Use Cases for SARS-CoV-2 Assays

Prepared by Halteres Associates, March 20, 2020

Use Case 1: Triage of symptomatic individuals in an epidemic setting

  • The intended use is to determine if a symptomatic individual in an epidemic setting has a reasonable likelihood of a current infection warranting temporary isolation pending confirmatory testing
  • Target use settings can be divided into two groups:
    • Group 1: Sites with temporary (days) or fulltime residents such as assisted living centers, cruise ships, hospitals and quarantine facilities.
    • Group 2: Other settings could include public and community health centers, primary care facilities, urgent care clinics, and emergency departments in outbreak areas where symptomatic individuals could be expected to visit for work-up.
  • If nasal or nasopharyngeal swabs are required, proper collection (e.g., swab) and sample introduction to testing device needed (e.g., swab introduction port) will be necessary
  • Typically, a confirmatory test using different targets is needed, unless clinical performance is very high
  • Information and communications technologies (ICT) to capture and report data for reporting to other stakeholders is needed (e.g. healthcare workers, MOH, Public Health, CDC, WHO). If a differential diagnostic is performed, in addition to a confirmatory test, association of the triage test data with these diagnostic test results is desirable.
  • The preferred sample type is still under investigation, though nasal and nasopharyngeal swabs remain common choices
  • Other potential sample types used by some laboratories and test developers for COVID-19 include oral fluid, bronchial lavage, sputum, blood, urine and feces
  • It may not be practical to obtain and process all sample types in all settings. “Sample-to-results” procedures should be carefully considered and matched to the end user capabilities.
  • The intended use settings can be roughly divided into two groups with different testing requirements.
    • In group 1, individuals can likely be isolated and confirmation testing can be conducted remotely;
    • Testing in the second set of sites is more problematic since unless the confirmation testing can be conducted on site and rapidly it will not be possible to keep patients on site long enough to isolate them to prevent potential transmissions.
  • A triage test that permits the majority of symptomatic patients to leave if they have a negative result (low probability of SARS CoV-2 infection; high sensitivity, high negative predictive value) would limit the need to isolate and test for confirmation of infection.
  • On the other hand, the test requires an acceptable specificity so that few people are unnecessarily quarantined. Even in an epidemic setting it is likely that most persons with symptoms do not have COVID-19.
  • In most of the intended use settings, a point of care format test is desirable, ideally one that is designed to meet CLIA-waiver requirements. While an instrument-free format has merit in many target use settings, the desire to capture and communicate information as well as features delivering improved test performance may favor automated solutions.
  • Tests designed for decentralized testing (e.g., Point of Care (POC)) should take into account the requirements across the wide variety of potential testing locations, environments, operators and regulatory requirements
  • It is likely that medical practitioners and technical staff in the target use settings will be wearing some form of personal protective equipment (PPE). Therefore, for broadest utility, the test should be designed to be used by individuals wearing PPE.
  • The potential use of a triage test in an epidemic setting is tied to the availability of an acceptable confirmation test. Confirmatory testing solutions/algorithms appropriate for the intended use setting should be recommended. A multi-day send out confirmation test is only practical (though not preferred) in the Group 1 sites.
  • The turnaround time should be maximally 1 hour, preferably 15 minutes or less
  • For broadest utility, it is preferable that the test be CLIA waivable for use by minimally trained users in decentralized testing settings
  • Price targets* (to the end user) are likely to be <$25 USD for the US, but considerably less in low and middle-income countries (LMICs). Frequently, established reimbursement is dependent on the type of assay technology used.

Use Case 1: Triage of symptomatic individuals in an epidemic setting

Description

  • The intended use is to determine if a symptomatic individual in an epidemic setting has a reasonable likelihood of a current infection warranting temporary isolation pending confirmatory testing
  • Target use settings can be divided into two groups:
    • Group 1: Sites with temporary (days) or fulltime residents such as assisted living centers, cruise ships, hospitals and quarantine facilities.
    • Group 2: Other settings could include public and community health centers, primary care facilities, urgent care clinics, and emergency departments in outbreak areas where symptomatic individuals could be expected to visit for work-up.

Other Possible Technologies Required

  • If nasal or nasopharyngeal swabs are required, proper collection (e.g., swab) and sample introduction to testing device needed (e.g., swab introduction port) will be necessary
  • Typically, a confirmatory test using different targets is needed, unless clinical performance is very high
  • Information and communications technologies (ICT) to capture and report data for reporting to other stakeholders is needed (e.g. healthcare workers, MOH, Public Health, CDC, WHO). If a differential diagnostic is performed, in addition to a confirmatory test, association of the triage test data with these diagnostic test results is desirable.

Samples

  • The preferred sample type is still under investigation, though nasal and nasopharyngeal swabs remain common choices
  • Other potential sample types used by some laboratories and test developers for COVID-19 include oral fluid, bronchial lavage, sputum, blood, urine and feces
  • It may not be practical to obtain and process all sample types in all settings. “Sample-to-results” procedures should be carefully considered and matched to the end user capabilities.

Comments

  • The intended use settings can be roughly divided into two groups with different testing requirements.
    • In group 1, individuals can likely be isolated and confirmation testing can be conducted remotely;
    • Testing in the second set of sites is more problematic since unless the confirmation testing can be conducted on site and rapidly it will not be possible to keep patients on site long enough to isolate them to prevent potential transmissions.
  • A triage test that permits the majority of symptomatic patients to leave if they have a negative result (low probability of SARS CoV-2 infection; high sensitivity, high negative predictive value) would limit the need to isolate and test for confirmation of infection.
  • On the other hand, the test requires an acceptable specificity so that few people are unnecessarily quarantined. Even in an epidemic setting it is likely that most persons with symptoms do not have COVID-19.
  • In most of the intended use settings, a point of care format test is desirable, ideally one that is designed to meet CLIA-waiver requirements. While an instrument-free format has merit in many target use settings, the desire to capture and communicate information as well as features delivering improved test performance may favor automated solutions.
  • Tests designed for decentralized testing (e.g., Point of Care (POC)) should take into account the requirements across the wide variety of potential testing locations, environments, operators and regulatory requirements
  • It is likely that medical practitioners and technical staff in the target use settings will be wearing some form of personal protective equipment (PPE). Therefore, for broadest utility, the test should be designed to be used by individuals wearing PPE.
  • The potential use of a triage test in an epidemic setting is tied to the availability of an acceptable confirmation test. Confirmatory testing solutions/algorithms appropriate for the intended use setting should be recommended. A multi-day send out confirmation test is only practical (though not preferred) in the Group 1 sites.
  • The turnaround time should be maximally 1 hour, preferably 15 minutes or less
  • For broadest utility, it is preferable that the test be CLIA waivable for use by minimally trained users in decentralized testing settings
  • Price targets* (to the end user) are likely to be <$25 USD for the US, but considerably less in low and middle-income countries (LMICs). Frequently, established reimbursement is dependent on the type of assay technology used.
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