1. Developing CT Screening Guidelines for Women >25: The Over 20 Study & The Over 25 Evaluation Region II IPP Meeting NYC, NY May 17, 2007

2. “An evaluation of the performance/appropriateness of national chlamydia (CT) screening guidelines when applied to non-pregnant adult women seeking family planning services in California.”

3. Background: The Problem “Excessive” CT screening in populations with low CT morbidity has implications:  Not an effective use of limited resources  CA uses 3% as cost-effective cut-off  May lead to a higher proportion of false positive test results

4. Background: The Problem (CA) Among adult women, CA FP setting has relatively low CT rates but high volume of screening:  Significantly less CT in women age >25 than in younger women, yet screening rates are similar  Almost 50% of all screening occurs in this older age-group  CT prevalence in this population >25 is <3%  CT rates for women age 21-25 <3% in some areas

5. Background: Why Not Stop Screening Older Women Altogether?  Detecting/treating CT infections has been shown to reduce such adverse sequelae as PID, infertility  The vast majority of CT infections in all women, including women >25, are asymptomatic or “silent”:  Over 70% of CT in women >25 do not present with clear clinical indications for testing  Screening is the only effective mechanism for detecting “silent infections” No Screening = Missing >70% of CT in this population

6. Background: The Solution: Targeted Screening Evidence-based targeted screening strategies:  Can identify a sub-population with higher CT %  A balance between saving resources and still reducing the burden of CT in lower-prevalence populations TS!

7. Background: Who to Target? Clear guidelines needed to target CT screening in adult women:  Though national recommendations support targeted screening for women >25, they are:  Not well-defined  Inconsistent, and/or  Inefficient

8. The Over 20 Study

9. The Over 20 Study Research Objectives Among non-pregnant women age 21-30 seeking family planning services:  Determine predictors of CT infection  Develop efficient targeted screening strategies for CT infection, specifically in women >25  Determine whether targeted screening is appropriate for the population of women 21-25

10. The Over 20 Study Study Methods Patient Eligibility Criteria:  Female clients seeking FP services  Age 21-30  Not pregnant  Sexually Active (self-report of vaginal sex in past 12 months) Study Design: Cross-sectional

11. The Over 20 Study Study Methods Data collected & methods:  Self-administered patient questionnaires:  Demographics, relationship status, sexual behavior, STD history  Clinician-completed clinical evaluations:  Reason for visit, birth control, STD contact, STD history, symptoms, clinical signs & diagnoses, presumptive CT/GC Rx  Laboratory databases:  CT & GC test results

12. The Over 20 Study Results : Participating Agencies & Project Timeline  Participating Sites: 9 clinics (3 CA FP agencies) all performing universal screening  Timeline: two phases May 2003 to May 2004 August 2004 to November 2005

13. The Over 20 Study Results: Final Study Sample Study Forms Submitted for Unique, Eligible, CT-Tested Clients* and Successfully Matched with Lab Result Data AgencyStudy Forms% CT Positive Total4,2924.2% Agency A2,9824.5% Agency B1,0423.3% Agency C2684.9% * = Age 21-30 years

14. The Over 20 Study: Total Sample Results: Demographics Age (Years) CT Positives n = 180 CT Tested N = 4,292

15. The Over 20 Study: Total Sample Results: Demographics Race/Ethnicity CT Positives n = 180 CT Tested N = 4,292

16.  Report of current contact (exposure) to an STD  CT-indicative clinical syndrome diagnosed on exam:  Cervicitis: endocervical discharge, cervical friability, or cervical inflammation  Pelvic inflammatory disease (PID): Adnexal/uterine tenderness or cervical motion tenderness  New STD (confirmed or presumptively treated) diagnosed in-office on day of visit (trichomoniasis; presumptive HSV, GC, or genital warts; syphilis, HIV) Patients with Clinical Indications for CT Testing excluded from screening analysis:

17. The Over 20 Study Results (Age 21-30): CT Prevalence & Proportion of Cases by Clinical Presentation ~Exclusion Criteria Applied to Screening Analysis~ 27 % of CT Cases 73 % of CT Cases Total CT-tested Participants N = 4,292 n CT+ = 180 4.2 % CT+ Patients with clinical indications for CT testing: N = 550 n CT+ = 48  STD contacts  Cervicitis or PID  New STD dx 8.7 % CT+ Patients screened for CT: N = 3,742 n CT+ = 132  No STD contact  No cervicitis or PID  No new STD dx 3.5 % CT+ 87 % of Pop. Tested13 % of Pop. Tested

18. Patients screened for CT: N = 3,742 n CT+ = 132  No STD contact  No cervicitis or PID  No new STD dx (except GC+) 3.5 % CT+ Patients age 21-25 screened for CT: N = 2655 n CT+ = 100 3.8 % CT+ Patients age 26-30 screened for CT: N = 1,087 n CT+ = 32 2.9 % CT+ CT Prevalence >3% justifies universal screening

19. Risk factors predictive or protective for CT infection (statistically significantly):  Partners possible other partners (3 or 12 mos) §  More than 1 or 2 partners (3 or 12 mos)  BV  Married*  Stable relationship (married, engaged or living with partner)*  New partner in past 3 mos (p-value = 0.06) The Over 20 Study Summary of Univariate Findings: Women age 26-30 years * Protective against CT infection in univariate analysis § Independently associated with CT in multivariate analysis (p-value <0.05)

20. The Over 20 Study “Partner possible other partners” Actual Question Studied: Q:At anytime within the past 12 months *, did any of your male partners have sex (of any type) with someone else while they were still in a sexual relationship with you? A:  Yes, definitely  Not sure, it is possible  No, it is very unlikely * Also asked about the past 3 months in a separate question. Answers combined

21. 1.14.94679  Ptr possible other ptrs 2.05.41635  BV 02.9100 Universal Screening 2.18.71338  >2 Ptr in 12 mos 2.34.83250  >1 Ptr in 12 mos 2.45.12339  New Partner in 3 mos The Over 20 Study: Screening Analysis Results: Performance of Selective Screening Algorithms Age 26-30 1.54.45075  Stable Relationship % CT+ in pop not Screened % CT+ in pop Screened % Pop Screened N = 1,087 % Cases Detected N = 32 Algorithm of Selected Criteria:

22. 0.03.1198100 Current USPSTF recommendations*:  Multiple ptr (>1 in 12 mos)  New ptr (3 mos)  CT hx (12 mos)  Unmarried  Inconsistent condom use (3 mos) 0.64.66193 Over 20 Study results:  BV  Ptr possible other ptrs (12 mos)  >2 ptrs (12 mos) 1.55.04976 Current CDC recommendations*:  Multiple ptr (>1 in 12 mos)  New ptr (3 mos)  CT hx (12 mos) 02.9100 Universal Screening The Over 20 Study: Screening Analysis Results: Performance of Selective Screening Algorithms Age 26-30 % CT+ in pop not Screened % CT+ in pop Screened % Pop Screened N = 1,087 % Cases Detected N = 32 Algorithm of Selected Criteria: * Approximate replication

23. The Over 20 Study Key Study Limitations  Convenience sample of clinics mostly located on California’s central coast and in the central valley -- may not be representative of overall CA FP population  Unknown if results applicable to women > 30

24. The Over 25 Evaluation IPP Scantron Data Chart Abstraction

25. The Over 25 Evaluation: IPP Scantron Data Benefits & Strengths Can use existing IPP data collected via Scantron forms (~3,000) from CA Project Area and Los Angeles CT prevalence monitoring sites:  Scantron forms newly revised 7/06 with influence from Over 20 Study result – similar data  CPA and LA Scantron forms now identical  ~ 20 geographically diverse clinic sites across CA  Data collected from CT-tested patients of all ages

26. The Over 25 Evaluation: IPP Scantron Data Challenges & Limitations  Needed some supplemental data not available on forms (e.g., BV status)  Forms had never been validated  Clinic sites already targeting CT screening in women > age 25 -- data bias –May give inflated prevalence rates –May underestimate associations between risk factors and CT –% of population screened in algorithms may not be accurate

27. The Over 25 Evaluation: Chart Abstraction Design/Methods Design: Case-Control Chart Abstraction Use Scantron forms to pull sample of medical record charts for abstraction:  All CT-positive patients (~100)  A random-sample of CT-negative patients, chosen by clinic site, using a 4 negatives:1 positive ratio (~400)  Collect supplemental data for research purposes  Collect identical data, as possible, for validation purposes

28.  Successfully abstracted 82% of sample goal (446/544 charts in total; 83/100 CT+ charts): ~ 8% pregnant ~ 1.5% males Other issues: wrong DOBs – out of eligible age range; clients not tested for CT; missing charts  Data concordance: Demographics/other core variables: > 90% Lab data: > 95% CT symptoms: 96% of No’s / 33% of Yes’s Clinical data: 96% of No’s / 38% of Yes’s Behavioral data: 60-97% of No’s / 38-60% of Yes’s The Over 25 Evaluation: IPP Scantron Data Validation Results

29. Summary of Study Differences Over 20 StudyOver 25 Evaluation Study design Cross-sectional: self report, clinician report and lab results Case-Control: chart review Sample population Non-pregnant female patients Age range26-3026-44 # Clinics participating917 Clinic types 8 FP-only and 1 community clinic 3 FP-only, 3 FP/STD integrated, 9 community, 2 free clinics Clinic locations 8 CPA sites (3 central coast, 4 central valley, 2 Sacramento); 1 LA site (Santa Monica) 8 CPA sites (3 San Bern Co., 1 north, 2 southern border, 2 central valley); 9 LA sites (diverse) Clinic CT screening protocol Universal – all agesTargeted in ages > 25 CT prevalenceLow to moderateModerate to high

30. CA Chlamydia Rates by County, 2005 7/2006 Provisional Data - CA DHS STD Control Branch Rate per 100,000 < 100 100 to 199 200 to 299 300 + Over 20 & Over 25 Site Distributions Over 20 Study: Age 26-30 Over 25 Evaluation: Age 26-44

31. The Over 25 Evaluation: Total *Weighted Chart Abstraction Sample Results Total Sample: Age (Years) CT Positives n = 83 CT Tested N = 2,634*

32. n = 83 N = 2,616* Over 25 Evaluation * Weighted sample Results Total Samples: Race/Ethnicity CT Positives CT Tested Over 20 Study N = 4,292 n = 180

33. The Over 25 Evaluation Results (Age 26-44): CT Prevalence & Proportion of Cases by Clinical Presentation ~Exclusion Criteria Applied to Screening Analysis~ 29 % of CT Cases 71 % of CT Cases Total CT-tested Participants N = 2,634 n CT+ = 83 3.2 % CT+ Patients with clinical indications for CT testing: N = 346 n CT+ = 24  STD contacts  Cervicitis or PID  New STD dx 6.9 % CT+ Patients screened for CT: N = 2,287 n CT+ = 59  No STD contact  No cervicitis or PID  No new STD dx 2.6 % CT+ 87 % of Pop. Tested13 % of Pop. Tested

34. Patients screened for CT: Age 26-44 N = 2,287 n CT+ = 59  No STD contact  No cervicitis or PID  No new STD dx (except GC+) 2.6 % CT+ Patients age 26-30 screened for CT: N = 1,162 n CT+ = 41 3.5 % CT+ Patients age 31-44 screened for CT: N = 1,126 n CT+ = 18 1.6 % CT+

35. Risk factors predictive for CT infection (statistically significantly):  Age < 30 (26-30) §  Partners possible other partners (no time frame) §  New partner (2 mos)  Vaginal DC on exam – unknown etiology (not cervicitis, trich, BV, or yeast)  More than 1 partner (12m) (p-value = 0.13)  Complaints of pain or bleeding with sex, pelvic pain, or spotting (p-value = 0.18)  Asian race (p-value = 0.18) The Over 25 Evaluation Summary of Univariate/Multivariate Findings: Women age Over 25 (26-44) § Independently associated with CT in multivariate analysis (p-value <0.05)

36. Risk factors predictive for CT infection:  Age < 35 (31-35) (p-value = 0.12)  Partners possible other partners (no timeframe) (p-value = 0.26) The Over 25 Evaluation Summary of Univariate/Multivariate Findings: Women age Over 30 (31-44)

37. Summary of Cross-Study Statistical Findings: Risk factors predictive of CT infection Younger agen/a √: Age 26-30 Partner possible other partners (12m) √√ >1 ptr (12m)√Borderline New ptr (2-3m)Borderline√ CT+ (12m) Vaginal DC on exam – unknown etiology √ BV√ Complaints of pain or bldg w/sex, pelvic pain, or spotting Borderline Over 25 Eval Age 26-44 Over 20 Study Age 26-30 Predictive Risk Factor

38. 1.55.04976 Current CDC recommendations ± :  Multiple ptr (>1 in 12 mos)  New ptr (2 mos)  CT hx (12 mos) £ Actual number of cases and screened population varies by algorithm due to missing values ± Approximate replication 0.84.57093 Current CDC recommendations ± plus:  Ptr possible other ptrs 02.9100 Universal Screening % CT+ in pop not Screened % CT+ in pop Screened % Pop Screened £ N = 1,087 % Cases Detected £ N = 32 Algorithm of Selected Criteria: The Over 20 Study: Screening Analysis Results: Performance of Selective Screening Algorithms Age > 25 (26-30) 0.54.47596 Current CDC recommendations ± plus:  Ptr possible other ptrs  Vaginal DC-no known etiology 0.64.27896 Current CDC recommendations ± plus:  Ptr possible other ptrs  BV 0.64.27996 Current CDC recommendations ± plus:  Ptr possible other ptrs  Vaginal DC-no known etiology  BV

39. 1.17.45288 Current CDC recommendations ± plus:  Ptr possible other ptrs  Vaginal DC-no known etiology 1.47.54481 Current CDC recommendations ± plus:  Ptr possible other ptrs 2.36.03558 Current CDC recommendations ± :  Multiple ptr (>1 in 12 mos)  New ptr (2 mos)  CT hx (12 mos) 1.63.55169  Age 26-30 02.6100 Universal Screening % CT+ in pop not Screened % CT+ in pop Screened % Pop Screened* N = 2,228 % Cases Detected £ N = 59 Algorithm of Selected Criteria: The Over 25 Evaluation: Weighted Screening Analysis Results: Performance of Selective Screening Algorithms Age > 25 (26-44) £ Actual number of cases and screened population varies by algorithm due to missing values * Abstracted random sample weighted-up to full tested population by site ± Approximate replication 1.74.77087 Current CDC recommendations ± plus:  Ptr possible other ptrs  BV 1.44.97390 Current CDC recommendations ± plus:  Ptr possible other ptrs  Vaginal DC-no known etiology  BV

40. 1.Partner(s) possibly having had other concurrent partners (during past 12 mos) was the strongest predictor of CT in these research projects; 2.Other fairly consistent behavioral predictors of CT included:  > 1 partners in past 12 mos  New partner in past 2-3 mos 3.Younger age, specifically age 26-30, was a strong demographic predictor of CT 4.Possible clinical predictors include: BV and Vaginal DC on exam with no known etiology Implications for Screening Recommendations for Non-Pregnant Women > Age 25

41.  Testing based on clear clinical indications: Current contact (exposure) to any STD Clinical signs of cervicitis or PID Newly confirmed or presumptively treated other STD dx ? Additional discussion about other clinical considerations for clinician discretion: Vaginal DC on exam with unknown etiology (cervicitis?) BV dx in some populations  Retesting: Encourage CT+ clients RTC in 3 mos  Targeted Screening based on risk factors: Partner possible other partners during past 12 mos!!! More than 1 partner during past 12 mos (more than 2 partners) New partner during past 2-3 mos  Additional discussion: higher CT risk often associated with younger age – emphasis on prioritizing age 26-30 Proposed CT Testing & Screening Recommendations for Non-Pregnant Women > Age 25

42. CADHS-STD Joan Chow, Heidi Bauer, Erika Samoff, Gail Bolan CFHC Melanie Deal, Christy Ngo, Jackie Provost, Rebecca Braun, Lani Pasion Lab Partners Quest Diagnostics, Medical Group Pathology Laboratory, UCSF Chlamydia Research Laboratory (Julius Schachter), Planned Parenthood Mar Monte Laboratory (Jill A. MacAfee) And all The Over 20 & Over 25 Participating Clinic Sites For further information, please contact: Holly Howard at hhoward@dhs.ca.gov Acknowledgements Thank you!