Evaluation of genetic tests

Question 1

What are the 4 components of the ACCE model?

Answer 1

Analytical validity
Clinical validity
Clinical utility
Ethical, legal, social implications

Question 2

What is analytical validity?

Answer 2

How well does the test measure what it claims it’s measuring? Also measures whether it can do so accurately and repeatedly, and if its sensitive enough

Question 3

What is clinical validity?

Answer 3

How well does the test product predict the disease state? Is the thing being tested actually associated with the disease?

Question 4

What is clinical utility?

Answer 4

How useful is the test result? Does it actually help the patient’s health outcomes and quality of life, or provide insight into next steps, or identify people at risk, or diagnose a disease

Question 5

What is ethical validity?

Answer 5

How well does the test meet the expected ethical standards? Is there informed consent and everything is voluntary, and can everyone access the test?

Question 6

What is test sensitivity?

Answer 6

The proportion of affected individuals who are correctly identified as being affected

Question 7

What are the 6 key performance indicators for analytical validity?

Answer 7

1. Sensitivity
2. Specificity
3. False positive rate
4. False negative rate
5. Positive predictive rate
6. Negative predictive rate

Question 8

How do we assess the sensitivity of a genetic test?

Answer 8

Number of correctly identified affected individuals/total number of known affected individuals

Question 9

What is test specificity?

Answer 9

Proportion of unaffected individuals correctly identified to be unaffected

Question 10

How do we assess the specificity of a genetic test?

Answer 10

Number of correctly identified unaffected individuals/total number of known unaffected individuals

Question 11

What is the false positive rate?

Answer 11

Number of unaffected individuals incorrectly identified as being affected

Question 12

How do we assess the false positive rate of a genetic test?

Answer 12

Number of incorrectly identified unaffected individuals/total number of individuals who tested positive

Question 13

What is the false negative rate?

Answer 13

Number of affected individuals incorrectly identified as being unaffected

Question 14

How do we assess the false negative rate of a genetic test?

Answer 14

Number of incorrectly identified affected individuals/total number of individuals who tested negative

Question 15

What is the positive predictive value?

Answer 15

Fraction of affected individuals who tested positive who truly have the condition

Question 16

How do we assess the positive predictive value of a test?

Answer 16

Number of affected individuals who tested positive/total number of individuals who tested positive

Question 17

What is the negative predictive value?

Answer 17

Fraction of unaffected individuals who tested positive who truly don’t have the condition

Question 18

How do we assess the negative predictive value of a test?

Answer 18

Number of unaffected individuals who tested positive/total number of individuals who tested negative

Question 19

What sort of performance indicators for analytical validity do good tests have?

Answer 19

High selectivity, high specificity, low false positive and false negative rates

Question 20

Where do we get the test material for prenatal genetic testing?

Answer 20

• removal of a single cell from a blastocyst in IVF
• chorionic villus sampling, amniocentesis, umbilical cord blood
• Fetal DNA in maternal bloodstream

Question 21

Where do we get the test material for genetic tests on adults?

Answer 21

• peripheral blood
• cheek swab
• Biopsy of normal tissue or tumours
• Guthrie cards (neonates)