1. Confirmatory Testing of NAATs SHOULD be Routine for Chlamydia Infections in Populations with < 4% Prevalence Harold C. Wiesenfeld, M.D.,C.M. University of Pittsburgh School of Medicine Magee-Womens Hospital

2. Positive Predictive Value: The Influence of Disease Prevalence Zenilman. Sex Transm Infect 2003

3. Positive Predictive Value: The Influence of Disease Prevalence PPV at Specificity of: Prevalence98%99%99.5% 10%84%91%95% 5%71%83%90% 2%49%66%79% 1%32%49%66% 0.5%19%32%49%

4. Positive Predictive Value: The Influence of Disease Prevalence 95% Sensitivity 99% Specificity PrevalenceTestTrue InfectionPPV +- 10%+95910491% -5891896(95/104) 1009001000 4%+38104879% -2950952(38/48) 409601000 2%+19102966% -1970971(19/29) 209801000

5. BD ProbeTec Performance Multicenter Evaluation Female SwabMale Swab LabPrevalenceSPECPPV SPEC PPV IU13.4%95.776.896.186.8 JHU9.0%99.087.498.192.1 UCSF5.3%100 SJPHS4.4%99.284.6-- UAB15.1%98.692.195.286.3 UMMS10.9%98.677.780.050 CCF11.5%95.775.1-- Van Der Pol et al. J Clin Micro 2001

6. LCR Performance Multicenter Evaluation Female SwabMale Urine LabPrevalenceSPECPPV SPEC PPV IU13.4%98.892.597.089 JHU9.0%99.085.696.285.4 UCSF5.3%100 SJPHS4.4%99.488.5-- UAB15.1%99.395.995.297.3 UMMS10.9%98.589.180.066.7 CCF11.5%100 -- Van Der Pol et al. J Clin Micro 2001

7. Reproducibility of BD Probe-Tec Initial MOTA Scores 2,000-9,999>10,000 Repeat Positive 21175 Repeat Negative 56 Total26181 Culler. J Clin Micro 2003

8. Implications of a Positive CT Test Psychosocial Impact/Stigma Negative impact on sexual relationships Future Reproductive Morbidity Cost Resource Utilization

9. Implications of a Positive CT Test Psychosocial Impact –Shock –Depression –Anxiety –Guilt –Isolation –Shame –Stigma (?barrier to future STD care?)

10. Implications of a Positive CT Test Negative impact on sexual relationships –Destroyed relationships –Accusations of infidelity –Impaired intimacy –Less sexually desirable –Less sexual enjoyment

11. Implications of a Positive CT Test Future Reproductive Morbidity –Increased risk of Ectopic pregnancy Tubal factor infertility Chronic pelvic pain –Neonatal transmission

12. Implications of a False-Positive CT Test Short-Term Costs Confirmatory Testing Additional assay Small # of specimens in low prev. populations Lab issues No Confirmatory Testing Treatment Partner notification Partner treatment Screening for other STDs Counseling time

13. Implications of a Positive CT Test Long-Term Costs Resource Utilization False positive tests will lead to increased utilization of healthcare services ($$$) –Repeat screening for C. trachomatis Follow national screening recommendations –Increased healthcare utilization Patient is “labelled” All pelvic pain = PID (costs of treatment) Increased surveillance for ectopic pregnancy

14. Implications of a False-Positive CT Test Overall Costs Confirmatory Testing Additional assay No Confirmatory Testing Treatment Partner notification Partner treatment Screening for other STDs Counseling time Repeat testing Future testing and work-up for possible STD-related illness (e.g. PID, ectopic pregnancy) Reduce costs

15. Is Educating Physicians on the Proper Interpretation of STD Tests a Viable Strategy?

16. Will Providers Properly Counsel Patients? 71% of PA primary care physicians report adequate STD training in residency (Ashton, Cook, Wiesenfeld et al. Sex Transm Dis 2002) 38% of adults were asked about STDs during routine checkups in the last year (Tao, Irwin & Kasler Am J Prev Med 2000) Only 32% of primary care physicians report screening a sexually active teen for CT (Cook, Wiesenfeld, Ashton et al. J Adol Health 2001) Only 61% of PCPs met criteria for adequate STD knowledge (Wiesenfeld, Cook et al. Unpublished data) QUALITY OF STD CARE VARIES AND IS IMPERFECT

17. “Clinicians must know the approximate prevalence of the condition of interest in the population being tested; if not, reasonable interpretation is impossible” David A. Grimes & Kenneth F. Shulz Uses and Abuses of Screening Tests Lancet 2002

18. What do the Providers Know About False Positive STD Tests? NOT MUCH! Survey of local providers: –94% underestimated the false-positive rate of a NAAT CT test in a low prevalence population –Most physicians vastly underestimated the false positive rate of CT NAAT testing: Two-thirds estimated the false positive rate of < 5% in a population where the risk of a positive test being a false positive is 50%

19. Do Physicians Currently Follow Recommendations Concerning False-Positive Tests? CDC (MMWR Oct 18, 2002): “Patients with positive screening test results require counseling regarding…the possibility of a false-positive result” Survey: 76% of physicians rarely (<1%) inform patients with a positive CT NAAT result that it may be a false positive

20. Do Physicians Currently Follow Recommendations Concerning False-Positive Tests? CDC (MMWR Oct 18, 2002): “Because therapy for CT is safe and should not be delayed, therapy can be offered while awaiting additional test results…” Survey: 18% of physicians would offer empiric treatment before or in lieu of retesting

21. Is Educating Physicians on the Proper Interpretation of STD Tests a Viable Strategy? Doubtful

23. Should Confirmatory Testing of NAATs be Routine for Chlamydia Infections in Populations with < 4% Prevalence? YES Not labor intensive Additional costs small (small #s) Reduction in costs incurred with false-positive tests (short and long-term) Eliminate unnecessary adverse psychosocial impact Feasibility of providers incorporating counseling on false-positive results is questionable Improved quality of care for our patients

24. “Remember: a clinician, not a laboratory test, makes a diagnosis. Overinterpretation of test results is the first cost of molecular diagnostics” Jeffrey Klausner, MD Clin Infect Dis 2004