Table 1.

Definitions, non-digital, and digital examples for eight biomarker types.

Type	Definitiona	Non-digital example	Digital example
Resilience biomarkerb	A specific type of a diagnostic, monitoring, or response biomarker measured as the response to an external challenge to reflect the resilience of the biological system	Cytokine response to the PhenFlex challenge indicates low inflammatory resilience in metabolically compromised individuals (25)	Continuous glucose variation is higher in prediabetic and diabetic individuals with glucose dysregulation (26)
Diagnostic biomarker	A biomarker used to detect or confirm presence of a health status, disease or condition of interest or to identify individuals with a health or disease subtype.	Increased fasting plasma glucose or hemoglobin A1c indicate the presence of type 2 diabetes	Atrial fibrillation is diagnosedc using photoplethysmography in a smart watch (27)
Monitoring biomarker	A biomarker measured serially for assessing status of health or a disease or medical condition or for evidence of exposure to (or effect of) a medical product, a lifestyle change, or an environmental agent	Regular glucose finger pricks are used to manage insulin administration in type 1 diabetes patients	Calibration-free continuous glucose monitoring is used for monitoring type 2 diabetes patients (28)
Response biomarker	A biomarker used to show that a biological response has occurred in an individual who has been exposed to a medical product, a lifestyle change, or an environmental agent	Serum LDL cholesterol reduction with cholesterol lowering agents or lifestyle changes	Hyperglycemic peak reduction with exercise as an add-on intervention in type 2 diabetes patients using metformin (29). Hyperglycemic peaks were measured with continuous glucose monitoring
Predictive biomarker	A biomarker used to identify individuals who are more likely than similar individuals without the biomarker to experience a favorable or unfavorable effect from exposure to a medical product, a lifestyle change, or an environmental agent	Individuals with insulin resistance in the muscle benefit from a Mediterranean diet, whereas individuals with insulin resistance in the liver mostly benefit from a low-fat diet (30)	Wearable heart rate, skin conductance, skin temperature, and activity patterns were used to define digital phenotypes characterized by poor health indicators and high depression, anxiety and stress scores (31)
Prognostic biomarker	A biomarker used to identify likelihood of a clinical event, disease recurrence or progression in patients who have the disease or medical condition of interest.	Augmented C-reactive protein (CRP) levels indicate increased likelihood of recurrent artery disease events in patients with unstable angina	Spatial memory, prospective memory, executive function, and psychomotor processing speed were assessed with a smartphone app to define a prognostic biomarker for progression to dementia in people with mild cognitive impairment (32)
Safety biomarker	A biomarker measured before or after an exposure to a medical product, a lifestyle change, or an environmental agent to indicate the likelihood, presence, or extent of toxicity as an adverse effect	Increased levels of plasma creatinine phosphokinase indicate statin intolerance in the muscles (33)	QT prolongation, a cardiac safety biomarker, was reliably identified using a wearable ECG monitoring system (34)
Susceptibility/risk biomarker	A biomarker that indicates the potential for developing a disease or medical condition in an individual who does not currently have clinically apparent disease or the medical condition	High CRP levels indicate greater likelihood of developing incident coronary disease (35)	Autonomic imbalance, measured by reduced heart rate variability, may serve as a risk factor for cardiovascular disease (36)

^aDefinitions are adapted from BEST glossary also include health status and lifestyle interventions (24);

^bAdded to the list to highlight the specific characteristic of a resilience biomarker;

^cAt the moment, this is not a medical diagnosis.