Populational PKPD Analysis Flashcards

1
Q

The ______ used to measure drug concentrations also has variability.

A

Assays.

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2
Q

Variability is not a major concern for what drugs.

A

Those that don’t have a narrow therapeutic window.

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3
Q

Factors affecting PK/PD are known as ____________

A

Covariates.

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4
Q

This form of PK analysis focuses on:
1. Homogenous Population
2. Single Dose Studies
3. Small Study Groups
4. Intensive Sampling

A

Traditional PK analysis

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5
Q

This form of PK analysis focuses on:
1. Phase II/III Trials
2. Heterogenous patient population
3. Lack of simple experimental paradigm
4. Sparse sampling strategies
5. Complicated and time-intensive analysis.

A

Routine Clinical Trials.

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6
Q

Quantitative relationship between parameter values and co-variates.

A

Covariate Model of Populational Analysis

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7
Q

Variability of parameter values across populations of patients.

A

Statistical Model of Populational Analysis.

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8
Q

Analyzes mean PK parameters.

A

Structural Model of Populational analysis.

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9
Q

In populational analysis what is epsilon?

A

The distance from the population to the observed data for an individual patient.

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10
Q

Estimate population mean parameters by treating all data as if it were from the same individual.

A

Naive Pooled Data

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11
Q

Estimate each individual’s PK and then use individual parameters to estimate the population mean parameters.

A

Standard Two-Stage Model

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12
Q

This is the gold standard of populational analysis.

A

Nonlinear Mixed Effects Modeling.

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13
Q

Estimates fixed and random effect populational parameters simulataneously.

A

Nonlinear Mixed Effects Modeling.

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14
Q

Use prior distribution of parameters in a population of subjects and data from an individual to estimate the individual’s parameters.

A

Bayesian Estimation.

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15
Q

In _____________, all data points are assumed to arise from a single individual.

A

Naive Pooled Data

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16
Q

Name the Analysis:
Advantages: Very Simple, Not limited by patients

Disadvantage: Individual’s are lost, no covariate influence, no separation of error soruce.

A

Naive Pooled Data

17
Q

What are the steps to the Standard-Two Stage Model.

A
  1. Individual Fitting-> Model is identified separately in all subjects obtaining parameter estimates.
  2. Report Central Tendencies.-> The population mean (theta) and covariance (omega^2) are calculated as the sample mean and covariance.
18
Q

What are the disadvantages to the standard two-stage analysis?

A
  1. Requires Rich Data from every individual.
  2. Ignores the precision of the individual estimates.
  3. Overestimates the population variance.
19
Q

What approach can be used regardless of whether data is rich or sparase?

A

Nonlinear Mixed Effects Modeling.

20
Q

In this form of analysis, one stage is needed estimating fixed effects and random effects simultaneously.

A

Non-Linear Mixed Effects Modeling.

21
Q

_________ refers to features common to the entire population. (mean PK parameters, Covariate Factors)

A

Fixed Effects.

22
Q

________________ refers to populational variability and measurement of uncertainties. (Interindividual, between occasion variability, residual variability)

A

Random Effects.

23
Q

What is ETA on a mixed effects modeling graph of log Cp vs time?

A

The distance between the population mean and individual parameter. This accounts for random effects.

24
Q

What is epsilon on a mixed effects modeling graph of log Cp vs time?

A

The distance between the predicted and observed parameter values for an individual.

25
Q

Measure of the “spread” of the probability density.

A
  1. Standard Deviation (omega)
  2. Variance (omega^2)
26
Q

When looking at a distribution curve, what does a wider curve suggest?

A

The wider the curve, the more variability between the subjects in a populational analysis. Ideally we want to account for any potential covariates, to adjust the data appropriately and reduce the overall width of the distribution curve.

27
Q

Symbol for variance.

A

Omega^2

28
Q

What are some potential sources of residual variability?

A
  1. Measurement error in parameter or time.
    ~Assay error
    ~Investigator or patient non-complicance.
  2. PK/PD model misspecification.
    ~Model Inappropriate
    ~Model Incomplete
    ~Intraindividual variability
    ~data errors.
29
Q

Population PK parameters include:

A
  1. Mean Parameter Values
  2. Quantitative Relationships between parameter values and covariates.
  3. Variability of parameter values across populations of patients.
30
Q

The one compartment model following an IV bolus dose is an example of which populational model?

A

Structural Model

31
Q

The weight, age, genotype of the subjects is associated with which populational model?

A

Covariate

32
Q

The between subject, occasion, and residual variability are associated with which populational model?

A

Statistical.

33
Q

Which software is used for Nonlinear Mixed Effect Modeling?

A

NONMEM