1	CLIA Waiver Guidance Carol C. Benson¹ and Marina V. Kondratovich² ¹Associate Director, Division of Chemistry and Toxicology Devices, OIVD, CDRH, FDA ² Statistician, Division of Biostatistics, OSB, CDRH, FDA FDA-Industry IVD Roundtable Meeting, May 11, 2006
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3	Demonstrating “Accuracy” -Quantitative Selection of Comparative Method (CM): Type A – Reference Method; Type B – Traceable method (measurement values with the same degree of trueness as reference method or reference materials; Type C – Traceable method (measurement values with small systematic bias, which may be clinically tolerable).
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13	Quantitative Performance Criteria Establish Allowable Total Error (ATE) (for 95% of differences for WM and CM): values of WM that fall within ATE zones are values that can be tolerated without invalidating the medical usefulness of the WM results. Establish Limits for Erroneous Results (LER) (no observations in LER): when WM values fall within LER zones, potential harm can occur to the patients if these results are utilized in medical decision making.
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18	Demonstrating “Accuracy” – Qualitative Study Design Selection of comparative method: type A – quantitative reference method; type B – quantitative traceable of type B; type C – quantitative traceable of type C; type D –qualitative reference method; type E – qualitative method which was tested by reference specimen panels (e.g, panels prepared by WHO, CDC, NIST).
19	Demonstrating “Accuracy” – Qualitative Study Design 3 or more clinical sites and intended users (9) 120 samples positive by CM 120 samples negative by CM Prospective patient samples, archival, contrived matrix-specific. Each sample split (or pair of samples): one part for test system (WM) and other part for comparator method (CM).
20	Demonstrating “Accuracy” – Qualitative Statistical Analysis Positive and negative agreements between WM and CM (95% two-sided CI) – for every site and combined
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27	Some Comments on Entire Guidance “…This is a tremendous guideline. One simple comment is that it could be envisioned to apply to all diagnostic assays, not just waiver assays.” “This draft Guidance must be withdrawn… The “accuracy” study for waiver should only be required to demonstrate that the waived user can operate the device as well as a professional user.” “Agreement studies” in 2001 FDA Guidance.
28	Plan Forward Draft guidance - solicit comments Revise draft to final guidance Issue proposed rule Issue final rule