(722 days)
The Athelas Home is indicated for the quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary whole blood. The Athelas Home system is for In Vitro Diagnostic use and for prescription use only. The Athelas Home is only to be used with Athelas Home Test Strips. The Athelas Home is indicated for use by patients and caregivers within home settings with results viewable by health care professionals. The Athelas Home is intended for patients at risk of neutropenia. For patients with psychiatric conditions, clinical judgement should be exercised when deciding the end-user, based on the instructions for use (IFU) of Athelas Home, the treating physician should determine which patients are competent to perform the test by themselves. The Athelas Home is indicated for adult populations only (aged 21 and older).
Results obtained with the Athelas Home should not be the sole basis for patient diagnosis, treatment or management of leukopenia and neutropenia. All results should be evaluated by a healthcare provider.
The Athelas Home is intended to be used by a single person and should not be shared.
Prescription Use Only.
The Athelas Home is identical to the Athelas One K181288 in its technology, all software, the analytes measured, all components, and usage process. The Athelas Home has additional software and quality control safeguards to enable at-home usage of the device. Additionally, results generated from the Athelas Home are not shown to end-patients, rather are transmitted via the software directly to their healthcare provider. The Athelas Home also has Remote Lockout capabilities, such that a healthcare provider or manufacturer can remotely lock-out a device for safety in usage.
Athelas Home is indicated for the quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary whole blood. The Athelas Home system is for In Vitro Diagnostic use and for prescription use only. The Athelas Home is only to be used with Athelas Home Test Strips. The Athelas Home is indicated for use by patients and clinicians within home and point-of-care settings, with results viewable by health care professionals only. The Athelas Home is indicated for operation by adult populations only (aged 21 and older).
The Athelas Home is not indicated to completely replace a patient's monitoring regimen on reference lab systems. Prescribers should continue monitoring patients using traditional lab-based means as deemed necessary and possible.
The Athelas Home is not indicated to return results directly to patients. The Athelas Home directly transfers results to a health-care professional for interpretation and analysis. The Athelas Home is not indicated to directly diagnose or assist in disease management. Rather, the Athelas Home should be used to quantify WBC and Neut% only, with all decision making owned by the physician as per standard of care.
The Athelas Home uses image processing and microfluidics in order to measure WBC and NEUT% values from whole blood in point-of-care and home settings. For further technological details refer to Athelas One K181288 application.
The Athelas Home device is an automated differential cell counter designed for at-home quantitative determination of white blood cells (WBC) and Neutrophil percentages (NEUT%) in capillary whole blood. The following details describe the acceptance criteria and the studies performed to demonstrate the device meets these criteria.
Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria | Reported Performance (Athelas Home) |
|---|---|---|
| WBC Precision | 7.5% CV above 2 K/µL WBC | At-Home Precision Study: 5.4% CV (combined patient and QC material self-test) |
| 0.25 K/µL SD below 2 K/µL WBC | ||
| WBC Bias/Error | ±7.5% error above 2 K/µL WBC | At-Home Method Comparison: Mean Bias 0.0 K/µL (0.0% bias) |
| ±0.25 K/µL error below 2 K/µL WBC | ||
| Neutrophil % Precision | 5% SD OR 15% CV | At-Home Precision Study: 1.2% SD (combined patient and QC material self-test) |
| Neutrophil % Bias | ±10% bias or ±5% Neut% total error (whichever larger) | At-Home Method Comparison: Mean Bias -0.5 (1.3% bias) |
| Linearity (WBC) | R² > 0.99 (Implicit) | R²=0.997, Slope=1.013, Intercept=0.0449 |
| LoD (WBC) | Below LoQ | 0.079 K/µL |
| LoQ (WBC) | Below 1.0 K WBC/µL | 0.44 K WBC/µL |
| Interfering Substances | No interference with measurements | Tested substances found not to interfere; all spiked samples performed within evaluation criteria. |
| Specimen Stability | 24-hour stability met criteria | Overall, all samples tested within 24 hours of collection time met pre-set acceptance criteria. |
| Test Strip Stability | 15-week expiration | 16-week study showed no statistically significant degradation/drift over 105 days (justifies 15 weeks). |
| Flagging Accuracy | ≥ 90% (for morphological flags) | % Positive Agreement (Sensitivity) = 90.91%, % Negative Agreement (Specificity) = 96.71%, % Overall Agreement = 94.87% |
| At-Home Usage Error Rate | Not explicitly stated but implied low | Over 94% of tests run successfully with no errors. |
| Environmental Robustness (Fill-Volume) | Error if too little/much blood, or accurate results if within acceptable variability | Fill-volume study found device robust; errors for 0 µL, accurate results otherwise meeting bias criteria. |
| Environmental Robustness (Tilt) | Error if tilted, or accurate results | No significant bias in both parameters across tilt orientations and samples. |
| Environmental Robustness (Drop) | Continue to function or return appropriate error codes | All devices continued to pass functional tests after drop and vibration. |
| Environmental Robustness (Temperature) | Retain performance characteristics after extreme temperatures | Both device and test-strip met performance specifications after exposure to extreme temperatures. |
| Environmental Robustness (Humidity) | Test-strips function within specifications | All eight test-strips found to be within specifications for both fill time and color. |
Study Details
2. Sample Size and Data Provenance
- At-Home Precision Study:
- Patient In-home Whole Blood Studies Self-Test: 24 patients, 2 replicates per sample. Data provenance: US, prospective (at-home settings).
- Patient In-home QC Material Repeatability Self-Test: 10 patients, 3 replicates per sample. Data provenance: US, prospective (at-home settings).
- Linearity (WBC): 10 samples (pooled patient blood), 4 replicates across 4 devices.
- LoD (WBC): 5 low-level samples, 2 replicates per sample across 2 test strip lots (60 strips each) and 2 instruments, over 3 days. Total of 60 measurements per lot.
- LoQ (WBC): 4 independent low-level whole blood samples, 3 replicates per sample, 1 instrument, 2 test-strip lots, over 3 days.
- Specimen Stability: 9 different venous blood samples (low, normal, high WBC levels).
- Test Strip Stability: Not explicitly stated but likely from the Athelas One predicate device data.
- Method Comparison (Athelas One vs. Sysmex XE-5000): 312 patient samples. Data provenance: US, 3 point-of-care sites.
- Flagging Comparison (Athelas One vs. Sysmex XE-5000): Used data from the 312 patient samples from the method comparison study.
- Matrix Comparison (Capillary vs. Venous blood on Athelas One): 59 patients.
- At-Home Method Comparison (Athelas Home vs. Athelas One): 165 samples. Data provenance: US, at-home settings.
- At-Home Usability Analysis: 32 users.
- Fill-Volume Testing: 3 samples (low, medium, high WBC), each tested at 0, 1.4, 3.4, and 5.4 µL fill volumes.
- Device Tilt Testing: 3 samples, each tested in 4 tilt conditions (Condition 1, 2, 3, 4).
- Device Drop Testing: 12 devices.
- Device and Test-Strip Temperature Testing: 3 devices and 3 test-strip lots, each tested in 3 environment conditions, with 9 replicates per condition.
- Humidity Flex Testing: 8 test-strips, each subjected to specific humidity conditions.
3. Number of Experts Used to Establish Ground Truth and Qualifications
- The document does not explicitly state the number or qualifications of experts used to establish ground truth for the test sets.
- For the Method Comparison studies, the Sysmex XE-5000 analyzer was used as the predicate/reference method. This is a legally marketed device and its results implicitly serve as a clinical reference for ground truth.
- For the 'Target Evaluation Criteria' which defines the device's precision/bias goals, these were "chosen based on CLSI clinical precision/bias recommendations for WBC and Neut%." This refers to standardized clinical laboratory guidelines, which are developed by expert consensus.
4. Adjudication Method
- The document does not describe a formal adjudication method (e.g., 2+1, 3+1) for establishing ground truth in the context of expert review.
- Instead, the ground truth for performance studies (precision, linearity, method comparison, etc.) was generally established by comparison to a predicate device (Sysmex XE-5000) or by following CLSI guidelines for analytical performance evaluation. This implies a reference standard rather than multi-expert consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was specifically described where human readers' performance with and without AI assistance was evaluated. The device is an "Automated Differential Cell Counter," meaning it is intended to perform the cell counting automatically, and human involvement is primarily in interpreting the results provided by the device, not in assisting in the primary cell counting task. The usability studies focus on ease of use by patients/caregivers and remote result viewing by healthcare professionals, not on human-in-the-loop performance improvement in cell counting.
6. Standalone Performance
- Yes, extensive standalone performance was done. The precision, linearity, LoB, LoD, LoQ, interfering substances, specimen stability, and test strip stability studies were all conducted to evaluate the performance of the Athelas Home device itself, independent of immediate human intervention beyond operating the device as intended. The "Method Comparison" studies (both clinical and at-home) compare the device's measurements directly against a predicate device, representing its core analytical performance.
7. Type of Ground Truth Used
- Reference Instrument/Predicate Device: For quantitative measurements (WBC, NEUT%), the Sysmex XE-5000 automated hematology analyzer was used as the reference/predicate device. This represents an established clinical standard.
- CLSI Guidelines: Performance metrics and study designs (e.g., precision, linearity, stability) were based on CLSI (Clinical and Laboratory Standards Institute) recommendations. These are widely accepted standards in laboratory medicine.
- Known Concentrations: For studies like LoD, LoQ, and linearity, samples with known or precisely diluted concentrations were used.
- Functional Criteria: For flex testing (fill-volume, tilt, drop, temperature, humidity), the ground truth was whether the device continued to function within specified performance criteria (e.g., meeting bias/precision goals or returning appropriate error codes).
8. Sample Size for the Training Set
- The document refers to the Athelas Home as "identical to the Athelas One K181288 in its technology, all software, the analytes measured, all components, and usage process." It also states, "As per Agency guidance in presubmission (Q190305), studies from the Athelas One were used to support the Athelas Home because the devices are identical."
- This implies that the training data for the underlying algorithm (computer vision-based image analysis for cell counting and classification) would have been used for the Athelas One, and subsequently transferred to the Athelas Home.
- However, the specific sample size for the training set (e.g., number of images, number of cases, specific data augmentation applied) is not provided in this document. It mentions the "software" is identical, suggesting the trained model is the same.
9. How the Ground Truth for the Training Set Was Established
- Given that the Athelas Home utilizes "computer vision based image analysis" to count and classify cells, the ground truth for training such an algorithm typically involves manual expert annotation of cell types (e.g., white blood cells, neutrophils) on images of blood smears.
- However, similar to the training set size, the document does not explicitly detail how the ground truth for the training set's image analysis algorithm was established (e.g., number of expert annotators, their qualifications, consensus method for disagreements). This information would likely be found in the original Athelas One 510(k) submission (K181288) or internal company documentation. The reference to "A microfluidic test strip channel creates a stained monolayer of white blood cells. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision based image analysis" describes the overall process but not the ground truth generation for the training of that computer vision system.
§ 864.5220 Automated differential cell counter.
(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”