Search Results
Found 1 results
510(k) Data Aggregation
(603 days)
MammaPrint® is a gualitative in vitro diagnostic test service, performed in a single laboratory, using the gene expression profile of fresh breast cancer tissue samples to assess a patients' risk for distant metastasis (up to 10 years for patients less than 61 years old, up to 5 years for patients ≥ 61 years).
The test is performed for breast cancer patients with Stage I or Stage II disease, with a tumor size of ≤ 5.0 cm and lymph node negative. The MammaPrint result is indicated for use by physicians as a prognostic marker only, along with other clinicopathological factors.
The MammaPrint service is a microarray based gene expression analysis of a tumor. The analysis is based on several processes: isolation of RNA from frozen tumor tissue sections, DNA'se treatment of isolated RNA, linear amplification and labeling of DNA'se treated RNA, cRNA purification, hybridization of the cRNA to the MammaPrint microarray, scanning the MammaPrint microarray and data acquisition (feature extraction), index calculation and determination of the risk of distant recurrence in breast cancer patients.
The MammaPrint analysis is designed to determine the gene activity of specific genes in a tissue sample compared to a reference standard. The result is an expression profile, or fingerprint, of the sample.
The correlation of the sample expression profile to a template (the mean expression profile of 44 tumors with a known good clinical outcome) is calculated and the molecular profile index of the sample is determined (Low Risk, High Risk).
Here's a breakdown of the acceptance criteria and the study information for the MammaPrint® device, based on the provided text:
MammaPrint® Acceptance Criteria and Study Information
1. Acceptance Criteria and Reported Device Performance
The provided document primarily focuses on analytical performance as internally validated and clinical performance as demonstrated through peer-reviewed studies. It doesn't explicitly state "acceptance criteria" in a typical pass/fail numerical sense for clinical performance, but rather presents the performance achieved by the device in various clinical settings.
| Acceptance Criteria Category | Specific Metric/Description | Reported Device Performance/Finding |
|---|---|---|
| Analytical Performance | Accuracy of measurement (based on repeated experiments of control samples) | 98.5% Analytical Accuracy of measurement |
| Accuracy of classifying a sample as High Risk or Low Risk | At least 98.9% (i.e., 1.1% false negative classification) | |
| Percentage of "Borderline Samples" | Less than 5% of analyzed samples are considered "Borderline Samples" | |
| Classification accuracy for "Borderline Samples" | Approximately 90% (i.e., 10% chance of false classification) | |
| Clinical Performance | Assessment of risk for distant metastasis (up to 10 years for patients < 61 years) (Nature Paper) | Within 5 year metastasis risk by profile multivariate OR 18 |
| Metastasis-free survival by profile at 10 years (low risk vs. high risk) (NEJM Paper) | Low risk profile 87%, high risk profile 44% (at 5 yrs: 93% and 56% respectively) | |
| Highly reproducible MammaPrint as diagnostic tool (MammaPrint Paper) | Highly reproducible (demonstrated by comparison to Nature and NEJM studies) | |
| Metastasis-free survival by profile at 10 years (low risk vs. high risk) (Transbig Paper - European validation) | Low risk profile 88%, high risk profile 71% (at 5 yrs: 96% and 83% respectively) | |
| Metastasis-free survival by profile at 5 years (low risk vs. high risk) in older age patients (55-87 yrs) ("Older Age" NKI/AVL series) | Low risk profile 94%, high risk profile 75% | |
| Overall Conclusion | "Equivalent performance in the age extended patient group up to 87 years old at 5 years metastasis free survival." | Achieved: "MammaPrint is a clinically and analytically accurate prognostic marker for providing a risk assessment of distant metastasis of breast cancer." |
| "MammaPrint analytical methodology is identical to the FDA cleared MammaPrint device with 510k number K070675." | Substantial equivalence shown for analytical performance; therefore, no need to show substantial equivalence for analytical performance for this submission (K081092) beyond confirming identity with the predicate device's methods. Validation studies listed above demonstrate clinical performance in specific populations and with extended age range compared to the predicate. |
2. Sample Sizes Used for the Test Set and Data Provenance
The document describes several clinical studies, which served as the basis for clinical performance validation. These studies effectively act as the "test set" for demonstrating clinical utility.
| Study | Sample Size (Test Set) | Data Provenance |
|---|---|---|
| Nature Paper (1) | 78 patients | Retrospective (implied by "Development of breast cancer prognosis 70-gene profile") |
| NEJM Paper (2) | 151 patients | Retrospective ("consecutive series of breast cancer patients") |
| MammaPrint Paper (3) | Not specified | Focused on reproducibility of prior studies on MammaPrint. |
| Transbig Paper (4) | 302 patients | Retrospective ("Independent European validation"). Implies multiple European countries by "European validation." |
| "Older Age" NKI/AVL series (5) | 177 patients | Retrospective ("consecutive series of breast cancer patients"). NKI/AVL is a Dutch cancer institute, implying Dutch data. |
| Analytical Performance Validation | More than 190 independent analyses (for accuracy) | Agendia (The Netherlands), and a three-way inter-laboratory comparison study between three independent laboratories in three different countries (Dutch, French and U.S.). |
| Analytical Performance Validation | 2500 samples / 5000 hybridizations (for QC cut-off) | Performed at Agendia (The Netherlands). |
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The MammaPrint test determines a "risk of distant recurrence." The "ground truth" in these studies is the actual clinical outcome, specifically distant metastasis-free survival. This type of ground truth is established through long-term follow-up of patients, typically overseen by clinical oncologists and other medical professionals, rather than a panel of experts reviewing images or other diagnostic outputs to establish a consensus. The studies are retrospective analyses of patient cohorts with known clinical outcomes.
Therefore, the concept of "number of experts used to establish ground truth" with specific qualifications in the traditional sense (e.g., radiologists for imaging) does not directly apply here. The "ground truth" is the observed patient outcome over time, documented by treating physicians and medical records.
4. Adjudication Method for the Test Set
Given that the ground truth is patient outcomes (distant metastasis-free survival) over many years, an adjudication method for a "test set" like 2+1 or 3+1 typically used for medical image review is not applicable. Clinical outcomes are factual events recorded over time.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study is mentioned in the provided text. MammaPrint is a gene expression profiling test, not an imaging device or a tool directly interpreted by human readers in the same way an MRI or X-ray would be. Its output is a risk classification (Low Risk, High Risk), which is directly provided to the physician for consideration alongside other clinical factors. The improvement in human reader performance with AI assistance is not a relevant metric for this type of device.
6. Standalone (Algorithm Only) Performance
Yes, the studies presented demonstrate the standalone performance of the MammaPrint algorithm. The clinical studies (Nature, NEJM, Transbig, Older Age NKI/AVL) evaluate the prognostic power of the MammaPrint profile (generated by the algorithm) in predicting distant metastasis-free survival. The reported metastasis-free survival rates for "low risk profile" and "high risk profile" directly reflect the algorithm's ability to stratify patients based solely on its gene expression analysis.
7. Type of Ground Truth Used
The type of ground truth used for the clinical studies is patient outcomes data, specifically distant metastasis-free survival. This is a robust and objective measure of a patient's disease progression.
8. Sample Size for the Training Set
The document states that the Nature Paper (1) describes the "Development of breast cancer prognosis 70-gene profile (LNO, <55)" using 78 patients. This study likely represents the initial cohort used to develop or train the 70-gene signature that underlies MammaPrint. While not explicitly called a "training set" in the modern machine learning sense, this cohort was instrumental in defining the profile.
The MammaPrint algorithm itself correlates a sample's expression profile to a template (the mean expression profile of 44 tumors with a known good clinical outcome). These 44 tumors could be considered part of the "training" or reference data for the algorithm's core functionality.
9. How the Ground Truth for the Training Set Was Established
For the "Nature Paper" (which describes the development of the 70-gene profile):
- The ground truth would have been established through long-term clinical follow-up and patient outcomes data, similar to the test sets. Patients in this development cohort would have had their distant metastasis status recorded over a period of years (e.g., 5-year metastasis risk).
- For the 44 tumors used to create the "template" for the MammaPrint Index calculation, their "known good clinical outcome" would have been established based on observed excellent patient prognosis/long-term metastasis-free survival from clinical records.
Ask a specific question about this device
Page 1 of 1