Biomarker test development and validation

Question 1

Explain the different stages of biomarker development

Question 2

Describe the fundamentals of technical validation.
Definition
Why perform it?

Answer 2

prove that method measures protein of interested in reliable manner
–> develop (standard) protocol (lab protocol to follow to get wanted results)

• precision
• sensitivity/ Limitations of qualification
• linearity of dilution
• recovery
• parallelism
• sample stability
• selectivity/ specificity

Question 3

What is the A / T / N Framework?

Answer 3

• current fluid biomarkers
  Amyloid (Aß42 / Aß40 ration)
  Tau (p-Tau)
  Neurodegeneration (t-Tau, NfL)

Question 4

Assay validation
- definition
- why?

Answer 4

the process of proving that an analytical method is acceptable for its intended purpose

• minimise analytical and instrumental error
• give reliable and reproducible results
• ensure quality of assay results
• to be assured of correctness of results
• confirm that assay measures what it intends to measure

Question 5

Describe the fundamentals of clinical validation.
Definition
Why perform it?

Answer 5

Measurement in clinical cohort
→ Disease groups and controls
→ Matched for age and sex
→ Equal group sizes
→ Power
→ Independent cohort

Question 6

What are the steps within validation?

Answer 6

Technical validation –> pilot study –> clinical validation