The CoagCare Anticoagulation Management System (CoagCare®) is an interactive, internet-based (web-based), rules-based expert software system for the long-term management of patients undergoing warfarin anticoagulation therapy. The system is an accessory to prescription home-use prothrombin time devices that measure International Normalized Ratios (INRs), and it facilitates remote clinical management between patient and caregiver.

Device Description

The CoagCare system is a software accessory to prescription-home use prothrombin time (INR) devices for effective anticoagulation management with warfarin. System Overview: The system consists of two components, the CoagCare Patient Interface and the CoagCare Caregiver Interface, both of which are accessed through an internet browser. The interface provides a structured therapeutic regimen developed for the individual patient. It prompts the patient for INR values, symptoms, and other disease related data, and provides the patient with recommended doses of warfarin and an INR testing schedule that can be adjusted based on parameters specified by the patient's caregiver. The patient is given recommendations for warfarin doses for each day until the next time of required INR testing. In cases of marked abnormal INR readings or disease signs or symptoms suggestive of over-treatment, the Patient Interface instructs the patient to contact his/her healthcare provider for further instructions.

The second component of the CoagCare system is the Caregiver Interface. The caregiver monitoring the patient's anticoagulant therapy accesses the Caregiver Interface at least daily. The Caregiver Interface is programmed to automatically identify patient problems such as patients who report thromboembolic or hemorrhagic symptoms, failure to check their INR on a prescribed day, etc. The Caregiver Interface prioritizes problems requiring the caregiver's attention. Once patients have checked their INRs and transmitted their results, if the caregiver agrees with the warfarin dosing instructions provided by the patient interface, no further interventions are required for that day. Patients with markedly abnormal results or recurrent problems are prioritized for caregiver intervention, whereas stable patients are listed with their results, eliminating the need for direct patient contact by the caregiver. The Caregiver Interface also allows the caregiver to override therapeutic instructions provided by the Patient Interface, or send a text message to the patient through the Patient interface. (For more emergent issues, the patient can be contacted directly by the caregiver by telephone.)

AI/ML Overview

Here's an analysis of the CoagCare Anticoagulation Management System based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implicit)	Reported Device Performance
Improvement in Time in Therapeutic Range (TTR) for warfarin anticoagulation therapy. (Implicit. The core utility of such a system is to better manage anticoagulation, and TTR is a key metric.)	Increase in TTR from 62.5% (prior to CoagCare) to 73.5% (during CoagCare study), representing an 11% increase. This improvement was statistically significant (p = 0.008). The site effect was non-significant (p=0.87), indicating consistent improvement across sites.
Efficiency for Caregivers in managing patients.	Caregivers at all 3 sites reported that it took between 15 and 25 minutes a day to manage between 20 and 58 patients. The report notes, "Due to the automation provided by CoagCare, managing 48 patients with CoagCare did not take much more time than managing 20." This indicates an improvement in efficiency, though a specific quantitative target (e.g., reduce time by X%) is not explicitly stated as an acceptance criterion.
Patient Satisfaction with home management using CoagCare.	Between 92% and 100% of all patients reported:
	* They preferred home management with CoagCare to traditional point-of-care treatment.
	* They felt they were being monitored more closely with CoagCare.
	* Their INRs were in better control with home management.
Safety and Effectiveness for intended use.	The clinical studies demonstrated that patients and caregivers can successfully use the CoagCare system to produce improved outcomes and a high degree of patient satisfaction, leading to the conclusion that the system is safe and effective for its intended use. (This is a summary conclusion based on the observed improvements and patient feedback).

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size: 100 patients
- 58 patients at Duke University Medical Center
- 22 patients at the University of New Mexico Medical Center
- 20 patients from a private practice in Miami
Data Provenance: United States (Duke University, University of New Mexico, Miami private practice). The study was prospective, as patients were "switched to home INR monitoring and followed with the CoagCare system for six months" or "remained on the system from 3 to 4 months." Data on TTR prior to CoagCare was retrospective (likely collected from patient records before the intervention).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The document does not explicitly state the number or qualifications of experts used to establish a "ground truth" for the test set in the traditional sense of diagnostic accuracy studies. The study evaluates the effectiveness of the system in managing anticoagulation, where the "ground truth" is inferred from patient INR values (measured by home INR devices) and the resulting time in therapeutic range. The "caregivers" (physicians, nurses, pharmacists, or licensed professionals) monitoring the patients are the experts involved in overseeing the system and making clinical judgments.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method for the test set as would typically be done for diagnostic interpretations. The CoagCare system provides recommendations, and caregivers monitor and can override instructions. The "ground truth" for TTR is derived from INR measurements and the patient's adherence to the warfarin dosing recommendations generated by the system (or overridden by the caregiver).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

This was not a traditional MRMC study. It was a comparative effectiveness study comparing patient outcomes with the CoagCare system to their outcomes without the system (their historical TTR). The "readers" (caregivers) involved in managing the patients using the CoagCare system had their efficiency and satisfaction assessed.

Effect Size of Human Readers Improve with AI vs. without AI assistance: The study primarily focuses on patient outcomes (TTR) and caregiver efficiency.
- Patient Outcome (TTR): The TTR increased by 11% (from 62.5% to 73.5%) with the CoagCare system (which includes AI-like capabilities for dosing recommendations and problem prioritization) compared to prior management. This suggests the system assists caregivers in achieving better patient outcomes.
- Caregiver Efficiency: Caregivers managing between 20-58 patients reported it took only 15-25 minutes a day. The note "managing 48 patients with CoagCare did not take much more time than managing 20" strongly suggests an improvement in caregiver efficiency due to the system's automation, but a specific "effect size" of improvement (e.g., X% more patients managed per hour) is not quantified or compared to an unassisted baseline.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done

No, a standalone performance study was not done. The CoagCare system is explicitly described as a "software accessory" that facilitates "remote clinical management between patient and caregiver." The system provides recommendations, but "caregivers have the ability to override therapeutic instructions" and "requires tight professional oversight." It is a human-in-the-loop system.

7. The Type of Ground Truth Used

The primary "ground truth" or outcome measure used was:

Outcomes Data: Specifically, the Time in Therapeutic Range (TTR) for International Normalized Ratios (INR) in warfarin-treated patients. This is a direct clinical outcome measure.
Patient Feedback/Satisfaction: Self-reported patient preferences and perceptions of monitoring and control.
Caregiver Reports: Reports on the time taken to manage patients.

8. The Sample Size for the Training Set

The document does not mention a distinct "training set" for the CoagCare system. The system "utilizes published and generally accepted algorithms to adjust medication doses and make treatment decisions." This implies that the algorithms were developed based on existing medical knowledge and clinical guidelines, rather than being trained on a specific, separate dataset within the context of this 510(k) submission.

9. How the Ground Truth for the Training Set Was Established

As no specific training set is mentioned for the algorithm (which is described as rule-based using "published and generally accepted algorithms"), the concept of "ground truth for the training set" as it relates to machine learning models is not applicable here. The "ground truth" for these general algorithms would have been established through extensive medical research, clinical trials, and expert consensus over many years, leading to the "published and generally accepted algorithms" mentioned.

Summary

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Image /page/0/Picture/0 description: The image shows contact information for a business. The address is 3804 Sweeten Creek Rd. in Chapel Hill, NC 27514. The phone number is (919)419-7228 and the fax number is (919) 419-9088.

AUG 1 6 2005

This summary of 510(k) safety and effectiveness information is befing submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is K050821.

807.92 (a)(1): Name:	Zycare, Inc.
Address:	3804 Sweeten Creek Road
Chapel Hill, NC 27514
Phone:	(919) 419-7228
Contact:	Mr. Steve D. Holdaway, MBA

807.92 (a)(2): Device Name -- trade name and common name, and classification

Trade name:	CoagCare® Anticoagulation Management System(CoagCare®)
Common name:	Software accessory to prescription-home useprothrombin time (INR) devices for effectiveanticoagulation management with warfarin
Classification:	CoagCare® is considered an unclassified accessory toINR test systems; INR test systems are regulatedunder 21 CFR 864.7750, Class II: 81 GJS.The device regulation for a "calculator/dataprocessing module for clinical use" (21 CFR862.2100) exempts such Class I devices from 510(k)requirements. This regulation is not entirelyapplicable, however, since the exemption only appliesto data processors for clinical laboratory use, and nothome use or use in clinic settings.

Trade name:

CoagCare® Anticoagulation Management System(CoagCare®)

Common name:

Software accessory to prescription-home useprothrombin time (INR) devices for effectiveanticoagulation management with warfarin

Classification:

CoagCare® is considered an unclassified accessory toINR test systems; INR test systems are regulatedunder 21 CFR 864.7750, Class II: 81 GJS.The device regulation for a "calculator/dataprocessing module for clinical use" (21 CFR862.2100) exempts such Class I devices from 510(k)requirements. This regulation is not entirelyapplicable, however, since the exemption only appliesto data processors for clinical laboratory use, and nothome use or use in clinic settings.

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807.92 (a)(3): Identification of the legally marketed predicate device

The CoagCare® Anticoagulation Management System is substantially equivalent to the Diacare® Monitoring System, K882001, cleared October 18, 1988; the Diacare system was cleared for the clinical management of diabetes mellitus.

807.92 (a)(4): Device Description

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807.92 (a)(5): Intended use

The CoagCare Anticoagulation Management System (CoagCare) is an interactive internet-based (web-based) software system for the long-term management of patients undergoing warfarin anticoagulation therapy. The system is an accessory to prescription home-use prothrombin time devices that measure International Normalized Ratios (INRs), and it facilitates remote clinical management between patient and caregiver.

807.92 (a)(6): Technological Similarities and Differences to Predicate

The following chart describes similarities and differences between the CoagCare system and the Diacare system (the predicate).

CHARACTERISTIC	CoagCare	Diacare (K882001)
Intended Use	Software (web-based) system usedin the patient's home for themanagement and monitoring ofINR levels and dosingrecommendations in patients beingtreated with anticoagulationtherapy (warfarin); automatessupervision of patients	Hardware/software system used inthe patient's home for themanagement and monitoring ofglucose and insulin levels inpatients being treated for diabetes;automates supervision of patients
System Functions	Screens the data for problems,prioritizes patient records forphysician review, monitorsimplementation of a homemedication dosing algorithm;physician can manage patientsremotely	Screens the data for problems,prioritizes patient records forphysician review, monitorsimplementation of a homemedication dosing algorithm;physician can manage patientsremotely
Route of Information Transfer	Secure internet web-site withdedicated servers	Direct server dial-in

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CHARACTERISTIC	CoagCare	Diacare (K882001)
Data Output	Printable reports	Printable reports
Patient Identification	Secured through passwords andsecure website	Hardware based, meter connectedto phone line by patient
Safety Features	Requires tight professionaloversight in the event ofunexpected results or symptoms	Requires tight professionaloversight in the event ofunexpected results or symptoms
Testing Environment	Home use with professionaloversight	Home use with professionaloversight
System Components	Proprietary internet-enabledsoftware, patient interface and caregiver interface	Proprietary software, patientinterface and care giver interface
Risk to Patient	Minimal, system will enforcecontact with health careprofessional in the event ofunexpected results/symptoms	Minimal, system will enforcecontact with health careprofessional in the event ofunexpected results/symptoms
Required IVD Component	Requires INR meter to obtainclinical INR results	Requires glucose meter to obtainclinical glucose results
Management Decision	Systems utilizes published andgenerally accepted algorithms toadjust medication doses and maketreatment decisions	Systems utilizes published andgenerally accepted algorithms toadjust medication doses and maketreatment decisions

The differences between the two data management systems do not raise new issues of safety and effectiveness.

807.92 (b)(1): Brief Description of Non-clinical data

Non-clinical studies are not relevant to software accessories.

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807.92 (b)(2): Brief Description of Clinical Data

The CoagCare Anticoagulation Management System was evaluated in comprehensive clinical studies at three sites. Fifty-eight patients at Duke University Medical Center and 22 patients at the University of New Mexico Medical Center, and 20 patients from a private practice in Miami who had been on warfarin for at least six months were recruited for the study. Patients at the Duke and New Mexico sites were switched to home INR monitoring and followed with the CoagCare system for six months. Patients in the Miami site remained on the system from 3 to 4 months. The overall INRs of all patients averaged 62.5% time in therapeutic range (TTR) prior to the start of CoagCare. This value increased to 73.5% TTR during the study, an 11% and statistically significant improvement ( p=. 008). The site e ffect w as n on-significant ( p=. 87), suggesting that the improvement in TTR was not statistically distinguishable across the sites. The increase in TTR seen with the CoagCare system could reasonably interpreted to reflect a clinically important improvement. Caregivers at all 3 sites reported that it took between 15 and 25 minutes a day to manage between 20 and 58 patients. Due to the automation provided by CoagCare, managing 48 patients with CoagCare did not take much more time than managing 20. Between 92% and 100% of all patients reported that they preferred home management with CoagCare to traditional point-of-care treatment, that they felt that they were being monitored more closely with CoagCare and that their INRs were in better control with home management.

807.92 (b)(3): Conclusions from Clinical Testing

In summary, we have demonstrated that patients and caregivers can successfully use the CoagCare system to produce improved outcomes and a high degree of patient satisfaction. The studies show that the CoagCare system is safe and effective for intended use.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

AUG 1 6 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Steven D. Holdaway, MBA Chief Executive Officer ZyCare, Inc. 3804 Sweeten Creek Road Chapel Hill, NC 27514

Re: K050821

Trade/Device Name: CoagCare Anticoagulation Management System (CoagCare®) Regulation Number: 21 CFR 864.5400 Regulation Name: Coagulation instrument Regulatory Class: Class II Product Code: KQG Dated: July 25, 2005 Received: July 26, 2005

Dear Mr. Holdaway:

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. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2 -

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Robert Beckerh

Robert L. Becker, Jr., MD, PA Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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March 29, 2005

STATEMENT OF INTENDED USE

K050821 510(k) Number (if Known):

Device Name: CoagCare Anticoagulation Management System (CoagCare®)

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Division/Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K050821

Page 8 of 1 Section 1- Statutory Requirements

Regulation Number and Section

§ 864.5400 Coagulation instrument.

(a)
Identification. A coagulation instrument is an automated or semiautomated device used to determine the onset of clot formation for in vitro coagulation studies.(b)
Classification. Class II (special controls). A fibrometer or coagulation timer intended for use with a coagulation instrument is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.