(200 days)
Cholesterol 1,2,3TM is an in vitro diagnostic test for the quantification of skin cholesterol. Cholesterol 1,2,3TM uses a detector reagent that reacts with skin cholesterol in proportion to the amount of cholesterol on the surface of the epidermis. An indicator reagent (horseradish peroxidase substrate) is added and color allowed to develop. Color intensity is proportional to the amount of bound skin cholesterol in the palmar surface of the skin. The color intensity (hue) can be measured objectively by use of a handheld reflectance spectrophotometer.
Skin cholesterol as measured by Cholesterol 1,2,3TM can be used as part of risk assessment for coronary heart disease in persons with a history of myocardial infarction and/or in persons suspected of having significant multi-vessel coronary artery disease (>50% stenosis in >1 vessel as diagnosed by coronary angiography) where further diagnostic evaluation is being considered. Test results, when considered in conjunction with clinical evaluation, blood cholesterol tests and other risk factors identified for coronary artery disease, will aid the physician in focusing diagnostic and patient management options.
The Cholesterol 1,2,3TM spectrophotometer in conjunction with the Cholesterol 1,2,3™ reagents are intended for use in the quantitative determination of cholesterol in the epidermal layer of the skin.
Here's a breakdown of the acceptance criteria and the study details for the Cholesterol 1,2,3™ device, based on the provided text:
Acceptance Criteria and Device Performance
The provided document does not explicitly state specific, quantifiable acceptance criteria (e.g., "sensitivity must be >X%", "accuracy must be >Y%"). Instead, it presents performance data in relation to the intended use. The closest indicators of "acceptance" are the statistical significance of skin cholesterol's contribution to risk and the ROC AUC for predicting multi-vessel CAD.
However, based on the Summary of Performance Data and the FDA's final decision, the implicit acceptance criteria appear to be centered around the device's ability to demonstrate:
- Correlation with Multi-Vessel Coronary Artery Disease (CAD): Show that increasing skin cholesterol levels correlate with an increased risk of significant multi-vessel CAD, especially in certain HDL ranges.
- Correlation with Prior Myocardial Infarction (MI): Show that increasing skin cholesterol levels correlate with an increased probability of prior MI, especially in certain HDL ranges.
- Lack of ability to rule out CAD: Acknowledge that the test cannot be used to rule out coronary artery disease.
- No correlation with HDL: Demonstrate that skin cholesterol measurements are independent of HDL levels.
- Precision/Reproducibility: Demonstrate reliable and consistent measurements.
- Safety and Effectiveness: Satisfy the FDA that the device is substantially equivalent to predicate devices for its specified indications for use, with appropriate limitations.
Here's a table summarizing the reported device performance against these implicit criteria:
| Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|
| 1. Correlation with Multi-Vessel CAD | |
| (Increased risk with higher skin cholesterol, especially in specific HDL ranges) | - Statistically Significant Contribution: Logistic regression analysis showed skin cholesterol had a statistically significant contribution (p=0.01) to the risk of significant multi-vessel CAD, even after adjusting for HDL. |
- ROC AUC: Area under receiver operating characteristics curve for skin cholesterol was 0.56 (95% CI: 0.52-0.61) for predicting significant multi-vessel CAD.
- Observed Trends: Risk of significant multi-vessel CAD increased with skin cholesterol levels in subjects with HDL 41 mg/dL, risk was highest in the middle skin cholesterol tertile. |
| 2. Correlation with Prior MI
(Increased probability with higher skin cholesterol, especially in specific HDL ranges) | - Observed Trends: Probability of prior MI increased with skin cholesterol in individuals with low HDL levels. For HDL > 41 mg/dL, history of MI was lowest in the first skin cholesterol tertile and highest in the second tertile. |
| 3. Cannot be used to rule out CAD
(Significant percentage of subjects in lowest skin cholesterol tertile still have CAD) | - Document explicitly states: "skin cholesterol level cannot be used to rule out coronary artery disease as even in the lowest skin cholesterol tertile significant percentages of subjects had coronary artery disease (only 26.9% of angiography subjects with skin cholesterol (50% stenosis in >1 vessel as diagnosed by coronary angiography)." The document does not specify the number or qualifications of experts (e.g., cardiologists, interventional radiologists) who performed or interpreted the coronary angiographies.
- Ground Truth for MI: "history of myocardial infarction (MI)." The source and qualification of those who established the history of MI are not specified.
4. Adjudication Method for the Test Set:
- The document does not specify an adjudication method for the coronary angiography results or the history of MI. It simply states that disease was "diagnosed by coronary angiography" or "history of MI."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No. This study is a standalone performance study of the device itself, correlating its measurements with clinical outcomes (CAD, MI). It does not involve human readers interpreting device outputs in a comparative effectiveness setting (AI vs. without AI assistance).
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes. The study presents the performance of the Cholesterol 1,2,3™ device (spectrophotometer and reagents) in directly quantifying skin cholesterol and then correlating these quantitative measurements with clinical outcomes. There is no mention of a human-in-the-loop process for interpreting the "hue angle" measurement; it's a direct output of the device.
7. The Type of Ground Truth Used:
- Clinical Outcomes/Pathology (Angiography):
- Coronary Artery Disease: Significant multi-vessel coronary artery disease (>50% stenosis in >1 vessel as diagnosed by coronary angiography). Angiography is considered a clinical gold standard for assessing coronary stenosis.
- Myocardial Infarction: History of prior myocardial infarction. This is typically established through patient records, clinical diagnosis, and potentially previous diagnostic tests.
- Expert Consensus: Implied for the diagnosis from angiography/MI records, though not explicitly stated as an "expert consensus process" for this study.
8. The Sample Size for the Training Set:
- The document does not explicitly describe a separate training set for the device's development or the analysis presented. The 750 individuals appear to be the cohort used for the performance evaluation study. For the precision analysis, smaller groups (e.g., 20 candidates for within-day/day-to-day, 10 candidates for batch-to-batch) were used to validate the device's measurement consistency.
9. How the Ground Truth for the Training Set was Established:
- As no separate training set is detailed, information on how its ground truth was established is not provided. The ground truth for the evaluation was established as described in point 7.
§ 862.1475 Lipoprotein test system.
(a)
Identification. A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.