Ability of an in vitro medical assay to conform to predefined quality specifications (e.g. as defined by the Stockholm Conference hierarchy or in clinical guidelines) 

Example

• Universal definition of myocardial infarction recommends that high sensitivity Tn assays must have acceptable imprecision, i.e. ≤ 10% CV, at the 99th percentile of normal. 
  

A characteristic that is an indicator of normal biological or pathogenic processes, or pharmacologic responses to a therapeutic intervention.

Examples

• cTn-s are biomarkers of cardiac diseases associated with myocardial ischemia and necrosis
• HbA_1c is a biomarker of altered glycosylation in hyperglycaemic states, such as diabetes mellitus
  

Consequences of testing beyond clinical effectiveness and cost-effectiveness (e.g. acceptability, social, psychological, legal, ethical, societal, organizational consequences and other aspects). 

Example

• Psychological impact of genetic testing for familial hypercholesterolemia: An RCT in a population previously aware of their hypercholesterolemia found that finding a mutation by genetic testing did not reduce patients' perceptions of control over the disease and adherence to risk-reducing behaviors, but did affect their perceptions of how control is most effectively achieved. 
  

Ability of a test to improve health outcomes that are relevant to the individual patient.

Example

• The clinical effectiveness of BNP testing for diagnosis of heart failure in patients presenting to emergency with acute dyspnea were investigated in RCTs that compared the addition of BNP testing with standard investigations alone followed by routine care. A meta-analysis of these RCTs reported that addition of BNP testing decreased length of hospital stay by ~1 day; possibly reduced admission rates, but did not affect 30-day mortality rates.
  

A description of typical processes of care in managing a specific condition in a specific group of patients.

Example

• Clinical pathways by NICE in the UK

Ability of a biomarker to conform to predefined clinical specifications in detecting patients with a particular clinical condition or in a physiological state.

Example

• Diagnostic test: In patients presented to emergency with chest pain and low to intermediate likelihood for ACS, the hs-cTnT assay was compared with a conventional cTnT method and CT angiography as the gold standard for diagnosing ACS.  At the optimal hs-cTnT cut point of 8.62ng/L, sensitivity for ACS was 76% and specificity was 78%, and hs-cTnT above the 99th percentile strongly predicted ACS. Compared with the conventional cTnT method, hsTnT detected 27% more ACS cases.
  
• Prognostic test: In elderly patients presenting to primary care with symptoms of heart failure the risk for cardiovascular mortality (adjusted for age, sex, impaired estimated glomerular filtration rate, and anaemia) increased 2.5-fold with a plasma NT-proBNP concentration >507 ng/L; 2-fold with hs-cTnT >99th percentile; 3-fold when both biomarkers were elevated.
  

A cost-effectiveness analysis compares the changes in costs and in health effects of introducing a test, to assess the extent to which the test can be regarded as providing value for money.

Example

• Point of care testing (PoCT) in general practice: A cost-effectiveness analysis based on an RCT of nearly 5,000 patients followed up for 18 months in Australian general practices compared the incremental costs and health outcomes associated with a clinical strategy of PoCT for INR, HbA1c, lipids, and albumin:creatinine ratio (ACR) to those of pathology laboratory testing. Under base-case assumptions, PoCT was more cost-effective and effective for ACR than standard pathology. For HbA1c, POCT was more expensive but also more effective than standard pathology with an incremental cost-effectiveness ratio of $40 per patient maintained in the therapeutic range, while INR was more costly but less effective and therefore not cost-effective.
  

A characteristic or event that can be measured to assess the impact of clinical care on an individual’s health. It describes or reflects how an individual feels, functions or survives.

Example

• Blood pressure, stroke, physical function, quality of life, death.
  

A measurement procedure undertaken on a biological specimen which measures the quantity of the biomarker (see below) intended to be measured; i.e. the measurand.

Examples

• Two-site immunoenzymatic (“sandwich”) assay using electrochemiluminescence detection for cardiac Troponin (cTn) measurement
  
• Cation exchange chromatography or boronate affinity chromatography or by a latex agglutination immunoassay measured HbA1c 

In vitro medical tests or testing strategies utilize laboratory assays of biomarkers in a specific clinical context and for a specific clinical purpose (see below), in a specific patient population.

Example

• Serial cTn testing for diagnosing acute coronary syndrome (ACS) in patients with symptoms of acute chest pain.
• HbA1c as a monitoring test to assess treatment effect in type 1 or type 2 diabetic patients.

The proportion of individuals with a negative test result who truly do not have the target condition.

The proportion of individuals with a positive test result who truly have the target condition.

In individuals with a confirmed diagnosis, the presence of a predictive biomarker is used to identify individuals who are more likely to experience a favorable or unfavorable effect from a specific intervention or exposure than individuals where the biomarker is absent.  Predictive biomarkers may be used to refine criteria for disease classification.

Example

• Tumour estrogen receptor status in women with breast cancer, to identify those who will respond to endocrine therapy such as tamoxifen.
  

In individuals with a confirmed diagnosis, the presence or level of a prognostic biomarker is used to identify the likelihood of a clinical event, disease recurrence or progression, independent of the effects of a specific intervention. 

Example

• CD4+ lymphocyte count in individuals with human immunodeficiency virus, to identify those at elevated risk of progression to Acquired Immunodeficiency Syndrome.
  

In an individual without clinically apparent disease, a risk biomarker is used to indicate the potential for developing a disease or sensitivity to an exposure.

Example

• In individuals with no prior history of cardiovascular disease, low density lipoprotein to identify those with an elevated risk of cardiovascular disease.
  

The condition or classification of disease the test is intended to detect.

Test purpose describes the intended clinical application of the test and how the test information will be used to improve clinical management in practice.

Example:

• HbA1c as a diagnostic marker of diabetes mellitus.
• HbA1c as a monitoring test to assess diabetes control.
• hs-cTn for diagnosing ACS.
• hs-cTn as a prognostic marker for cardiovascular morbidity and mortality.

The proportion of individuals with the target condition present who are correctly identified by the biomarker.

The proportion of individuals with the target condition absent who are correctly identified by the biomarker.

Unmet clinical need refers to any missing of inadequately performing component of a clinical pathway.

Examples

• Need for improved tests (improved diagnostic information for timely triage) for women presenting with symptoms of threatened preterm labor to identify those at a very low risk of progressing to labor who can safely avoid admission and treatment.
  

• Need for improved rapid rule out (increased sensitivity / NPV) tests of ACS for patients presenting with chest pain in the ED (e.g. single baseline test) to enable timely patient management decisions to avoid unnecessary admission.