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

Positive Predictive Value:The Influence of Disease Prevalence

Zenilman. Sex Transm Infect 2003

Positive Predictive Value:The Influence of Disease Prevalence

PPV at Specificity of:

Prevalence 98% 99% 99.5%

10% 84% 91% 95%

5% 71% 83% 90%

2% 49% 66% 79%

1% 32% 49% 66%

0.5% 19% 32% 49%

Positive Predictive Value:The Influence of Disease Prevalence

95% Sensitivity 99% Specificity

Prevalence Test True Infection PPV

+ -

10% + 95 9 104 91%

- 5 891 896 (95/104)

100 900 1000

4% + 38 10 48 79%

- 2 950 952 (38/48)

40 960 1000

2% + 19 10 29 66%

- 1 970 971 (19/29)

20 980 1000

BD ProbeTec PerformanceMulticenter Evaluation

Female Swab Male Swab

Lab Prevalence SPEC PPV SPEC PPV

IU 13.4% 95.7 76.8 96.1 86.8

JHU 9.0% 99.0 87.4 98.1 92.1

UCSF 5.3% 100 100 100 100

SJPHS 4.4% 99.2 84.6 - -

UAB 15.1% 98.6 92.1 95.2 86.3

UMMS 10.9% 98.6 77.7 80.0 50

CCF 11.5% 95.7 75.1 - -

Van Der Pol et al. J Clin Micro 2001

LCR PerformanceMulticenter Evaluation

Female Swab Male Urine

Lab Prevalence SPEC PPV SPEC PPV

IU 13.4% 98.8 92.5 97.0 89

JHU 9.0% 99.0 85.6 96.2 85.4

UCSF 5.3% 100 100 100 100

SJPHS 4.4% 99.4 88.5 - -

UAB 15.1% 99.3 95.9 95.2 97.3

UMMS 10.9% 98.5 89.1 80.0 66.7

CCF 11.5% 100 100 - -

Van Der Pol et al. J Clin Micro 2001

Reproducibility of BD Probe-Tec

Initial MOTA Scores

2,000-9,999 >10,000

Repeat Positive

21 175

Repeat Negative

5 6

Total 26 181

Culler. J Clin Micro 2003

Implications of a Positive CT Test

• Psychosocial Impact/Stigma

• Negative impact on sexual relationships

• Future Reproductive Morbidity

• Cost

• Resource Utilization

Implications of a Positive CT Test

• Psychosocial Impact– Shock– Depression– Anxiety– Guilt– Isolation– Shame– Stigma (?barrier to future STD care?)

Implications of a Positive CT Test

• Negative impact on sexual relationships– Destroyed relationships– Accusations of infidelity– Impaired intimacy– Less sexually desirable– Less sexual enjoyment

Implications of a Positive CT Test

• Future Reproductive Morbidity– Increased risk of

• Ectopic pregnancy• Tubal factor infertility• Chronic pelvic pain

– Neonatal transmission

Implications of a False-Positive CT TestShort-Term Costs

Confirmatory Testing

Additional assay• Small # of specimens in

low prev. populations

• Lab issues

No Confirmatory Testing

TreatmentPartner notificationPartner treatmentScreening for other STDsCounseling time

Implications of a Positive CT TestLong-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

Implications of a False-Positive CT TestOverall Costs

Confirmatory Testing

Additional assay

No Confirmatory Testing

TreatmentPartner notificationPartner treatmentScreening for other STDsCounseling timeRepeat testingFuture testing and work-up for

possible STD-related illness (e.g. PID, ectopic pregnancy)

Reduce costs

Is Educating Physicians on the Proper Interpretation

of STD Tests a

Viable Strategy?

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

“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

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%

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

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

Is Educating Physicians on the Proper Interpretation

of STD Tests a

Viable Strategy?

Doubtful

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

“ 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