screening and its useful tools thomas songer, phd basic epidemiology south asian cardiovascular...

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