For an investigational study to be exempt under 21 CFR 812.2(c)(3), clinical
investigators must use a medically established means of diagnosis (e.g., another
cleared or approved IVD or culture) of the disease or condition as the basis for
decisions regarding treatment of all subjects participating in the study. 21 CFR
812.2(c)(3)(iv). Additionally, test results from the exempt IVD investigation
should not influence patient treatment or clinical management decisions before
the diagnosis is established by a medically established product or procedure.
If an investigational test uses a new technology or represents a significant
technological advance, established diagnostic products or procedures may not be
adequate to confirm the diagnosis provided by the investigational IVD. For
example, if an investigational test is designed to identify an infection at the
earliest stages of viral infection (before formation of antibodies), established
diagnostic products or procedures that rely on the detection of antibodies to the
virus would be inadequate to confirm diagnoses. Under these conditions the
study would not meet the criteria for exemption under 812.2(c)(3) since the
testing could not be confirmed with a medically established diagnostic product or
procedure. You may consider whether the device is a non-significant risk device
subject to abbreviated IDE requirements (21 CFR 812.2(b)).
