What should be included in study designs for comparison and reproducibility studies that support a Dual Submission?

When designing comparison and reproducibility studies to support a Dual Submission, FDA recommends that applicants evaluate test performance in settings designed to replicate, as closely as possible, the actual CLIA-waived settings, patients/samples, and test operators. Therefore, study designs should include the following:

• Testing sites that are representative of the intended use of the waived test.
• Subject populations that are representative of the intended patient population(s).
• Intended sample type and matrix.
• Untrained operators representative of those at intended waived settings. We encourage you to enroll operators with the least amount of training that might be encountered at the types of sites for which this device is intended.
• Testing should be integrated into the daily workflow of the site where the operators are often multitasking between patient care, testing, and other duties.

The appropriate design of the studies and data analysis is strongly influenced by the type of the candidate test. Therefore:

• A quantitative test is a test that gives numerical results (e.g. concentration of an analyte in a patient sample) which are referenced to a measuring interval and standards.
• A binary qualitative test is a test that provides only two outputs (e.g. positive/negative or yes/no).

If your test is a different type of test from the two types described above (e.g. qualitative with multiple nominal categories, semi-quantitative, a multi-analyte assay with algorithmic analyses), please contact FDA through a Pre-Submission for discussion of study designs.

If the candidate test is intended to be used at Point-of-Care (POC) non-waived sites in addition to waived sites and the intended use patient population at the CLIA-waived sites in the comparison study does not sufficiently represent the intended use patient population at POC non-waived sites, FDA recommends that you address this issue by also including one or a few POC non-waived sites in the study. At any included POC non-waived sites, trained operators representative of those at intended POC non-waived sites should perform testing with the candidate test.

The recommendations for comparison and reproducibility studies described in this guidance are for studies that include the type of samples that are typical of CLIA-waived devices (for example, capillary whole blood samples). If you plan to pursue a 510(k) clearance for POC non-waived use for additional sample types beyond those for which you are requesting a CLIA waiver in your Dual Submission, please contact FDA through a Pre-Submission for discussion of study designs.

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