(336 days)
Not Found
Unknown
The summary describes the device as estimating Hgb response and generating dose recommendations based on patient data, which could potentially involve AI/ML, but it does not explicitly state the use of these technologies. The performance studies are based on simulations and clinical trials, but the methodology for the "estimation" and "generation" of recommendations is not detailed enough to confirm AI/ML.
No
The device provides dosage recommendations and assists clinical judgment, but it does not directly administer treatment or physically interact with the patient to provide therapy.
No
SAM is intended to help clinicians manage chronic anemia by providing ESA dosage recommendations, not to diagnose a condition. It uses patient data and estimates Hgb response to generate treatment recommendations, which doctors then review in conjunction with other diagnostic measurements and clinical judgment.
Yes
The device is described as a "web application" and accessed using a "web-enabled application (for example, a web browser or a web-enabled electronic health record system)". It explicitly states "No components of SAM are required to be installed at end user or healthcare provider locations." This strongly indicates it is a software-only device.
Based on the provided information, this device is not an In Vitro Diagnostic (IVD).
Here's why:
- IVDs are used to examine specimens derived from the human body. The intended use and device description clearly state that SAM is a web application that obtains, tracks, and trends patient data (like hemoglobin levels) and provides ESA dosage recommendations. It does not perform any tests on biological samples.
- The device's function is to assist clinicians in managing anemia based on existing patient data. It uses this data to generate dosage recommendations, but it does not perform the diagnostic testing itself. The diagnostic measurements (like Hgb levels) are inputs to the system, not outputs of the system's core function.
Therefore, SAM falls under the category of a clinical decision support system or a medical device software, but not an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
SAM is a web application used to obtain, track and trend patient data pertaining to the management of anemia, and to provide a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin (Hgb) levels in hemodialysis patients. The device is intended to help clinicians manage chronic anemia.
The device is not a substitute for, but rather intended to assist, clinical judgment. The ESA dosing regimen options calculated by this device are intended to inform the optimization of the dosage of ESAs in accordance with their approved labeling in conjunction with clinical history, symptoms, and other diagnostic measurements, as well as the clinicians' judgment. No medical decision should be based solely on the patient Hgb response to dosing regimen options calculated by this device.
Product codes (comma separated list FDA assigned to the subject device)
MQS
Device Description
SAM is a web application used to obtain, track and trend patient data pertaining to the management of anemia, and to provide a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin (Hgb) levels in hemodialysis patients. The device is intended to help clinicians manage chronic anemia.
Healthcare professionals access SAM using a web-enabled application (for example, a web browser or a web-enabled electronic health record system) communicating with the SAM web application server. Patient information is obtained by SAM from healthcare provider Electronic Medical Records. No components of SAM are required to be installed at end user or healthcare provider locations.
SAM estimates individual patient's Hgb response to ESAs. The results of this estimation are used to generate new patient-specific ESA dose recommendation to achieve target Hgb level specified by the physician. The ESA dose recommendation is reviewed by the physician, who after considering any additional relevant information about patient's condition, decides whether to follow or override the presented ESA dose recommendation.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Adult stage 5 chronic kidney disease patients
Intended User / Care Setting
Physician/Clinicians/Nurses
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Simulation Testing
Study type: In silico three way cross over simulation
Sample size: 2430 patient simulations
Key Results:
The approaches resulted in differences in respect to time to target with SAM taking longer to reach the target Hgb. The mean Hgb achieved was similar between SAM and AMP1, but AMP2 routinely exceeded the target Hgb range of 10 to 12 g/dL. SAM had lower Hgb variability. SAM resulted in a greater percent of Hgb observations within the target range and a lower utilization of ESA.
Clinical Studies
First trial: a randomized, controlled, double blind trial.
Sample size: 62 subjects, 52 completed.
Key Results: The proportion of hemoglobin concentrations within the target range was greater for SAM (72.5%) than control (61.9%) (p=0.003). There was no difference in a Composite Safety Event (CSE) as a combination of All-Cause Mortality (ACM), Myocardial Infarction (MI), Cerebrovascular Accident (CVA), and (exacerbation of) Congestive Heart Failure (CHF).
Second trial: a combination of a case controlled and cross sectional study.
Key results: Efficacy was maintained over the 45 month long term follow up where hemoglobin concentrations within the target range ranged from 76.8% to 86.3% for SAM compared to 73.5% to 89.1% for PhySoft AMS™. Safety was maintained over the 45 month long term follow up where hemoglobin concentrations above 12.9 g/dL ranged from 1.5% to 8.7% for SAM compared to 5.9% to 9.4% for PhySoft AMS™. No statistical difference was observed between SAM and PhySoft AMS™ performance.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Simulation Testing:
Mean Hgb (g/dL), Hgb Standard Deviation (g/dL), Percent Hgb 10 to 12, ESA Dose (units).
Clinical Studies:
Proportion of hemoglobin concentrations within target range, Composite Safety Event (ACM, MI, CVA, CHF), hemoglobin concentrations above 12.9 g/dL.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 876.5820 Hemodialysis system and accessories.
(a)
Identification. A hemodialysis system and accessories is a device that is used as an artificial kidney system for the treatment of patients with renal failure or toxemic conditions and that consists of an extracorporeal blood system, a conventional dialyzer, a dialysate delivery system, and accessories. Blood from a patient flows through the tubing of the extracorporeal blood system and accessories to the blood compartment of the dialyzer, then returns through further tubing of the extracorporeal blood system to the patient. The dialyzer has two compartments that are separated by a semipermeable membrane. While the blood is in the blood compartment, undesirable substances in the blood pass through the semipermeable membrane into the dialysate in the dialysate compartment. The dialysate delivery system controls and monitors the dialysate circulating through the dialysate compartment of the dialyzer.(1) The extracorporeal blood system and accessories consists of tubing, pumps, pressure monitors, air foam or bubble detectors, and alarms to keep blood moving safely from the blood access device and accessories for hemodialysis (§ 876.5540) to the blood compartment of the dialyzer and back to the patient.
(2) The conventional dialyzer allows a transfer of water and solutes between the blood and the dialysate through the semipermeable membrane. The semipermeable membrane of the conventional dialyzer has a sufficiently low permeability to water that an ultrafiltration controller is not required to prevent excessive loss of water from the patient's blood. This conventional dialyzer does not include hemodialyzers with the disposable inserts (Kiil type) (§ 876.5830) or dialyzers of high permeability (§ 876.5860).
(3) The dialysate delivery system consists of mechanisms that monitor and control the temperature, conductivity, flow rate, and pressure of the dialysate and circulates dialysate through the dialysate compartment of the dialyzer. The dialysate delivery system includes the dialysate concentrate for hemodialysis (liquid or powder) and alarms to indicate abnormal dialysate conditions. This dialysate delivery system does not include the sorbent regenerated dialysate delivery system for hemodialysis (§ 876.5600), the dialysate delivery system of the peritoneal dialysis system and accessories (§ 876.5630), or the controlled dialysate delivery system of the high permeability hemodialysis system § 876.5860).
(4) Remote accessories to the hemodialysis system include the unpowered dialysis chair without a scale, the powered dialysis chair without a scale, the dialyzer holder set, dialysis tie gun and ties, and hemodialysis start/stop tray.
(b)
Classification. (1) Class II (performance standards) for hemodialysis systems and all accessories directly associated with the extracorporeal blood system and the dialysate delivery system.(2) Class I for other accessories of the hemodialysis system remote from the extracorporeal blood system and the dialysate delivery system, such as the unpowered dialysis chair, hemodialysis start/stop tray, dialyzer holder set, and dialysis tie gun and ties. The devices subject to this paragraph (b)(2) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.
0
Image /page/0/Picture/0 description: The image contains the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
January 16, 2019
Dosis, Inc. % E.J. Smith Consultant Smith Associates 1468 Harwell Ave. Crofton, MD 21114
Re: K180410
Trade/Device Name: Smart Anemia Manager (SAM) Regulation Number: 21 CFR§ 876.5820 Regulation Name: Hemodialysis System and Accessories Regulatory Class: II Product Code: MQS Dated: December 7, 2018 Received: December 11, 2018
Dear E.J. Smith:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies.
1
You must comply with all the Act's requirements. including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see
https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803). please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Carolyn Y. Neuland -S
for
Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K180410
Device Name Smart Anemia Manager (SAM)
Indications for Use (Describe)
SAM is a web application used to obtain, track and trend patient data pertaining to the management of anemia, and to provide a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin (Hgb) levels in hemodialysis patients. The device is intended to help clinicians manage chronic anemia.
The device is not a substitute for, but rather intended to assist, clinical judgment. The ESA dosing regimen options calculated by this device are intended to inform the optimization of the dosage of ESAs in accordance with their approved labeling in conjunction with clinical history, symptoms, and other diagnostic measurements, as well as the clinicians' judgment. No medical decision should be based solely on the patient Hgb response to dosing regimen options calculated by this device.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) Summary
| Company Name:
Company Address: | Dosis, Inc.
353 Sacramento Street
Suite 1811
San Francisco, CA 94111 |
|-------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------|
| Telephone:
Contact Person: | 650 383 0186
Shivrat Chhabra |
| Summary Preparation Date: | 01/14/2019 |
| Device Description:
Device Name:
Common Name:
Classification Name
Regulatory Class:
Product Code:
C.F.R. Section: | Smart Anemia Manager (SAM)
Anemia Software Management
Hemodialysis System and Accessories
Class II
MQS
21 CFR 876.5820 |
PREDICATE DEVICE:
| Manufacturer | Product Name | 510(k) Number |
|---|---|---|
| Physician Software Systems, LLC | PhySoft AMS™ | K130579 |
DEVICE DESCRIPTION:
SAM is a web application used to obtain, track and trend patient data pertaining to the management of anemia, and to provide a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin (Hgb) levels in hemodialysis patients. The device is intended to help clinicians manage chronic anemia.
Healthcare professionals access SAM using a web-enabled application (for example, a web browser or a web-enabled electronic health record system) communicating with the SAM web application server. Patient information is obtained by SAM from healthcare provider Electronic Medical Records. No components of SAM are required to be installed at end user or healthcare provider locations.
SAM estimates individual patient's Hgb response to ESAs. The results of this estimation are used to generate new patient-specific ESA dose recommendation to achieve target Hgb level specified by the physician. The ESA dose recommendation is reviewed by the physician, who after considering any additional relevant information about patient's condition, decides whether to follow or override the presented ESA dose recommendation.
4
INDICATIONS FOR USE:
SAM is a web application used to obtain, track and trend patient data pertaining to the management of anemia, and to provide a schedule of erythropoiesis-stimulating agent (ESA) dosage recommendations to help achieve and maintain target hemoglobin (Hgb) levels in hemodialysis patients. The device is intended to help clinicians manage chronic anemia.
The device is not a substitute for, but rather intended to assist, clinical judgment. The ESA dosing regimen options calculated by this device are intended to inform the optimization of the dosage of ESAs in accordance with their approved labeling in conjunction with clinical history, symptoms, and other diagnostic measurements, as well as the clinicians' judgment. No medical decision should be based solely on the patient Hgb response to dosing regimen options calculated by this device.
| | Dosis | Physicians Software
System, LLC | Similarities and
Difference |
|----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------|
| Product Name | SAM | PhySoft AMS™ | |
| Indications for Use
Statement | SAM is a web application
used to obtain, track and
trend patient data
pertaining to the
management of anemia,
and to provide a schedule of
erythropoiesis-stimulating
agent (ESA) dosage
recommendations to help
achieve and maintain target
hemoglobin (Hgb) levels in
hemodialysis patients. The
device is intended to help
clinicians manage chronic
anemia.
The device is not a
substitute for, but rather
intended to assist, clinical
judgment. The ESA dosing
regimen options calculated
by this device are intended
to inform the optimization
of the dosage of ESAs in
accordance with their
approved labeling in
conjunction with clinical
history, symptoms, and
other diagnostic
measurements, as well as
the clinicians' judgment. No
medical decision should be | PhySoft AMS™ is a web
application used to obtain,
track and trend patient data
pertaining to the
management of anemia, and
to provide a schedule of
erythropoiesis-stimulating
agent (ESA) dosage
recommendations to help
achieve and maintain target
hemoglobin levels in dialysis
patients. PhySoft AMS™ is
intended to help physicians,
nurses, clinicians and anemia
managers manage anemia in
adult stage 5 chronic kidney
disease (CKD) patients.
The PhySoft AMS™ is not a
substitute for, but rather
intended to assist, clinical
judgment. The ESA dosing
regimen options calculated by
this device are intended to be
used by qualified and trained
medical personnel to inform
the optimization of the
dosage of ESAs in accordance
with their approved labeling
in conjunction with clinical
history, symptoms, and other
diagnostic measurements as | Same |
SUBSTANTIALLY EQUIVALENCE DISCUSSION:
5
K180410
Page 3 of 9
| based solely on the patient
Hgb response to dosing
regimen options calculated
by this device. | well as the medical
professional's clinical
judgment. No medical
decision should be based
solely on the
patient Hgb response to
dosing regimen options
calculated by this device. | |
| -------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -- |
|---|
| Parameters | Dosis | Physicians Software System, LLC | Similarities and Differences |
|---|---|---|---|
| 510(k) Number: | K130579 | ||
| Product Code | MQS | MQS | Same |
| Regulation Number | 21 CFR 876.5820 | 21 CFR 876.5820 | Same |
| Principle of Operation | Track and trend Hgb and ESA | ||
| dosages which can be used to | |||
| determine future ESA dosages | Track and trend Hgb and ESA | ||
| dosages which can be used to | |||
| determine future ESA dosages | Same | ||
| Technology | Application used to trend | ||
| patient data collected during | |||
| each dialysis treatment | Application used to trend | ||
| patient data collected during | |||
| each dialysis treatment | Same | ||
| Patient Demographics | Adult stage 5 chronic kidney | ||
| disease patients | Adult stage 5 chronic kidney | ||
| disease patients | Same | ||
| Intended User | Physician/Clinicians/Nurses | Physician/Clinicians/Nurses | Same |
| Data Storage | Data is stored electronically | Data is stored electronically | Same |
| Data Management | Generates reports and graphs | ||
| to assist anemia management | Generates reports and graphs | ||
| to assist anemia management | Same | ||
| Safeguards/Alerts | System flags patients who | ||
| exceed limits | System flags patients who | ||
| exceed limits | Same | ||
| Technological Characteristics | |||
| Parameters | Dosis | Physicians Software System, LLC | Similarities and Differences |
| 510(k) Number: | |||
| Product Code | MQS | K130579 | |
| MQS | Same | ||
| Regulation Number | 21 CFR 876.5820 | 21 CFR 876.5820 | Same |
| Principle of Operation | Track and trend Hgb and ESA dosages which can be used to determine future ESA dosages | Track and trend Hgb and ESA dosages which can be used to determine future ESA dosages | Same |
| Technology | Application used to trend patient data collected during each dialysis treatment | Application used to trend patient data collected during each dialysis treatment | Same |
| Patient Demographics | Adult stage 5 chronic kidney disease patients | Adult stage 5 chronic kidney disease patients | Same |
| Intended User | Physician/Clinicians/Nurses | Physician/Clinicians/Nurses | Same |
| Data Storage | Data is stored electronically | Data is stored electronically | Same |
| Data Management | Generates reports and graphs to assist anemia management | Generates reports and graphs to assist anemia management | Same |
| Technology/Algorithm | Uses individualized dose response model to compute patient dose response. | Uses individualized dose response model to compute patient dose response. | Same |
| Account for effects of last ESA dose. | Account for effects of multiple prior ESA dosages. | In SAM effect of multiple prior ESA dose is embedded in Hgb trend. | |
| Estimates ongoing dosing schedules to achieve target Hgb levels using close-loop approach. | Estimates ongoing dosing schedules to achieve target Hgb levels using open-loop approach. | In SAM close-loop allows for potential mismatch | |
| Technological Characteristics | |||
| Parameters | Dosis | Physicians Software | |
| System, LLC | Similarities | ||
| and | |||
| Differences | |||
| between | |||
| model and | |||
| patient. | |||
| Data Entry | Patient data is transferred | ||
| electronically from existing | |||
| healthcare provider | |||
| information systems. | Patient data is transferred | ||
| electronically from existing | |||
| healthcare provider | |||
| information systems. | Same | ||
| Data Storage | Data is stored | ||
| electronically in a remote | |||
| database server | Data is stored | ||
| electronically on local or | |||
| remote database server | SAM does not | ||
| store data | |||
| locally | |||
| Data Network Access | Data is accessed over | ||
| secure internet | |||
| connections. | Data is accessed over | ||
| secure internet | |||
| connections. | Same | ||
| Safeguards/Alerts | System flags patients who | ||
| exceed limits | System flags patients who | ||
| do not respond as | |||
| predicted and may have | |||
| undetected health issues | |||
| that do not fit the most | |||
| probable model. | SAM does not | ||
| flag | |||
| undetected | |||
| health issues. | |||
| Minimum Data | |||
| Requirement | Evaluates patient readiness | ||
| for application of algorithm | |||
| to model ESA dose-Hgb | |||
| response (sufficient history | |||
| of Hgb and ESA dosing). | SAM does not | ||
| have a | |||
| minimum | |||
| dosing history | |||
| requirement | |||
| only requires | |||
| a single HgB | |||
| measurement. |
6
7
Discussion of Similarities and Differences:
Similarities
- . SAM has the same indications for use, principle of operation, technology, patient demographics, intended users, data storage, data management, safe guards and alerts, technology/algorithm, data entry, and data network access and raises no new issues of safety and effectiveness, as a result of this submission.
- . SAM has a similar algorithm as the predicate device. Both software systems were verified and validated using the recommendations found in FDA's Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices,
8
Document issued on: May 11, 2005 and the results raises no new issues of safety and effectiveness.
Differences
- The combination of past ESA doses will impact future HgB concentrations and SAM uses the most recent ESA dose as a predictor of future HgB. Additional information on past ESA dose is present in HgB trend. Both methods use past ESA dose in different ways for the same end result.
- . SAM uses close loop control and therefore can better acknowledge and adjust for errors in drug dosing and the measurement of HgB. This should lead to at least similar accuracy compared to the predicate and is a superior method when compared to open loop control.
- . SAM only stores data on a remote HIPPA compliant server and avoids the potential problem with local data storage and potential data incursion. There is no effect on predictive performance due to data storage methods.
- SAM and the predicate both identify when the observed HgB is different from the prediction. SAM uses this information in the close loop control methodology to improve the prediction in the future. The predicate only flags the individual as not responding as expected and might be able to suggest the cause but does not adjust the prediction to account for this error like a close loop control method. The impact should not be substantially different between methods except that close loop control can potentially lead to improved future predictions.
- . SAM does not have a minimum data requirement to estimate patient response and can make recommendations based on a single HgB measurement. This difference will allow SAM to make recommendations in patients that the predicate cannot.
Non-clinical Performance Tests
Simulation Testing
The performance of the SAM software was tested through simulation and comparison to anemia management using usual practice in the form of an anemia management protocol in use at 2 large dialysis providers.
Purpose
Demonstrate the efficacy and safety of the SAM software in the dosing of erythropoietin (ESA) for the treatment of anemia in a simulated patient population compare to usual care.
Subjects
Anemic subjects were simulated based on their response to an ESA using the concepts published on the pharmacodynamics of erythropoietin (Uehlinger et al. Clin Pharmacol
9
Ther 51:76-89, 1992). Subject had a broad range of responsiveness that encompassed that observed in the target population.
Study Design
In silico three way cross over simulation.
Outcome Variables
Methods
A pool of 2430 patients were created based on a range of ESA response measures and red blood cell life spans essentially generating a cohort of test subjects that range to hyper to hypo responsive to ESA. ESA dosing was then simulated to achieve steady state hemoglobin concentrations using the SAM software or conventional therapy using an anemia management protocol 1 or 2 (AMP1 or AMP2). Noise was introduced into the system to simulate the uncertainty in the measurement of hemoglobin between 0.0 and 1.0 g/dL. We recorded the mean achieve hemoglobin, time to steady state, hemoglobin variability, percent in target range, and mean ESA/week. A total of 26,730 simulations were run for each protocol. Target range was a hemoglobin between 10.0 and 12.0 g/dL. The goal was to demonstrate non-inferiority to AMP 1 and 2 in mean hemoglobin, percent in target range and hemoglobin standard deviation.
Results
The results of the simulations are shown in the following tables:
| | Time to Target (weeks) | | | Mean Hgb (g/dL) | | | Hgb Standard Deviation
(g/dL) | | |
|-----------------|------------------------|------|------|-----------------|------|-----------|----------------------------------|------|-----------|
| Noise
(g/dL) | AMP1 | AMP2 | SAM | AMP1 | AMP2 | Dosis SAM | AMP1 | AMP2 | Dosis SAM |
| 0.0 | 5.2 | 4.5 | 12.6 | 11.2 | 12.3 | 10.9 | 0.5 | 1.4 | 0.2 |
| 0.1 | 5.4 | 4.5 | 12.4 | 11.2 | 12.3 | 10.9 | 0.6 | 1.4 | 0.3 |
| 0.2 | 5.3 | 4.6 | 11.9 | 11.1 | 12.3 | 10.9 | 0.6 | 1.5 | 0.4 |
| 0.3 | 5.3 | 4.8 | 11.6 | 11.1 | 12.4 | 10.9 | 0.7 | 1.6 | 0.4 |
| 0.4 | 5.5 | 4.5 | 11.0 | 11.1 | 12.4 | 10.9 | 0.8 | 1.7 | 0.5 |
| 0.5 | 5.5 | 4.7 | 10.2 | 11.0 | 12.4 | 10.9 | 0.9 | 1.8 | 0.6 |
| 0.6 | 5.5 | 4.5 | 9.8 | 11.0 | 12.4 | 10.9 | 1.0 | 1.8 | 0.7 |
| 0.7 | 5.2 | 4.8 | 9.5 | 11.0 | 12.5 | 10.8 | 1.1 | 1.9 | 0.9 |
| 0.8 | 5.2 | 4.7 | 8.9 | 11.0 | 12.6 | 10.8 | 1.2 | 2.0 | 0.9 |
| 0.9 | 5.7 | 4.7 | 8.3 | 11.0 | 12.7 | 10.8 | 1.3 | 2.1 | 1.1 |
| 1.0 | 5.7 | 4.5 | 7.7 | 11.0 | 12.7 | 10.8 | 1.4 | 2.2 | 1.2 |
Time to target, Mean achieved Hgb, and Standard Deviation for AMP1, AMP2, and SAM
The approaches resulted in differences in respect to time to target with SAM taking longer to reach the target Hgb. The mean Hgb achieved was similar between SAM and AMP1, but AMP2 routinely exceeded the target Hgb range of 10 to 12 g/dL. SAM had lower Hgb variability. The impact of these observations can be seen in the next table
10
| Noise
| (g/dL) | Percent Hgb 10 to 12 | ESA Dose (units) | ||||
|---|---|---|---|---|---|---|
| AMP1 | AMP2 | SAM | AMP1 | AMP2 | Dosis SAM | |
| 0.0 | 67.7 | 50.1 | 74.1 | 11217 | 11554 | 7356 |
| 0.1 | 67.2 | 50.6 | 74.0 | 11186 | 11575 | 7352 |
| 0.2 | 65.5 | 49.3 | 73.9 | 11116 | 11759 | 7344 |
| 0.3 | 61.4 | 47.5 | 72.7 | 10869 | 11834 | 7337 |
| 0.4 | 57.6 | 46.1 | 70.6 | 10709 | 11910 | 7338 |
| 0.5 | 53.5 | 44.1 | 66.8 | 10455 | 12013 | 7307 |
| 0.6 | 51.0 | 41.7 | 62.7 | 10282 | 12147 | 7289 |
| 0.7 | 47.4 | 38.1 | 58.2 | 10252 | 12560 | 7277 |
| 0.8 | 45.4 | 36.7 | 55.8 | 10218 | 12651 | 7239 |
| 0.9 | 42.9 | 34.7 | 51.0 | 10131 | 12925 | 7232 |
| 1.0 | 40.2 | 33.2 | 48.0 | 9852 | 13074 | 7167 |
comparing the percent of Hgb concentrations within the target range of 10 to 12 g/dL and the amount of ESA used to achieve this result.
SAM resulted in a greater percent of Hgb observations within the target range and a lower utilization of ESA.
Other Testing
- . ISO 14971 Second edition 2007-03-01, Medical devices - Application of risk management to medical devices.
- . Software Verification and Validation were conducted based on the use of Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices, Document issued on: May 11, 2005
Clinical Studies
Executive Summary
SAM software was tested in 2 clinical trials. The first trial was a randomized, controlled, double blind trial against standard of care conducted in 62 subjects over a 12 month period. 52 subject completed the study. The proportion of hemoglobin concentrations within the target range was greater for SAM (72.5%) than control (61.9%) (p=0.003). There was no difference in a Composite Safety Event (CSE) as a combination of All-Cause Mortality (ACM), Myocardial Infarction (MI), Cerebrovascular Accident (CVA), and (exacerbation of) Congestive Heart Failure (CHF). The second trial was a combination of a case controlled and cross sectional study. Efficacy was maintained over the 45 month long term follow up where hemoglobin concentrations within the target range ranged from 76.8% to 86.3% for SAM compared to 73.5% to 89.1% for PhySoft AMS™. Safety was maintained over the 45 month long term follow up where hemoglobin concentrations above 12.9 g/dL ranged from 1.5% to 8.7% for SAM compared to 5.9% to 9.4% for PhySoft AMS™. No statistical difference was observed between SAM and PhySoft AMS™ performance.
11
Conclusion
Smart Anemia Manager (SAM) is substantially equivalent in Indications for Use, principle of operation and technological characteristics to the predicate device. SAM is substantially equivalent in clinical performance as demonstrated in comparison of published performance measures with the predicate device. Dosis. Inc.'s software validation and verification has demonstrated the safety and effectiveness of the SAM software in anemia management for hemodialysis patients and it is the conclusion of Dosis, Inc., that the SAM raises no new questions of safety and effectiveness and is substantially equivalent to the predicate device.