Biomarkers, Precision Medicine and Drug Development

Flashcards covering definitions, types, validation processes, statistical assessments, and clinical trial designs for biomarkers as presented in the lecture.

How did the 2003 definition describe a biomarker?

It is a biological characteristic that serves as an objective measure, meaning it will not change the outcome if measured multiple times.

According to the transcript, should biomarkers be thought of as signs or symptoms?

Biomarkers should be thought of as 'signs', as 'symptoms' are more likely a clinical outcome.

What are the three essential components of a biological marker (biomarker)?

1) A biological characteristic (target), 2) that can be objectively measured (measure), and 3) is clinically or biologically informative (relevance).

Why is a cognitive assessment not considered a biological marker?

It is not a biological marker because it is not testing a specific biological substrate.

How does the transcript define a surrogate clinical end-point according to Temple (1999)?

A laboratory measurement or physical sign used in therapeutic trials as a substitute for a clinically meaningful end point that represents how a patient feels, functions, or survives.

What is the difference between Analytical Validation and Clinical Validation for novel biomarkers?

Analytical Validation assesses measurement performance characteristics (accuracy and precision), while Clinical Validation provides evidence linking the biomarker with biology and a clinical endpoint.

What are the three elements required in a Biomarker Description?

Biomarker Identity (name, identifier, acronym, source, type), Biologic Plausibility, and Measurement Method.

What is a Diagnostic Biomarker?

A biomarker used to detect or confirm the presence of a disease or condition or to identify individuals with a subtype of the disease.

Provide two examples of Diagnostic Biomarkers mentioned in the text.

1) Blood sugar or hemoglobin A1c ($HbA1c$) for Type 2 diabetes mellitus, and 2) Repeated blood pressure readings for essential hypertension.

What is the definition of a Monitoring Biomarker?

A biomarker measured repeatedly to assess the status of a disease or medical condition, or to collect evidence of exposure to a medical product or environmental agent.

How is a Susceptibility/Risk Biomarker defined?

A biomarker indicating the potential for developing a disease or medical condition in an individual who does not currently have clinically apparent disease.

What is the purpose of a Pharmacodynamic/response Biomarker?

It is used to show that a biological response has occurred in an individual exposed to a medical product or an environmental agent.

What is a Safety Biomarker?

A biomarker measured before or after exposure to a medical product or environmental agent to indicate the likelihood, presence, or extent of toxicity as an adverse effect.

What is the key difference between Predictive and Prognostic Biomarkers?

Predictive biomarkers identify treatment effects and how an individual will respond to a specific exposure, while Prognostic biomarkers identify the likelihood of a clinical event or disease progression regardless of treatment.

In the context of the ROC curve, what does the Area Under the Curve (AUC-ROC) represent?

It is a metric of performance: an AUC-ROC of $1$ implies perfect classification, while an AUC-ROC of $0.5$ indicates performance at random chance.

How is Diagnostic Accuracy calculated?

$$\text{Diagnostic Accuracy} = \frac{TP + TN}{TP + TN + FP + FN}$$

What is Sensitivity in the context of biomarkers?

The ability to detect a disease in patients in whom the disease is truly present (True Positive rate).

What is Specificity in the context of biomarkers?

The ability to rule out the disease in patients in whom the disease is truly absent (True Negative rate).

How does disease prevalence affect Sensitivity and Specificity?

Sensitivity and Specificity are intrinsic properties of the test and are not markedly influenced by prevalence.

How does disease prevalence affect Positive Predictive Value (PPV)?

If prevalence is low, the PPV will be lower (more false alarms); if prevalence is high, the PPV increases.

In the Biomarker Innovation Matrix, what is 'Repurposing' (Category 2)?

Using existing technology to measure a new target, which is highly efficient because machinery and training are already established.

What is an Enrichment design in clinical trials?

A prospective strategy using a patient characteristic to select a study population in which the detection of a drug effect is more likely.

What is an All-comer design?

A design where all patients are screened and randomized regardless of biomarker status, often used when treatment benefits need to be understood in both negative and positive groups.

Why is Cerebrospinal Fluid (CSF) withdrawal rarely performed despite being informative for brain states?

CSF withdrawal is a very risky procedure and is typically only done in emergency cases.

What is the difference between Intra-individual and Inter-individual variability?

Intra-individual variability refers to differences in the same subject over time (e.g., diurnal cycles), while Inter-individual variability refers to differences between different subjects (e.g., genetics, diet).