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Adaptive Method For Dosing With Feedback

DOSING - PHARMACOGENETICS

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Abhijna V.B
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87 views17 pages

Adaptive Method For Dosing With Feedback

DOSING - PHARMACOGENETICS

Uploaded by

Abhijna V.B
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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Seminar on

BAYESIAN THEORY WITH


ADAPTIVE METHOD OR
DOSING WITH FEEDBACK
 Bayesian probability is one of the most
popular interpretations of the concept of
probability.
 The Bayesian interpretation provides a
standard set of procedures and formula to
perform this calculation.
 Bayesian probability interprets the
concept of probability as "a measure of a
state of knowledge" in contrast to
interpreting it as a frequency or a
physical property of a system.
 Its name is derived from the 18th century
statistician Thomas Bayes, who pioneered
some of the concepts
 According to the objectivist view, the rules of
Bayesian statistics can be justified by
requirements of rationality and consistency
and interpreted as an extension of logic.
 According to the subjectivist view, the state
of knowledge measures a "personal
belief".Many modern machine learning
methods are based on objectivist Bayesian
principles
 Given some data and some
hypothesis, the posterior probability
that the hypothesis is true is
proportional to the product of the
likelihood multiplied by the
prior probability.
 For simplicity, the "prior probability"
is often abbreviated as the "prior"
and the "posterior probability" as the
"posterior"
Introduction to Bayesian
Theory
 Bayesian theory was originally developed to
improve forecast accuracy by combining
subjective prediction with improvement from
newly collected data.
 In the diagnosis of disease, the physician
may make a preliminary diagnosis based on
both sets of information. Bayesian theory
provides a method to weigh the prior
information (eg.physical diagnosis) and new
information (e.g., results from laboratory
tests) to estimate a new probability for
predicting the disease.
 In developing drug dosage regimen we assess the
patient’s medication history and then use average or
population pharmacokinetic parameters appropriate
for the patient’s condition to calculate the initial
dose.
 After the initial dose, plasma or serum drug
concentrations are obtained from the patient that
provides new information to assess the adequacy of
the dosage.
 The dosing approach of combining old information
with new involves a “feedback” process and to some
degree inherent in many dosing methods involving
some parameter readjustment when new serum drug
concentrations become known.
 Because of inter-and intrasubject variability the
pharmacokinetic parameters of an individual
patient must be estimated from limited data in
the presence of
random error (assays ,etc)known covariates
variables such as clearance , weight, and disease
factor etc.
 Bayesian methods often employ a special
weighted-least squares(WLS)approach and
allow improved estimation of patient
pharmacokinetic parameters when there is a
lot of variation in data
 Where,
 H is a hypothesis, and D is the data.
 Prob (H) =the probability of the patient’s
parameter within the assumed population
distribution.(PRIOR Probability)
 Prob(D/H)=the probability of measured
concentration within the population, and
 P(D) is the marginal probability of D.
 P(H | D) is the posterior probability: the probability
that the hypothesis is true, given the data and the
previous state of belief about the hypothesis.
Example 01

 False positive test.


 True positive test.
Example 2

 Relation of Therapeutic
concentration of theophylline with
adverse effect
 Example of bayesian method with
alternative method to determine the
parameter
 Advantage :
Bayesian approach is the improvement in
estimating the patients pharmacokinetic
parameters based on Bayesian probability
versus an ordinary least-square based
programe
 Disadvantage:
Bayesian method is the subjective selection of
prior probability. Therefore , it is not
considered to be unbiased by many
staticians for drug approval purposes
Adaptive method or dosing
with feed back
 In dosing drugs with therapeutic
ratios, an initial dose is calculated
based on mean population
pharmacokinetic parameters.
 More blood samples are drawn
ph.parameter increasingly more
reliable
 This type of approach has been
referred to as adaptive or bayesian
adaptive method with feedback
 Many least squares and weighted
least square algorithms are available
for estimating pk.parameters.
 Advantage is the ability to input
known information into the
programe, so that the search for real
pharmacokinetic parameter is more
efficient and perhaps, more precise
ORDINARY LEAST SQUARE
METHOD
BAYES ESTIMATOR

 When Pk parameter, p is estimated from a set


of plasma grug concentration data (ci) having
several potential sources of error with
different variances OLS is no longer adequate.
 Weighted least squares equation
the equation represents the

least square estimation of the concentration


by minimizing deviation squares and
deviation of population parameters squares is
called as BAYES ESTIMATOR
`

 Bayesian (ELS) : uses NONMEM


 Other available
 NPME2 : non parametric maximum
expectation maxmization method
 FOEM
 P-PHARM
Thank you

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