Who is the manufacturer of APTIMA COMBO 2 ASSAY?

Gen-Probe, Inc. filed the 510(k) submission for APTIMA COMBO 2 ASSAY (K111409).

What is the FDA product code for APTIMA COMBO 2 ASSAY?

LSL. It is classified under 21 CFR 866.3390 as a Class 2 device in the Microbiology panel.

What is the regulatory pathway for APTIMA COMBO 2 ASSAY?

510(k) clearance (submission type: Traditional).

What are the predicate devices for APTIMA COMBO 2 ASSAY?

TIGRIS® DTS® GEN-PROBE® APTIMA COMBO 2® Assay (K060652).

Who can help prepare an FDA 510(k) submission like APTIMA COMBO 2 ASSAY?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

APTIMA COMBO 2 ASSAY

K111409 · Gen-Probe, Inc. · LSL · May 3, 2012 · Microbiology

Device Facts

Record ID	K111409
Device Name	APTIMA COMBO 2 ASSAY
Applicant	Gen-Probe, Inc.
Product Code	LSL · Microbiology
Decision Date	May 3, 2012
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.3390
Device Class	Class 2
Attributes	Pediatric

Intended Use

The APTIMA COMBO 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease using the PANTHER System as specified. On the PANTHER System, the assay may be used to test the following specimens from symptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt Solution, and patient-collected vaginal swab specimens. 'Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.

Device Story

The APTIMA Combo 2 Assay is an in vitro diagnostic test for Chlamydia trachomatis and Neisseria gonorrhoeae. It uses target capture, transcription-mediated amplification (TMA), and hybridization protection assay (HPA) technologies. Specimens are collected in transport tubes that stabilize rRNA. In the laboratory, the PANTHER System automates the process: target capture using magnetic microparticles isolates rRNA; TMA amplifies specific 23S rRNA (CT) and 16S rRNA (GC) regions; HPA uses chemiluminescent DNA probes to detect amplicons. The system measures light emission as Relative Light Units (RLU). Kinetic profiles (rapid 'flasher' for CT, slower 'glower' for GC) allow differentiation. Results are determined by RLU cut-offs and kinetic curve types. The device aids clinicians in diagnosing urogenital infections. It benefits patients by providing accurate, automated detection of these pathogens from various specimen types.

Clinical Evidence

Prospective, multicenter clinical study (n=580 males, n=1332 females) across 7 US sites. Performance compared to an infected status algorithm (two reference NAATs). For CT detection, sensitivity ranged from 97.2% to 100% and specificity from 98.5% to 100% across specimen types. For GC detection, sensitivity ranged from 97.7% to 100% and specificity from 99.6% to 100%. Analytical studies included sensitivity (LOD), precision, and carryover (0% carryover rate).

Technological Characteristics

Uses target capture, transcription-mediated amplification (TMA), and hybridization protection assay (HPA). Detection via chemiluminescent acridinium ester-labeled DNA probes. Automated platform (PANTHER System). Qualitative assay. No changes to assay reagents from predicate.

Indications for Use

Indicated for the qualitative detection and differentiation of Chlamydia trachomatis and Neisseria gonorrhoeae rRNA in symptomatic and asymptomatic individuals using clinician-collected endocervical, vaginal, or male urethral swabs, clinician-collected PreservCyt gynecological specimens, or patient-collected vaginal swabs.

Regulatory Classification

Identification

Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identify Neisseria spp. from cultured isolates. Additionally, some of these reagents consist of Neisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence of Neisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Neisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.

Predicate Devices

TIGRIS® DTS® GEN-PROBE® APTIMA COMBO 2® Assay (K060652)

Related Devices

K180681 — Aptima Combo 2 Assay (Panther System) · Hologic, Inc. · Jun 13, 2018
K132251 — APTIMA COMBO 2 ASSAY (PANTHER SYSTEM) · Hologic / Gen-Probe Incorporated · Oct 17, 2013
K200866 — Aptima Combo 2 Assay (Panther System), Aptima Combo 2 Assay (Tigris) System) · Hologic, Inc. · May 17, 2020

Submission Summary (Full Text)

{0}------------------------------------------------ K111409 Gen-Probe Incorporated # 510(k) SUMMARY # MAY - 3 2012 # APTIMA Combo 2® Assay on the PANTHER System ## Sponsor/Contact Information Submitted By: Name: Address: Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121 (858) 410-8000 ## Company Contact: Jody J. Fleming Contact: Regulatory Affairs Manager Phone: 858-410-8634 Fax: 858-410-7876 Email: jody.fleming@gen-probe.com Date Prepared: May 1, 2012 {1}------------------------------------------------ ## General Information | Trade Name: | APTIMA Combo 2® Assay | |-----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Common or Usual Name: | Ribosomal RNA (rRNA) target-amplified nucleic acid probe test for the in vitro diagnostic detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae | | Classification Names: | DNA Probe, Nucleic Acid Amplification, Chlamydia DNA Reagents, Neisseria | ## APTIMA Combo 2 Assay | Device Description | DNA Probe, Nucleic Acid Amplification, Chlamydia | |--------------------|--------------------------------------------------| | Medical Specialty | Microbiology | | Product Code | MKZ | | Device Class | 1 | | Regulation number | 866.3120 | | Device Description | DNA Reagents, Neisseria | |--------------------|-------------------------| | Medical Specialty | Microbiology | | Product Code | LSL | | Device Class | 2 | | Regulation number | 866.3390 | # Substantially Equivalent Devices: APTIMA Combo 2 Assay; K032194 This pre-market application is to clear the APTIMA Combo 2 Assay for use on the PANTHER System. The APTIMA Combo 2 Assay was cleared on the predicate TIGRIS System on December 24, 2003 (K032194). Clearance of this 510(k) will add the PANTHER System as an optional platform. No changes were introduced to the APTIMA Combo 2 Assay reagents. {2}------------------------------------------------ #### Device Description The APTIMA Combo 2 Assay combines the technologies of target capture, TMA, and DKA. Specimens are collected and transferred into their respective specimen transport tubes. The transport solutions in these tubes release the rRNA targets and protect them from degradation during storage. When the APTIMA Combo 2 Assay is performed in the laboratory, the farget rRNA molecules are isolated from specimens by use of capture oligomers via target capture that utilizes magnetic microparticles. The capture oligomers contain sequences complementary to specific regions of the target molecules as well as a string of deoxyadenosine residues. A separate capture oligomer is used for each target. During the hybridization step, the sequence specific regions of the capture oligomers bind to specific regions of the target molecules. The capture oligomer:target complex is then captured out of solution by decreasing the temperature of the reaction to room temperature. This temperature reduction allows hybridization to occur between the deoxyadenosine region on the capture oligomer and the poly-deoxythymidine molecules that are covalently attached to the magnetic particles. The microparticles, including the captured target molecules bound to them, are pulled to the side of the reaction vessel using magnets and the supernatant is aspirated. The particles are washed to remove residual specimen matrix that may contain amplification reaction inhibitors. After the target capture steps are completed, the specimens are ready for amplification. Target amplification assays are based on the ability of complementary oligonucleotide primers to specifically anneal and allow enzymatic amplification of the target nucleic acid strands. The APTIMA Combo 2 Assay replicates a specific region of the 23S rRNA from CT and a specific region of the 16S rRNA from GC via DNA intermediates. A unique set of primers is used for each target molecule. Detection of the rRNA amplification product sequences (amplicon) is achieved using nucleic acid hybridization. Single-stranded chemiluminescent DNA probes, which are complementary to a region of each target amplicon, are labeled with different acridinium ester molecules. The labeled DNA probes combine with amplicon to form stable RNA:DNA hybrids. The Selection Reagent differentiates hybridized from unhybridized probe, eliminating the generation of signal from unhybridized probe. During the detection step, light emitted from the labeled RNA:DNA hybrids is measured as photon signals in a luminometer, {3}------------------------------------------------ and are reported as Relative Light Units (RLU). In DKA, differences in the kinetic profiles of the CT and GC labeled probes allow for the differentiation of signal; kinetic profiles are derived from measurements of photon output during the detection read time. The chemiluminescent detection for CT signal has very rapid kinetics and has the "flasher" kinetic type. The chemiluminescent detection reaction for GC signal is relatively slower and has the "glower" kinetic type. Assay results are determined by a cut-off based on the total RLU and the kinetic curve type. #### Intended Use The AC2 Assay intended use is stated below. The APTIMA COMBO 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease using the PANTHER System as specified. On the PANTHER System, the assay may be used to test the following specimens from symptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt Solution, and patient-collected vaginal swab specimens'. 'Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use. {4}------------------------------------------------ # Comparison to Predicate : · · A comparison of the AC2 Assay on the PANTHER System with the predicate TIGRIS System is summarized below. | Item | AC2 on TIGRIS System (Predicate Device) | AC2 on PANTHER System | |---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Device Class | II | II | | Regulation Specialty | Microbiology | Microbiology | | Qualitative /Quantitative Assay | Qualitative | Qualitative | | Function | Detection and differentiation of rRNA from Chlamydia trachomatis and Neisseria gonorrhoeae | Detection and differentiation of rRNA from Chlamydia trachomatis and Neisseria gonorrhoeae | | Indications For Use / Intended Use | Detection and differentiation of rRNA from Chlamydia trachomatis and Neisseria gonorrhoeae on the DTS and TIGRIS Systems. | Detection and differentiation of rRNA from Chlamydia trachomatis and Neisseria gonorrhoeae on the PANTHER System. | | Specimen Types | Female specimens: • Vaginal swab • Endocervical swab • ThinPrep in PreservCyt solution • Urine Male Specimens: • Urethral Swab | Female specimens: • Vaginal swab • Endocervical swab • ThinPrep in PreservCyt solution Male Specimens: • Urethral Swab | | Item | AC2 on TIGRIS System (Predicate Device) | AC2 on PANTHER System | | | Swabs: After collection, transport and store swab in transport tube at 2- 30°C and test within 60 days. If longer storage is desired, freeze at -20°C to -70°C for up to 365 days. | Swabs: After collection, transport and store swab in transport tube at 2- 30°C and test within 60 days. If longer storage is desired, freeze at -20°C to -70°C for up to 365 days. | | Specimen Transport/Storage | ThinPrep Liquid Pap in PreservCyt: Transport and store in PreservCyt solution at 2-30°C for up to 30 days. After transfer to APTIMA specimen transfer tube, store at 15-30°C for 14 days or store at 2-8°C for 30 days. If longer storage is desired, freeze at -20°C to -70°C for up to 365 days. Urine: After collection, transfer urine to transport tube within 24 hours and store at 2-30°C; Must be assayed within 30 days after transfer. If held longer, freeze -at -20°C to -70°C for up to 365 days. | ThinPrep Liquid Pap in PreservCyt: Transport and store in PreservCyt solution at 2-30°C for up to 30 days. After transfer to APTIMA specimen transfer tube, store at 15-30°C for 14 days or store at 2-8°C for 30 days. If longer storage is desired, freeze at -20°C to -70°C for up to 365 days. | | Type of Assay | Nucleic Acid Amplification Test | Nucleic Acid Amplification Test | | Technology* | Target Capture (TC), Transcription-Mediated Amplification (TMA), Hybridization Protection Assay . (HPA) | Target Capture (TC), Transcription-Mediated Amplification (TMA), Hybridization Protection Assay (HPA) | | Detection Format | HPA which provides relative light units (RLUs) that are assessed against an established assay cutoff | HPA which provides relative light units (RLUs) that are assessed against an established assay cutoff | ## Comparison to Predicate Device {5}------------------------------------------------ *A number of Gen-Probe APTIMA assays (that are based on TC, TMA, and HPA technologics) have been cleared by FDA including: the AC2 Assay (K060652), the APTIMA CT Assay (K061413) and the APTIMA GC Assay (K061509) for use on the automated TIGRIS System and the semiautomated DTS Systems. {6}------------------------------------------------ ## Performance Data #### Brief Description of Non-Clinical Data The following studies were conducted to support analytical performance of the PANTHER System. #### Analytical Sensitivity Study Chlamydia trachomatis analytical sensitivity (limits of detection) was determined by directly comparing dilutions of CT organisms in the APTIMA COMBO 2 assay. The analytical sensitivity claim for the assay is 1 IFU/assay (7.25 IFU/swab, 9.75 IFU/mL, PreservCyt Solution liquid Pap). However, dilutions of less than 1 IFU/assay tested positive in the APTIMA COMBO 2 Assay (for this study, 100% positivity was observed in samples containing CT concentrations of 0.03 IFU/mL). Neisseria gonorrhoeae analytical sensitivity (limits of detection) was determined by directly comparing dilutions of GC organismsin the APTIMA COMBO 2 Assay. The analytical sensitivity claim for the assay is 50 cells/assay (362 cells/swab, 488 cells/mL PreservCyt Solution liquid Pap). However, dilutions of less than 50 cells/assay tested positive in the APTIMA COMBO 2 Assay (for this study, 100% positivity was observed in samples containing GC concentrations of 0.04 CFU/mL). Within Laboratory Precision Study APTIMA COMBO 2 Assay precision was evaluated at Gen-Probe using the PANTHER System. Testing was performed using three PANTHER Systems and three lots of assay reagents. Testing was performed over 24 days. Reproducibility panel members were created using negative PreservCyt Solution liquid Pap specimens and STM. The positive panel members were created by spiking CT and/or GC organisms to the targeted concentrations shown in Table 1. {7}------------------------------------------------ . . For each panel member, Table 1 presents mean RLU, between-instrument, between-lot, between-run, within-run, and overall variation as SD and percent CV. Percent agreement with expected results is also shown. Page 8 of 26 {8}------------------------------------------------ ## Table 1. PANTHER System Within Laboratory Precision Data | | Target Concentration | | | | Mean | Between Instruments | | Between Lots | | Between Runs | | Within Runs | | Total | | |--------|----------------------|----------------|--------------|--------------|----------------|------------------------|-----------|-----------------|-----------|-----------------|-----------|----------------|-----------|---------------|-----------| | Matrix | CT (IFU/mL) | GC (CFU/mL) | Agreed/ N | Agrmt (%) | RLU (x1000) | SD (x1000) | CV (%) | SD (x1000) | CV (%) | SD (x1000) | CV (%) | SD (x1000) | CV (%) | SD (x1000) | CV (%) | | STM | 0 | 0 | 96/96 | 100 | 6 | 0.1 | 1.0 | 0.9 | 13.5 | 0.0 | 0.0 | 1.0 | 15.7 | 1.3 | 20.1 | | | 0.25 | 0 | 95/95 | 100 | 1226 | 70.0 | 5.7 | 20.0 | 1.6 | 8.4 | 0.7 | 47.1 | 3.8 | 87.1 | 7.1 | | | 2.5 | 0 | 96/96 | 100 | 1249 | 78.0 | 6.2 | 6.1 | 0.5 | 0.0 | 0.0 | 32.9 | 2.6 | 84.8 | 6.8 | | | 25 | 0 | 95/95 | 100 | 1268 | 72.9 | 5.7 | 15.3 | 1.2 | 0.0 | 0.0 | 39.6 | 3.1 | 84.3 | 6.6 | | | 0 | 12.5 | 96/96 | 100 | 1081 | 18.4 | 1.7 | 28.6 | 2.6 | 0.0 | 0.0 | 26.7 | 2.5 | 43.2 | 4.0 | | | 0 | 125 | 96/96 | 100 | 1266 | 29.8 | 2.4 | 0.0 | 0.0 | 8.9 | 0.7 | 27.6 | 2.2 | 41.6 | 3.3 | | | 0 | 1250 | 96/96 | 100 | 1309 | 29.4 | 2.2 | 0.0 | 0.0 | 9.8 | 0.8 | 31.8 | 2.4 | 44.4 | 3.4 | | | 2.5 | 125 | 96/96 | 100 | 2456 | 86.6 | 3.5 | 0.0 | 0.0 | 0.0 | 0.0 | 53.0 | 2.2 | 101.5 | 4.1 | | | 2.5 | 2500 | 96/96 | 100 | 2509 | 73.1 | 2.9 | 0.0 | 0.0 | 19.8 | 0.8 | 46.8 | 1.9 | 89.0 | 3.5 | | | 1000 | 2500 | 96/96 | 100 | 2496 | 31.7 | 1.3 | 6.1 | 0.2 | 0.0 | 0.0 | 193.7 | 7.8 | 196.3 | 7.9 | | | 1000 | 125 | 96/96 | 100 | 2471 | 83.6 | 3.4 | 9.4 | 0.4 | 0.0 | 0.0 | 52.4 | 2.1 | 99.1 | 4.0 | | PCyt | 0 | 0 | 96/96 | 100 | 7 | 0.0 | 0.0 | 0.8 | 11.7 | 0.0 | 0.0 | 1.5 | 22.4 | 1.7 | 24.7 | | | 0.25 | 0 | 96/96 | 100 | 1113 | 92.3 | 8.3 | 30.1 | 2.7 | 0.0 | 0.0 | 63.6 | 5.7 | 116.0 | 10.4 | | | 2.5 | 0 | 96/96 | 100 | 1194 | 62.5 | 5.2 | 24.8 | 2.1 | 0.0 | 0.0 | 47.0 | 3.9 | 82.1 | 6.9 | | | 25 | 0 | 95/95 | 100 | 1222 | 65.1 | 5.3 | 26.4 | 2.2 | 14.7 | 1.2 | 35.0 | 2.9 | 79.8 | 6.5 | | | 0 | 12.5 | 93/93 | 100 | 994 | 33.3 | 3.3 | 36.9 | 3.7 | 16.0 | 1.6 | 26.2 | 2.6 | 58.4 | 5.9 | | | 0 | 125 | 95/95 | 100 | 1189 | 40.1 | 3.4 | 4.5 | 0.4 | 10.9 | 0.9 | 21.4 | 1.8 | 47.0 | 4.0 | | | 0 | 1250 | 95/95 | 100 | 1239 | 37.7 | 3.0 | 7.5 | 0.6 | 13.6 | 1.1 | 18.0 | 1.5 | 44.6 | 3.6 | | | 2.5 | 125 | 95/95 | 100 | 2333 | 99.7 | 4.3 | 35.3 | 1.5 | 12.6 | 0.5 | 48.9 | 2.1 | 117.2 | 5.0 | Agent = ageemen, CV = cellicient of variation, N = multion liggio = Pesserv, V.V = reblive light uni. 3D = standad deviation, STM = swab casport masjium. Nee; Variability form some to reasonal the variability de to hose tures is very stall. Were this econs, the minimity so messeed with standed levision and 54.7 kset o (). {9}------------------------------------------------ # Carryover Studies for the PANTHER System A multi-run analytical study was conducted using spiked panels on three PANTHER Systems. Carryover was assessed using approximately 20% high titer GC samples dispersed between negative samples. The runs included clusters of high positive samples with clusters of negative samples as well as single high positives dispersed in a specific pattern within the run. High titer samples were made using GC rRNA spiked into STM to give a final concentration equivalent to 2.5 x 108 CFU/mL. Testing was carried out using 5 runs on cach of three PANTHER Systems. Carryover was calculated from a total of 2938 valid negative results. The overall carryover rate was 0% with a 95% confidence interval of 0-0.1%. {10}------------------------------------------------ ## Brief Description of Clinical Data ## Prevalence The prevalence of CT and GC in patient populations depends on risk factors such as age, gender, the presence or absence of symptoms, the type of clinic, and the sensitivity of the test used to detect infections. A summary of the prevalence of three CT and GC disease outcomes, as determined by the APTIMA COMBO 2 Assay on the PANTHER System in the clinical trial, is shown in Tables 2, 3, and 4 by specimen type and clinical site. Table 2. Prevalence of CT+/GC- Infections as Determined by the APTIMA COMBO 2 Assay by Specimen Type and Clinical Site | | CT+/GC- Prevalence % (# positive/# tested with valid results) | | | | |------|---------------------------------------------------------------|---------------------------------------------------------------|---------------|----------------------| | Site | Male Urethral Swab | Clinician- Collected/Patient -collected Vaginal Swab | PreservCyt | Endocervical Swab | | 1 | 0(-) | 9.9 (21/212) | 8.9 (20/225) | 10.4 (20/193) | | 2 | 13.9 (28/202) | 8.3 (19/230) | 8.8 (21/239) | 8.2 (19/231) | | 3 | 1.3 (1/76) | 2.7 (6/222) | 3.1 (7/226) | 2.7 (6/223) | | 4 | 24.4 (33/135) | 11.7 (40/342) | 10.2 (35/342) | 11.3 (38/337) | | 5 | 0(-) | 4.5 (1/22) | 4.8 (1/21) | 4.3 (1/23) | | 6 | 21.5 (28/130) | 11.9 (13/109) | 8.7 (10/115) | 8.8 (10/114) | | 7 | 16.7 (1/6) | 3.2 (5/157) | 2.5 (4/161) | 2.6 (4/152) | | All | 16.6 (91/549) | 8.1 (105/1294) | 7.4 (98/1329) | 7.7 (98/1273) | PreservCyt = PreservCyt Solution Liquid Pap {11}------------------------------------------------ : | | CT-/GC+ Prevalence % (# positive/# tested with valid results) | | | | |------|---------------------------------------------------------------|---------------------------------------------------------------|---------------|----------------------| | Site | Male Urethral Swab | Clinician- Collected/Patient- collected Vaginal Swab | PreservCyt | Endocervical Swab | | 1 | 0 ( - ) | 3.3 (7/212) | 2.7 (6/225) | 3.1 (6/193) | | 2 | 5.9 (12/202) | 3.9 (9/230) | 4.6 (11/239) | 4.8 (11/231) | | 3 | 1.3 (1/76) | 0.5 (1/222) | 0.4 (1/226) | 0.4 (1/223) | | 4 | 1.5 (2/135) | 1.5 (5/342) | 1.5 (5/342) | 1.8 (6/337) | | 5 | 0 ( - ) | 0.0 (0/22) | 0.0 (0/21) | 0.0 (0/23) | | 6 | 5.4 (7/130) | 3.7 (4/109) | 1.7 (2/115) | 1.8 (2/114) | | 7 | 0.0 (0/6) | 2.5 (4/157) | 2.5 (4/161) | 2.6 (4/152) | | All | 4.0 (22/549) | 2.3 (30/1294) | 2.2 (29/1329) | 2.4 (30/1273) | Table 3. Prevalence of CT-/GC+ Infections as Determined by the APTIMA COMBO 2 Assay by Specimen Type and Clinical Site PreservCyt = PreservCyt Solution Liquid Pap Table 4. Prevalence of CT+/GC+ Infections as Determined by the APTIMA COMBO 2 Assay by Specimen Type and Clinical Site | Site | Male Urethral Swab | CT+/GC+ Prevalence % (# positive/# tested with valid results) Clinician- Collected/Patient- collected Vaginal Swab | PreservCyt | Endocervical Swab | |------|-----------------------|--------------------------------------------------------------------------------------------------------------------------------|---------------|----------------------| | | | | | | | 2 | 3.0 (6/202) | 1.3 (3/230) | 0.8 (2/239) | 0.9 (2/231) | | 3 | 0.0 (0/76) | 0.0 (0/222) | 0.0 (0/226) | 0.0 (0/223) | | 4 | 4.4 (6/135) | 1.2 (4/342) | 0.9 (3/342) | 0.9 (3/337) | | 5 | 0 (-) | 0.0 (0/22) | 0.0 (0/21) | 0.0 (0/23) | | 6 | 0.8 (1/130) | 0.9 (1/109) | 0.9 (1/115) | 0.9 (1/114) | | 7 | 0.0 (0/6) | 0.6 (1/157) | 0.6 (1/161) | 0.7 (1/152) | | All | 2.4 (13/549) | 1.3 (17/1294) | 1.1 (14/1329) | 1.1 (14/1273) | PreservCyt = PreservCyt Solution Liquid Pap {12}------------------------------------------------ Positive and Negative Predictive Values for Hypothetical Prevalence Rates The estimated positive and negative predictive values (PPV and NPV) of the APTIMA COMBO 2 Assay for different hypothetical prevalence rates are shown for each specimen type in Table 5. The PPV and NPV are derived for different hypothetical prevalence rates using the sensitivity and specificity estimates for each specimen type from the clinical performance study (see Table 6 and Table 9). | Specimen Type | Hypothetical Prevalence (%) | CT Detection | | GC Detection | | |-------------------------------------------------------------------------------|--------------------------------|--------------|---------|--------------|---------| | | | PPV (%) | NPV (%) | PPV (%) | NPV (%) | | Male Urethral Swab | 1 | 53.1 | 100 | 100 | 100 | | | 2 | 69.6 | 100 | 100 | 100 | | | 5 | 85.5 | 100 | 100 | 100 | | | 10 | 92.6 | 100 | 100 | 100 | | | 15 | 95.2 | 100 | 100 | 100 | | | 20 | 96.6 | 100 | 100 | 100 | | | 25 | 97.4 | 100 | 100 | 100 | | Clinician- Collected Vaginal Swab/ Patient-Collected Vaginal Swab | 1 | 38.9 | 100 | 70.6 | 100 | | | 2 | 56.3 | 99.9 | 82.9 | 100 | | | 5 | 76.8 | 99.9 | 92.6 | 99.9 | | | 10 | 87.5 | 99.7 | 96.3 | 99.7 | | | 15 | 91.7 | 99.5 | 97.7 | 99.6 | | | 20 | 94.0 | 99.3 | 98.3 | 99.4 | | | 25 | 95.5 | 99.1 | 98.8 | 99.2 | | PreservCyt Solution Liquid Pap | 1 | 100 | 100 | 100 | 100 | | | 2 | 100 | 100 | 100 | 100 | | | 5 | 100 | 99.9 | 100 | 100 | | | 10 | 100 | 99.8 | 100 | 100 | | | 15 | 100 | 99.7 | 100 | 100 | | | 20 | 100 | 99.6 | 100 | 100 | | | 25 | 100 | 99.4 | 100 | 100 | | Endocervical Swab | 1 | 58.5 | 100 | 85.8 | 100 | | | 2 | 74.0 | 99.9 | 92.4 | 100 | | | 5 | 88.0 | 99.9 | 96.9 | 100 | | | 10 | 93.9 | 99.7 | 98.5 | 100 | | | 15 | 96.1 | 99.5 | 99.1 | 100 | | | 20 | 97.2 | 99.3 | 99.3 | 100 | | | 25 | 97.9 | 99.1 | 99.5 | 100 | Table 5. Positive and Negative Predictive Values for Hypothetical Prevalence Rates by Specimen Type {13}------------------------------------------------ # Clinical Study Results A prospective, multicenter clinical study was conducted to establish the performance characteristics of the APTIMA COMBO 2 Assay on the PANTHER System. Specimens were collected from symptomatic and asymptomatic men (n=580) and women (n=1332) enrolled from 7 geographically and ethnically diverse US clinical sites, including obstetrics and gynecology, family planning, public health, and STD clinics. Subjects were classified as symptomatic if symptoms were reported by the subject. Subjects were classified as asymptomatic if the subject did not report symptoms. Of the 580 male subjects, none were <18 years of age, 72 were 18 to 20 years of age, 201 were 21 to 25 years of age, and 307 were >25 years of age. Of the 1332 female subjects, 11 were 14 to 15 years of age, 59 were 16 to 17 years of age, 319 were 18 to 20 years of age, 401 were 21 to 25 years of age, and 542 were >25 years of age. Up to 2 specimens were collected from each male subject (1 urethral swab and 1 first-catch urine, in that order) and up to 4 specimens were collected from each female subject (1 first-catch urine, 1 vaginal swab, 1 PreservCyt Solution liquid Pap specimen, and 1 endocervical swab, in that order). All specimens were clinician-collected except urine specimens and approximately half of the vaginal swab specimens, which were collected by the subject at the clinic. Approximately half of the PreservCyt Solution liquid Pap specimens were collected with a broom-type device and half were collected with a spatula and cytobrush. Samples were prepared for APTIMA testing in accordance with the appropriate APTIMA specimen collection kit package insert instructions. All evaluable samples (567 male urethral swab, 1319 vaginal swab, 1330 PreservCyt, and 1310 endocervical swab samples) were tested with the APTIMA COMBO 2 Assay on the PANTHER System in accordance with package insert instructions. The samples were split amongst three laboratories (two external laboratories and GEN-PROBE). Samples with initial invalid, equivocal, or error results were retested. Eighteen (18) male urethral swab, 25 vaginal swab, 1 PreservCyt, and 37 endocervical swab specimens had final invalid results and were excluded from the analyses. Most of the invalid results were due to insufficient sample volume. One vaginal swab and 1 endocervical swab had final CT equivocal results and 1 PreservCyt and 1 endocervical swab had final GC equivocal results and were excluded from the analyses. {14}------------------------------------------------ Male urethral swab, male and female urine, and PreservCyt samples were tested with cleared nucleic acid amplification tests (NAATs) to establish the infected status. The infected status algorithm used results from two specimen types and two reference NAATs. Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs. For female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt specimens, the subject was categorized as infected; however, for the evaluation of the non-urine specimen types, the specimens were considered non-infected. Subjects that could not be categorized as infected or not infected were excluded from the performance analyses. ## Chlamydia trachomatis Performance Results Performance characteristics of the APTIMA COMBO 2 Assay were estimated by comparing PANTHER System results to the infected status algorithm. Table 6 shows the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the APTIMA COMBO 2 Assay for CT detection and the prevalence of CT (based on the infected status) in each specimen type. | Spec Type | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)¹ | Specificity % (95% CI)¹ | PPV % (95% CI)² | NPV % (95% CI)² | |--------------|------|-----|----|------|----|--------|----------------------------|----------------------------|---------------------|---------------------| | MS | 549 | 100 | 4 | 445 | 0 | 18.2 | 100 (96.3-100) | 99.1 (97.7-99.7) | 96.2 (90.8-98.9) | 100 (99.2-100) | | CVS/ PVS | 1274 | 104 | 18 | 1149 | 3 | 8.4 | 97.2 (92.1-99.0) | 98.5 (97.6-99.0) | 85.2 (78.8-90.5) | 99.7 (99.3-99.9) | | PCyt | 1311 | 112 | 0 | 1197 | 2 | 8.7 | 98.2 (93.8-99.5) | 100 (99.7-100) | 100 (96.9-100) | 99.8 (99.4-100) | | FS | 1254 | 104 | 8 | 1139 | 3 | 8.5 | 97.2 (92.1-99.0) | 99.3 (98.6-99.6) | 92.9 (87.1-96.7) | 99.7 (99.3-99.9) | Table 6. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false negative, FP = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value. PCyt = PreservCyt Solution liquid Pap, PV = positive predictive value, Prev = prevalent-collected vaginal swab, Spec = specimen, TN = true negative. TY = true positive. ' Score Cl 2 PPV 95% CI computed from the exact 95% CI for the positive likelihood ratio, NPV 95% CI computed from the exact 95% CI from the negative likelihood ratio. Table 7 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for CT detection and the prevalence of CT (based on the infected status) in each specimen type by symptom status. CT prevalence was higher in symptomatic men and women. {15}------------------------------------------------ | Spec Type | Sx Status | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)¹ | Specificity % (95% CI)¹ | PPV % (95% CI)² | NPV % (95% CI)² | |--------------|--------------|-----|----|----|-----|----|-----------|-------------------------------|-------------------------------|---------------------|---------------------| | MS | Sym | 238 | 59 | 1 | 178 | 0 | 24.8 | 100 (93.9-100) | 99.4 (96.9-99.9) | 98.3 (91.5-100) | 100 (98.0-100) | | | Asym | 311 | 41 | 3 | 267 | 0 | 13.2 | 100 (91.4-100) | 98.9 (96.8-99.6) | 93.2 (82.5-98.5) | 100 (98.7-100) | | CVS/ PVS | Sym | 810 | 73 | 8 | 729 | 0 | 9.0 | 100 (95.0-100) | 98.9 (97.9-99.4) | 90.1 (82.3-95.5) | 100 (99.5-100) | | | Asym | 464 | 31 | 10 | 420 | 3 | 7.3 | 91.2 (77.0-97.0) | 97.7 (95.8-98.7) | 75.6 (63.1-86.2) | 99.3 (98.1-99.8) | | PCyt | Sym | 838 | 76 | 0 | 762 | 0 | 9.1 | 100 (95.2-100) | 100 (99.5-100) | 100 (95.4-100) | 100 (99.5-100) | | | Asym | 473 | 36 | 0 | 435 | 2 | 8.0 | 94.7 (82.7-98.5) | 100 (99.1-100) | 100 (91.1-100) | 99.5 (98.5-99.9) | | FS | Sym | 794 | 71 | 5 | 718 | 0 | 8.9 | 100 (94.9-100) | 99.3 (98.4-99.7) | 93.4 (85.9-97.8) | 100 (99.5-100) | | | Asym | 460 | 33 | 3 | 421 | 3 | 7.8 | 91.7 (78.2-97.1) | 99.3 (97.9-99.8) | 91.7 (79.9-98.0) | 99.3 (98.1-99.8) | ## Table 7. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection by Symptom Status Asym = asymplomatic, CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urettral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PV = positive predictive value, Prev = prevalent-collected vaginal swab, Spec = specimen, Sx = symplom, Sym = symplomatic, TN = true negative, TP = true positive. l Score Cl 2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the negative likelihood ratio. Table 8 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for CT detection and the prevalence of CT (based on the infected status) in each specimen type by clinical site. CT prevalence varied across clinical sites, as expected. {16}------------------------------------------------ | Table 8. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection by | | | |--------------------------------------------------------------------------------------|--|--| | Clinical Site | | | | Spec Type | Site | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)¹ | Specificity % (95% CI)¹ | PPV % (95% CI)² | NPV % (95% CI)² | |--------------|------|-----|----|----|-----|----|-----------|----------------------------|----------------------------|---------------------|---------------------| | MS | 1 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC | | | 2 | 202 | 34 | 0 | 168 | 0 | 16.8 | 100 (89.8-100) | 100 (97.8-100) | 100 (90.3-100) | 100 (98.0-100) | | | 3 | 76 | 0 | 1 | 75 | 0 | 0.0 | NC | 98.7 (92.9-99.8) | 0.0 (NC) | 100 (NC) | | | 4 | 135 | 36 | 3 | 96 | 0 | 26.7 | 100 (90.4-100) | 97.0 (91.5-99.0) | 92.3 (80.9-98.3) | 100 (96.6-100) | | | 5 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC | | | 6 | 130 | 29 | 0 | 101 | 0 | 22.3 | 100 (88.3-100) | 100 (96.3-100) | 100 (88.9-100) | 100 (96.7-100) | | | 7 | 6 | 1 | 0 | 5 | 0 | 16.7 | 100 (20.7-100) | 100 (56.6-100) | 100 (6.9-100) | 100 (80.4-100) | | CVS/ PVS | 1 | 211 | 23 | 6 | 182 | 0 | 10.9 | 100 (85.7-100) | 96.8 (93.2-98.5) | 79.3 (64.2-91.2) | 100 (98.2-100) | | | 2 | 230 | 18 | 4 | 206 | 2 | 8.7 | 90.0 (69.9-97.2) | 98.1 (95.2-99.3) | 81.8 (64.7-93.9) | 99.0 (97.1-99.9) | | | 3 | 213 | 6 | 0 | 206 | 1 | 3.3 | 85.7 (48.7-97.4) | 100 (98.2-100) | 100 (64.1-100) | 99.5 (98.1-100) | | | 4 | 335 | 40 | 4 | 291 | 0 | 11.9 | 100 (91.2-100) | 98.6 (96.6-99.5) | 90.9 (79.8-97.3) | 100 (98.8-100) | | | 5 | 21 | 1 | 0 | 20 | 0 | 4.8 | 100 (20.7-100) | 100 (83.9-100) | 100 (6.5-100) | 100 (95.3-100) | | | 6 | 107 | 11 | 3 | 93 | 0 | 10.3 | 100 (74.1-100) | 96.9 (91.2-98.9) | 78.6 (56.4-94.6) | 100 (96.8-100) | | | 7 | 157 | 5 | 1 | 151 | 0 | 3.2 | 100 (56.6-100) | 99.3 (96.4-99.9) | 83.3 (47.4-99.5) | 100 (98.3-100) | | PCyt | 1 | 225 | 27 | 0 | 198 | 0 | 12.0 | 100 (87.5-100) | 100 (98.1-100) | 100 (88.1-100) | 100 (98.3-100) | | | 2 | 239 | 23 | 0 | 216 | 0 | 9.6 | 100 (85.7-100) | 100 (98.3-100) | 100 (86.3-100) | 100 (98.4-100) | | | 3 | 217 | 7 | 0 | 210 | 0 | 3.2 | 100 (64.6-100) | 100 (98.2-100) | 100 (65.7-100) | 100 (98.7-100) | | | 4 | 335 | 38 | 0 | 295 | 2 | 11.9 | 95.0 (83.5-98.6) | 100 (98.7-100) | 100 (91.5-100) | 99.3 (97.8-99.9) | | | 5 | 21 | 1 | 0 | 20 | 0 | 4.8 | 100 (20.7-100) | 100 (83.9-100) | 100 (6.5-100) | 100 (95.3-100) | | | 6 | 113 | 11 | 0 | 102 | 0 | 9.7 | 100 (74.1-100) | 100 (96.4-100) | 100 (75.2-100) | 100 (97.0-100) | | | 7 | 161 | 5 | 0 | 156 | 0 | 3.1 | 100 (56.6-100) | 100 (97.6-100) | 100 (57.8-100) | 100 (98.4-100) | Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swah, NPV = negative value, PCy1 = PreservCyt Solution liquid Pap, PPV = postive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = true negative, TP = true positive. ' Score Cl 2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the cract 95% Cl from the negative likelihood ratio. {17}------------------------------------------------ | Spec Type | Site | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)¹ | Specificity % (95% CI)¹ | PPV % (95% CI)² | NPV % (95% CI)² | |--------------|------|-----|----|----|-----|----|--------|----------------------------|----------------------------|---------------------|--------------------| | FS | 1 | 193 | 24 | 3 | 166 | 0 | 12.4 | 100 (86.2-100) | 98.2 (94.9-99.4) | 88.9 (73.6-97.5) | 100 (98.0-100) | | | 2 | 231 | 19 | 2 | 209 | 1 | 8.7 | 95.0 (76.4-99.1) | 99.1 (96.6-99.7) | 90.5 (73.4-98.6) | 99.5 (97.7-100) | | | 3 | 214 | 6 | 0 | 207 | 1 | 3.3 | 85.7 (48.7-97.4) | 100 (98.2-100) | 100 (64.1-100) | 99.5 (98.1-100) | | | 4 | 330 | 39 | 2 | 288 | 1 | 12.1 | 97.5 (87.1-99.6) | 99.3 (97.5-99.8) | 95.1 (84.8-99.3) | 99.7 (98.2-100) | | | 5 | 22 | 1 | 0 | 21 | 0 | 4.5 | 100 (20.7-100) | 100 (84.5-100) | 100 (6.5-100) | 100 (95.5-100) | | | 6 | 112 | 11 | 0 | 101 | 0 | 9.8 | 100 (74.1-100) | 100 (96.3-100) | 100 (75.2-100) | 100 (97.0-100) | | | 7 | 152 | 4 | 1 | 147 | 0 | 2.6 | 100 (51.0-100) | 99.3 (96.3-99.9) | 80.0 (40.0-99.4) | 100 (98.4-100) | Table 8. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection by Clinical Site (continued) Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PPV = positive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = true negative, TP = true positive. 1 Score Cl 2 YPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the exact 95% Cl from the negative likelihood ratio. Table 9 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for GC detection and the prevalence of GC (based on the infected status) in each specimen type. | Spec Type | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)1 | Specificity % (95% CI)1 | PPV % (95% CI)2 | NPV % (95% CI)2 | |--------------|------|----|----|------|----|-----------|----------------------------|----------------------------|---------------------|--------------------| | MS | 546 | 34 | 0 | 512 | 0 | 6.2 | 100 (89.8-100) | 100 (99.3-100) | 100 (90.2-100) | 100 (99.3-100) | | VS | 1258 | 42 | 5 | 1210 | 1 | 3.4 | 97.7 (87.9-99.6) | 99.6 (99.0-99.8) | 89.4 (78.6-96.1) | 99.9 (99.6-100) | | PCyt | 1293 | 43 | 0 | 1250 | 0 | 3.3 | 100 (91.8-100) | 100 (99.7-100) | 100 (92.1-100) | 100 (99.7-100) | | FS | 1238 | 42 | 2 | 1194 | 0 | 3.4 | 100 (91.6-100) | 99.8 (99.4-100) | 95.5 (85.4-99.4) | 100 (99.7-100) | Table 9. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PV = positive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = true negative, TV = true positive. Score CI 2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the exact 95% Cl from the negative likelihood ratio. {18}------------------------------------------------ Table 10 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for GC detection and the prevalence of GC (based on the infected status) in each specimen type by symptom status. GC prevalence was higher in symptomatic men but similar in symptomatic and asymptomatic women. Table 10. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection by Symptom Status | Spec Type | Sx Status | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)¹ | Specificity % (95% CI)¹ | PPV % (95% CI)² | NPV % (95% CI)² | |--------------------|--------------|-----|----|----|-----|----|-----------|----------------------------|----------------------------|---------------------|--------------------| | MS | Sym | 236 | 31 | 0 | 205 | 0 | 13.1 | 100 (89.0-100) | 100 (98.2-100) | 100 (89.5-100) | 100 (98.3-100) | | MS | Asym | 310 | 3 | 0 | 307 | 0 | 1.0 | 100 (43.9-100) | 100 (98.8-100) | 100 (44.4-100) | 100 (99.3-100) | | CVS/ PVS | Sym | 802 | 27 | 4 | 771 | 0 | 3.4 | 100 (87.5-100) | 99.5 (98.7- 99.8) | 87.1 (72.6-96.1) | 100 (99.6-100) | | CVS/ PVS | Asym | 456 | 15 | 1 | 439 | 1 | 3.5 | 93.8 (71.7-98.9) | 99.8 (98.7- 100) | 93.8 (74.0-99.8) | 99.8 (98.9-100) | | PCyt | Sym | 829 | 27 | 0 | 802 | 0 | 3.3 | 100 (87.5-100) | 100 (99.5-100) | 100 (88.0-100) | 100 (99.6-100) | | PCyt | Asym | 464 | 16 | 0 | 448 | 0 | 3.4 | 100 (80.6-100) | 100 (99.1-100) | 100 (81.3-100) | 100 (99.3-100) | | FS | Sym | 785 | 26 | 1 | 758 | 0 | 3.3 | 100 (87.1-100) | 99.9 (99.3-100) | 96.3 (82.4-99.9) | 100 (99.5-100) | | FS | Asym | 453 | 16 | 1 | 436 | 0 | 3.5 | 100 (80.6-100) | 99.8 (98.7-100) | 94.1 (74.3-99.8) | 100 (99.3-100) | | Spec Type | Site | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)¹ | Specificity % (95% CI)¹ | PPV % (95% CI)² | NPV % (95% CI)² | | MS | 1 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC | | | 2 | 201 | 18 | 0 | 183 | 0 | 9.0 | 100 (82.4-100) | 100 (97.9-100) | 100 (83.1-100) | 100 (98.2-100) | | | 3 | 76 | 1 | 0 | 75 | 0 | 1.3 | 100 (20.7-100) | 100 (95.1-100) | 100 (6.4-100) | 100 (98.7-100) | | | 4 | 135 | 8 | 0 | 127 | 0 | 5.9 | 100 (67.6-100) | 100 (97.1-100) | 100 (68.8-100) | 100 (97.7-100) | | | 5 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC | | | 6 | 128 | 7 | 0 | 121 | 0 | 5.5 | 100 (64.6-100) | 100 (96.9-100) | 100 (65.8-100) | 100 (97.7-100) | | | 7 | 6 | 0 | 0 | 6 | 0 | 0.0 | NC | 100 (61.0-100) | NC | 100 ( NC ) | | CVS/ PVS | 1 | 207 | 13 | 2 | 192 | 0 | 6.3 | 100 (77.2-100) | 99.0 (96.3-99.7) | 86.7 (64.6-98.3) | 100 (98.4-100) | | | 2 | 230 | 12 | 0 | 217 | 1 | 5.7 | 92.3 (66.7-98.6) | 100 (98.3-100) | 100 (77.8-100) | 99.5 (97.9-100) | | | 3 | 206 | 1 | 0 | 205 | 0 | 0.5 | 100 (20.7-100) | 100 (98.2-100) | 100 (6.4-100) | 100 (99.5-100) | | | 4 | 331 | 8 | 1 | 322 | 0 | 2.4 | 100 (67.6-100) | 99.7 (98.3-99.9) | 88.9 (59.1-99.7) | 100 (99.1-100) | | | 5 | 21 | 0 | 0 | 21 | 0 | 0.0 | NC | 100 (84.5-100) | NC | 100 ( NC ) | | | 6 | 106 | 3 | 2 | 101 | 0 | 2.8 | 100 (43.9-100) | 98.1 (93.2-99.5) | 60.0 (24.6-92.8) | 100 (98.0-100) | | | 7 | 157 | 5 | 0 | 152 | 0 | 3.2 | 100 (56.6-100) | 100 (97.5-100) | 100 (57.8-100) | 100 (98.3-100) | | PCyt | 1 | 220 | 13 | 0 | 207 | 0 | 5.9 | 100 (77.2-100) | 100 (98.2-100) | 100 (78.0-100) | 100 (98.5-100) | | | 2 | 239 | 13 | 0 | 226 | 0 | 5.4 | 100 (77.2-100) | 100 (98.3-100) | 100 (78.0-100) | 100 (98.6-100) | | | 3 | 210 | 1 | 0 | 209 | 0 | 0.5 | 100 (20.7-100) | 100 (98.2-100) | 100 (6.4-100) | 100 (99.5-100) | | | 4 | 331 | 8 | 0 | 323 | 0 | 2.4 | 100 (67.6-100) | 100 (98.8-100) | 100 (68.6-100) | 100 (99.1-100) | | | 5 | 21 | 0 | 0 | 21 | 0 | 0.0 | NC | 100 (84.5-100) | NC | 100 ( NC ) | | | 6 | 111 | 3 | 0 | 108 | 0 | 2.7 | 100 (43.9-100) | 100 (96.6-100) | 100 (44.6-100) | 100 (98.1-100) | | | 7 | 161 | 5 | 0 | 156 | 0 | 3.1 | 100 (56.6-100) | 100 (97.6-100) | 100 (57.8-100) | 100 (98.4-100) | | Spec Type FS | Site | n | TP | FP | TN | FN | Prev % | Sensitivity % (95% CI)¹ | Specificity % (95% CI)¹ | PPV % (95% CI)² | NPV % (95% CI)² | | 1 | 1 | 189 | 12 | 1 | 176 | 0 | 6.3 | 100 (75.8-100) | 99.4 (96.9-99.9) | 92.3 (68.6-99.8) | 100 (98.2-100) | | 2 | 2 | 231 | 13 | 0 | 218 | 0 | 5.6 | 100 (77.2-100) | 100 (98.3-100) | 100 (78.0-100) | 100 (98.5-100) | | 3 | 3 | 207 | 1 | 0 | 206 | 0 | 0.5 | 100 (20.7-100) | 100 (98.2-100) | 100 (6.4-100) | 100 (99.5-100) | | 4 | 4 | 327 | 8 | 1 | 318 | 0 | 2.4 | 100 (67.6-100) | 99.7 (98.2-99.9) | 88.9 (59.1-99.7) | 100 (99.1-100) | | 5 | 5 | 22 | 0 | 0 | 22 | 0 | 0.0 | NC | 100 (85.1-100) | NC | 100 (NC) | | 6 | 6 | 110 | 3 | 0 | 107 | 0 | 2.7 | 100 (43.9-100) | 100 (96.5-100) | 100 (44.6-100) | 100 (98.1-100) | | 7 | 7 | 152 | 5 | 0 | 147 | 0 | 3.3 | 100 (56.6-100) | 100 (97.5-100) | 100 (57.9-100) | 100 (98.3-100) | Asym = asymptomatic, CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false negative, FP = false positive, FS = female endocervical swab, NPV = negative predictive value, PCy = PreservCyt Solution liquid Pap, PV = positive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, Sx = symptom, Sym = symptomatic, TN = true negative, TP = true positive. Score Cl 2 PPV 95% CI computed from the exact 95% CI for the positive likelihood ratio, NPV 95% CI computed from the exact 95% CI from the negative likelihood ratio. Table 11 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for GC detection and the prevalence of GC (based on the infected status) in each specimen type by clinical site for the clinical performance study. GC prevalence varied across clinical sites, as expected. {19}------------------------------------------------ Table 11. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection by Clinical Site Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PPV = positive predictive value, Prev = prevalent-collected vaginal swab, Spcc = specimen, TN = true negative, TV = true positive. ' Score CI 2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the exact 95% Cl from the negative likelihood ratio. {20}------------------------------------------------ Table 11. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection by Clinical Site (continued) CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false negative, FP = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PPV = positive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = 1rue negative, TV = true positive. Score CI 2 PPV 95% Cl computed from the exact 95% CI for the positive likelihood ratio, NPV 95% CI computed from the exact 95% Cl from the negative likelihood ratio. The frequency of test outcomes from reference NAAT and investigational PANTHER System testing is summarized in Table 13 for CT and in Tables 16 and Tables 16 and Table 15 for GC. {21}------------------------------------------------ . | | | Assay Results | | | | | | |--------------------|----|---------------|------------|----------------|----------------|-----|------| | | | AC2 DTS | ACT TIGRIS | AC2 PANTHER | Symptom Status | | | | CT Infected Status | MS | MU | MS | MU | MS | Sym | Asym | | Infected | + | + | + | + | + | 50 | 37 | | Infected | + | + | + | + | NA | 4 | 1 | | Infected | + | + | + | - | + | 2 | 0 | | Infected | + | + | + | + | + | 4 | 2 | | Infected | + | - | + | - | + | 3 | 2 | | Not Infected | + | + | - | - | - | 0 | 1 | | Not Infected | + | - | - | - | + | 0 | 1 | | Not Infected | + | - | - | - | - | 1 | 1 | | Not Infected | - | - | + | - | - | 3 | 2 | | Not Infected | - | - | - | + | - | 1 | 1 | | Not Infected | - | - | - | - | + | 1 | 2 | | Not Infected | - | - | - | - | - | 173 | 262 | | Not Infected | - | - | - | - | NA | 10 | 9 | | Not Infected | NA | - | - | - | NA | 1 | 2 | Table 12. CT Infected Status for Performance Evaluation in Male Urethral Swab Specimens AC2 = APTIMA COMBO 2, ACT = APTIMA CT Assuy, Asym = asymptomatic, DTS = DTS Systems, MS = male urethral swab, MU = male urine, NA = result not available, PANTHER System, Sym = symptomatic, TIGRIS = TIGRIS DTS System . . : . . : . {22}------------------------------------------------ | | | | | Assay Results | | | | | | |-----------------------|------------|----|---------------|---------------|---------|----------------|----|----------------|------| | CT Infected Status | AC2 TIGRIS | | ACT TIGRIS | | | AC2 PANTHER | | Symptom Status | | | | PCyt | FU | PCyt | FU | CVS/PVS | PCyt | FS | Sym | Asym | | Infected | + | + | + | + | + | + | + | 62 | 26 | | Infected | + | + | + | + | + | + | + | 0 | 1 | | Infected | + | + | + | + | + | + | NA | 3 | 0 | | Infected | + | + | + | + | + | + | + | 0 | 2 | | Infected | + | + | + | + | + | + | + | 0 | 1 | | Infected | + | + | + | + | NA | + | + | 1 | 1 | | Infected | + | + | + | + | NA | + | NA | 2 | 1 | | Infected | + | + | + | + | + | + | + | 4 | 1 | | Infected | + | - | + | + | NA | + | NA | 0 | 1 | | Infected | + | - | + | + | + | + | + | 4 | 0 | | Infected | + | - | + | + | + | + | + | 0 | 1 | | Infected | + | NA | + | NA | + | + | + | 0 | 1 | | Infected | + | NA | + | NA | + | + | + | 0 | 1 | | Infected | + | NA | + | NA | + | + | + | 0 | 1 | | Infected¹ | - | + | - | + | + | - | + | 1 | 1 | | Infected¹ | - | + | - | + | + | - | - | 2 | 0 | | Infected¹ | - | + | - | + | + | - | + | 1 | 1 | | Not Infected | + | - | - | - | - | - | + | 0 | 2 | | Not Infected | - | + | - | - | - | - | + | 1 | 0 | | Not Infected | - | - | + | - | + | - | + | 0 | 1 | | Not Infected | - | - | + | - | + | - | - | 5 | 0 | | Not Infected | - | - | - | + | + | - | + | 0 | 1 | | Not Infected | - | - | - | + | + | - | NA | 0 | 1 | | Not Infected | - | - | - | + | - | - | + | 1 | 3 | | Not Infected | - | - | - | - | + | - | + | 1 | 0 | | Not Infected | - | - | - | - | + | - | - | 2 | 7 | | Not Infected | - | - | - | - | + | - | NA | 2 | 0 | | Not Infected | - | - | - | - | + | - | + | 2 | 2 | | Not Infected | - | - | - | - | + | - | - | 680 | 396 | | Not Infected | - | - | - | - | - | - | NA | 29 | 8 | | Not Infected | - | - | - | - | + | NA | - | 1 | 0 | | Not Infected | - | - | - | - | NA | + | - | 17 | 4 | | Not Infected | - | - | - | - | NA | - | NA | 8 | 1 | | Not Infected | - | NA | - | - | - | - | - | 8 | 6 | | Not Infected | - | NA | - | - | - | - | NA | 0 | 1 | | Not Infected | NA | - | - | - | + | 1 | - | 0 | 1 | | Not Infected | NA | - | - | - | - | - | NA | 1 | 0 | | Not Infected | NA | - | - | - | NA | - | + | 1 | 0 | Table 13. CT Infected Status for Performance Evaluation in Female Vaginal Swab, PreservCyt Solution Liquid Pap, and Endocervical Swab Specimens AC2 = APTIMA COMBO 2, ACT = APTIMA CT Assoy, Asym = asymplomatic, CVS = clinician-collected vaginal swab, FS = female endocervical swab, FU = female urine, NA = result not available, I'ANTHER System, PCy = PreservCyt Solution liquid Pap. I'VS = patient-collected vaginal swab, Sym = symptomatic, TIGRIS = TIGRIS DTS System For the evaluation of the non-urine specimen types, the specimens were considered non-infected. {23}------------------------------------------------ #### AC2 Assay on PANTHER | Assay Results | | | | | | Symptom Status | | |--------------------|---------|----|---------|----|----------------------|----------------|------| | GC Infected Status | AC2 DTS | | AGC DTS | | AC2 PANTHER MS | Sym | Asym | | | MS | MU | MS | MU | | | | | Infected | + | + | + | + | + | 30 | 2 | | Infected | + | + | + | + | NA | 0 | 1 | | Infected | + | - | + | - | + | 1 | 1 | | Infected | NA | + | NA | + | NA | 1 | 0 | | Not Infected | - | - | NA | NA | - | 205 | 307 | | Not Infected | - | - | NA | NA | NA | 14 | 9 | # Table 14. GC Infected Status for Performance Evaluation in Male Urethral Swab Specimens AC2 = APTIMA COMBO 2, AGC = APTIMA GC Assay, Asym = asymplomatic, DTS = DTS Systems, MS = male urechral swab, MU = male urine, NA = result not available, PANTHER = PANTHER System, Sym = symptomatic, TIGRIS = TIGRIS DTS System Table 15. GC Infected Status for Performance Evaluation in Female Vaginal Swab, PreservCyt Solution Liquid Pap, and Endocervical Swab Specimens | | AC2 TIGRIS | | AGC TIGRIS | | | AC2 PANTHER | | | Symptom Status | |-----------------------|------------|----|---------------|----|-------------|----------------|----|-----|----------------| | GC Infected Status | PCyt | FU | PCyt | FU | CVS/ PVS | PCyt | FS | Sym | Asym | | Infected | + | + | + | + | + | + | + | 22 | 10 | | Infected | + | + | + | + | + | + | NA | 1 | 0 | | Infected | + | + | + | - | + | + | + | 1 | 0 | | Infected | + | + | + | = | + | + | + | 0 | 1 | | Infected | + | - | + | - | + | + | + | 3 | 3 | | Infected | + | - | + | - | + | + | + | 0 | 1 | | Infected | + | NA | + | NA | + | + | + | 0 | 1 | | Not Infected | + | NA | - | - | + | = | - | 0 | 1 | | Not Infected | - | - | NA | NA | + | - | + | 0 | 1 | | Not Infected | - | - | NA | NA | + | - | - | 3 | 0 | | Not Infected | - | - | NA | NA | + | -…

APTIMA COMBO 2 ASSAY

Device Facts

Intended Use

Device Story

Clinical Evidence

Technological Characteristics

Indications for Use

Regulatory Classification

Identification

Predicate Devices

Related Devices

Submission Summary (Full Text)

Panel 1

Section Matches

Product Code Matches

Special Control Matches

My Alerts

APTIMA COMBO 2 ASSAY

Device Facts

Intended Use

Device Story

Clinical Evidence

Technological Characteristics

Indications for Use

Regulatory Classification

Identification

Predicate Devices

Related Devices

Submission Summary (Full Text)

Panel 1

Section Matches

Product Code Matches

Special Control Matches

My Alerts

Create Alert

Search Filters

Agent Token

Welcome

Check your email

Welcome!