L2: Clinical Validation Flashcards
Define a biomarker and matrices they can be measured in.
Biological property whose in vitro measurement or identification is useful for the diagnosis, prognosis, treatment and follow up of humane disease. Biomarkers can be measured in: sera/plasma, urine, CSF, saliva, stool, synovial fluid etc.
What are a few types of biomarkers?
proteins, trace elements, hormones, drugs, vitamins, lipids
What are the ideal characteristics of a biomarker?
- Non-invasive, easily measured, inexpensive and produce rapid results
- Should be obtained from readily available sources
- Should have high sensitivity (allowing early detection and no overlap in disease and healthy patients)
- Should have high specificity (greatly up or down regulated in disease samples and unaffected by comorbid conditions)
- Should vary rapidly in response to treatment
- Should aid in risk stratification and possess prognostic value in terms of outcomes
- Should provide insight into underlying mechanism
List a few measurement methods for biomarkers.
CE, ELISA, MS, POCT, Spectrophotometry
Describe the role of biomarkers in screening and their clinical utility
Role: identify disease in apparently healthy individuals, requires high specificity, inexpensive to assay
Utility:
- used to identify apparently healthy people who may be at increased risk of a disease or condition (e.g. FIT)
- usually have high sensitivity to ensure true positive results are detected
- usually have lower specificity and produces more false positive results
- screening results need to be followed up with diagnostic or confirmatory test
Describe the role of biomarkers in diagnosis and their clinical utility
Role: high sensitivity, high tissue specificity
Utility:
- diagnose particular disease or condition based on clinical suspicion
- typically required to have excellent sensitivity and specificity
- if confirmatory test follows, specificity can be somewhat lower
Describe the role of biomarkers in confirmation and their clinical utility
- verification or confirmation of test results allows clinicians to establish a diagnosis (e.g. colonoscopy for FIT)
- design to be specific and have high PPV
Describe the role of biomarkers in prognosis and their clinical utility
Role: monitor patients with chronic disease, low intra-individual variability, reflect response to treatment
Utility:
- Help assess a patient’s future risk (HIV to AIDs)
- difference from a diagnostic test is the need for longer follow-up and need to include specific time frame
Describe the role of biomarkers in monitoring and their clinical utility
- Periodic measurement to guide management of chronic or recurrent condition (e.g. HbA1c every three months)
- Can be divided into five phases: 1) pretreatment, establish response, 3) monitoring treatment, 4) adjustment to establish control, 5) cessation of treatment
Define Evidence Based Laboratory Medicine (EBLM)
- defined as using the best research evidence and laboratory medicine expertise to aid in disease diagnosis and stratifying risk
- information from expert advice and textbooks often lag behind current medical and scientific literature
- EBLM allows to acquire, appraise, and analyze the most recent data in real time
- leads to improved care of patients, improved health outcomes, and effective use of resources
Describe the elements of EBLM.
6-step method for conducting reviews. Provides framework to conduct review and understand how to assess effectiveness of QI practices.
1) Ask: frame the question
2) Acquire: identify sources and relevant studies
3) Appraise: create an evidence base by applying screening criteria related to topics, questions, and practices
4) Analyze: standardize, summarize, and rate strength of body of evidence
5) Apply: Disseminate findings for review
6) Audit/Assess: conduct audit to assess application and determine need to create new focused questions
Framing the question: define PICOTS.
P (patients): what are the patients symptoms or demographics?
I (intervention): what test is being considered?
C (comparator): what is the reference or gold standard?
O (outcome): what is the endpoint of interest?
T (timing): what is the target timeframe for studies?
S (setting): what are the clinical setting for studies to have been conducted?
Define diagnostic sensitivity.
Proportion of those with the target disease that receive a positive result.
TP/TP+FNx100%
Define diagnostic specificity.
Proportion of individuals without the target disease that receive a negative result.
TN/TN+FPx100
Scenario: In a study with a cohort of 1500 patients, 750 had the target disease. The study found 630 patients had a true positive result and 165 had a false positive result. What was the diagnostic specificity and sensitivity of the assay?
SPECIFICITY: 78%
SENSITIVITY: 84%
