Chapter 1 General of Clinical Laboratory

1. Chapter 1General of Clinical Laboratory LI Ping

2. General of clinical laboratory • Principles to clinical laboratory • The interpretation of laboratory tests • The ethical practice

3. Principle to clinical laboratory Responsibilities Collection of Information Collection of Specimens (Informed consent 、 Adequate privacy) Performance of Test Reporting of Result Storage and Retention of Medical Records Access to Medical Records

4. Responsibilities • The patient----assurance the quality and integrality of the service • Colleague and professional -----maintain professional reputation, aim to contribute the advancement of profession • Society----contribute to the general well-being of society ; comply with relevant laws and regulations of professional activities.

5. Collection of information • Identify adequately patients and specimens • Enable the test to be correctly interpreted • Other legitimate purposes

6. Performance of the test Accreditation program Patients interests Works with high skill and competence Process standard Good performance of tests

7. Reporting of Result • Test results are confidential unless disclosure is authorized. • Report the results correctly and timely • Provide the consultation about the selection and interpretation of tests properly

8. Access to Medical Records Who?? • clinician requesting the test; • the patient; • laboratory and hospital staff if required for the management of the patient; • other authorized individuals. When a request is made for access to test results by an authorized person, the laboratory must first satisfy itself as tothe identity of the person making the request.

9. INTERPRET LABORATORY TEST suboptimum selection Biological variability ,improper or inconsistent preparation Testing Cycle Select test Minimize variability No confusion and misunderstanding about test results Patients prepare for sampling Make clinical decision Improper or inconsistant Collection Check 、report result Collect specimen Inadequate RVs Improper provision Analyze specimen Pre-process of specimen Analytical variabilty

10. Biologic variatinon Endogenous biorhythms for physiologic parameters Different constitutional factors and lifestyle among subjects within-subject variation subject-to –subject variation Biological variation • Biological rhythms • Constitutional factors • Extrinsic factors Width of the test’s Referenc interval (RI) the diagnostic efficiency of a laboratory test

11. Three types of Biological rhythms

12. Biologic variation endogenous biorhythms for physiologic parameters Different constitutional factors and lifestyle among subjects within-subject variation subject-to –subject variation Biological variation • Biological rhythms • Constitutional factors • Extrinsic factors Width of the test’s Referenc interval (RI) the diagnostic efficiency of a laboratory test

13. Biologic variabilty —— Constitutional factor Age rapid physiologic changes 、hemolysis 、 bilirubin infants Plasma protein enzyme sex hormones Age specific reference limits children age constant until menopause in women and middle age in men adults elderly age-related differences in nutrition 、intercurrent disease

14. Biologic variabilty –Constitutional factor Genetic heterogeneity Genetic heterogeneity phenotypic differences Different reactivity towards nucleic acid probes and antibodies Different concentration of analyte false-negative Misleading

15. Biologic variabilty - Extrinsic Factors Posture rennin aldosterone catecholamines homeostasis of vascular tone vascularinterstitial space stand supine plasma volume H2O Small analyte Concentration of nondiffusibl analyte

16. Biologic variabilty – Extrinsic Factors Exercise • shifts in plasma water • glomerular filtration rate • urine production • release of macromolecules from cells and tissues

17. Biologic variabilty - Extrinsic Factors Diet meal related fasting related • Recommendation : duration of fasting before specimen collection is typically 12 hours TG TC BUN GLU …….. Lac Acetone Glucagons ……….

18. Biologic variabilty –Extrinsic Factors Drug • Types of Interference —— Analytical interference Physiologic interference • Recommendation —— Recognize drugs’ potential for occurrence, withdraw medications before sampling whenever possible, Evaluat any suspicious results in light of a subject’s medication history.

19. Biologic variabilty-Extrinsic Factors Pregnancy hyperventilation plasma volume erythrocyte mass altered distribution of cardiac output plasma protein synthesis endocrinologic changes

20. Biologic variation-summary • Biological rhythms—— Circadian , Ultradian ,Infradian rhythms • Constitutinal factors—— Gender, age, gene • Extrinsic factors—— Posture, Exercise, Diet, Drugs, Pregnancy , Caffeine, Alcohol use, Oral Contraceptives, Intercurrent Illness

21. Establish and validate RVs Establish clinical performance characteristics • Help clinician to select the most effective tests and testing strategies • Help clinician to translate laboratory results into a probability statement • Help the laboratory director to focus the resources of the laboratory on tests with the highest clinical relevance Why? How ? phase II and phase III clinical trials Collect data

22. Establish and validate RVs ??? How to assure the validity of the parameters derived from clinical trials? • Use gold standard to define every subject’s status • A broad spectrum of healthy and diseased subjects, include patients with a wide range of clinical presentations. • CIs should be calculated for all the parameters that are estimated. • When new test compares with the old test, assure sample of patients large enough and data exactly .

23. Sensitivity and Specificity

24. Sensitivity and Specificity Sensitivity(Se)=TP/ (TP+FN) Express the probability that a diseased subject will have an abnormal result Express the probability that a nondiseased patient will have a result within the RI Specificity(Sp)=TN/(TN+FP)

25. Predictive Value The probability that a subject with a positive test result truly has the disease The probability that a subject with a negative test result truly is healthy . PVs are only accurate when the test is applied to populations with a disease prevalence that is similar to that of the study sample. PV+ =TP /(TP+FP ) PV- =TN/(TN+FN ) Note

26. ROC Curves ?? What is ROC curve used for ? • Determine the most efficient decision threshold or cutoff value for a laboratory test. • Compare the relative clinical accuracies of different laboratory tests in a particular clinical setting

27. ROC Curves

28. Likelihood Ratios • LHR express the probability that a particular will occur in a diseased subject divided by the probability that the same outcome will occur in a nondiseased subject. • For continous variable test,LHRs can be established for different ranges of test results, so the magnitude of a test result provides additional discriminatory power LHR+ =Se/(1-Sp) =TP rate/FP rate LHR-=(1-Se)/Sp =FN rate/TN rate

29. Likelihood Ratios • TP rate represent benefit of the test ,FP rate represents the costs associated with testing ,so LHR+ represents a cost-benefit ratio .It is similar to LHR-. • The LHR+ and LHR- allow the direct estimation of the posttest probability of disease in view of the new information contributed by the test result . LHR+ =TP rate/FP rate

30. Likelihood Ratios • LHR allow the information from different modalities to be combined in serial diagnostic schemes or “critical pathways” for which overall predictive values can be calculated.

31. Estimating LHR from ROC Curves LHRs for a particular test can also be obtained directly form a ROC curve by evaluating the slopes of the curve in different regions • continuous variable test • positive /negative test • test that classified into more than two intervals

32. ETHICAL PRACTICE Definitions Ethical practice can be regarded as appropriate technical practice accompanied by integrity in attitudes and behavior. • Medical laboratory services are an integral part of medical services, • The same standards and ethical principles that govern the delivery of clinical services will also apply to the delivery of laboratory services. Why Do We Need Ethics?

33. ETHICAL PRACTICE • Technically competent service • Consultation (select and interpret the tests) • Protect the patients’ interests • Confidentiality • Medical ethics exist for the protection of patients, and this protection must not be compromised. Doctor-Patient Relationship Common Requirements Of Medical Laboratory Ethics Special Requirements Of Medical Laboratory Ethics

34. Principles Of Ethics Autonomy、Beneficence、Nonmaleficence 、Justice The ethical standards of those working in medical laboratories are derived from medical ethics and incorporate the same principles. Medical Ethics Ethics In Medical Laboratories

35. Thanks!