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Screening and its Useful Tools
Thomas Songer, PhD
Basic Epidemiology
South Asian CardiovascularResearch Methodology Workshop
Screening
• The early detection of– disease
– precursors of disease
– susceptibility to disease
in individuals who do not show any signs of disease
Goel
Purpose of Screening• Aims to reduce morbidity and mortality from
disease among persons being screened
• Is the application of a relatively simple, inexpensive test, examinations or other procedures to people who are asymptomatic, for the purpose of classifying them with respect to their likelihood of having a particular disease
• a means of identifying persons at increased risk for the presence of disease, who warrant further evaluation
Diagnosis = Screening
• Screening tests can also often be used as diagnostic tests
• Diagnosis involves confirmation of presence or absence of disease in someone suspected of or at risk for disease
• Screening is generally in done among individuals who are not suspected of having disease
Susceptible Host
Subclinical Disease
Clinical Disease
Stage of Recovery, Disability, or Death
Point of Exposure
Screening
Onset of symptoms
Diagnosis sought
Natural History of DiseaseDetectable subclinical disease
Screening Process
TestNegative
Re-screen
Unaffected
Intervene
Affected
TestPositive
Population(or target group)
Screening
ClinicalExam
Examples of Screening Tests
• Questions
• Clinical Examinations
• Laboratory Tests
• Genetic Tests
• X-rays
Goel
Validity of Screening Tests
• Sensitivity
• Specificity
• Positive Predictive Value
• Negative Predictive Value
Paneth
Key Measures
TerminologyValidity is analogous to accuracy
The validity of a screening test is how well the given screening test reflects another test of known greater accuracy
Validity assumes that there is a gold standard to which a test can be compared
Paneth
Present Absent
Positive a b
Negative c d
a + b
c + d
a + c b + d
DiseaseS
cree
nin
gT
est
N
DiseaseS
cree
nin
gT
est
Present Absent
PositiveTrue
positives
Negative
Falsepositives
Falsenegatives
Truenegatives
Sensitivity
• Proportion of individuals who have the disease who test positive (a.k.a. true positive rate)
• tells us how well a “+” test picks up disease
a
a + c=Sensitivityyes no
+ a b
- c d
a + b
c + d
a + c b + d
Disease
Scr
eeni
ngT
est
N
Specificity• Proportion of individuals who don’t have
the disease who test negative (a.k.a. true negative rate)
• tell us how well a “-” test detects no disease
d
b + d=Specificityyes no
+ a b
- c d
a + b
c + d
a + c b + d
Disease
Scr
eeni
ngT
est
N
Screening Principles• Sensitivity
– the ability of a test to correctly identify those who have a disease• a test with high sensitivity will have few false negatives
• Specificity– the ability of a test to correctly identify those who
do not have the disease• a test that has high specificity will have few false
positives
Predictive Value• Measures whether or not an individual
actually has the disease, given the results of a screening test
• Affected by – specificity
– prevalence of preclinical disease
– Sensitivity
• Prevalence = a + c
a + b + c + d
Present Absent
Positive a b
Negative c d
a + b
c + d
a + c b + d
DiseaseS
cree
nin
gT
est
N
Positive Predictive Value
• Proportion of individuals who test positive who actually have the disease
a
a + b=P.P.V.yes no
+ a b
- c d
a + b
c + d
a + c b + d
Disease
Scr
een
ing
Tes
t
N
Negative Predictive Value
• Proportion of individuals who test negative who don’t have the disease
d
c + d=N.P.V.yes no
+ a b
- c d
a + b
c + d
a + c b + d
Disease
Scr
een
ing
Tes
t
N
Present Absent
Positive 48 3
Negative 2 47
51
49
50 50
Disease
Scr
een
ing
Tes
t
100
A test is used in 50 people with disease and50 people without. These are the results.
Paneth
Present Absent
Positive 48 3
Negative 2 47
51
49
50 50
Disease
Scr
een
ing
Tes
t
100Sensitivity = 48/50Specificity = 47/50Positive Predictive Value = 48/51Negative Predictive Value = 47/49 Paneth
So… you understand the accuracy of a screening test …
What is the next step?
Put screening to use in the population
Considerations in Screening
Severity
Prevalence
Understand Natural History
Diagnosis & Treatment
Cost
Efficacy
Safety
Criteria for a Successful Screening Program
• Disease– present in population screened
– high morbidity or mortality; must be an important public health problem
– early detection and intervention must improve outcome
Criteria for a Successful Screening Program
• Disease– The natural history of the disease
should be understood, such that the detectable sub-clinical disease stage is known and identifiable
Criteria for a Successful Screening Program
• Screening Test– should be relatively sensitive and
specific
– should be simple and inexpensive
– should be very safe
–must be acceptable to subjects and providers
Criteria for a Successful Screening Program
• Have an Exit Strategy– Facilities for diagnosis and appropriate
treatments should be available for individuals who screen positive
– It is unethical to offer screening when no services are available for subsequent treatment
Screening Strategies
• Cost-effective• Intervention appropriate
to the individual• Fails to deal with the
root causes of disease• Subjects motivated• Small chance of reducing
disease incidence
• Potential to alter the root causes of disease
• Large chance of reducing disease incidence
• Small benefit to the individual
• Poor subject motivation• Problematic risk-benefit
ratio
High-Risk Strategy Population Approach
NCI Guidelines for Screening Mammography
“There is a general consensus among experts that routine screening every 1-2 years with
mammography and clinical breast exam can reduce breast cancer mortality by about one-
third for women ages 50 and over.”
“Experts do not agree on the role of routine screening mammography for women ages 40 to
49. To date, RCTs have not shown a statistically significant reduction in mortality in
this age.”
Screening is not always free of risk
In population screening….
False positives tend to swamp true positives in populations, because most diseases we test for are rare
Paneth
Risks of Screening
• True Positives– “labeling effect” (classified as diseased
from the time of the test forward)
• False Positives– anxiety
– fear of future tests
– monetary expense
Risks of Screening
• False Negatives– delayed intervention
– disregard of early signs or symptoms which may lead to delayed diagnosis
Sources of Bias in the Evaluation of Screening Programs
• Lead time bias
• Length bias
• Volunteer bias
Lead time bias
• Lead time: interval between the diagnosis of a disease at screening and the usual time of diagnosis (by symptoms)
Diagnosis by screening
Diagnosis via symptoms
Lead Time
Bias in Screening:
Lead-Time Bias
•Consider a condition where the natural history allows for an earlier diagnosis, however, survival does not improve despite identifying it earlier •A screening program here will…
– over-represent earlier diagnosed cases– survival will appear to increase
• but in reality, it is increased by exactly the amount of time their diagnosis was advanced by the screening program
– Thus there is no benefit to screening from a survival standpoint.
Lead time bias
• Assumes survival is time between screen and death
• Does not take into account lead time between diagnosis at screening and usual diagnosis.
Diagnosis by screening
in 1994
Deathin 2008
Survival = 14 years
Lead time bias
Diagnosis by
screeningin 1994
Usual time of diagnosis
via symptomsin 1998
Lead Time 4 years
Deathin 2008
True Survival = 10 years
Survival = 14 years
Bias in Screening:
• Most chronic diseases, especially cancers, do not progress at the same rate in everyone.
• Any group of diseased people will include some in whom the disease developed slowly and some in whom it developed rapidly.
• Screening will preferentially pick up slowly developing disease (longer opportunity to be screened) which usually has a better prognosis
Paneth
Length Bias
Len
gth
bias
OBiological onset of disease
Screening
YSymptoms
Begin
DDeath
PDisease
detectable via screening
O DP Y
O DP Y
O DP Y
O DP Y
O DP Y
O P Y D
Time
Volunteer bias
• Type of bias where those who choose to participate are likely to be different from those who don’t
• Volunteers tend to have:
– Better health
– Lower mortality
– Likely to adhere to prescribed medical regimens