TABLE 2.

Contrived versus “real-life” home setting considerations

Parameter	Contrived environment for index test			“Real-life” home setting for index test
	Clinic capture	Community recruitment	Preenrollment	Clinic capture	Community recruitment	Preenrollment
Description	Patients seeking clinical care are recruited, subject is directed to run the test, and HCW collects the reference sample.	Community members meeting inclusion criteria are called to contrived study site to run the test, and HCW collects the reference sample.	Participants are enrolled before illness develops; if they trigger criteria, subject is called to contrived study site to run the test, and HCW collects the reference sample.	Patients seeking clinical care are recruited, HCW collects the reference sample, and subject is given a test to take home to run.	Community members meeting inclusion criteria are delivered a test to run at home and also to collect a reference sample that is returned by mail/courier.	Enrolled participants receive a test to hold (prepositioned); if they trigger criteria, they are directed to run the test at home and collect a reference sample that is returned by mail/courier.
Recruitment options	Recruit subjects presenting at clinical site. Recruit based on review of  electronic medical records  for those meeting certain  criteria and ask to attend  clinic.	Recruit via social media, community organizations, advertising.	Recruit via social media, community organizations, advertising.	Recruit subjects presenting at clinical site.	Recruit via social media, community organizations, advertising.	Recruit via social media, community organizations, advertising.
Index test	Participant at clinic	Participant at clinic	Participant at clinic	Participant at home	Participant at home	Participant at home
Reference sample	Collection by HCW at clinic	Collection by HCW at clinic	Collection by HCW at clinic	Collection by HCW at clinic	Participant at home	Participant at home
Representative of intended population	Poor to good: controlled recruitment provides more certainty about ILI/symptom presence but misses those not seeking care. Potentially higher severity of illness.	Variable: highly dependent on recruiting message; can be good if recruiting message mimics test-seeking behavior without incentive-driven bias. Potentially lower severity of illness.	Variable: highly dependent on recruiting message; can be excellent if recruitment is designed to capture representative sample. Potential lower severity of illness.	Poor to good: controlled recruitment avoids those without ILI or symptoms but misses those who are not seeking care. Potentially higher severity of illness.	Variable: highly dependent on recruiting message; can be good if recruiting message mimics test-seeking behavior without incentive-driven bias. Potential lower severity of illness.	Variable: highly dependent on recruiting message; can be excellent if recruitment is designed to capture representative sample. Potential lower severity of illness.
Efficiency (prevalence, recruitment, test cost)	Likely higher prevalence.	Likely lower prevalence. Likely lower participation due to need to travel to clinic.	Likely lower prevalence. Likely lower participation due to need to travel to clinic. Many tests go unused.	Likely higher prevalence. Some tests will go unused due to lack of direct supervision.	Likely lower prevalence. Some tests will go unused due to lack of direct supervision.	Likely lower prevalence. Many tests will not be triggered and will go unused.
Logistical burden	Good: centralized logistics but requires significant HCW involvement and associated costs.	Poor: significant recruitment effort and significant HCW involvement and associated costs.	Poor: upfront recruitment effort, extended study duration, and significant HCW involvement and associated costs.	Excellent: centralized logistics and minimal HCW involvement.	Poor: significant recruitment efforts and significant HCW involvement, test delivery must be rapid and can be expensive.	Good to excellent: upfront recruitment efforts, extended study duration, but low overhead during study. An app or web-based system is likely needed to query for triggers.
Reference sample validity	Excellent: standard of care sample; also can be opportunity to validate new sampling methods.	Excellent: standard of care sample; also can be opportunity to validate new sampling methods.	Excellent: standard of care sample; also can be opportunity to validate new sampling methods.	Excellent: standard of care sample; also can be opportunity to validate new sampling methods.	Variable: dependent on FDA acceptance of sampling method and chain of custody.	Variable: dependent on FDA acceptance of sampling method and chain of custody.
Index test sampling and training bias	Subject may be “trained” after experiencing HCW test (if performed first); may perform differently if observed; sample order can be randomized.	Subject may be “trained” after experiencing HCW test (if performed first); may perform differently if observed; sample order can be randomized.	Subject may be “trained” after experiencing HCW test (if performed first); may perform differently if observed; sample order can be randomized.	Subject may be “trained” after experiencing HCW test (if performed first).	Excellent: sampling order can be randomized to prevent favoring one test.	Excellent: sampling order can be randomized to prevent favoring one test.
Option for OTC testing	No	No	Maybe	No	Yes	Yes
Option for Rx home use testing	Yes	Maybe	Maybe	Yes	Maybe	Maybe