(118 days)
an indicator of osteoblastic activity which is intended to be used as an aid in the management of postmenopausal osteoporosis and Paget's disease
Tandem®-R Ostase® is an in vitro device for the quantitative measurement of skeletal alkaline phosphatase (sALP) in human serum. The assay is a solid-phase, two-site immunoradiometric assay. Samples containing sALP are reacted with a plastic bead (solid phase) that is coated with a monoclonal antibody directed toward a specific site on the sALP molecule and, simultaneously, with a second radiolabeled monoclonal antibody directed toward a different antigenic site on the sALP molecule. Following formation of the solidphase/sALP/radiolabeled antibody sandwich, the bead is washed to remove unbound labeled antibody. The radioactivity bound to the solid phase is measured in a gamma counter. The amount of radioactivity measured is directly proportional to the concentration of sALP in the test sample, which is determined from a standard curve. The standard curve is based on the concurrent testing of Tandem-R Ostase calibrators ranging from 0 to 120 µg sALP/L.
This looks like a 510(k) premarket notification for a medical device, which typically focuses on demonstrating substantial equivalence to a predicate device rather than comprehensive clinical trials with strict acceptance criteria found in PMA applications. As such, the provided text does not contain the detailed information you're requesting regarding quantitative performance metrics, study designs, sample sizes, expert involvement, and ground truth establishment in the traditional sense of a clinical validation study.
Here's an analysis based on the provided text, highlighting what can be extracted and what information is missing:
The core of this submission is to demonstrate "substantial equivalence" of the Tandem-R Ostase assay to a previously cleared predicate device (K930810), specifically regarding an expanded indication for use. This means the focus is less on proving absolute performance against a set acceptability standard, but rather showing that it performs as well as or identically to the predicate, and that the new indication does not raise new safety or effectiveness concerns.
1. A table of acceptance criteria and the reported device performance
Based on the provided text, specific quantitative acceptance criteria and detailed device performance metrics (e.g., sensitivity, specificity, accuracy against a gold standard) are not explicitly stated. The primary "acceptance criterion" for this 510(k) is demonstrating substantial equivalence to the predicate device and that the expanded indication poses no new safety or effectiveness issues.
| Acceptance Criteria (Inferred from 510(k) context) | Reported Device Performance (as stated in text) |
|---|---|
| Technological Characteristics: Identical to predicate device (K930810) | "technological characteristics that are identical to those of the predicate device. The components, manufacture, specifications, and procedure for the Tandem-R Ostase assay remain unchanged from those of the previously-cleared device (#K930810)." |
| Intended Use (Analyte & Specimen Matrix): Unchanged from predicate | "The intended use of Tandem-R Ostase remains unchanged from the predicate with respect to the analyte being measured (skeletal alkaline phosphatase) and the specimen matrix (human serum)." |
| Safety & Effectiveness with new indications (Postmenopausal Osteoporosis & Paget's Disease management): No new issues raised. | "It has been demonstrated in this premarket notification that Paget's disease of bone and postmenopausal osteoporosis are both bone disorders in which patients undergoing therapy can be managed with the aid of Tandem-R Ostase." "No new issues of safety or effectiveness are raised by the change in indication for use. The Tandem-R Ostase assay remains both safe and effective when used as indicated in the product labeling." |
| Clinical Value for new indications: Clinically useful for managing patients with postmenopausal osteoporosis and Paget's disease. | "This premarket notification includes clinical data demonstrating that the Tandem-R Ostase assay provides the clinician with information that is of value in the management of patients with postmenopausal osteoporosis and Paget's disease." |
2. Sample size used for the test set and the data provenance
- Sample Size for Test Set: Not specified. The text mentions "clinical data" but does not quantify the number of patients or samples included in this data.
- Data Provenance: Retrospective/Prospective: Not specified. Country of origin: Not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable/Not specified. Since this is an in vitro diagnostic (IVD) assay measuring a biomarker (sALP), the "ground truth" would typically relate to accurately measuring sALP concentrations and correlating these with clinical conditions. The text implies the clinical utility of the assay for managing patients, rather than a diagnostic decision that requires expert interpretation of images or complex data. Therefore, there's no mention of experts establishing a ground truth in the way one would for diagnostic imaging.
4. Adjudication method for the test set
- Not applicable/Not specified. Adjudication methods (like 2+1, 3+1) are typically used when subjective interpretations or diagnoses from multiple experts need to be reconciled, such as in imaging studies. For an IVD measuring a quantitative biomarker, this would not be a standard requirement. The "clinical data" mentioned would likely involve correlations between sALP levels and patient management decisions or disease progression, rather than adjudicating diagnostic calls.
5. 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
- Not applicable. This is an in vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers interpreting output. Therefore, an MRMC study is not relevant to this type of device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Partially applicable, but not framed as "standalone performance" in the AI sense. The Tandem-R Ostase assay itself is a standalone laboratory test. Its performance (e.g., analytical accuracy, precision, linearity) is inherent to the assay and doesn't involve a human-in-the-loop for its result generation. The "clinical data" would have been used to demonstrate that the results from this standalone assay are valuable for clinicians in patient management. The text confirms the assay's procedure is "unchanged" from the predicate, implying its standalone analytical performance is equivalent.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- Inferred Clinical Outcomes/Management Decisions. The text states that the "clinical data demonstrating that the Tandem-R Ostase assay provides the clinician with information that is of value in the management of patients with postmenopausal osteoporosis and Paget's disease." This suggests the ground truth was related to established clinical diagnoses of these conditions and how the sALP levels (measured by the assay) correlated with patient management strategies or clinical outcomes, rather than a single "ground truth" diagnosis established by pathology or expert consensus for each case. The "value in management" is the key here.
8. The sample size for the training set
- Not applicable/Not specified. This is not a machine learning or AI device that requires a training set in the conventional sense. The "training" for the assay itself would refer to its development and optimization, which isn't described in terms of a data set.
9. How the ground truth for the training set was established
- Not applicable. As above, this is not an AI/ML device that uses training data with established ground truth. The "ground truth" for the assay's development would be analytical standards and known concentrations during its chemical and biological development.
In summary: The provided text is a 510(k) summary focused on demonstrating substantial equivalence and expanding an indication for use for an in vitro diagnostic test. It emphasizes that the device's technological characteristics and core intended use (analyte, matrix) are unchanged. The "study" mentioned refers to collecting "clinical data" to support the expanded indications for managing postmenopausal osteoporosis and Paget's disease, but it does not provide the granular detail typically associated with clinical validation studies for novel devices or AI algorithms. The lack of specific quantitative performance metrics, detailed sample sizes, and expert involvement for ground truth adjudication is typical for such a submission where the primary argument rests on equivalence to an already cleared device.
§ 862.1050 Alkaline phosphatase or isoenzymes test system.
(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.