1. Region I Laboratory Update CDC National Infertility Prevention Project Wells Beach, Maine June 15, 2010 Richard Steece, Ph.D., D(ABMM) Laboratory Consultant CDC National Infertility Prevention Project DrRSteece@aol.com

2. Laboratory Update 1.Role of Private Laboratories in the Infertility Prevention Project 2.Verification and Validation of Alternate Specimens (e.g. rectal, pharyngeal, etc.) 3.Chlamydia Point of Care Tests 4.CDC Laboratory Guidelines for CT/GC

3. Infertility Prevention Project (1988) Firmly established the Family Planning Program, the Sexually Transmitted Disease Program and the Public Health Laboratory as full partners.

4. Role of Private Laboratories in the Infertility Prevention Project Definition: Private Laboratory LabCorp, Quest, etc. History of Private Laboratories with the IPP Pennsylvania - Private Laboratories were clearly established solely as a service provider. Need for a Position Statement Budget Problems Outsourcing the Testing (PA, AZ, NM)

5. Role of Private Laboratories in the Infertility Prevention Project Need for a Position Statement (Cont.) Recent Meeting Region IX The Laboratory Subcommittee asked the National Chlamydia Laboratory Committee to discuss a proposed draft statement for clarification of the role of the private laboratories in the IPP

6. NATIONAL CHLAMYDIA LABORATORY COMMITTEE POLICY STATEMENT INFERTILITY PREVENTION PROJECT Public Infertility Prevention Project (IPP) funding is awarded to the State Health Departments and Project Areas from the Centers for Disease Control and Prevention (CDC). Funds are then distributed to local government jurisdictions and family planning partners in accordance with an approved plan. In regards to laboratory services, CDC has encouraged the use of public health laboratories. The National Chlamydia Laboratory Committee (NCLC) recommends the use of public health laboratories. However, some IPP partners have used private laboratories for selected Sexually Transmitted Disease (STD) testing. Minimally each State’s Project Area is required to provide representation and expertise from local and/or state government public health laboratories; these representatives provide leadership for laboratory-related policy and programmatic topics and decision-making regardless of whether they provide direct testing services or not. Their expertise in quality assurance, laboratory data procurement, evidence-based applied research, procedure development and oversight of all laboratories performing IPP testing is paramount. Public health laboratories provide collaborative leadership with other state and local public health representatives to the Region’s projects and the laboratory members providing laboratory science leadership on laboratory issues to Regional IPP programs. Private laboratory involvement is limited to testing services and is not policy in nature; therefore, it is not appropriate for private laboratories to have members on Regional IPP Committees, Regional IPP Laboratory Committees, or the NCLC. Approved by the National Chlamydia Laboratory Committee – 03-01-2010

7. Role of Private Laboratories in the Infertility Prevention Project Need for a Position Statement (Cont.) The NCLC has distributed the policy to the Regional Laboratory Chairs, Regional Coordinators, and CDC for distribution. The NCLC request that each Regional Laboratory Subcommittee endorse this policy, discuss with their partners in the IPP, and approve this policy within each region.

8. Verification and Validation of Alternate Specimens Rectal and pharyngeal swabs –Encourage manufacturer to seek FDA clearance –External specimen bank has been established Specific for GenProbe (at this time) Home collected vaginal swabs APHL / CDC STD Steering Committee Workgroups have developed Verification Protocols –Involved CMS (CLIA) –Part of revised CDC Laboratory guidelines

9. Requestor should send an email to Ms. Carol Farshy (cef1@cdc.gov) asking for assistance Ms Farshy will send them an email requesting certain information so CDC can triage the requests Verification and Validation of Alternate Specimens

10. 1) Type of nucleic acid amplification test that will be used to test rectal and pharyngeal specimens in your laboratory: 2) Approximate number of clinical enquires received to test rectal and pharyngeal specimens for C. trachomatis and N. gonorrhoeae over the past 6 months: 3) Approximate number of clinical specimens tested from men who have sex with men (indicate if you are unable to determine this estimate): Verification and Validation of Alternate Specimens

11. The number of available specimens is extremely limited and CDC will prioritize the requests according to anticipated volume/need. Verification and Validation of Alternate Specimens

12. Recommendation for Single Use Devices for Point-of-Care Chlamydia Tests http://www.region8ipp.com/Docs/02%20NCLC%20POC.pdf

13. Point-of-Care Chlamydia Tests Clearview (Inverness)Sensitivity 87.0%73.9% Specificity 98.8% Quidel QuickVueSensitivity 92.0%78.2% Specificity 98.6% Package InsertAdjusted Sensitivity

14. Guidelines for the Laboratory Detection of Chlamydia trachomatis and Neisseria gonorrhoeae Testing Recommendations from the expert consultation meeting January 13-15, 2009

15. Framework Experts: – Public Health Laboratory Directors – STD Program Directors – STD Clinicians – STD Laboratory Researchers – FDA and CMS

16. Committee Members Stefanie Akselrod FDA Julius Schachter University of California James Beebe PHL, San Luis Obispo, CA Steven Shapiro CDC Gary Budnick PHL, Connecticut Shari Shea APHL Joan Chow CA Dept of Public Health Melissa Singer CMS George Dizikes PHL, Illinois Rick Steece National IPP Program Yetty Fakile CDC Lisa Steele CDC Dennis Ferrero CA Assoc. of PHL Directors Bobbie Van der Pol Indiana University School of Medicine Charlotte Gaydos Johns Hopkins University Katherine Whitaker FDA Tom Gift CDC Dean Willis PHL, Florida Sarah Guerry LA County DOH Medical Director Kelly Wrobleswski APHL Bob Johnson CDC Scott Zimmerman PHL, Erie County, NY

17. Framework Target Audience: – Laboratory Directors, technicians, clinicians and disease control personnel Key Questions: – Refinements or gaps from the 2002 “Screening Tests to Detect Chlamydia trachomatis and Neisseria gonorrhoeae Infections” – Reviewed literature and prepared tables of evidence prior to consultation meeting at CDC

18. Overview of Key Questions Performance Characteristics: – Sensitivity and specificity of reported tests stratified by anatomic site Screening Applications: – Optimal specimen type – Economic considerations Laboratory Confirmation: – Repeat testing – Medico-legal issues

19. Meeting Summary: Performance Characteristics All culture and non-culture tests may generate false-positive results –C–Clinician education Nucleic acid amplification tests (NAATs) have superior performance to all other tests –P–Performance characteristics comparisons will be based on published data –T–These are the tests labs should be using to detect CT and GC regardless of presentation Culture is still useful in certain circumstances –G–GC susceptibility testing –D–Detect mutant strains –S–Should be maintained

20. Serology – Should not be used for the Dx of non-LGV CT infections – Should not be used for the Dx of LGV rectal infections – Useful for the Dx of inguinal LGV infections Direct Detection of LGV – All FDA cleared NAATs detect LGV and non-LGV CT but are unable to distinguish the strains – Homebrew assays have been reported for the direct detection of LGV but the data are insufficient to make a recommendation on their utility

21. Meeting Summary: Performance Characteristics Need for additional data: – Utility of LGV specific tests Clinical and laboratory – Studies on the length of time that newer NAATs will remain positive due to the presence residual DNA after treatment – Performance of NAATs with ocular specimens

22. Meeting Summary: Screening Applications Vaginal swabs are the optimal specimen type for use with NAATs – Studies demonstrate equal performance to endocervical swabs and slightly better performance than urine – Ease of collection and transport

23. Meeting Summary: Screening Applications* Vaginal swabs are the optimal specimen type for use with NAATs – Studies demonstrate equal performance to endocervical swabs and slightly better performance than urine – Ease of collection and transport Vaginal swab and urine specimens are not intended to replace cervical exams and endocervical specimens for the Dx of female urogenital infections Urine is the preferred specimen type for testing males with NAATs

24. Meeting Summary: Screening Applications NAATs have superior performance to culture for the detection of rectal CT and GC infections – NAATs are not cleared for rectal specimens by the FDA – CDC funded an external specimen bank to facilitate an off-label establishment study – Protocol and guidelines developed by the APHL/CDC STD Steering Committee www.aphl.org/aphlprograms/infectious/std/Documents/NAATR ectalSwabs.pdf These are not prescriptive and must be reviewed by local CLIA surveyors

25. Meeting Summary: Screening Applications NAATs have superior performance to culture for the detection of pharyngeal GC infections – Some NAATs report cross-reaction and these may require repeat testing by an alternative method – NAATs are not cleared for pharyngeal specimens by the FDA – CDC funded an external specimen bank to facilitate an off- label establishment study – Protocol and guidelines developed by the APHL/CDC STD Steering Committee www.aphl.org/aphlprograms/infectious/std/Documents/NAATThroatS wabs.pdf These are not prescriptive and must be reviewed by local CLIA surveyors

26. Meeting Summary: Screening Applications Pooling specimens for testing with NAATs is an acceptable method to reduce costs without compromising performance

27. Meeting Summary: Laboratory Confirmation Routine repeat testing of NAAT positive specimens is not recommended for CT Routine repeat testing of NAAT positive specimens is not recommended for GC unless there are a significant number of false-positive test results, in clinical studies, due to cross-reaction with non-gonococcal Neisseria species

28. Meeting Summary: Laboratory Confirmation Medico-legal issues (ASM Symposia 05-2010) – Data supports the use of NAATs in adult cases of sexual abuse – Limited data on the use of NAATs in cases involving children

29. Guidelines for the Laboratory Detection of Chlamydia trachomatis and Neisseria gonorrhoeae Testing Next Steps – Meeting summary available on APHL website www.aphl.org/aphlprograms/infectious/std/Documents/C TGCLabGuidelinesMeetingReport.pdf www.aphl.org/aphlprograms/infectious/std/Documents/C TGCLabGuidelinesMeetingReport.pdf – Publish background papers in a journal supplement – Publish the entire revised laboratory guidelines document as a Reports and Recommendations supplement in MMWR

30. Lots of tears The End - Questions