Screening and Early Detection

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Screening and Early Detection

• Epidemiological Basis for Disease Control Fall
  2001

Joel L. Weissfeld, M.D. M.P.H.
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Objectives

• Theoretical justification for disease control
  through early detection of disease.
• Concepts and quantitative methods used to
  evaluate a screening test.

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Definitions

• Screening program -- comprehensive disease
  control activity based on the identification and
  treatment of persons with either unrecognized
  disease or unrecognized risk factors for disease.
• Screening test -- specific technology (survey
  questionnaire, physical observation or
  measurement, laboratory test, radiological
  procedure, etc.) used to help identify persons
  with unrecognized disease or unrecognized risk
  factors for disease.

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Definitions

• Primary prevention -- disease control approach
  based on the elimination or reduction of risk
  factors for disease. Primary prevention aims to
  prevent the occurrence of disease. Primary
  prevention may use screening tests to identify
  persons with risk factors.

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Definitions

• Secondary prevention -- disease control approach
  based on the active identification and treatment
  of persons with unrecognized disease. Secondary
  prevention aims to prevent the occurrence of
  adverse outcomes from disease (such as fatal
  outcomes), without necessarily reducing the
  occurrence of disease. Secondary prevention must
  screen to identify persons with unrecognized
  disease.

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Generalities

• Screening often implies a public health related
  activity involving asymptomatic or healthy
  subjects coming from the general population.
• Case-finding refers to special clinical efforts
  to recognize disease among persons who consult a
  health professional.

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Two essential attributes of successful secondary
prevention

• Screening must accomplish early detection of
  disease. The screening program must detect
  disease in asymptomatic persons or in
  sympto-matic persons not recognized to have
  disease. Relative to background conditions,
  screening must identify affected persons at an
  earlier time point in the natural history of
  disease.
• The act of early detection increases the
  effectiveness of treatments for the disease.

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Evaluation framework used by US Preventive
Services Task Force

• Assess burden of suffering.
• Assess properties of the screening test.
• Determine the efficacy, effectiveness, and
  cost-effectiveness of early detection.

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Important properties of a screening test

• Screening is simple, inexpensive, and easily
  diffused through the population.
• The act of screening is safe and acceptable.
• The screening test is reliable.
• The screening test is accurate.

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Reliability

• Kappa -- an appropriate reliability measure (or
  measure of agreement) for a screening test which
  gives a categor-ical result.
• Intraclass correlation coefficient -- an
  appropriate reliability measure for a screening
  test, which gives a quantitative result.

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Cohens Kappa

• Po a d proportion observed agreement
• Pe P1P2 Q1Q2 proportion expected
  agreement
• kappa (Po - Pe)/(1 - Pe)

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Origin of the term

• Screening implies a simple process, which
  classifies persons into one of two groups.
• Members of the group with a positive (or
  abnormal) screening test result have disease with
  a probability high enough to justify diagnostic
  testing (for confirmation of disease presence)
  and/or medical therapies (for prevention of
  adverse outcomes from disease).
• Members of the group with a negative (or normal)
  screening test result have disease with a
  probability too low to justify diagnostic testing
  (for confirmation of disease presence) and/or
  medical therapies (for prevention of adverse
  outcomes from disease).

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Comparison of screening test results against gold
standard

• A screening test may produce only a categorical
  (positive or negative) result. Important
  concepts include disease prevalence, test
  sensitivity, test specificity, positive
  predictive value, negative predictive value,
  proportion test positive, proportion test
  negative, and disease yield.

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Classification of screening test results against
gold standard
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Classification of screening test results against
gold standard
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Comparison of screening test results against gold
standard

• Sensitivity and specificity are said to be
  properties of the screening test. That is,
  sensitivity and specificity of a screening test
  may be relatively independent of the population
  being screened.

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Comparison of screening test results against gold
standard

• For rare conditions, specificity has a major
  impact on positive prediction (Bayes Theorem).
  Despite a direct effect on yield, sensitivity has
  quantitatively less impact on positive prediction.

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Deriving Bayes theorem
Step 1 Specify the prevalence (P) of disease
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Deriving Bayes theorem
Step 2 Use sensitivity (Se) to distribute test
results among the diseased
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Deriving Bayes theorem
Step 3 Use specificity (Sp) to distribute test
results among the non-diseased
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Deriving Bayes theorem
Step 4 Determine the proportion testing positive
and the proportion testing negative
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Deriving Bayes theorem
Step 5 Equate PPV and NPV with appro-priate
expressions from Step 5
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Comparison of screening test results against gold
standard

• A screening test may produce quantitative values.
  However, for decision-making purposes, a
  screening program must convert quantitative test
  results into two (or more) discrete categories.
  The screening program has a choice of different
  cutpoint(s), which may be used to categorize test
  results. In general, the choice of cutpoint(s)
  will affect values for sensitivity and
  specificity. Analysis of receiver operating
  characteristic (ROC) curves provides a graphical
  method for studying the effects of different
  cutpoints on the performance (sensitivity and
  specificity) of a screening test. ROC curve
  analysis also provides a method for comparing
  competing screening tests.

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Net effects from screening

• True negatives are exposed to the costs,
  inconvenience, and hazards of screening. True
  negatives may be reassured by knowledge of a
  negative screening test result.
• False positives are exposed to the costs,
  inconvenience, and hazards of screening and
  follow-up diagnostic evaluations. The falsely
  positive screening test result may cause
  psychological and emotional distress.

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Net effects from screening

• False negatives are exposed to the costs,
  inconvenience, and hazards of screening. False
  negatives may be falsely reassured by knowledge
  of a negative screening test result. False
  negatives represent lost opportunities to prevent
  adverse outcomes from disease.
• True positives are exposed to the costs,
  inconvenience, and hazards of screening,
  follow-up diagnostic evaluations, and therapeutic
  interventions. Only true positives have an
  opportunity to benefit from medical therapy.

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Generalities

• Specificity is often the major determinant of the
  costs and feasibility of a screening program.
• Sensitivity establishes the maximum extent (upper
  bound) to which a screening program is capable of
  producing health benefit.