Search Results

The Bayer Immuno 1™ Her-2/neu Assay is an in vitro, diagnostic device intended for use in the quantitative determination of HER-2/neu in human serum. HER-2/neu values obtained may be used in the follow-up and monitoring of patients with metastatic breast cancer. HER-2/neu values should be used in conjunction with information available from clinical and other diagnostic procedures in the management of breast cancer. The clinical utility of the serum measurement of HER-2/neu as a prognostic indicator for early detection of recurrence and in the management of patients on immunotherapy regimens has not been fully established.

The Bayer Immuno I™ HER-2/neu Assay utilizes a well-established immunoassay technology in which one monoclonal HER-2/neu antibody (NB-3) is conjugated to fluorescein (designated Reagent 1, or R1) and the Fab' fragment of another monoclonal HER-2/neu antibody (TA-1) is conjugated to alkaline phosphatase (Reagent 2, or R2). The R1 and R2 conjugates are reacted with patient sample, calibrator, or control and are incubated at 37℃ on the system. Immuno 1 Magnetic Particles coated with an antifluorescein antibody (mIMP™ Reagent) are then added and a second incubation occurs during which the antibody complex is bound. The magnetic particles complexed with the immunological sandwich are then washed to separate unbound molecules, and a colorimetric substrate is added. The rate of conversion of substrate to a compound with absorbance at 405 and 450 nm is measured is proportional to the concentration of HER-2/neu in the sample. A cubic-through-zero curve-fitting algorithm is used to generate standard curves.

The assay has a range of zero to 250 ng/mL. The Bayer SETpoint™ HER-2/neu Calibrators consist of a set of six calibrator levels at 0, 10, 25, 60, 125, and 250 ng/mL. The Bayer TESTpoint™ HER-2/neu Controls consist of a set of three control levels at approximately 15, 50 and 100 ng/mL.

The provided document describes the Bayer Immuno 1™ HER-2/neu Assay, an in vitro diagnostic device for the quantitative determination of HER-2/neu in human serum for monitoring metastatic breast cancer patients.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Details

1. Sample size used for the test set and the data provenance:

   • Clinical Study Test Set: 60 patients with metastatic breast cancer for longitudinal monitoring. The study used "retrospective serum samples from three clinical sites in the United States."
   • Specificity Test Set (detection limit): 480 replicates of the zero calibrator.
   • Reproducibility Test Set: A human serum pool (approx. 15 ng/mL), and various calibrator and control levels. The number of replicates varied per level, up to 640 replicates for some calibrators tested over 80 runs.
   • Assay Performance Studies (interference, linearity, hook effect, parallelism): Varied sample sizes (e.g., "five individual serum samples" for linearity, "patient samples" and "pools of serum" for interference, "patient samples with HAMA, RF titers, or autoimmune diseases" for heterophilic antibodies). No specific total numbers for these are provided.
   • Data Provenance: Predominantly from the United States (three clinical trial sites). The clinical study was retrospective.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience):

   • The document states, "Clinical data were gathered during well controlled investigations conducted by qualified experts." It also mentions "Hospitals, medical centers and other health care organizations" and "qualified investigators." However, it does not specify the exact number or precise qualifications of these experts (e.g., "radiologist with 10 years of experience").
   • For the clinical study, "serial changes in serum HER-2/neu were correlated with changes in clinical status." The "clinical status" is the ground truth, which would have been determined by these "qualified experts" based on "clinical and other diagnostic procedures."

3. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

   • The document does not explicitly describe a formal adjudication method (like 2+1 or 3+1) for establishing the clinical ground truth. It simply states that "clinical status" was used, presumably reflecting the standard diagnostic practice at the three clinical sites.

4. 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:

   • This is not an AI/imaging device. It is an in vitro diagnostic assay. Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study with human readers assisting AI or vice-versa is not applicable and was not performed. The device's utility is evaluated by correlation with clinical status, not by improving human interpretation of images.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

   • Yes, the performance characteristics (e.g., reproducibility, sensitivity, linearity) and the clinical utility were evaluated for the "Immuno 1 HER-2/neu Assay" as a standalone device. The "indications for use" state that "HER-2/neu values should be used in conjunction with information available from clinical and other diagnostic procedures," implying it's an aid, but its performance as a measurement tool is standalone.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • For the clinical utility study, the ground truth was "changes in clinical status" of metastatic breast cancer patients due to "progression of disease." This would be based on a combination of clinical assessments, potentially including various diagnostic procedures and outcomes data, determined by medical experts. It does not explicitly mention pathology as the primary ground truth for monitoring changes over time, though initial diagnosis would involve pathology.

7. The sample size for the training set:

   • The document does not specify a separate training set size for the algorithms within the device. This assay is a chemiluminescent immunoassay using established technology and a cubic-through-zero curve-fitting algorithm. The "training" for such systems typically involves determining the standard curve and calibrating the system. The calibrators themselves define the reference points for the curve. The document states "The Bayer SETpoint™ HER-2/neu Calibrators consist of a set of six calibrator levels," which are used to generate standard curves.

8. How the ground truth for the training set was established:

   • For the analytical performance (e.g., calibrators), the "ground truth" (i.e., assigned concentrations) is established through rigorous internal validation and standardization methods during the manufacturing and development of the calibrator materials. The document mentions "recombinant 3T3 mouse cell line 3-30" as the source of antigen and "Western blot analysis" for characterization, indicating controlled biochemical processes for establishing the integrity and concentration of the calibrator material concentrations. For the curve-fitting algorithm, the "ground truth" is derived from these established calibrator concentrations.

Ask a specific question about this device