(105 days)
TBS iNsight is a software provided for use as a complement to both DXA analysis and clinical examination. It computes the antero-posterior spine DXA examination file and calculates a score (Trabecular Bone Score - TBS) that is compared to those of the age matched controls. The TBS is derived from the texture of the DXA image and has been shown to be related to bone microarchitecture.
TBS iNsight provides as an option an assessment of 10-year fracture risk. It provides an estimate of 10-year probability of hip fracture and 10-year probability of a major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture). This estimate is based on the WHO's FRAX® Fracture Risk Assessment Tool, after adjustment for the TBS. The tool has been validated for Caucasian and Asian men and post-menopausal women between 40 and 90 years old.
TBS provides information independent of BMD value: it is used as a complement to the data obtained from the DXA analysis and the clinical examination (questioning by the clinician about patient history, bioassay of bone resorption markers...).
The results can be used by a physician in conjunction with other clinical risk factors as an aid in the diagnosis of osteoporosis and other medical conditions leading to altered trabecular bone microarchitecture, and ultimately in the assessment of fracture risk.
The TBS score can assist the health care professional in monitoring the effect of treatments on patients across time. Overall fracture risk will depend on many additional factors that should be considered before making diagnostic or therapeutic recommendations. The software does not disease or recommend treatment regimens. Only the health care professional can make these judgments.
TBS iNsight is a software application provided for use as a complement to bone mineral density (BMD) acquired from dual energy X-ray absorptiometry (DXA) and other clinical risk factors for osteoporosis and fragility fracture. It calculates a score (Trabecular Bone Score - TBS) derived from the texture of the DXA image of the anterior-posterior (AP) lumbar spine and has been shown to be related to bone microarchitecture. The method analyzes X-ray based images acquired by DXA imaging systems and produces the TBS based on the computation of an Adapted Experimental Variogram (modified fractal-like approach). This variogram is used to measure the degree of spatial variation between pairs of data points in a spatial dimension of a region of a digital image.
The absolute TBS values for the same equivalent tissue thickness vary slightly between GE and Hologic systems. Additionally, within each system, variability in TBS values can be observed across different scan modes. To address these differences, corrections are applied that are both device-specific and mode-specific. For instance, TBS is corrected differently for GE and Hologic systems to account for inherent differences in tissue thickness assessment. Furthermore, corrections are also tailored separately for each scan mode within the same system, ensuring that TBS measurements remain consistent and reliable regardless of the scan mode used. These device-specific and mode-specific corrections are necessitated by differences in the dynamic range of tissue thickness measurements between GE and Hologic devices. The variations arise due to differences in the methodologies used to assess tissue thickness. To harmonize these discrepancies and ensure measurement accuracy, correction fits derived from ex-vivo data are applied individually to each device and scan mode. This approach ensures the accuracy and consistency of TBS measurements across all configurations.
The device is intended to be used for bone health assessment in medical facilities employing one or more DXA system(s) to which the subject device is connected. These facilities are usually hospitals, clinics, healthcare centers, radiology practices and medical imaging centers. The software is designed to be used by qualified clinical professionals (including physicians, radiologists and DXA technicians) and the physicians are solely responsible for making all final patient management decisions.
The provided text does not contain a discrete table of acceptance criteria nor explicit reported device performance metrics against such criteria in a tabular format. However, based on the Performance Testing Summary & Conclusions section (pages 9-10), the acceptance criteria can be inferred from the studies described. The reported performance is woven into the narrative of the study results.
Here's an attempt to derive the information requested:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Inferred from study objectives) | Reported Device Performance (TBS iNsight V4) |
|---|---|
| Accuracy of TBS V4 in reflecting bone microarchitecture (vs. microCT) | Strong and statistically significant correlations with parameters such as trabecular number and separation. Maintained or exceeded correlations established with the predicate. |
| Agreement between TBS V4 and Predicate Software | Excellent agreement, with correlation coefficients exceeding 0.99. Bland-Altman statistics confirmed negligible differences between versions across multiple DXA systems. |
| Reproducibility (Precision and Least Significant Change - LSC) in ex vivo settings | Precision and LSC values comparable to or slightly improved over the predicate, consistent across various DXA systems. |
| Reproducibility (Precision and LSC) in in vivo settings (clinical conditions with repositioning) | Met or exceeded precision standards established by the International Society for Clinical Densitometry (ISCD), with LSC values within acceptable thresholds. |
| Validity of Tissue Thickness (TT) Range | Validated in-vivo, establishing a valid tissue thickness range of 7-30 cm, aligning with physiological parameters for TBS calculations. |
| Applicability across diverse demographic groups (population-specific reference curves) | Generation of population-specific reference curves for age, sex, and ethnicity. Comparisons with the predicate software confirmed statistical equivalence, reinforcing reliability across diverse demographic groups, including multi-ethnic populations in the United States. |
| Performance in fracture risk assessment (TBS-adjusted FRAX and BMD T-scores) | Demonstrated similar TBS-adjusted FRAX and BMD T-scores for major osteoporotic and hip fractures compared to the predicate, using data from over 17,000 individuals across 14 international cohorts. |
| Effectiveness for treatment monitoring (TBS-adjusted FRAX and BMD T-scores over time) | Demonstrated effectiveness for accurately outputting TBS-adjusted FRAX and BMD T-scores over time for treatment monitoring, with substantial equivalence to the predicate, in a large cohort of postmenopausal women with osteoporosis. |
| Software Verification and Validation | Demonstrated specified requirements are met and the software functions as intended. |
| Cybersecurity Compliance | Controls and processes implemented; documentation and testing demonstrate alignment with FDA guidance ("Cybersecurity in Medical Devices") and Section 524B of the FD&C Act. |
| Substantial Equivalence (Overall Device Performance) | TBS version 4.0 demonstrates substantially equivalent performance in the assessment of bone quality and TBS-adjusted FRAX and BMD T-scores compared to the predicate device. Standalone validation studies confirm performance, reliability, and utility across diverse populations and DXA systems. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Clinical Association Study 1 (Correlation with microCT):
- Sample Size: 30 human cadaver lumbar vertebrae.
- Data Provenance: Not explicitly stated, but "human cadaver lumbar vertebrae" implies a laboratory-based, retrospective study.
- Clinical Association Study 2 (Agreement between V4 and Predicate):
- Sample Size: 15 human cadaver vertebrae.
- Data Provenance: Not explicitly stated, but "human cadaver vertebrae" implies a laboratory-based, retrospective study. Measurements were performed on "multiple DXA systems."
- Analytical Reproducibility (Ex Vivo Study):
- Sample Size: Not explicitly stated, but "dried human lumbar vertebrae," likely similar to the cadaver studies.
- Data Provenance: Retrospective, laboratory-based.
- Analytical Reproducibility (In Vivo Study):
- Sample Size: 132 participants.
- Data Provenance: Not explicitly stated, but "scanned on four different DXA systems" with "repositioning between scans" indicates a prospective, controlled clinical study.
- Performance and Utility (Fracture Risk Assessment):
- Sample Size: Over 17,000 individuals across 14 international cohorts.
- Data Provenance: International cohorts, implying retrospective data from multiple countries.
- Performance and Utility (Treatment Monitoring):
- Sample Size: A "large cohort" of postmenopausal women with osteoporosis. Specific number not provided.
- Data Provenance: Not explicitly stated, but likely retrospective clinical data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish ground truth for the various test sets.
- For microCT correlation: Micro-computed tomography (microCT) is an objective imaging technique, so human expert interpretation for ground truth might not be directly applicable in the same way as, for example, image interpretation by radiologists.
- For in vivo studies: The ground truth for bone microarchitecture or fracture risk assessment, as implied by the use of ISCD standards and FRAX, are typically established by clinical diagnosis and follow-up, rather than a panel of experts explicitly reviewing the test set images for ground truth.
4. Adjudication Method for the Test Set
The document does not describe any adjudication methods (e.g., 2+1, 3+1) for establishing ground truth from expert readers for the test sets.
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
- No, an MRMC comparative effectiveness study was not explicitly described in the provided text. The studies focus on the device's standalone performance, its agreement with the predicate device, and its correlation with bone microarchitecture ground truth (microCT), as well as its utility for fracture risk assessment and treatment monitoring.
- The text describes the device as a "complement to both DXA analysis and clinical examination" and states that "The results can be used by a physician in conjunction with other clinical risk factors." While it aids physicians, the document does not include a comparative study evaluating how human reader performance (e.g., diagnosis or risk assessment accuracy) improves with TBS iNsight V4 assistance versus without it.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, a standalone performance assessment was conducted. The "Standalone Performance Testing Summary" section (page 9) explicitly states that "Software Verification and Validation demonstrate specified requirements are met and the software functions as intended."
- Furthermore, the "Clinical Association" and "Analytical Reproducibility" studies directly evaluate the performance of TBS version 4.0 in calculating TBS values and their correlation with microCT independently, and their agreement/reproducibility compared to the predicate, without human intervention in the calculation process.
7. The Type of Ground Truth Used
- Pathology/Objective Measurement: For establishing the relationship between TBS and bone microarchitecture, micro-computed tomography (microCT) measurements were used as the ground truth (e.g., for trabecular number and separation). This is an objective measurement of bone structure.
- Clinical Diagnosis/Outcomes Data: For "fracture risk assessment" and "treatment monitoring," the ground truth implicitly refers to the clinically established reference values (e.g., those used in FRAX) and potentially actual fracture outcomes data from the cohorts. The studies confirm that TBS V4 provides "similar TBS-adjusted FRAX and BMD T-scores" and is effective for monitoring, suggesting that it aligns with known clinical indicators and outcomes.
- Predicate Device Performance: For demonstrating "agreement" and "substantial equivalence," the performance of the predicate device (TBS iNsight V3) serves as a comparative ground truth or benchmark.
8. The Sample Size for the Training Set
The document does not provide information regarding the sample size used for the training set for the TBS iNsight V4 algorithm.
9. How the Ground Truth for the Training Set Was Established
The document does not provide information on how the ground truth for any training set was established, as the details of algorithm development and training are not included. The focus is on the performance testing of the final device version.
§ 892.1170 Bone densitometer.
(a)
Identification. A bone densitometer is a device intended for medical purposes to measure bone density and mineral content by x-ray or gamma ray transmission measurements through the bone and adjacent tissues. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.