTD) level and control the probability of overdosing p...