Chapter 1 General of Clinical Laboratory

LI Ping

General of clinical laboratory

Principles to clinical laboratory

The interpretation of laboratory tests

The ethical practice

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

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.

Collection of information

Identify adequately patients and specimens

Enable the test to be correctly interpreted

Other legitimate purposes

Performance of the test

Accreditation program

Patients interests

Process standard

Works with high skill and competence

Good performance of tests

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

Access to Medical Records

• 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 to the identity of the person making the request.

Who??

Who??

INTERPRET LABORATORY TEST

Select test

Patients prepare for sampling

Collect specimen

Pre-process of specimen

Analyze specimen

Check 、 report result

Make clinical decision

Biological variability ,imprope

r or inconsistent preparation

Improper or inconsistant Collection

Improper provision

suboptimum selection

Analytical variabilty

Inadequate RVs

Minimize variability No confusion and misunderstanding about test results

Testing Cycle

Biologic variatinon

Endogenous biorhythms for physiologic parameters

Different constitutional factors and lifestyle among subjects

within-subject variation subject-to –subject variation

Biological variation

Width of the test’s Referenc interval (RI)

the diagnostic efficiency of a laboratory test

Biological rhythms

Constitutional factors Extrinsic factors

Three types of Biological rhythms

Circadian Rhythms

Ultradian Rhythms

Infradian Rhythms

Cycle time 24h <24h >24h

Character Consistent

Predictable

Inconsistent

Unpredictable

unknow

solution rhythm-adjusted RVs

stimulation and suppression tests

unknow

example Number and activity of blood cell

gonadal hormone

menstrual cycle

Biologic variation

endogenous biorhythms for physiologic parameters

Different constitutional factors and lifestyle among subjects

within-subject variation subject-to –subject variation

Biological variation

Width of the test’s Referenc interval (RI)

the diagnostic efficiency of a laboratory test

Biological rhythmsConstitutional

factors Extrinsic factors

Biologic variabilty —— Constitutional factor

infants

children

adults

elderly

rapid physiologic changes

、 hemolysis 、 bilirubin

Plasma protein enzyme sex hormones

constant until menopause in women and middle age in men

age-related differences in nutrition 、 intercurrent disease

Agespecific

reference limits

age

Age

Biologic variabilty –Constitutional factor

Genetic heterogeneity

phenotypic differences

Different concentration of analyte

Different reactivity towards nucleic acid probes and antibodies

false-negative

Misleading

Genetic heterogeneity

Biologic variabilty - Extrinsic Factors

vascular interstitial

space

supine stand

H2OSmall analyte

plasma volume

Concentration of nondiffusibl analyte

homeostasis of vascular tone

rennin aldosterone

catecholamines

Posture

Biologic variabilty – Extrinsic Factors

• shifts in plasma water

• glomerular filtration rate

• urine production

• release of macromolecules from cells and tissues

Exercise

Biologic variabilty - Extrinsic Factors

meal related fasting related

Recommendation : duration of fasting before specimen collection is typically 12 hours

TGTC

BUNGLU……..

LacAcetone

Glucagons……….

Diet

Biologic variabilty – Extrinsic Factors

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.

Drug

Biologic variabilty- Extrinsic Factors

plasma volume

erythrocyte mass

plasma protein synthesis

altered distribution of cardiac output

endocrinologic changes

hyperventilation

Pregnancy

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

Establish and validate RVs

Establish clinical performance characteristics

Why?

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

How ? Collect data phase II and phase III

clinical trials

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 .

???

Sensitivity and Specificity

Disease status

Test result Total

Positive negative

Disease TP FN TP +FN

Healthy FP TN FP +TN

Total TP +FP FN+TN TP+FP +TN+FN

Sensitivity and Specificity

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

Sensitivity(Se)=TP/ (TP+FN)

Specificity(Sp)=TN/(TN+FP)

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

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

??

ROC Curves

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

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

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.

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

ETHICAL PRACTICE

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.

Definitions

Why Do We Need Ethics?

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

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