Biostatistics in Biomarker Validation

Biomarkers can be used for …

• to aid in disease diagnosis or prognosis

• to evaluate risk of disease

• for monitoring disease progression

• for monitoring/ predicting response to treatment

• to identify subjects most likely to respond to treatment

• to determine most appropriate treatment for a patient

• to identify early signs of drug toxicity

What is biomarker validation

ensuring that a biomarker is reliable for the intended application

Define validation

The process of assessing the biomarker and its measurement performance characteristics, and determining the range of conditions under which the biomarker will give reproducible accurate data

Biomarker development phases

• biomarker discovery

• analytical validation

• clinical validation

What is clinical validation

establishing the clinical usefulness of a biomarker

Internal vs. external validation in terms of biomarkers

Internal validation refers to assessing a biomarker's performance using the same dataset it was developed on, while external validation involves testing its performance on independent datasets to confirm its generalizability and robustness. ***

Some common metrics of performance

• sensitivity

• specificity

• positive predictive value

• negative predictive value

Binary marker vs. binary outcome

• marker: biomarker is present or absent in sample

• outcome: progression vs. no progression

common measures of prediction accuracy

include sensitivity, specificity, positive predictive value, and negative predictive value. These metrics evaluate how well a biomarker predicts outcomes. ***

Specificity is what

Proportion of non cases that are correctly predicted as negative by the biomarker

how to interpret the value of 1 - specificity?

A specificity value - 1 indicates the proportion of negatives (non-cases) that are incorrectly classified as positives

Perfectly performing test would …

• correctly detect all cases

• Have a negative result for all non cases

What is positive predictive value (ppv)

The proportion of subjects with a positive test who actually have the disease

What is a negative predictive value?

the proportion of subjects with a negative test who are actually free from the disease/ condition/ mutation

What is a continuous variable?

Can assume any value within a specified interval of values assumed by the variable

What is a continuous marker?

A biomarker that can take on any value within a range and provides a measure of the biological condition over time.

Using cut-points can what?

can generalize notion of sensitivity and specificity to continuous markers

what is the optimal value?

a biomarker with 100% sensitivity and 100% specificity