(329 days)
No
The device description states it combines results into a numerical score, and the performance studies describe standard statistical metrics (sensitivity, specificity, PPV, NPV). There is no mention of AI, ML, or training/test sets in the context of model development, only clinical study data.
No.
The device is a qualitative serum test intended to aid in assessing the likelihood of malignancy for an ovarian adnexal mass and does not provide therapy.
Yes
The device is intended to "aid in assessing whether a premenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery," which clearly indicates a diagnostic purpose. It helps in the assessment of a medical condition.
No
The device description explicitly states that the test system consists of the ARCHITECT HE4 assay, the ARCHITECT CA 125 Il assay, and the ARCHITECT i2000SR, which is a hardware instrument capable of calculating the ROMA score. This indicates the device includes hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's a "qualitative serum test" that combines results from other tests (ARCHITECT HE4 and ARCHITECT CA 125 II) and menopausal status to produce a score. This score is used to aid in assessing the likelihood of malignancy in women with ovarian adnexal masses. This clearly indicates the analysis of a biological sample (serum) to provide information about a patient's health status.
- Device Description: The description confirms it's a "qualitative serum test" and details the components involved, including immunoassays performed on the ARCHITECT i2000SR instrument. This further supports its nature as a diagnostic test performed on a biological sample.
- Sample Type: The test uses "serum," which is a biological fluid.
- Purpose: The purpose is to provide information to aid in the assessment of malignancy likelihood, which is a diagnostic purpose.
The fact that it's not a stand-alone diagnostic assay and must be interpreted in conjunction with clinical and radiological assessment does not negate its classification as an IVD. Many IVDs are used as part of a broader diagnostic process.
N/A
Intended Use / Indications for Use
ARCHITECT Risk of Ovarian Malignancy Algorithm (ROMA) is a qualitative serum test that combines the results of ARCHITECT HE4, ARCHITECT CA 125 II and menopausal status into a numerical score.
ARCHITECT ROMA is intended to aid in assessing whether a premenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. ARCHITECT ROMA 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. ARCHITECT ROMA must be interpreted in conjunction with an independent clinical and radiological assessment. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: ARCHITECT ROMA 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 ARCHITECT ROMA carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
Product codes
ONX
Device Description
ARCHITECT ROMA is a qualitative serum test that combines the results of 2 analytes, HE4 (ARCHITECT HE4) and CA125 (ARCHITECT CA 125 II) and menopausal status into a numerical score between 0.0 and 10.0. The premenopausal status must be based on ovarian function determined with information available from clinical evaluation and medical history.
The test system consists of the ARCHITECT HE4 assay, the ARCHITECT CA 125 Il assay and the ARCHITECT i2000SR. The ARCHITECT i2000SR is capable of calculating the ROMA score. The immunoassays are performed according to the directions detailed in each product insert.
Both ARCHITECT HE4 and ARCHITECT CA 125 II are previously 510(k) cleared Class II devices (K093957 and K042731 respectively). The ARCHITECT HE4 assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of HE4 antigen in human serum. The assay is to be used as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. Serial testing for patient HE4 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer. ARCHITECT CA 125 II assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of CA125 reactive determinants in human serum and plasma on the ARCHITECT i System and was previously cleared as an aid in monitoring response to therapy for patients with epithelial ovarian cancer.
Using an algorithm and the value of the 2 analytes, ARCHITECT ROMA scores (numerical score from 0.0-10.0) for both premenopausal and postmenopausal will be calculated and indicate a low likelihood or high likelihood for finding malignancy on surgery.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
ovarian adnexal mass
Indicated Patient Age Range
over age 18
Intended User / Care Setting
Clinical and Hospital laboratories
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
The effectiveness of ROMA was determined in a prospective, multi-center, blinded clinical trial for premenopausal and postmenopausal women presenting with an adnexal mass requiring surgical intervention.
A total of 459 women were evaluated in the study. For each patient, an initial cancer risk assessment was completed, providing an assessment of the patient's mass as benign or malignant. The corresponding histopathology reports were collected after surgery.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical study: Risk of Ovarian Malignancy Algorithm in Patients Presenting with an Adnexal Mass
Sample Size: 459 women (250 premenopausal and 209 postmenopausal)
Key results:
The stratification of 422 women (48 with epithelial ovarian cancer and 374 with benign disease) into low likelihood and high likelihood groups for finding malignancy on surgery using ARCHITECT ROMA is shown in the table below.
Premenopausal (N=238)
- Sensitivity: 100.0% (9/9) (95% CI: 70.1, 99.2)
- Specificity: 86.5% (198/229) (95% CI: 81.4, 90.3)
- TP - FP: 86.5 (95% CI: 81.9, 91.0)
- PPV: 22.5% (9/40) (95% CI: 12.3, 37.4)
- NPV: 100.0% (198/198) (95% CI: 98.1, 99.9)
- Prevalence: 3.8% (9/238)
Postmenopausal (N=184)
- Sensitivity: 92.3% (36/39) (95% CI: 79.7, 97.2)
- Specificity: 85.5% (129/145) (95% CI: 78.9, 90.3)
- TP - FP: 77.8 (95% CI: 67.5, 88.2)
- PPV: 63.2% (36/57) (95% CI: 50.2, 74.4)
- NPV: 97.6% (124/127) (95% CI: 93.3, 99.2)
- Prevalence: 21.2% (39/184)
Adjunctive Use of ARCHITECT ROMA with ICRA (Premenopausal and Postmenopausal women combined for all cancers)
- Sensitivity: 87.1% (95% CI: 78.3, 92.6)
- Specificity: 75.7% (95% CI: 71.1, 79.7)
- PPV: 44.8% (95% CI: 37.5, 52.5)
- NPV: 96.3% (95% CI: 93.4, 97.9)
- TP - FP: 62.7 (95% CI: 54.2, 71.3)
- PLR: 3.578 (95% CI: 2.939, 4.355)
- NLR: 0.171 (95% CI: 0.098, 0.298)
- Prevalence: 18.5%
Adjunctive use ARCHITECT ROMA with ICRA produced a statistically significant improvement in the negative predictive value (NPV). The NPV for correctly classifying benign patients into the low likelihood group increased from 93.2 to 96.3%, making the adjunctive use of ARCHITECT ROMA with ICRA effective in ruling out malignancy.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Premenopausal (N=238)
- Sensitivity: 100.0% (9/9)
- Specificity: 86.5% (198/229)
- PPV: 22.5% (9/40)
- NPV: 100.0% (198/198)
Postmenopausal (N=184)
- Sensitivity: 92.3% (36/39)
- Specificity: 85.5% (129/145)
- PPV: 63.2% (36/57)
- NPV: 97.6% (124/127)
Adjunctive Use of ARCHITECT ROMA with ICRA (Premenopausal and Postmenopausal women combined for all cancers)
- Sensitivity: 87.1%
- Specificity: 75.7%
- PPV: 44.8%
- NPV: 96.3%
- True Positive rate - False Positive rate: 62.7
- Positive Likelihood Ratio: 3.578
- Negative Likelihood Ratio: 0.171
Predicate Device(s)
Reference Device(s)
Predetermined Change Control Plan (PCCP) - All Relevant Information
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
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 2, 2016
Fujirebio Diagnostics, Inc. Ms. Diana Dickson Director, Clinical and Regulatory Science 201 Great Valley Parkway Malvern, PA 19355
Re: K151502
Trade/Device Name: ARCHITECT ROMA Regulation Number: 21 CFR 866.6050 Regulation Name: Ovarian adnexal mass assessment score test system Regulatory Class: II Product Code: ONX Dated: April 18, 2016 Received: April 19, 2016
Dear Ms. Dickson:
This letter corrects our substantially equivalent letter of April 28, 2016.
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Kelly Oliner -S
For,
Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K151502
Device Name ARCHITECT ROMA
Indications for Use (Describe)
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.
ARCHITECT Risk of Ovarian Malignancy Algorithm (ROMA) is a qualitative serum test that combines the results of ARCHITECT HE4. ARCHITECT CA 125 II and menopausal status into a numerical score.
ARCHITECT ROMA is intended to aid in assessing whether a premenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. ARCHITECT ROMA 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. ARCHITECT ROMA must be interpreted in conjunction with an independent clinical and radiological assessment. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: ARCHITECT ROMA should not be used without an independent clinical fradiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of ARCHITECT ROMA carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
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Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
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3
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
A. 510(k) Number:
B. Purpose for Submission:
New device
C. Measurand:
ROMA (Risk of Ovarian Malignancy Algorithm) - Ovarian adnexal mass assessment score based on 2 serum analytes
D. Type of Test:
Software algorithm and 2 immunoassays
E. Applicant:
| Address: | Fujirebio Diagnostics, Inc.
201 Great Valley Parkway
Malvern, PA 19355 |
|-----------------|------------------------------------------------------------------------------|
| Contact person: | Diana Dickson
(610) 240-3917
dicksond@fdi.com |
Summary preparation date: April 18, 2016
F. Proprietary and Established Names:
ARCHITECT ROMA
G. Regulatory Information:
-
- Regulation section: 21 CFR §866.6050 - Ovarian adnexal mass assessment score test system
-
- Classification: Class II
-
- Product code: ONX; Ovarian adnexal mass assessment score test system
-
- Panel: 82, Immunology
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Image /page/4/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a blue abstract symbol on the left, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font than "Diagnostics, Inc."
H. Intended Use:
-
- Intended use(s): For In Vitro Diagnostic Use Only.
ARCHITECT Risk of Ovarian Malignancy Algorithm (ROMA'") is a qualitative serum test that combines the results of ARCHITECT HE4, ARCHITECT CA 125 II™ and menopausal status into a numerical score.
- Intended use(s): For In Vitro Diagnostic Use Only.
ARCHITECT ROMA is intended to aid in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. ARCHITECT ROMA 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. ARCHITECT ROMA must be interpreted in conjunction with an independent clinical and radiological assessment. The test is not intended as a screening or stand-alone diagnostic assay.
PRECAUTION: ARCHITECT ROMA 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 ARCHITECT ROMA carries the risk of unnecessary testing, surgery, and/or delaved diagnosis.
-
- Indication(s) for use: Same as Intended Use.
-
- Special conditions for use statement(s): Prescription use only
-
- Special instrument requirements: ARCHITECT i2000SR system
I. Device Description:
ARCHITECT ROMA is a qualitative serum test that combines the results of 2 analytes, HE4 (ARCHITECT HE4) and CA125 (ARCHITECT CA 125 II) and menopausal status into a numerical score between 0.0 and 10.0. The premenopausal status must be based on ovarian function determined with information available from clinical evaluation and medical history.
The test system consists of the ARCHITECT HE4 assay, the ARCHITECT CA 125 Il assay and the ARCHITECT i2000SR. The ARCHITECT i2000SR is capable of calculating the ROMA score. The immunoassays are performed according to the directions detailed in each product insert.
Both ARCHITECT HE4 and ARCHITECT CA 125 II are previously 510(k) cleared Class II devices (K093957 and K042731 respectively). The ARCHITECT HE4 assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of HE4 antigen in human serum. The assay is to be used as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. Serial testing for patient HE4 assay values should be used in conjunction with other clinical methods used for monitoring
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Image /page/5/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic element on the left, consisting of blue and green shapes resembling a water droplet or a stylized letter. To the right of the graphic is the text "FUJIREBIO" in a bold, blue sans-serif font, with the registered trademark symbol next to it. Below "FUJIREBIO" is the text "Diagnostics, Inc." in a smaller, black sans-serif font.
ovarian cancer. ARCHITECT CA 125 II assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of CA125 reactive determinants in human serum and plasma on the ARCHITECT i System and was previously cleared as an aid in monitoring response to therapy for patients with epithelial ovarian cancer.
Using an algorithm and the value of the 2 analytes, ARCHITECT ROMA scores (numerical score from 0.0-10.0) for both premenopausal and postmenopausal will be calculated and indicate a low likelihood or high likelihood for finding malignancy on surgery.
J. Substantial Equivalence Information:
-
- Predicate device name(s): ROMA™ (HE4 EIA + ARCHITECT CA 125 II)
-
- Predicate 510(k) number(s): K103358
-
- Comparison with predicate:
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Image /page/6/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a stylized graphic on the left, featuring blue and white shapes, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font, and "Diagnostics, Inc." is in a smaller font below it. A registered trademark symbol is located to the right of the word "FUJIREBIO".
| Similarities | ||
|---|---|---|
| ARCHITECT ROMA | ||
| (Proposed Device) | ROMA (HE4 EIA + | |
| ARCHITECT CA 125 II) | ||
| (Predicate Device) | ||
| K103358 | ||
| Device Type | ||
| Classification | In vitro diagnostic | |
| Class II | In vitro diagnostic | |
| Class II | ||
| Regulation Number | 21CFR § 866.6050 | |
| Ovarian adnexal mass | ||
| assessment score test | ||
| system | 21CFR § 866.6050 | |
| Ovarian adnexal mass | ||
| assessment score test | ||
| system | ||
| Product Usage | Clinical and Hospital | |
| laboratories | Clinical and Hospital | |
| laboratories | ||
| Intended Use | ARCHITECT Risk of Ovarian | |
| Malignancy Algorithm | ||
| (ROMATM) is a qualitative | ||
| serum test that combines the | ||
| results of ARCHITECT HE4, | ||
| ARCHITECT CA 125 IITM and | ||
| menopausal status into a | ||
| numerical score. | ||
| ARCHITECT ROMA is | ||
| intended to aid in assessing | ||
| whether a premenopausal or | ||
| postmenopausal woman who | ||
| presents with an ovarian | ||
| adnexal mass is at high or | ||
| low likelihood of finding | ||
| malignancy on surgery. | ||
| ARCHITECT ROMA 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. | ||
| ARCHITECT ROMA must be | ||
| interpreted in conjunction with | ||
| an independent clinical and | ||
| radiological assessment. | ||
| The test is not intended as a | ||
| screening or stand-alone | ||
| diagnostic assay. | The Risk of Ovarian | |
| Malignancy Algorithm | ||
| (ROMATM) is a qualitative | ||
| serum test that combines the | ||
| results of HE4 EIA, | ||
| ARCHITECT CA 125 IITM and | ||
| menopausal status into a | ||
| numerical score. | ||
| ROMA is intended to aid in | ||
| assessing whether a | ||
| premenopausal or | ||
| postmenopausal woman who | ||
| presents with an ovarian | ||
| adnexal mass is at high or | ||
| low likelihood of finding | ||
| malignancy on surgery. | ||
| ROMA 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. ROMA must be | ||
| interpreted in conjunction with | ||
| an independent clinical and | ||
| radiological assessment. The | ||
| test is not intended as a | ||
| screening or stand-alone | ||
| diagnostic assay. | ||
| Black box warning | ||
| (PRECAUTION) | Should not be used without | |
| an independent clinical | ||
| (radiological evaluation and is | Should not be used without | |
| an independent clinical | ||
| (radiological evaluation and is | ||
| Similarities | ||
| ARCHITECT ROMA | ||
| (Proposed Device) | ROMA (HE4 EIA + | |
| ARCHITECT CA 125 II) | ||
| (Predicate Device) | ||
| K103358 | ||
| Specimen Collection | ||
| Method | Routine Phlebotomy | |
| Techniques | Routine Phlebotomy | |
| Techniques | ||
| Type of Specimen | Human Serum | Human Serum |
| Serum Analyte | HE4 and CA125 | HE4 and CA125 |
| Device Type | Algorithm | |
| (Qualitative, numeric) | Algorithm | |
| (Qualitative, numeric) | ||
| Equation used for test | Premenopausal woman: | |
| $Predictive Index (PI) = -12.0 +2.38LN[HE4] +0.0626LN[CA 125]$ | ||
| Postmenopausal woman: | ||
| $Predictive Index (PI) = -8.09 +1.04LN[HE4] + 0.732LN[CA125]$ | ||
| $ROMA = exp(PI) / [1 +exp(PI)] *10$ | Premenopausal woman: | |
| $Predictive Index (PI) = -12.0 +2.38LN[HE4] +0.0626LN[CA 125]$ | ||
| Postmenopausal woman: | ||
| $Predictive Index (PI) = -8.09 +1.04LN[HE4] + 0.732LN[CA125]$ | ||
| $ROMA = exp(PI) / [1 +exp(PI)] *10$ | ||
| Clinical Cut-off | Premenopausal: | |
| ARCHITECT ROMA score ≥ | ||
| 1.31 = High likelihood of | ||
| finding malignancy | ||
| ARCHITECT ROMA score 1 mg/mL and protein at ≥12 g/dL demonstrated interference. |
8 approximately 15 U/mL CA 125 II and 50 pM HE4
& approximately 40 U/mL CA 125 II and 60 pM HE4
ಳ approximately 100 U/mL CA 125 II and 100 pM HE4
-
f. Assay cut-off:
See Clinical Cutoff in M (4) below -
- Comparison studies:
- a. Method Comparison
ARCHITECT ROMA method comparison study was performed using specimens consistent with CLSI guideline EP9-A2-IR using the Deming and Passing-Bablok regression method to compare ARCHITECT ROMA to ROMA (HE4 EIA + ARCHITECT CA 125 II). The data are summarized in the following table.
| Menopausal
Status | Correlation
Coefficient
(r) | Regression | Intercept | 95% CI | Slope | 95% CI |
|----------------------|-----------------------------------|----------------|-----------|---------------|-------|-------------|
| Premenopausal | 0.983 | Deming | -0.097 | -0.165 -0.029 | 0.983 | 0.939 1.027 |
| | | Passing-Bablok | 0.005 | -0.038 0.029 | 0.924 | 0.870 0.996 |
| Postmenopausal | 0.999 | Deming | -0.041 | -0.074 -0.007 | 0.997 | 0.988 1.006 |
| | | Passing-Bablok | -0.015 | -0.044 0.005 | 0.997 | 0.987 1.004 |
b. Matrix Comparison
Serum is the only claimed matrix.
-
- Clinical studies:
- a. Clinical sensitivity:
See 3(c) below
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Image /page/15/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized blue and white graphic on the left, resembling a water droplet or a stylized leaf. To the right of the graphic, the company name "FUJIREBIO" is written in bold, blue capital letters, with "Diagnostics, Inc." written in a smaller font size below it.
-
b. Clinical specificity:
See 3(c) below -
C. Other clinical supportive data (when a. and b. are not applicable):
Risk of Ovarian Malignancy Algorithm in Patients Presenting with an Adnexal Mass The effectiveness of ROMA was determined in a prospective, multi-center, blinded clinical trial for premenopausal and postmenopausal women presenting with an adnexal mass requiring surgical intervention.
A total of 459 women were evaluated in the study. For each patient, an initial cancer risk assessment was completed, providing an assessment of the patient's mass as benign or malignant. The corresponding histopathology reports were collected after surgery.
The histopathological classifications of the 459 patients (250 premenopausal and 209 postmenopausal) are summarized in the table below.
| Histopathological | Total | Premenopausal | Postmenopausal | |||
|---|---|---|---|---|---|---|
| Classification | N | % | N | % | N | % |
| Benign Pathology | 374 | 81.5 | 229 | 91.6 | 145 | 69.4 |
| Low Malignant Potential | ||||||
| (LMP) /Borderline | 18 | 3.9 | 7 | 2.8 | 11 | 5.3 |
| Epithelial Ovarian Cancer | ||||||
| (EOC) | 48 | 10.5 | 9 | 3.6 | 39 | 18.7 |
| Non-EOC | 2 | 0.4 | 0 | 0.0 | 2 | 1.0 |
| Other Gynecological Cancer | 9 | 2.0 | 3 | 1.2 | 6 | 2.9 |
| Other Cancer | 7 | 1.5 | 1 | 0.4 | 6 | 2.9 |
| Metastatic Cancer | 1 | 0.2 | 1 | 0.4 | 0 | 0.0 |
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Image /page/16/Picture/1 description: The image is a logo for FUJIREBIO Diagnostics, Inc. The logo features a blue and white abstract design on the left, with the text "FUJIREBIO" in blue, bold letters to the right. Below the company name is the text "Diagnostics, Inc." in a smaller, gray font.
Use of ROMA for stratification into likelihood of finding malignancy on surgery
Using a preoperatively collected serum sample, ARCHITECT ROMA was determined and the patient was stratified into a low or a high likelihood group for finding malignancy on surgery. The stratification of the 459 patients (250 premenopausal and 209 postmenopausal) presenting with an adnexal mass into high likelihood of harboring malignant disease using ARCHITECT ROMA is shown in the table below.
| Total | Premenopausal | Postmenopausal | ||||
|---|---|---|---|---|---|---|
| N | % | N | % | N | % | |
| All EOC a | 45/48 | 93.8 | 9/9 | 100.0 | 36/39 | 92.3 |
| EOC Stage I + II | 9/12 | 75.0 | 3/3 | 100.0 | 6/9 | 66.7 |
| EOC Stage III + IV | 34/34 | 100.0 | 5/5 | 100.0 | 29/29 | 100.0 |
| LMP Tumors | 13/18 | 72.2 | 4/7 | 57.1 | 9/11 | 81.8 |
| Other Cancer b | 11/19 | 57.9 | 2/5 | 40.0 | 9/14 | 64.3 |
| All Cancer and LMP Tumors | 69/85 | 81.2 | 15/21 | 71.4 | 54/64 | 84.4 |
| a 2 EOC patients were unstaged | ||||||
| b non-epithelial ovarian cancer, other gynecologic, and non-gynecologic cancers |
The stratification of 422 women, 48 with epithelial ovarian cancer and 374 with benign disease, into low likelihood and high likelihood groups for finding malignancy on surgery using ARCHITECT ROMA is shown in the table below.
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Image /page/17/Picture/1 description: The image shows the logo for Fujirebio Diagnostics, Inc. The logo consists of a blue and green abstract shape on the left, followed by the company name in blue text. The word "FUJIREBIO" is in a larger, bolder font than "Diagnostics, Inc."
| Premenopausal (N=238) | Postmenopausal (N=184) | |||
|---|---|---|---|---|
| % (N) | 95% CIa | % (N) | 95% CIa | |
| Sensitivity | 100.0 (9/9) | (70.1,99.2) | 92.3 (36/39) | (79.7,97.2) |
| Specificity | 86.5 (198/229) | (81.4,90.3) | 85.5 (129/145) | (78.9,90.3) |
| TP - FP b | 86.5 | (81.9,91.0) | 77.8 | (67.5,88.2) |
| PPV c | 22.5 (9/40) | (12.3,37.4) | 63.2 (36/57) | (50.2,74.4) |
| NPV d | 100.0 (198/198) | (98.1,99.9) | 97.6 (124/127) | (93.3,99.2) |
| Prevalence | 3.8 (9/238) | 21.2 (39/184) | ||
| a Confidence Interval | ||||
| b True Positive rate - False Positive rate | ||||
| c Positive Predictive Value |
° Positive Predictive Value
ª Negative Predictive Value
Negative Predictive Value
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Image /page/18/Picture/1 description: The image contains the logo for Fujirebio Diagnostics, Inc. The logo features a stylized graphic on the left, consisting of blue and green shapes that resemble a water droplet or a stylized leaf. To the right of the graphic, the text "FUJIREBIO" is displayed in a bold, blue sans-serif font, with the registered trademark symbol (®) next to it. Below "FUJIREBIO", the words "Diagnostics, Inc." are written in a smaller, black sans-serif font.
Adjunctive use of ARCHITECT ROMA with ICRA for stratification into low likelihood and high likelihood groups for finding malignancy on surgery
The performance for the adjunctive use of ARCHITECT ROMA with ICRA (ARCHITECT ROMA and/or ICRA being positive for high likelihood of finding malignancy on surgery) was evaluated. Premenopausal and postmenopausal women combined for all cancers.
| Malignancy by Pathology a | ||||
|---|---|---|---|---|
| Initial Cancer Risk Assessment | ||||
| Positive b | Negative c | Total | ||
| ARCHITECT ROMA | Positive b | 56 | 12 | 68 |
| Negative c | 6 | 11 | 17 | |
| Total | 62 | 23 | 85 | |
| No Malignancy by Pathology a | ||||
| Initial Cancer Risk Assessment | ||||
| Positive b | Negative c | Total | ||
| ARCHITECT ROMA | Positive b | 20 | 32 | 52 |
| Negative c | 39 | 283 | 322 | |
| Total | 59 | 315 | 374 |
a All malignancies found including EOC, LMP, non-epithelial ovarian cancer, other gynecologic, and non-gynecologic cancers.
b High likelihood of finding malignancy on surgery
° Low likelihood of finding malignancy on surgery
Adjunctive use ARCHITECT ROMA with ICRA produced a statistically significant improvement in the negative predictive value (NPV). The NPV for correctly classifying benign patients into the low likelihood group increased from 93.2 to 96.3%, making the adjunctive use of ARCHITECT ROMA with ICRA effective in ruling out malignancy.
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Image /page/19/Picture/1 description: The image is a logo for Fujirebio Diagnostics, Inc. The logo features a blue and white abstract design on the left, followed by the company name in blue, bold letters. Below the company name, the words "Diagnostics, Inc." are written in a smaller, black font. The logo is clean and professional, with a focus on the company name and its diagnostic services.
| ICRA | ARCHITECT ROMA | Adjunctive | ||||
|---|---|---|---|---|---|---|
| % | 95% CI a | % | 95% CI a | % | 95% CI a | |
| Sensitivity | 72.9 | 62.7,81.2 | 80.0 | 70.3,87.1 | 87.1 | 78.3,92.6 |
| Specificity | 84.2 | 80.2,87.6 | 86.1 | 82.2,89.2 | 75.7 | 71.1,79.7 |
| PPV b | 51.2 | 42.4,60.0 | 56.7 | 47.7,65.2 | 44.8 | 37.5,52.5 |
| NPV c | 93.2 | 90.0,95.4 | 95.0 | 92.1,96.8 | 96.3 | 93.4,97.9 |
| TP - FP d | 57.2 | 46.8,67.5 | 66.1 | 56.7,75.5 | 62.7 | 54.2,71.3 |
| PLR e | 4.624 | 3.538,6.042 | 5.754 | 4.376,7.565 | 3.578 | 2.939,4.355 |
| NLR f | 0.321 | 0.226,0.457 | 0.232 | 0.152,0.356 | 0.171 | 0.098,0.298 |
| Prevalence | 18.5% | |||||
| a Confidence Interval | ||||||
| b Positive Predictive Value | ||||||
| c Negative Predictive Value | ||||||
| d True Positive rate - False Positive rate | ||||||
| e Positive Likelihood Ratio | ||||||
| f |
Negative Likelihood Ratio
4. Clinical cut-off:
The following cut-offs are used to interpret the result. The ARCHITECT ROMA score is between 0.0 and 10.0.
Premenopausal women:
ROMA score ≥1.31 High likelihood of finding malignancy
ROMA score