(85 days)
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No
The description details a standard immunoassay technology (CMIA) and its performance characteristics. There is no mention of AI/ML in the device description, intended use, or performance studies.
No.
This device is an in vitro diagnostic assay used to measure HE4 antigen levels to aid in monitoring ovarian cancer recurrence or progression. It does not directly treat or alleviate a condition, which are characteristics of a therapeutic device.
Yes
This device is a diagnostic device because its "Intended Use" states that it is "to be used as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer," which directly contributes to the diagnosis and management of a patient's condition.
No
The device is an in vitro diagnostic assay that involves chemical reactions and the measurement of relative light units, indicating the use of physical components and processes beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative determination of HE4 antigen in human serum" and is used "as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer." This involves testing a sample taken from the human body (serum) outside of the body to provide information about a medical condition.
- Device Description: The description details a "chemiluminescent microparticle immunoassay (CMIA)" which is a laboratory technique used to measure substances in biological samples. It describes the process of combining sample with reagents and measuring the resulting reaction, all of which are characteristic of in vitro diagnostic tests.
- Components: The description mentions "ARCHITECT HE4 Calibrators" and "ARCHITECT HE4 Controls," which are essential components used to ensure the accuracy and reliability of an in vitro diagnostic assay.
- Performance Studies: The document includes detailed performance studies (Method Comparison, Precision, Linearity, Sensitivity, Specificity, Interference) which are standard evaluations performed on IVD devices to demonstrate their analytical performance.
- Key Metrics: The inclusion of metrics like Sensitivity, Specificity, PPV, and NPV, particularly in the context of monitoring disease status, further confirms its role as a diagnostic tool.
- Predicate Device: The mention of a "Predicate Device" (K072939; HE4 EIA) indicates that this device is being compared to a previously cleared IVD device, a common practice in the regulatory pathway for IVDs.
All of these elements strongly indicate that the ARCHITECT HE4 assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Reagent Kit
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.
Calibrator Kit
The ARCHITECT HE4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
Control Kit
The ARCHITECT HE4 Controls are used for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
Product codes (comma separated list FDA assigned to the subject device)
JIT, JJX, OIU
Device Description
The ARCHITECT HE4 assay is a two-step immunoassay for the quantitative determination of HE4 antigen in human serum using CMIA technology with flexible assay protocols, referred to as Chemiflex.
In the first step, sample and 2H5 anti-HE4 coated paramagnetic microparticles are combined. HE4 antigen present in the sample binds to the anti-HE4 coated microparticles. After washing, 3D8 anti-HE4 acridinium-labeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs).
A direct relationship exists between the amount of HE4 antigen in the sample and the RLUs detected by the ARCHITECT i System optics.
The ARCHITECT HE4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
The ARCHITECT HE4 Controls are used for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
Clinical and Hospital laboratories
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison: 193 serum specimens were tested using the ARCHITECT HE4 assay and the HE4 EIA. The ARCHITECT HE4 assay is designed to have a slope of 1.0 ± 0.1 and a correlation coefficient (r) of ≥ 0.90 for serum specimens when compared to a commercially available HE4 EIA. Regression Method: Passing-Bablok, n=193. Slope (95% CI): 0.96 (0.93 to 1.00). Intercept (95% CI): -2.51 (-3.96 to -0.73). Correlation Coefficient: 0.97. ARCHITECT HE4 Specimen Range = 20.3 to 918.7 pmol/L. HE4 EIA Specimen Range = 21.9 to 762.3 pmol/L.
Precision: Study performed based on guidance from NCCLS document EP5-A2. Testing conducted at Fujirebio Diagnostics, Inc. using one lot of reagents, calibrators, and controls and at two external sites using two lots of reagents, calibrators, and controls. Three levels of controls and panels were assayed on one instrument per site in replicates of two at two separate times per day for 20 different days. Each instrument used a single calibration curve throughout the study. The ARCHITECT HE4 assay is designed to have an imprecision of ≤ 10% total CV.
Linearity: The ARCHITECT HE4 assay is designed to be linear across the measurement range of 20.0 to 1500.0 pmol/L. Samples were prepared by mixing serum panels with diluted wash buffer and tested with the ARCHITECT HE4 assay. Based on a study performed by guidance from the NCCLS document EP6-A, the ARCHITECT HE4 assay demonstrated linearity from 20.0 to 1500.0 pmol/L.
Sensitivity (LoB, LoD, LoQ): The ARCHITECT HE4 assay is designed to have a Limit of Detection (LoD) of ≤ 15 pmol/L and a Limit of Quantitation (LoQ) of ≤ 20 pmol/L. Study performed based on guidance from NCCLS document EP17-A with one zero-level HE4 sample and four low-level HE4 samples. Samples tested in a minimum of five replicates once per day for three different days using three reagent lots and two instruments. The Limit of Blank (LoB) was 0.1 pmol/L, the LoD was 0.2 pmol/L, and the LoQ was 0.2 pmol/L.
Specificity: Tumor markers evaluated for cross-reactivity with the ARCHITECT HE4 assay (CA 125, CA 15-3, CA 19-9, Carcinoembryonic Antigen (CEA), a-Fetoprotein (AFP)). Reactivities greater than 15 pmol/L HE4 (LoD) were not observed.
Interference: Recovery studies performed based on guidance from CLSI document EP7-A2 to compare potential interferents (Therapeutic Agents: Carboplatin, Cisplatin, Clotrimazole, Cyclophosphamide, Dexamethasone, Doxorubicin, Leucovorin, Melphalan, Methotrexate, Paclitaxel; Endogenous Substances: Bilirubin, Hemoglobin, Low Protein, High Protein, Triglycerides) to control results. Individual recovery of 100 ± 15% and a mean recovery of 100 ± 10%. Also evaluated Potentially Interfering Clinical Conditions (HAMA, RF).
Monitoring of Disease status in Patients Diagnosed with Epithelial Ovarian Cancer: A study was performed using the ARCHITECT HE4 assay as an aid in monitoring of disease status in epithelial ovarian cancer patients by assessing changes in HE4 levels in serial serum samples from 76 patients compared to changes in disease status. A total of 430 pairs of observations with an average of 6.7 observations per patient. A positive change in HE4 was defined as an increase in the value that was at least 14% greater than the previous value of the test. Fifty-four percent (54%) or 53/99 sequential pairs from patients with disease progression demonstrated an HE4 concentration increase of greater than or equal to 14%. Seventy-nine percent (79%) or 261/331 sequential pairs for patients with no disease progression demonstrated an HE4 concentration of less than 14%. Total concordance for this study was seventy-three percent (73%) or 314/430.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Monitoring of Disease status in Patients Diagnosed with Epithelial Ovarian Cancer:
At 10% change in HE4: Sensitivity=57%, Specificity=75%, PPV=40%, NPV=85%
At 14% change in HE4: Sensitivity=54%, Specificity=79%, PPV=43%, NPV=85%
At 20% change in HE4: Sensitivity=48%, Specificity=84%, PPV=48%, NPV=85%
At 25% change in HE4: Sensitivity=41%, Specificity=87%, PPV=49%, NPV=83%
At 50% change in HE4: Sensitivity=31%, Specificity=94%, PPV=60%, NPV=82%
At 75% change in HE4: Sensitivity=21%, Specificity=97%, PPV=66%, NPV=80%
At 100% change in HE4: Sensitivity=18%, Specificity=98%, PPV=69%, NPV=80%
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.
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.
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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
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.
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510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: _K093957
Submitter Information
MAR 1 8 2010
- Fujirebio Diagnostics, Inc. Address: 201 Great Valley Parkway Malvern, PA 19355 Stacey Dolan Contact person: (610) 240-3843 dolans@fdi.com
Summary preparation date: December 21, 2009
Name of Device
| Trade/Proprietary Name: | ARCHITECT HE4 Assay |
|---|---|
| ARCHITECT HE4 Calibrators | |
| ARCHITECT HE4 Controls |
- Tumor Associated Antigen Immunological Test System Common/Usual Name: Calibrator Quality control material (assayed and unassayed).
21 CFR 862.1660
Class II
்ப
- 21 CFR 866.6010 Regulation Number: 21 CFR 862.1150
Regulatory Class:
Product Code:
JIT JX
Predicate Device
HE4 EIA (K072939)
Device Description
The ARCHITECT HE4 assay is a two-step immunoassay for the quantitative determination of HE4 antigen in human serum using CMIA technology with flexible assay protocols, referred to as Chemiflex.
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In the first step, sample and 2H5 anti-HE4 coated paramagnetic microparticles are combined. HE4 antigen present in the sample binds to the anti-HE4 coated microparticles. After washing, 3D8 anti-HE4 acridinium-labeled conjugate is added to create a reaction mixture in the second step. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs).
A direct relationship exists between the amount of HE4 antigen in the sample and the RLUs detected by the ARCHITECT i System optics.
The ARCHITECT HE4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
The ARCHITECT HE4 Controls are used for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
Intended Use
Reagent Kit
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 coniunction with other clinical methods used for monitoring ovarian cancer.
Calibrator Kit
The ARCHITECT HE4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
Control Kit
The ARCHITECT HE4 Controls are used for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of HE4 antigen in human serum.
- For Company Company
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Statement of Substantial Equivalence
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.
The ARCHITECT HE4 assay is substantially equivalent to the HE4 EIA.. Both of the devices are IVD products and are indicated for the quantitative determination of HE4 antigen in human serum as well 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.
The regulatory submission will be prepared pursuant to Title 21CFR § 866.6010(b) which states Tumor Markers must comply with the following special controls;
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- Guidance document entitled "Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA".
-
- Voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards (NCCLS).
A comparison of the features of the ARCHITECT HE4 assay and the HE4 EIA: are as follows:
. 2014 2017 2017 2012 2012 2012
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| Similarities | ||
|---|---|---|
| ARCHITECT HE4 | ||
| (Proposed Device) | HE4 EIA | |
| (Predicate Device) | ||
| K072939 | ||
| Device Type | In vitro diagnostic | In vitro diagnostic |
| Classification | Class II | Class II |
| CFR section | 866.6010 | 866.6010 |
| Product Code | OIU | OIU |
| Product Usage | Clinical and Hospital laboratories | Clinical and Hospital laboratories |
| Intended Use | 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. | 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. | ||
| Type of Specimen | Human Serum | Human Serum |
| Specimen Collection | ||
| Method | Routine Phlebotomy Techniques | Routine Phlebotomy Techniques |
| Antigen Detected | HE4 | HE4 |
| Capture Antibody | Mouse monoclonal (2H5) | Mouse monoclonal (2H5) |
| Detection Antibody | Mouse monoclonal (3D8) | Mouse monoclonal (3D8) |
| Differences | ||
|---|---|---|
| ARCHITECT HE4 | ||
| (Proposed Device) | HE4 EIA | |
| (Predicate Device) | ||
| K072939 | ||
| Instrument System | ARCHITECT i System | Manual |
| Principle of Operation | Chemiluminscent Microparticle | |
| Immunoassay (CMIA) | Manual Enzymatic Immunoassay | |
| (EIA) | ||
| Calibrators | 6 Levels (0 - 1500 pmol/L) | 6 Levels (0 - 900 pM) |
| Controls | 3 Levels (50, 175 and 700 pmol/L) | 2 Levels (50 and 400pM) |
| Supplied as separate kit | Supplied with Kit | |
| Interpretation of Results | Calibrator Curve | Standard Curve |
·
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Performance Characteristics
Method Comparison:
The ARCHITECT HE4 assay is designed to have a slope of 1.0 ± 0.1 and a correlation coefficient (r) of ≥ 0.90 for serum specimens when compared to a commercially available HE4 EIA. One hundred and ninety-three serum specimens were tested using the ARCHITECT HE4 assay and the HE4 EIA. The data are summarized in the following table.
| Regression
Method | n | Slope
(95% CIa) | Intercept
(95% CIa) | Correlation
Coefficient |
|----------------------|-----|------------------------|---------------------------|----------------------------|
| Passing-Bablokb | 193 | 0.96
(0.93 to 1.00) | -2.51
(-3.96 to -0.73) | 0.97 |
ARCHITECT HE4 vs. HE4 EIA
ARCHITECT HE4 Specimen Range = 20.3 to 918.7 pmol/L
HE4 EIA Specimen Range = 21.9 to 762.3 pmol/L
a CI = Confidence Interval
b A linear regression method with no special assumptions regarding the distribution of the samples and measurement errors.
Precision:
The ARCHITECT HE4 assay is designed to have an imprecision of ≤ 10% total CV. A study was performed based on guidance from the National Committee for Clinical Laboratory standards (NCCLS) document EP5-A2. Testing was conducted at Fujirebio Diagnostics, Inc. using one lot of reagents, calibrators, and controls and at two external sites using two lots of reagents, calibrators, and controls. Three levels of controls and panels were assayed on one instrument per site in replicates of two at two separate times per day for 20 different days. Each instrument used a single calibration curve throughout the study.
Linearity:
The ARCHITECT HE4 assay is designed to be linear across the measurement range of 20.0 to 1500.0 pmol/L. Samples were prepared by mixing serum panels with diluted wash buffer and tested with the ARCHITECT HE4 assay. Based on a study performed by guidance from the NCCLS document EP6-A, the ARCHITECT HE4 assay demonstrated linearity from 20.0 to 1500.0 pmol/L.
Sensitivity (LoB, LoD, LoQ):
The ARCHITECT HE4 assay is designed to have a Limit of Detection (LoD) of ≤ 15 pmoИL and a Limit of Quantitation (LoQ) of ≤ 20 pmol/L. The LoQ is defined as the lowest amount of analyte in a sample that can be accurately quantitated with a total allowable error of ≤ 30%. A study was performed based on guidance from the NCCLS document EP17-A with one zero-level HE4 sample and four low-level HE4 samples.
The samples were tested in a minimum of five replicates once per day for three different days using three reagent lots and two instruments. The Limit of Blank (LoB) was 0.1 pmo//L, the LoD was 0.2 pmol/L, and the LoQ was 0.2 pmol/L.
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Specificity:
The tumor markers listed below were evaluated for cross-reactivity with the ARCHITECT HE4 assay. The tumor markers were prepared with ARCHITECT HE4 Calibrator A to achieve the concentrations indicated below. Reactivities greater than 15 pmol/L HE4 (LoD) were not observed.
| Tumor Marker | Tumor Marker
Concentration |
|--------------------------------|-------------------------------|
| CA 125, CA 15-3, and CA 19-9 | up to 3500 U/mL |
| Carcinoembryonic Antigen (CEA) | up to 1000 uq/L |
| a-Fetoprotein (AFP) | up to 400 ug/L |
Interference:
The ARCHITECT HE4 assay is designed to have an individual recovery of 100 ± 15% and a mean recovery of 100 ± 10% when comparing potential interferents to the control results. The interference studies were performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP7-A2.
Potentially Interfering Therapeutic Agents and Endogenous Substances
Recovery studies were performed to compare sera containing the following therapeutic agents and endogenous substances at the indicated interferent concentrations with control sera. The data are summarized in the following tables.
| Therapeutic Agent | Interferent
Concentration | % Recovery
Range | Mean %
Recovery |
|-------------------|------------------------------|---------------------|--------------------|
| Carboplatin | 500 µg/mL | 99 - 105 | 102 |
| Cisplatin | 165 µg/mL | 97 - 98 | 98 |
| Clotrimazole | 0.3 µg/mL | 99 - 103 | 101 |
| Cyclophosphamide | 500 µg/mL | 101 - 106 | 104 |
| Dexamethasone | 10 µg/mL | 97 - 105 | 101 |
| Doxorubicin | 1.16 µg/mL | 100 - 105 | 103 |
| Leucovorin | 2.68 µg/mL | 102 - 105 | 104 |
| Melphalan | 2.8 µg/mL | 98 - 104 | 101 |
| Methotrexate | 45 µg/mL | 96 - 100 | 98 |
| Paclitaxel | 3.5 ng/mL | 101 - 102 | 102 |
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גיינגענייעאַנגער יי
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| Endogenous
Substance | Interferent
Concentration | % Recovery
Range | Mean %
Recovery |
|-------------------------|------------------------------|---------------------|--------------------|
| Bilirubin | 20 mg/dL | 92 - 103 | 98 |
| Hemoglobin | 500 mg/dL | 104 - 113 | 108 |
| Low Protein | 3 g/dL | 101 - 107 | 103 |
| High Protein | 12 g/dL | 101 - 108 | 103 |
| Triglycerides | 3000 mg/dL | 94 - 104 | 98 |
Potentially Interfering Clinical Conditions
Six specimens positive for HAMA and six specimens positive for Rheumatoid Factor (RF) were evaluated at the indicated interferent concentration ranges. The data are summarized in the following table.
| Clinical
Condition | Interferent
Concentration Range | % Recovery
Range | Mean %
Recovery |
|-----------------------|------------------------------------|---------------------|--------------------|
| HAMA | 45 - 155 ng/mL | 91 - 108 | 102 |
| RF | 21 - 445 IU/mL | 98 - 111 | 103 |
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Image /page/7/Picture/1 description: The image shows the logo for FUJIREBIO Diagnostics, Inc. The logo consists of a stylized graphic to the left of the company name. The graphic is a combination of black and white shapes with vertical lines. The text "FUJIREBIO Diagnostics, Inc." is in a bold, sans-serif font, with "FUJIREBIO" on the top line and "Diagnostics, Inc." on the bottom line.
Monitoring of Disease status in Patients Diagnosed with Epithelial Ovarian Cancer
A study was performed using the ARCHITECT HE4 assay as an aid in monitoring of disease status in epithelial ovarian cancer patients by assessing changes in HE4 levels in serial serum samples from 76 patients compared to changes in disease status. A study involving a total of 430 pairs of observations was undertaken with an average number of 6.7 observations per patient. A positive change in HE4 was defined as an increase in the value that was at least 14% greater than the previous value of the test. This level of change takes into account the analytical variability of the assay. The data are summarized in the following table.
| Change in Disease State per Sequentlal Pair | |||||
|---|---|---|---|---|---|
| HE4 Concentration Change | No | ||||
| Progression | Progression | Total | |||
| less than 14% | 261 | 46 | 307 | ||
| greater than or equal to 14% | 70 | 53 | 123 | ||
| Total | 331 | 99 | 430 |
Fifty-four percent (54%) or 53/99 sequential pairs from patients with disease progression demonstrated an HE4 concentration increase of greater than or equal to 14%. Seventy-nine percent (79%) or 261/331 sequential pairs for patients with no disease progression demonstrated an HE4 concentration of less than 14%. The total concordance for this study was seventy-three percent (73%) or 314/430. Clinicians may wish to use other percent changes in HE4 concentration to reflect their preferences in the trade-off between sensitivity and specificity. The following table shows the resulting sensitivities and specificities of the ARCHITECT HE4 assay at various percent changes in ARCHITECT HE4 assay concentrations, together with the positive predictive values (PPV) and negative predictive values (NPV) for the population tested (99 sequential pairs from patients with disease progression and 331 sequential pairs from patients with no progression.)
| Percent (%)
Change in HE4 | Sensitivity a
(%) | Specificity b
(%) | PPV c
(%) | NPV d
(%) |
|------------------------------|----------------------|----------------------|--------------|--------------|
| 10 | 57 | 75 | 40 | 85 |
| 14 | 54 | 79 | 43 | 85 |
| 20 | 48 | 84 | 48 | 85 |
| 25 | 41 | 87 | 49 | 83 |
| 50 | 31 | 94 | 60 | 82 |
| 75 | 21 | 97 | 66 | 80 |
| 100 | 18 | 98 | 69 | 80 |
a Sensitivity is 100 x (number of sequential pairs with > 14% increase in HE4 concentration from patients with disease progression/total number of sequential pairs from patients with disease progression)
b Specificity is 100 x (number of sequential pairs with 14% increase in HE4 concentration from patients with disease progression/total number of sequential pairs > 14% increase in HE4 concentration)
d NPV = 100 x ( number of sequential pairs with