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The Clinical Relevance of a False Negative ELISA : Which ANA screening test is preferred by rheumatologists in an integrated health system?

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Rachita Bansal MD

David Bulbin DO

Alfred Denio MD

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Common methods of ANA screening

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HEp-2 / Immunofluorescence Assay (IFA)

- older, gold standard method

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Enzyme linked immunoassay (ELISA)

- relatively new method

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Advantages

Disadvantages

IFA

  • High specificity
  • Provides ANA pattern and titer information
  • Expensive
  • Labor intensive
  • Subjective interpretation
  • Not conducive to mass screening

ELISA

  • Automated
  • Cheaper
  • Simple to perform
  • Easier for mass screening
  • Requires purified antigens
  • Close quality control needed

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Current ANA screening strategy at GHS

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Study Design�

  • Prospective study

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  • Conducted at Integrated Health System (GHS)

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  • Rheumatology practice of 12 physicians

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Cost analysis provided

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Cost Analysis

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ELISA

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IFA

Direct cost difference (per test)

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$7.74

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$12

Tech cost difference (per test)

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$0.59/min

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$2.84/min

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Total

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$8.33

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$14.84

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ANA tests done by the GHS Central Lab in 2011 – 11,640

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ANA tests ordered by rheumatologists - 1,156

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ANA tests done by the GHS Central Lab in 2011 – 11,640

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ANA tests ordered by rheumatologists - 1,156

Cost of these ANA’s (1,156) with ELISA and reflexing the positives to IFA - $13,947

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Alternatively, total cost of screening these ANA’s (1,156) with IFA - $17,270

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ANA tests done by the GHS Central Lab in 2011 – 11,640

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ANA tests ordered by rheumatologists - 1,156

Cost of these ANA’s (1,156) with ELISA and reflexing the positives to IFA - $13,947

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Alternatively, total cost of screening these ANA’s (1,156) with IFA - $17,270

Added cost of initial screening of ANA’s (1,156) with ELISA 17,270 – 13,947 = $3,323

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Results

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Survey Questions

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To what degree did your clinical suspicion change based on + IFA finding?

High

7

Medium

5

Low

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Did you pursue further testing based on knowledge of + IFA?

Yes

9

No

21

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Would you start/change treatment based on the new results?

Yes

4

No

26

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Overall do you think the repeat testing of ANA by IFA was significant and was it important for you to know it ?

Yes

13

No

17

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Would you consider IFA titers of 1:40 or 1:80 as a positive test and want to know the result?

Yes

11

No

19

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Given relevance of the false negative ANA ELISA in your patient, and the added cost to the Central lab of screening all ANAs with IFA , what in your opinion is the most cost effective methodology for ANA screening?

Continue to screen all ANAs with ELISA

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Screen ANAs ordered by rheumatologists with IFA and all others with ELISA followed, if + by IFA

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13

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Conclusions

  • Significantly discordant results by the two ANA methodologies

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  • The finding of a Positive IFA ANA after a “False negative” ANA by ELISA methodology rarely changed rheumatologist’s management decisions

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  • Rheumatologists favored ELISA over IFA by a slim majority for ANA screening.

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Conclusions: continued

  • Lab has agreed to offer IFA for ANA screening to rheumatologists

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  • Further study of false positive rate of ELISA is necessary

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Thank you