(182 days)
The Aptima Trichomonas vaginalis (TV) assay is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of ribosomal RNA (rRNA) from Trichomonas vaginalis to aid in the diagnosis of trichomoniasis using the Panther system.
The assay may be used to test the following specimens from symptomatic or asymptomatic individuals: clinician-collected endocervical swabs, clinician-collected and patient-collected vaginal swabs (in a clinical setting), female and male urine, and specimens collected in PreservCyt Solution.
The Aptima TV assay involves the technologies of target capture, transcription-mediated amplification (TMA), and hybridization protection assay (HPA). Specimens are collected and transferred into their respective specimen transport tubes. The transport solution in these tubes releases the rRNA target and protects it from degradation during storage. When the Aptima TV assay is performed in the laboratory, the target rRNA is isolated from the specimens using a specific capture oligomer and magnetic microparticles in a method called target capture. The capture oligomer contains a sequence complementary to a specific region of the target molecule as well as a string of deoxyadenosine residues. During the hybridization step, the sequence-specific region of the capture oligomer binds to a specific region of the target molecule. 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 molecule 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 inhibitors. After the target capture steps are completed, the specimens are ready for amplification.
The provided text describes the analytical and clinical studies performed for the Aptima Trichomonas vaginalis Assay. Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values for sensitivity, specificity, PPA, or NPA. Instead, it presents the achieved performance. However, implicit acceptance criteria for NAAT assays generally involve high sensitivity and specificity. The reproducibility study tables show numerical targets for agreement (e.g., >95% positivity for LoD, 90.7% to 100% agreement for reproducibility).
| Metric / Parameter | Acceptance Criteria (Implicit/General) | Reported Device Performance (Aptima TV Assay) |
|---|---|---|
| Analytical Sensitivity (LoD) | 95% detection limit | 0.01 TV/mL in urine matrix; 0.003 TV/mL in swab matrix |
| Reproducibility (Agreement) | High agreement (e.g., typically >95%) | PreservCyt panel members: 90.7% to 100% agreement; Urine panel members: 100% agreement |
| Clinical Sensitivity | High | Patient-collected vaginal swab: 98.8% (95% CI: 95.6-99.7) |
| Male urine: 100% (95% CI: 91.6-100) | ||
| Clinical Specificity | High | Patient-collected vaginal swab: 99.4% (95% CI: 99.0-99.7) |
| Male urine: 99.8% (95% CI: 99.5-99.9) | ||
| Clinical PPA | High | Female urine: 100% (95% CI: 97.6-100) |
| Clinical NPA | High | Female urine: 100% (95% CI: 99.8-100) |
2. Sample Size Used for the Test Set and the Data Provenance
- Clinical Study 2 (Primary Test Set):
- Total evaluable specimens: 5502 specimens from 3820 evaluable subjects.
- Breakdown by specimen type:
- 1785 patient-collected vaginal swab specimens
- 1782 female urine specimens
- 1935 male urine specimens
- Data Provenance: Prospective, multicenter clinical study conducted at 11 geographically and ethnically diverse US clinical sites (obstetrics and gynecology, family planning, and STI clinics).
- Retrospective/Prospective: Primarily prospective. Samples were collected from consenting subjects in a prospective study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The document does not mention the use of human experts (e.g., radiologists, pathologists) to establish the ground truth. For this in vitro diagnostic (IVD) device, the ground truth was established by molecular testing.
4. Adjudication Method for the Test Set
The ground truth for the clinical test set was established using a "composite comparator method" or "patient infected status (PIS)" / "composite comparator algorithm (CCA)" based on results from up to three cleared NAATs.
- Method:
- Specimens were categorized as infected (PIS) or positive (CCA) if a positive result occurred in at least two of the comparator NAATs.
- Specimens were categorized as not infected or negative if at least 2 of the comparators results were negative.
- A third (tie-breaker) comparator was only required if the first 2 comparator results were discordant.
- Specimens that could not be categorized due to missing results from comparator assays were excluded.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, an MRMC comparative effectiveness study was not applicable and therefore not performed. This is an in vitro diagnostic (IVD) device for the detection of ribosomal RNA from Trichomonas vaginalis. It is a lab-based assay, not an imaging device that requires human readers to interpret results, or AI assistance for human reader improvement.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the performance reported (sensitivity, specificity, PPA, NPA) for the Aptima TV assay is its standalone performance. The assay itself is the "algorithm" in this context; it processes specimens and provides a qualitative result (positive/negative) without direct human interpretation of the assay's raw output for diagnosis. The study evaluates the device's ability to accurately detect the target in various specimens against the established ground truth.
7. The Type of Ground Truth Used
The ground truth used was established using a composite comparator method (sometimes referred to as a "gold standard" or "reference standard" in IVD studies), which relied on the results of multiple (up to three) cleared Nucleic Acid Amplification Tests (NAATs). This is a form of expert consensus among molecular assays.
8. The Sample Size for the Training Set
The document does not explicitly state the sample size for a separate "training set." For IVD assays, particularly those based on well-established molecular biology principles (like NAATs), development and optimization (analogous to "training") often use specific analytical panels or earlier development runs rather than a distinct, large "training set" of clinical samples as seen in machine learning/AI models. The studies described are primarily for validation.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" with established ground truth is not explicitly mentioned as a separate phase of the pivotal study, the establishment of ground truth for any developmental or optimization work would likely follow similar principles as the validation ground truth: using reference materials, spiked samples, or well-characterized clinical samples confirmed by established laboratory methods or multiple comparator assays. The document focuses on the validation and reproducibility of the assay.
§ 866.3860
Trichomonas vaginalis nucleic acid assay.(a)
Identification. ATrichomonas vaginalis nucleic acid assay is a device that consists of primers, probes, enzymes, and controls for the amplification and detection of trichomonas nucleic acids in endocervical swabs, vaginal swabs, and female urine specimens, from women symptomatic for vaginitis, cervicitis, or urethritis and/or to aid in the diagnosis of trichomoniasis in asymptomatic women. The detection of trichomonas nucleic acids, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of trichomoniasis caused byTrichomonas vaginalis .(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Nucleic Acid Amplification Assays for the Detection ofTrichomonas vaginalis; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.