Screening Tests for New Agents

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Screening Tests for New Agents

• Bruce L. Evatt, MD
• Atlanta, Georgia

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Why Test?Applications of New Tests

• Screening
• Diagnostic
• Research

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Screening Tests

• Mass Screening
• WHO guidelines (Watson Jungner 1968)
• Diabetes, Breast Ca, Prostate Ca etc.
• High degree Specificityr/o false positive
• Specific Preventive Application
• Blood donorseliminate possible infections
• High Sensitivityneed confirmatory tests

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Wilson and Jungner classic screening criteria1

• 1. The condition sought should be an
  important health problem.2. There should be an
  accepted treatment for patients with recognized
  disease.3. Facilities for diagnosis and
  treatment should be available.4. There should be
  a recognizable latent or early symptomatic
  stage.5. There should be a suitable test or
  examination.6. The test should be acceptable to
  the population.7. The natural history of the
  condition, including development from latent to
  declared disease, should be adequately
  understood.8. There should be an agreed policy
  on whom to treat as patients.9. The cost of
  case-finding (including diagnosis and treatment
  of patients diagnosed) should be economically
  balanced in relation to possible expenditure on
  medical care as a whole.10. Case-finding should
  be a continuing process and not a once and for
  all project.

Wilson JMG, Jungner G. Principles and practice of
screening for disease. Geneva WHO 1968.
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Emerging screening criteria proposed over the
past 40 years

• The screening program should respond to a
  recognized need. The objectives of screening
  should be defined at the outset. There should
  be a defined target population. There should
  be scientific evidence of screening program
  effectiveness. The program should integrate
  education, testing, clinical services and program
  management. There should be quality assurance,
  with mechanisms to minimize potential risks of
  screening. The program should ensure informed
  choice, confidentiality and respect for autonomy.
  The program should promote equity and access
  to screening for the entire target population.
  Program evaluation should be planned from the
  outset. The overall benefits of screening
  should outweigh the harm.

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Screening Tests

• Mass Screening
• WHO guidelines (Watson Jungner 1968)
• Diabetes, Breast Ca, Prostate Ca etc.
• High degree Specificityr/o false positive
• Specific Preventive Application
• Blood donorseliminate possible infections
• High Sensitivityneed confirmatory tests

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Donor Screening Test Decision
Major Considerations

• Is the Agent Pathogenic?
• How Common is the Agent in Blood Donors?
• What is the Sensitivity and Specificity of Tests?
• What are the Risks of not Screening?
• What is the cost of Screening? Impact on
  blood supply?
• What is the prevailing expert opinion?
• Political considerations?

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Examples of FDA Considerations

• Accuracy of testing
• Correct test interpretation
• The importance of supplemental testing for
  confirmation of positive results
• Management of psychological and social issues
• Availability of counseling
• Medical referral

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HIV (1984) vs vCJD (2009) Screening

• Good Screening test
• Confirmatory test
• Information on prevalence
• Good information on transmissibility
• Good info on sensitivity and specificity of test
• Good info on ultimate outcome of positive test

• Screening test
• No Confirmatory test
• Inadequate information on prevalence
• Inadequate information on transmissibility
• Some information on sensitivity and specificity
  of test
• Little information on ultimate outcome of
  positive test

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Screening Test Decision

• How bad the outcome
• Parvovirus vs HIV
• Debate can be endless
• Syphilis HbV core for non-A non-B Hepatitis
• To Screen donors can be the easiest part of
  equationwhat to do about informing donors of
  positive test?

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Options for Informing Donors of Positive Tests

• Youre positivedont come backplace on deferral
  list
• Dont telljust test each time and throw away
• Youre positivecounsel, and follow
  upwhoMedical referral?
• Pretest counseldonor decision to learn of
  results
• Lookback?

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When Problems Arise

• Good Screening testbut no confirmatory test.
• No known treatment.
• Unknown natural history of positive testhard to
  counsel..worry worry.
• Test info in medical recordshard to get
  insurancemedical treatment may be compromised.
• Unknown risk for other routes of
  transmissionpossible social outcasts.

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Historical Perspective

• HIV donor seropositivity
• Meaning
• Advice
• Referral
• HCV donor seropositivity
• Meaning
• Referral
• Recipients of blood products from donors who
  developed vCJD
• Blood recipientsLookback?
• Hemophilia patients

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Lookback for Hepatitis C Virus Donors
Purpose (Retrospective)

• To trace the blood products from HCV-positive
  donors who tested negative for the virus at an
  earlier date
• To trace those units collected before
  development of the HCV test
• To notify recipients who received blood products
  from a donor who tested positive for the virus at
  the time of a later blood donation.

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Initial Reasons for No Lookback for HCV

• First generation HCV blood screening assay had
  significant rate of false and false results.
• Lack of effective treatment.

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Research Study Screening

• Anonymous
• Simpler
• Determine prevalence
• Informed Consent
• Follow-up
• Determine sequela
• Determine natural history
• Determine transmissibility

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Target Populations

• World Wide?
• UK?
• Europe?
• Countries with current donor restrictions?
• Countries with mad cow disease?
• Countries with vCJD cases?
• Countries with test positive donors?

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Total Exports of MBM 1988 - 1993
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vCJD WORLDWIDE December 2007
UK 166 France
23 Republic of Ireland
5 USA 3 Canada
1 Saudi Arabia 1 Japan
1 Netherlands 2 Portugal
2 Spain 1