Mesalazine for the prevention of colorectal cancer: effects in patients with a history of sporadic adenomatous polyps
Ontology highlight
ABSTRACT:
DISEASE(S): Colon Adenomatous Polyp,Sporadic Colorectal Adenomas
PROVIDER: 2529518 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Lockwood2006 - AlzheimersDisease PBPK
model
A mathematical model to predict the
effectiveness of CI-1017 (muscarinic agonist) for Alzheimer's
disease by evaluating changes in ADAS-cog score.
This model is described in the article:
Application of clinical
trial simulation to compare proof-of-concept study designs for
drugs with a slow onset of effect; an example in Alzheimer's
disease.
Lockwood P, Ewy W, Hermann D,
Holford N.
Pharm. Res. 2006 Sep; 23(9):
2050-2059
Abstract:
OBJECTIVE: Clinical trial simulation (CTS) was used to
select a robust design to test the hypothesis that a new
treatment was effective for Alzheimer's disease (AD).
Typically, a parallel group, placebo controlled, 12-week trial
in 200-400 AD patients would be used to establish drug effect
relative to placebo (i.e., Ho: Drug Effect = 0). We evaluated
if a crossover design would allow smaller and shorter duration
trials. MATERIALS AND METHODS: A family of plausible drug and
disease models describing the time course of the AD assessment
scale (ADAS-Cog) was developed based on Phase I data and
literature reports of other treatments for AD. The models
included pharmacokinetic, pharmacodynamic, disease progression,
and placebo components. Eight alternative trial designs were
explored via simulation. One hundred replicates of each
combination of drug and disease model and trial design were
simulated. A 'positive trial' reflecting drug activity was
declared considering both a dose trend test (p < 0.05) and
pair-wise comparisons to placebo (p < 0.025). RESULTS: A 4 x
4 Latin Square design was predicted to have at least 80% power
to detect activity across a range of drug and disease models.
The trial design was subsequently implemented and the trial was
completed. Based on the results of the actual trial, a
conclusive decision about further development was taken. The
crossover design provided enhanced power over a parallel group
design due to the lower residual variability. CONCLUSION: CTS
aided the decision to use a more efficient proof of concept
trial design, leading to savings of up to US 4 M dollars in
direct costs and a firm decision 8-12 months earlier than a
12-week parallel group trial.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000673.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
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