Post on 07-Nov-2014
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Screening For Disease
SCREENING: DEFINITION
“The PRESUMPTIVE identification of UNRECOGNIZED disease or defect by the application of tests, exams or other procedures which can be applied RAPIDLY to sort out apparently well persons who PROBABLY have a disease from those who PROBABLY do not”*
Key Elements: disease/disorder/defect
screening test
population *Commission on Chronic Illness, 1957
Screening 3
Screening
Definition: Presumptive identification of an unrecognized disease or defect by the application of tests, examinations, or other procedures. Classifies asymptomatic people as likely or unlikely to have a disease or defect. Usually not diagnostic.
Screening 4
Screening
Purpose:
Delay onset of symptomatic or clinical disease. Improve survival.
Screening 5
Screening
For screening to be successful you need a:
Suitable disease Suitable test Suitable screening program
Screening 7
Suitable Disease
Has serious consequences Is progressive Disease treatment must be effective at an
earlier stage Prevalence of the detectable pre-clinical
phase must be high Examples of suitable diseases: breast
cancer, cervical cancer, hypertension
Screening 8
Natural History of Disease
20 30 40 50 60 70 Years
A B C D
Biological Disease Symptoms Death
Onset Detectable Develop
By Screening
Screening 9
Natural History of Disease
Total pre-clinical phase = A to C (Age 30 to Age 60) = 30 years
Detectable pre-clinical phase (DPCP) = B to C (Age 45 to Age 60) = 15 years
Screening 10
Natural History of Disease
DPCP varies with the test, the disease, and the individual
Lead Time: Duration of time by which the diagnosis is advanced as a result of screening. B to C (Age 45 to Age 60) = 15 years
Screening 11
Suitable Test
Ideally, it's inexpensive, easy to administer, has minimal discomfort has high level of validity and reliability
Valid Test: Does what it's supposed to do, that is, correctly classify people with pre-clinical disease as positive and people without pre-clinical disease as negative
Screening 12
Suitable Test
Reliable Test: Gives you same results on repetition
Validity is more important than reliability
Screening 13
Suitable Test
Yes No Total
Positive a b a + b
Negative c d c + d
Total a + c b + d a + b + c+ d
Disease Status (Truth)
Screening Test Result
Screening 14
Suitable Test
Measures of test validity
Sensitivity - enables you to pick up the cases of disease
Sensitivity = a / a + c = those that test positive / all with disease
Issues in Screening
Disease-Disease/disorder should be an important public health problem
High prevalenceSerious outcome
-Early Detection in asymptomatic (pre-clinical) individuals is possible
-Early detection and treatment can affect the course of disease (or affect the public health problem?)
Criteria for Evaluating a Screening Test
•Validity: provide a good indication of who does and does not have disease
-Sensitivity of the test
-Specificity of the test
•Reliability: (precision): gives consistent results when given to same person under the same conditions
•Yield: Amount of disease detected in the population, relative to the effort
-Prevalence of disease/predictive value
Validity of Screening Test (Accuracy)
- Sensitivity: Is the test detecting true cases of disease? (Ideal is 100%: 100% of cases are detected)
-Specificity: Is the test excluding those without disease? (Ideal is 100%: 100% of non-cases are negative)
True Cases of GlaucomaYes No
IOP > 22:Yes 50 100
No 50 1900
(total) 100 2000
Sensitivity = 50% (50/100) False Negative=50%Specificity = 95% (1900/2000) False Positive=5%
Screening for Glaucoma using IOP
Consider:
-The impact of high number of false positives: anxiety, cost of further testing
-Importance of not missing a case: seriousness of disease, likelihood of re-screening
Where do we set the cut-off for a screening test?
Reliability (reproducibility)
Inter-Observer Agreement in Grading Severity of Cataract
Examiner <1 1-<2 2-<3 3-<4 4 2
<1 10 2 1 0 0
1-<2 1 20 2 0 0
2-<3 0 1 20 1 0
3-<4 0 0 1 10 2
4 0 0 0 2 5
% Agreement = 81.3%Kappa = 0.76
Examiner 1: Grade
Yield from a Screening Test for Disease XPredictive Value
X
X
Screening Test
Negatives Positives
X
X
X
X
Yield from the Screening Test: Predictive Value
•Relationship between Sensitivity, Specificity, and Prevalence of Disease
Prevalence is low, even a highly specific test will give large numbers of False Positives
•Predictive Value of a Positive Test (PPV): Likelihood that a person with a positive test has the disease
•Predictive Value of a Negative Test (NPV): Likelihood that a person with a negative test does not have the disease
True Cases of GlaucomaYes No
IOP > 22:Yes 50 100
No 50 1900
(total) 100 2000
Specificity = 95% (1900/2000) False Positive=5%Positive Predictive Value =33%
Screening for Glaucoma using IOP
How Good does a Screening Test have to be?
-Seriousness of disease, consequences of high false positivity rate:
-Rapid HIV test should have >90% sensitivity, 99.9% specificity
-Screen for nearsighted children proposes 80% sensitivity, >95% specificity
-Pre-natal genetic questionnaire could be 99% sensitive, 80% specific
Principles for Screening Programs
1. Condition should be an important health problem2. There should be a recognizable early or latent
stage3. There should be an accepted treatment for
persons with condition4. The screening test is valid, reliable, with
acceptable yield5. The test should be acceptable to the population
to be screened6. The cost of screening and case finding should be
economically balanced in relation to medical care as a whole
Lead Time Bias
death
death
screen-detectable clinically evident
clinically evident
5 years
2 years
Lead Time Bias
Because of lead-time bias, it is necessary to look at disease-specific and age-specific death rates in screened and unscreened groups when assessing a screening intervention.
Time from diagnosis to death does not tell you if a screening test is effective
Diagnostic and Screening TestsDiagnostic and Screening Tests
Tests Tests
Diagnostic Screening
0
20
40
100
0 20 40 60
1-Specificity (FP/[TN+FP])
Sen
sit
ivit
y (
TP
/[TP
+FN
])
UrologicpracticeCommunityscreening
PSA Performance (ROC) CurvePSA Performance (ROC) Curve
80
60
80 100
Lead-time bias.
Jaar B G et al. CJASN 2008;3:601-609
©2008 by American Society of Nephrology
Screening Generally
Is to seek about certain problem in certain high risk gp.
Validity of Screening Test
Validity of test determined by ability to correctly categorise subjects to test-positive or test-negative
Disease status
Test
result Positive Negative Total
Positive a b a+b Negative c d c+d
Total a+c b+d
Validity of Screening Test cont...
Sensitivity = ability of test to give a positive result when disease is present
= a / a+c
Specificity= ability of test to give a negative result when disease is absent
= d / b+d
Predictive value is determined by sensitivity & specificity and also by the prevalence of preclinical diseas
Positive predictive value = probability that a person with a
positive test actually has the disease = a / a+b
Negative predictive value = probability that a person with a
negative test is truly disease-free = d / c+d
Validity of Screening Test cont...
What is a Pap Smear?
“Papanicolaou test” - 1941 Dr. Babes & Dr. Papanikolaou > 50% decrease in rates of cervical cancer in
developed countries over last 30 yrs due to widespread screening
A sample cervix cells from transformation zone.
junction of endocervix and ectocervix Use of spatula +/- cytobrush, broom stick 2 types – conventional, liquid-based Send for cytologic interpretation
Screening Guidelines
Start at age 21 (regardless of age of first intercourse) Age 21-29 screen every 2 years Age 30 + screen every 3 years if…
Negative cytology x3 previous Paps NIELM and negative HR HPV test in 1 year No history of high grade lesions
Annual screening if… Immunocompromised (ie. HIV, transplant pts) History of CIN II, III or cancer Exposure to DES in utero
Stop screening at 65 or 70 yrs if … 3 prior consecutive normal Paps No history of abnormal screening in last 10 yrs
Stop screening if hysterectomy for benign disease with no history of abnormal Pap smears
CRITERIA FOR SCREENING
Disease:Must be serious enoughMust be widespread enoughMust be fairly reliably
diagnosableMust be treatableMust be affordableHopefully legally defensible
Criteria for Screening Test 1. Simple & quick 2. Capable of being performed by
paramedics 3. Inexpensive 4. Acceptable to population 5. Accurate 6. Repeatable 7. Sensitive 8. Specific
Secondary Prevention of Ca.Cx. Key Point is to detect
precancerous lesions –BY- A good screening method
- PAP smear test is considered to be the gold standard – Has limitations ? Alternatives to Pap Smear – What are
they?
Why screening for cervical cancer? 1. Is relatively common in
unscreened women. 2. Has a relatively good
prognosis if found early stage in its natural course of disease.
3.Has a characteristic natural course that is a slow progression through a premalignant stage.
Why screening for cervical cancer? Cont… 4. A premalignant stage can be
detected by noninvasive means (the Pap smear , cervicography&VIA).
5. There are effective treatment modalities to eradicate premalignant lesions and early invasive cervical cancer.
Screening by Pap. Cx. Smear unscreened female have ten fold
risk > screened female
- Every sexually active female (18-35 y)- Specially, high risk group.
- Annually up to the age of 35y- No need to extend screening > 35y if smear is N.- At each pregnancy- If new risk factors appear after 35y.
d- If + ve smear colposcopy
c. When:
b. To whom :
a. Importance:
Alternatives to Cytology Visual Inspection of the cervix:
Unaided: Downstaging. Aided with acetic acid: VIA:
Naked eyeAided with acetic a and magnification( VIAM)
Cervicography ColposcopySpeculoscopy
Automated pap smear HPV DNA test Infrared Spectroscopy & Laser Fluorescence
Limitations of Pap Smear
• Complex laboratory test • Requires trained cytotechnician for reading
and pathologist for review• Continuous monitoring needed to maintain
high-quality results• Reports often take minimum 1-2 weeks to
obtain• Follow-up of women is difficult• Usually available only in large cities in many
countries
Comparison between : VIA and Cytology
Sensitivity(%) Specificity (%)
Cytology 47--62 60-95
VIA 76-84 79-83
Breast• Population - women, age 20 +
Breast self-examination Monthly, starting at age 20
Clinical breast examination Every three years, age 20-39
Annual, starting at age 40 *
Mammography Annually, starting at age 40 *
Beginning at age 40, annual clinical breast examination should be performed prior to mammography. Most other affluent countries recommend mammography every other year between ages 50 and 70.
Clinical Diagnosis
Disease Onset
No Disease
Asymptomatic Disease
Clinical Course
Primary
Remove Risk Factors
Secondary
Early Detection and Treatment
Tertiary
Reduce Complications
Levels of Prevention
Fletcher RF, Fletcher SW, Wagner EH. Clinical Epidemiology: The Essentials, 3rd ed. Williams and Wilkins, Baltimore, 1996.