B P2 C10 Biomarkers and Use in Precision Medicine Flashcards
NIH defined a _____, as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention
Biologic marker, or biomarker
The NIH working group defined a _____ endpoint as “a biomarker intended to substitute for a clinical endpoint.
Surrogate endpoint
A surrogate endpoint is expected to predict clinical benefit (or harm) or lack of benefit (or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence.
The NIH working group defined a _____ endpoint as “a characteristic or variable that reflects how a patient feels, functions, or survives.” Pivotal or phase III cardiovascular trials aspire to use clinical endpoints so defined.
Clinical endpoint
______ is the probability of testing positive when the disease is truly present and is defined mathematically as a/(a + c).
Sensitivity
As sensitivity increases, the number of individuals with disease who are missed by the test decreases, so a test with perfect sensitivity will detect all individuals with disease correctly
Sensitivity is “positive in disease”
_____ of a test is the probability of screening negative if the disease is truly absent and is defined mathematically as d/(b + d).
Specificity
A test with high specificity will rarely be positive when disease is absent and will therefore lead to a lower proportion of individuals without disease being incorrectly classified as test positive (false positives)
Specificity is “negative in health”
The _____ is the probability that an individual is truly disease free, provided that the test has a negative result, and is mathematically calculated as NPV = d/(c + d).
Negative predictive value (NPV)
High NPV can be anticipated when the disease is rare in the population being tested
The _____ is the probability that a person has the disease of interest, given that the individual tests positive, and is mathematically
calculated as **PPV = a/(a + b). **
Positive predictive value (PPV)
High PPV can be anticipated when the disease is common in the population being tested.
_____ is the ability of a test (or prognostic model) to separate those with disease or at high risk for disease (cases) from those without disease or at low risk for disease (controls).
Discrimination
The most common method used to measure discrimination has been the _____, which relates sensitivity (on the y axis) to (1 − specificity) (on the x axis) across a full range of cutoff values for the test or screening algorithm of interes
Area under the receiver operating characteristic (ROC) curve (AUC)
The _____ statistic is a tool that tests how well the average predicted risk within a given cell agrees with the observed risk of individuals who actually experience the event.
Reclassification calibration (RC)
Accordingly, the RC statistic addresses whether the predicted risk estimates after reclassification (using the new biomarker) are more accurate than before reclassification (with- out the new biomarker)
_____ is the ability of a predictive model to assign risk estimates accurately compared with the actual observed risk in the population being tested.
Calibration
Unlike discrimination, which is based solely on relative rankings of risk, calibration compares the risk predicted from a model or test with that actually observed.
Superior reclassification occurs when the new prediction model places case individuals into higher-risk categories and places control individuals into lower-risk categories ,and when the net shift in these two effects is in the overall correct direction. This characteristic can be addressed by using the _____, analogous to a test of discrimination (the ability to separate cases from controls) in the context of a reclassification table.
Net reclassification index (NRI)
A final but important test for any biomarker or biomarker panel when used for prognostication, _____ refers to the ability of the panel to function with clinically acceptable levels of sensitivity, specificity, discrimination, and calibration in external populations, distinct from the population used for generation of the panel.
External validation
When reclassification is not addressed across categories, an alternative measure is used, called the _____, based on the Yates slope, or the difference in predicted probabilities among case and control individuals.
Integrated discrimination improvement (IDI)
_____ also focus on the incremental usefulness of a given biomarker beyond simple clinical and non- clinical characteristics
Prognostic impact studies
Such studies tend to be less biologically driven than biomarker discovery work and recognize that prediction does not necessarily involve a causal pathway.
