INTRODUCTION TO BAYESIAN THEORY IN POPULATION PHARMACOKINETICS

The Bayesian view of probability is related to degree of belief. It is a measure of the plausibility of an
event given incomplete knowledge. It was originally developed to improve the forecast accuracy by
combining subjective prediction with improvement from newly collected data. Bayesian theory of
probability evaluates the probability of a hypothesis by specifying some prior probability, which is then
updated in the light of new relevant data.

For e.g. In the diagnosis of a disease, a physician may make a preliminary or differential diagnosis based
on the patient’s symptoms and physical examination (subjective evidence/ priori). The results from relevant
laboratory data when combined with the prior evidence a new diagnostic forecast is made.

Thus Bayesian method of probability provides a method to weigh the prior information (subjective
evidence) and the new information (objective evidence) to estimate a new probability for predicting the
disease.

This approach has been used in drug dosing for patients. Based on the patient’s medical history, an average
or population pharmacokinetic parameters appropriate for the patient’s condition (priori) are used to
calculate the initial dose. After the initial dose, the patient’s pharmacokinetic parameters (like Clearance
and volume of distribution)and plasma / serum drug concentrations are obtained from the patient that
provide new information to assess the adequacy of the dosage. Based on the new parameters, adjustments
are made.

Bayesian method gives better prediction to PK parameters of the patient and is particularly useful when
only a few blood samples are available. This approach is beneficial when data is scarce, noisy (erroneous),
or biased. Bayesian methods can be used to combine results from different experiments

Because of inter and intra subject variability, PK parameters of an individual patient must be estimated
from limited data in the presence of unknown random errors (assays etc ), known covariates and variables
such as clearance, weight, disease factors etc. in the presence of large amount of variation in data, Bayesian
approach employs weighted least-squares (WLS) to allow for improved estimation of patient’s
pharmacokinetic parameters by taking into consideration the mean of population PK parameters and their
variability.
For e.g.

After diagnosing a patient, the probability of having a particular disease was 0.4 according to the physician.
Based on the preliminary assessment, the physician ordered a lab test. Positive value has a 0.8 probability
of positively identifying the disease in patient s with the disease (true positive) and a 0.1 probability of
positive result in patients without the disease (false positive). From the prior information (physician’s
assessment)and the current patient specific data (lab tests), what is the posterior probability of the patient
having the disease using the Bayesian method?

Solution:

Prior Probability of having the disease (positive) = 0.4

Prior probability of not having the disease = 1-0.4 = 0.6

Ratio of disease positive : disease negative = 0.4/0.6= 2/3, implying that the physician’s assessment shows
that there is a 2/3 chance that the patient has the disease diagnosed by the physician

The probability of the patient actually having the disease can be better evaluated by including the lab
findings.

For the same patient,

Probability of a true positive = 0.8

Probability of a false positive = 0.1 (test wrongly identifying the disease)

Likelihood Ratio = 0.8/0.1 = 8/1

Combining the prior probability ratio with the likelihood ratio, the posterior probability may be achieved
at: Posterior probability ratio= (2/3) (8/1) = 16/3

Where 16= number of favorable events and 3 = number of unfavorable events

Posterior probability = 16/ (16+3) =

Because total number of events that can occur = 16 +3, and

Probability = total number of favorable events / total number of events

(Probability of an event occurring or not occurring will always lie between 0 to 1, with 0 being no
probability of the event occurring and 1 indicating a 100% chance of the event occurring, which in this case
will be the disease prediction for the patient.)

Posterior probability = (Likelihood probability * Prior probability)

Total number of events or occurances