(51 days)
Not applicable
Not Found
No
The device description explicitly states that the OvaCalc Software uses an "algorithm" to generate a score based on five analyte values. While the algorithm was derived using training data sets, the description does not mention any characteristics typically associated with AI/ML, such as neural networks, deep learning, or adaptive learning. The process described is a fixed calculation based on input values, not a system that learns or improves over time.
No
The device is an aid to assess the likelihood of malignancy for ovarian adnexal masses, which is diagnostic, not therapeutic.
No
The document explicitly states that "The test is not intended as a screening or stand-alone diagnostic assay." It is described as "an aid to further assess the likelihood that malignancy is present" when the physician's independent clinical and radiological evaluation does not indicate malignancy.
No
The device description explicitly states that the cleared test system consists of the software, instruments, assays, and reagents used to obtain the OVA1™ Test result. While the OvaCalc Software is a component, it is not the sole component of the medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it is a "qualitative serum test" and an "aid to further assess the likelihood that malignancy is present" using serum samples. This directly aligns with the definition of an in vitro diagnostic device, which is intended for use in the collection, preparation, and examination of specimens taken from the human body.
- Device Description: The description details the use of "immunoassays and reagents" to obtain results from serum samples. These are classic components of IVD tests.
- Input: The input is "serum samples," which are specimens taken from the human body.
- Performance Studies: The performance studies are based on testing "preoperative serum samples."
The device analyzes biological specimens (serum) outside of the body to provide information about a patient's health status (likelihood of malignancy). This is the core function of an IVD.
N/A
Intended Use / Indications for Use
The OVA1™ Test is a qualitative serum test that combines the results of five immunoassays into a single numerical score. It is indicated for women who meet the following criteria: over age 18; ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. The OVA 1 Test is an aid to further assess the likelihood that malignancy is present when the physician's independent clinical and radiological evaluation does not indicate malignancy. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: The OVA1™ Test should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of the OVA1™ Test carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
Product codes (comma separated list FDA assigned to the subject device)
ONX Serum, algorithm, ovarian cancer assessment test
Device Description
The OVA1™ Test uses OvaCalc Software to incorporate the values for 5 analytes from separately run immunoassays (described below) into a single numerical score between 0.0 and 10.0.
The cleared test system consists of the software, instruments, assays and reagents used to obtain the OVA1™ Test result. The immunoassays and reagents are sold separately from the OvaCalc Software. Users are instructed to use only those lots identified by Vermillion. The immunoassays are performed according to the manufacturers' directions detailed in each product insert. The analytes and corresponding tests and calibrators used in the OVA1™ Test are:
| Analyte | Device (Assay and Calibrator) | Instrument |
|---|---|---|
| CA 125 | Elecsys CA 125 II | |
| CA125 II CalSet | Roche Elecsys 2010 | |
| Prealbumin | N Antisera to Human Prealbumin and | |
| Retinal-binding Protein | ||
| N Protein Standard SL (human) | Siemens BN II | |
| Apolipoprotein | ||
| A-1 | N-Antisera to Human Apolipoprotein A-1 | |
| and Apolipoprotein B | ||
| N Apolipoprotein Standard Serum (human) | Siemens BN II | |
| β2-microglobulin | Human Beta-2 Microglobulin Latex | |
| Enhanced Nephelometric Kit (Binding Site) | Siemens BN II | |
| Transferrin | N Antisera to Human Transferrin and | |
| Haptoglobin | ||
| N Protein Standard SL (human) | Siemens BN II |
The user enters results of the five analytes manually into an Excel spreadsheet together with the headers needed by OvaCalc Software. There is no physical or electronic connection between the immunoassay devices and the OvaCalc Software. Using an algorithm and the values of these 5 analytes, the OvaCalc Software generates a single unit-less numerical score from 0.0 to 10.0.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Over 18 years of age
Intended User / Care Setting
Physician's office, clinical laboratory
Description of the training set, sample size, data source, and annotation protocol
Training set 1 consisted of 284 pre-operative serum samples from women with adnexal mass, obtained from the University of Kentucky: 175 benign diseases, 29 ovarian tumors of low malignant potential (LMP), 64 epithelial ovarian cancers, 3 other primary ovarian malignancies and 13 other malignancies. Complete laboratory data was available for 274 samples of which 109 were malignant and 175 were benign controls. Training set 2 consisted of a randomly selected subset of 146 pre-operative serum samples collected under a collection/enrollment protocol from the clinical trial serum specimen repository. Twenty-one (21) of these samples were not evaluable. The remaining set of 125 consisted of 89 benign diseases, 10 LMPs, 19 epithelial ovarian cancers, 1 primary and 3 non-primary ovarian cancers and 3 other malignancies.
Description of the test set, sample size, data source, and annotation protocol
The clinical validation study was a prospective, multicenter, double-blind clinical study. Study samples were collected from 27 demographically mixed subject enrollment sites that are representative of institutions where patients with ovarian masses typically undergo a complete clinical evaluation prior to surgical intervention. These sites included large and small medical centers (universities/community hospitals), small gynecology/obstetrics groups, gynecology/oncology practices, and subjects from HMO groups. Subjects were women over 18 with a documented pelvic mass following physical examination and clinical examination. Enrollment in the study was limited to those patients with planned surgical intervention. Patients who had a diagnosis of malignancy within the last 5 years with the exception of melanoma were excluded from the study. Pre-surgical assessments identifying the mass as benign or malignant were made based on a variety of clinical assessments. One imaging test was required and had to be performed within 12 weeks of surgery. Blinded sample testing was conducted at 3 laboratories using bar-coded serum aliquots. The OVA1™ Test results, in conjunction with other clinicopathologic variables (e.g., patient's symptoms, physical findings, imaging, CA-125 value), were compared to histopathology results for detecting the presence of ovarian malignancy.
A total of 743 patients were enrolled in the study. A total of 146 subjects were set aside as a training set (as described above). Seventy-four (74) subjects/specimens were eliminated due to missing information or lack of sample resulting in a final total of 516 evaluable subjects/samples. Menopausal status was self-reported. In cases where menopausal status was not identified, a cut off of 50 years of age was applied. A pre-surgical clinical assessment based on radiological findings and other clinical data was obtained by the physician for each patient.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Validation Study:
The clinical validation study was a prospective, multicenter, double-blind clinical study with 516 evaluable subjects.
Performance Characteristics of the OVA1™ Test as Used by Physicians Who Are Not Gynecologic Oncologists (non-GO):
- Sample size: 269 patients (age range 19-90) evaluated by non-GO physicians.
- Sensitivity: 87.5% (63/72) for all non-GO subjects, 80.8% (21/26) for pre-menopausal, 91.3% (42/46) for post-menopausal.
- Specificity: 50.8% (100/197) for all non-GO subjects, 56.8% (67/118) for pre-menopausal, 41.8% (33/79) for post-menopausal.
- NPV: 91.7% (100/109) for all non-GO subjects.
- PPV: 39.4% (63/160) for all non-GO subjects.
- The OVA1™ Test was statistically informative for the combined data and for pre-menopausal and post-menopausal subjects separately.
- Dual Assessment (Pre-surgical Assessment and OVA1™ Test) vs Single Assessment (Pre-surgical Assessment) for non-GO:
- Sensitivity increased from 72.2% (52/72) to 91.7% (66/72).
- Specificity decreased from 82.7% (163/197) to 41.6% (82/197).
- PPV decreased from 60.5% (52/86) to 36.5% (66/181).
- NPV increased from 89.1% (163/183) to 93.2% (82/88).
Performance Characteristics of the OVAT™ Test as Used by Gynecologic-Oncologists (GO):
- Sample size: 247 patients evaluated by gynecologic oncologists.
- Sensitivity: 96.6% (86/89) for all GO subjects, 94.7% (18/19) for pre-menopausal, 97.1% (68/70) for post-menopausal.
- Specificity: 32.9% (52/158) for all GO subjects, 43.1% (31/72) for pre-menopausal, 24.4% (21/86) for post-menopausal.
- NPV: 94.5% (52/55) for all GO subjects.
- PPV: 44.8% (86/192) for all GO subjects.
- Dual Assessment (Pre-surgical Assessment and OVA1™ Test) vs Single Assessment (Pre-surgical Assessment) for GO:
- Sensitivity increased from 77.5% (69/89) to 98.9% (88/89).
- Specificity decreased from 74.7% (118/158) to 25.9% (41/158).
- PPV decreased from 63.3% (69/109) to 42.9% (88/205).
- NPV increased from 85.5% (118/138) to 97.6% (41/42).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Sensitivity (Non-GO, All): 87.5% (63/72)
- Specificity (Non-GO, All): 50.8% (100/197)
- NPV (Non-GO, All): 91.7% (100/109)
- PPV (Non-GO, All): 39.4% (63/160)
- Sensitivity (GO, All): 96.6% (86/89)
- Specificity (GO, All): 32.9% (52/158)
- NPV (GO, All): 94.5% (52/55)
- PPV (GO, All): 44.8% (86/192)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Not applicable
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.6050 Ovarian adnexal mass assessment score test system.
(a)
Identification. An ovarian/adnexal mass assessment test system is a device that measures one or more proteins in serum or plasma. It yields a single result for the likelihood that an adnexal pelvic mass in a woman, for whom surgery is planned, is malignant. The test is for adjunctive use, in the context of a negative primary clinical and radiological evaluation, to augment the identification of patients whose gynecologic surgery requires oncology expertise and resources.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Ovarian Adnexal Mass Assessment Score Test System.” For the availability of this guidance document,see § 866.1(e).(c)
Black box warning. Under section 520(e) of the Federal Food, Drug, and Cosmetic Act these devices are subject to the following restriction: A warning statement must be placed in a black box and must appear in all advertising, labeling, and promotional material for these devices. That warning statement must read:
0
510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
- A. 510(k) Number: K081754
- B. Purpose for Submission: New Device
- C. Measurand: Score based on 5 serum analytes
- D. Type of Test: Software algorithm and 5 immunoassays
- E. Applicant: Vermillion, Inc.
- F. Proprietary and Established Names: OVA1™ Test
G. Regulatory Information:
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- Regulation section:
- 21 CFR 866.6050 Ovarian adnexal mass assessment score test system
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- Classification: Class II
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- Product code: ONX Serum, algorithm, ovarian cancer assessment test
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- Panel:
Immunology (82)
H. Intended Use: 1. Intended use:
The OVA1™ Test is a qualitative serum test that combines the results of five immunoassays into a single numerical score. It is indicated for women who meet the following criteria: over age 18; ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. The OVA 1 Test is an aid to further assess the likelihood that malignancy is present when the physician's independent clinical and radiological evaluation does not indicate malignancy. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: The OVA1™ Test should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of the OVA1™ Test carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
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- Indications for Use: Same as Intended Use.
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- Special conditions for use statement(s): Prescription Use only.
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- Special instrument requirements: The Siemens BNTM II System for the measurement of Prealbumin (also known as
1
Transythretin; TT), Apolipoprotein A-1 (Apo A-1), B2-microglobulin (B2M), and Transferrin (Tfr). The Roche Elecsys® 2010 for the measurement of CA 125. Both instrument systems are FDA cleared.
I. Device Description:
The OVA1™ Test uses OvaCalc Software to incorporate the values for 5 analytes from separately run immunoassays (described below) into a single numerical score between 0.0 and 10.0.
The cleared test system consists of the software, instruments, assays and reagents used to obtain the OVA1™ Test result. The immunoassays and reagents are sold separately from the OvaCalc Software. Users are instructed to use only those lots identified by Vermillion. The immunoassays are performed according to the manufacturers' directions detailed in each product insert. The analytes and corresponding tests and calibrators used in the OVA1™ Test are:
| Analyte | Device (Assay and Calibrator) | Instrument |
|---|---|---|
| CA 125 | Elecsys CA 125 II | |
| CA125 II CalSet | Roche Elecsys 2010 | |
| Prealbumin | N Antisera to Human Prealbumin and | |
| Retinal-binding Protein | ||
| N Protein Standard SL (human) | Siemens BN II | |
| Apolipoprotein | ||
| A-1 | N-Antisera to Human Apolipoprotein A-1 | |
| and Apolipoprotein B | ||
| N Apolipoprotein Standard Serum (human) | Siemens BN II | |
| β2-microglobulin | Human Beta-2 Microglobulin Latex | |
| Enhanced Nephelometric Kit (Binding Site) | Siemens BN II | |
| Transferrin | N Antisera to Human Transferrin and | |
| Haptoglobin | ||
| N Protein Standard SL (human) | Siemens BN II |
J. Substantial Equivalence Information:
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- Predicate device name(s): Not applicable
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- Predicate K number(s): Not applicable
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- Comparison with predicate: Not applicable
K. Standard/Guidance Document Referenced (if applicable):
ISO 14971:2007 Medical Devices-Application of Risk Management to Medical Devices, International Organization for Standardization, 200 Edition. CLSI guideline EP5-A2 "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline."
L. Test Principle:
The individual assays for prealbumin, apolipoprotein A1 and transferrin each contain a biomarker specific rabbit polyclonal antibody which forms an immune complex with the target when reacted with a serum specimen. The immune complexes are
2
proportional to the concentration of biomarker in the serum specimen for each specific assay. The assay for ß2-microglobulin consists of polystyrene particles coated with a monospecific antiserum to ß2-microglobulin which aggregate when mixed with serum specimen ß2-microglobulin. These aggregates are proportional to the concentration of B2-microglobulin in the serum specimen. The Siemens BNTM II System is an automated immunonephelometer.
The CA 125 II assay uses 2 mouse monoclonal antibodies to CA 125. The quantity of CA 125 present is then measured by chemiluminescence emission. The Roche Elecsys® 2010 is an automated analyzer with electrochemiluminescence detection. The amount of analyte in each assay is determined against the calibration curve. Each assay uses its own specific calibrator and controls.
The user enters results of the five analytes manually into an Excel spreadsheet together with the headers needed by OvaCalc Software. There is no physical or electronic connection between the immunoassay devices and the OvaCalc Software. Using an algorithm and the values of these 5 analytes, the OvaCalc Software generates a single unit-less numerical score from 0.0 to 10.0.
M. Performance Characteristics (if/when applicable):
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- Analytical performance:
- a. Precision: Precision performance of the OVA1™ Test was evaluated in accordance with CLSI guideline EP5-A2 "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline." Five serum specimens spanning the OVA1™ Test score range (range of numerical results for OVA1™ Test: 0.0 to 10.0) were tested over 20 days, two runs per day, and two replicates per run. There were no unevaluable results. Total percent coefficient of variation (%CV) ranged from 1.0 to 7.4%.
| Sample | n | OVA1
(Mean) | Within-run | | Between-run | | Total | |
|--------|----|----------------|------------|-----|-------------|-----|-------|-----|
| | | | SD | %CV | SD | %CV | SD | %CV |
| 1 | 80 | 2.74 | 0.065 | 2.4 | 0.011 | 0.4 | 0.091 | 3.3 |
| 2 | 80 | 3.39 | 0.101 | 3.0 | 0.099 | 2.9 | 0.159 | 4.7 |
| 3 | 80 | 3.74 | 0.149 | 4.0 | 0.097 | 2.6 | 0.192 | 5.1 |
| 4 | 80 | 4.69 | 0.290 | 6.2 | 0.000 | 0.0 | 0.349 | 7.4 |
| 5 | 80 | 9.94 | 0.061 | 0.6 | 0.051 | 0.5 | 0.098 | 1.0 |
Lot-to-Lot precision: Five serum specimens and a minimum of two control sera from the same lot that vield two different OVA1™ Test scores (e.g., high and low, or low and near cutoff score) were analyzed at one site with three different reagent kit lots and calibrators over three different days by one operator. Reagents and calibrators were analyzed as shown:
3
| Day | Calibrator | Reagent Lots | ||
|---|---|---|---|---|
| 1 | 1 | A | B | C |
| 2 | 2 | B | C | B |
| 3 | 3 | C | A | A |
Note: ß2M calibrators and reagents are kit specific and are not interchangeable between kits. Therefore the three lots were analyzed on 3 separate days, and calibrators and reagents were not mixed between the lots (as shown) for this assay. For each of the five specimens and the two controls, the mean and standard deviation (SD) for the between-lot component of variance for each sample were calculated. The %CV for imprecision was