Biomarkers and surrogate markers

Question 1

What is a biomarker

Answer 1

any biochemical, physiological, structural or genetic measurement that describes a biological or pathophysiological process and/or pharmacological response

Question 2

Give 2 examples of biomarkers in a clinical trial

Answer 2

1. symptoms
2. investigations - samples, images, physiology

Question 3

How can biomarkers be used pre-clinically

Answer 3

to determine the efficacy and safety of drugs and this may predict a clinical response

Question 4

name 3 ways biomarkers can be used clinically

Answer 4

1. in phase 1 studies to support mechanic hypothesis, predict toxicity of drug, estimate dose response relationship
2. in phase 2 and 3 studies to identify the appropriate patients for the trial, to indicate treatment safety or efficacy, identify subgroups of patients most likely to benefit from the treatment
3. in healthcare to identify patients where new medicine is clinically indicated, monitor benefits and harms

Question 5

Describe some advantages of using biomarkers in clinical studies

Answer 5

1. simple, less expensive than clinical endpoints
2. can be analysed repeatedly over a short period of time e.g. ECG
3. clinical trials can be done with fewer subjects over a shorter period of time
4. ethically more appropriate

Question 6

Describe some disadvantages of using biomarkers in clinical studies

Answer 6

a disease biomarker may not be useful if:

• it is measured inaccurately
• it does not change with chosen intervention
• it does not predict the clinical endpoint
• it is altered by confounding factors
• it is only weakly associated with the disease - multiple biomarkers may be more beneficial

Question 7

What does it take for a biomarker to become a surrogate marker

Answer 7

being able to link biomarker with biological processes and clinical endpoints - described by the Bradford Hill criteria

Question 8

what is a surrogate marker

Answer 8

a biomarker that predicts a clinically meaningful outcome

Question 9

What does the bradford hill criteria state

Answer 9

that biomarkers, in order to become surrogate markers need to meet these guidlines:

• strength
• consistency
• specificity
• temporality
• biological gradient
• plausibility
• coherence
• experimental evidence
• analogy

Question 10

What is a surrogate outcome

Answer 10

substitutes for clinically meaningful outcomes

solid scientific evidence that surrogate predicts a clinical outcome

can give an answer more quickly than clinically meaningful outcomes