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Title:
INFUSION SET REPLACEMENT REMINDER
Document Type and Number:
WIPO Patent Application WO/2013/033025
Kind Code:
A1
Abstract:
Described are methods and systems to remind the patient to replace the infusion set by using not only the elapsed time since the last infusion set change, but also in the number of therapy events such as basal changes, correction boluses, drug sensitivity (ISF) changes and drug to carbohydrate ratio (I:C) changes upon detection of high analyte concentration over a defined period of time as an indicator that a set replacement is recommended. The reminder may also be activated by both high analyte concentration and occurrence of one or more therapy events.

Inventors:
STAR CYNTHIA (US)
JAHN LUIS G (US)
Application Number:
PCT/US2012/052536
Publication Date:
March 07, 2013
Filing Date:
August 27, 2012
Export Citation:
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Assignee:
ANIMAS CORP (US)
STAR CYNTHIA (US)
JAHN LUIS G (US)
International Classes:
A61M5/168
Foreign References:
US20090326722A12009-12-31
US20100094251A12010-04-15
US20110178499A12011-07-21
US20100292634A12010-11-18
Other References:
BECKER: "Pediatric Use of Insulin Pumps", LONGER INFUSION SITE LIFETIME WITH NOVOLOG DIABETES CARE, vol. 25, no. 9, September 2002 (2002-09-01), pages 1663
Attorney, Agent or Firm:
JOHNSON, Philip, S. et al. (One Johnson & Johnson PlazaNew Brunswick, NJ, US)
Download PDF:
Claims:
What is claimed is:

1. A method of reminding users to change a drug infuser connected to a drug delivery device, the method comprising the steps of:

conducting an analyte measurement of a physiological fluid of a user;

determining whether a value related to an analyte measurement is greater than an analyte threshold;

in the event the determining step is true, evaluating whether a therapy event has occur and if true, incrementing a therapy event counter by one;

querying whether an elapsed time between a duration of a current therapy event from a starting point and a durational threshold is less than a preset time window interval; and

in the event the querying step is true, annunciating a reminder to replace the infuser.

2. A method of reminding users to change a drug infuser connected to a drug delivery device, the method comprising the steps of:

conducting an analyte measurement of a physiological fluid of a user;

determining whether a value related to an analyte measurement is greater than an analyte threshold;

in the event the determining step is true, evaluating whether a therapy event has occur and if true, incrementing a therapy event counter by one;

evaluating whether a difference between a value of a current therapy event counter and a numerical sequence of a prior therapy event added with one is greater or equal to a therapy event threshold;

in the event the evaluating step is true, querying whether an elapsed time between a duration of a current therapy event from a starting point and a duration of a prior therapy event from the starting point is less than a preset time window interval; and

in the event the querying step is true, annunciating a reminder to replace the infuser.

3. The method of one of claim 1 or claim 2, further comprising:

ascertaining whether the user has previously infused drug to the user subsequent to the determining step; and

in the event the ascertaining step is true, setting a drug on board flag as equal to one otherwise setting the drug on board flag as equal to zero.

4. The method of claim 3, in which the step of incrementing the therapy event counter further comprises recording the number of therapy events (i) and time (Ti) of occurrence of event constituting a therapy event.

5. The method of claim 1, further comprising the steps of:

inquiring whether a sum of the number of therapy events and the value of the drug on board flag is greater than a therapy adjustment threshold; and

in the event the inquiring step returns a true then performing the querying step.

6. The method of claim 3, in which the preset time window interval comprises about 3 hours.

7. The method of claim 3, in which the therapy adjustment threshold comprises about four adjustments.

8. The method of claim 3, further comprising recording a change of the infuser by the user.

9. The method of claim 1, in which the incrementing step comprises:

incrementing a counter by 1 whenever a therapy event occurs;

setting the counter equal to the value obtained in the incrementing step; linking a time duration of the therapy event to the counter, with the time duration being measured from change of the infuser to the therapy event;

defining a durational threshold based on the counter and a threshold value.

10. The method of claim 9, in which the durational threshold comprises a time duration linked to a counter value defined by a sum of a difference between the value of the counter and the threshold Nth and one.

1 1. The method of claim 9, in which the duration of last therapy events is determined by:

determining a time duration as linked to a specified value of the counter;

calculating the durational threshold;

obtaining a difference between the time duration linked to the specified counter value and the durational threshold.

12. The method of claim 5, further comprising annunciating to the user a reminder to replace the infuser whenever a time period greater than maximum site duration.

13. The method of claim 8, wherein the maximum site duration comprises about three (3) days.

14. The method of claim 3, wherein the analyte threshold comprises a threshold of about 180 milligrams of analyte per decilitre of blood.

15. A method of reminding users to change a drug infuser connected to a drug delivery device, the method comprising the steps of:

conducting an analyte measurement of a physiological fluid of a user; determining whether a value related to the analyte measurement is greater than an analyte threshold;

in the event the determining step is false, querying as to whether a total duration of infuser being installed to the drug delivery device is greater than a maximum duration and if true, annunciating a reminder to replace the infuser;

in the event the determining step is true, inquiring as to whether drug was previously infused and if true, setting a drug on board flag as equal to one otherwise setting the drug on board flag as equal to zero; recording a number of therapy events and a time associated with such therapy adjustment event;

incrementing a therapy event counter upon the recording of the therapy event; investigating whether a sum of the number of therapy adjustment event and other therapy events and a value of the drug on board flag is greater than a therapy adjustment threshold;

in case the investigating returns a true, querying whether an elapsed time between a duration of a current therapy event from a starting point and a durational threshold is less than a preset time window interval; and

in the event the querying step is true, annunciating a reminder to replace the infuser.

16. The method of claim 15, further comprising:

evaluating whether the user has previously infused drug to the user prior to the starting step; and

in the event the evaluating step is true, setting a drug on board flag to one.

17. The method of claim 15, in which the maximum duration comprises about 3 days.

18. The method of claim 15, in which the preset time window interval comprises any value from about one to about four hours.

19. The method of claim 15, further comprising recording a change of the infuser by the user.

20. The method of claim 15, further comprising annunciating to the user a reminder to replace the infuser whenever a time period greater than a maximum duration is exceeded.

21. The method of claim 15, further comprising incrementing an event number whenever the determining step of the analyte is true and referencing a time to the event number.

22. The method of claim 21, further comprising determining whether a sum of the drug on board flag and the number of drug therapy event is greater than a preset event threshold.

23. The method of claim 15, in which the incrementing step comprises:

incrementing a counter by 1 whenever a therapy event occurs;

setting the counter equal to the value obtained in the incrementing step;

linking a time duration of the therapy event to the counter, with the time duration being measured from change of the infuser to the therapy event;

defining a durational threshold based on the counter and a threshold value.

24. A drug infusion system comprising:

an analyte sensor configured to sense analyte in physiological fluid of a user and provide signals representative of the quantity of analyte in the fluid;

an infuser disposed on a body surface of the user, the infuser having an infusion line for delivery of fluid through the infuser;

a drug delivery device configured to deliver a drug to the user through the infusion line, the drug delivery device being controlled based upon control signals provided to a controller; and

a controller configured to receive the signals of the analyte sensor and provide control signals to the drug delivery device, the controller further configured to annunciate a reminder to replace the infuser whenever the signal representative of the analyte amount is greater than a predetermined value and an elapsed time between a duration of a current therapy event and a durational threshold is less than a preset time window interval.

25. The drug infusion system of claim 24, in which the analyte sensor comprises a

continuous analyte sensor in wireless communication with the controller.

26. The drug infusion of claim 24, in which the drug delivery device comprises a drug delivery device in wireless communication with the controller.

27. The drug infusion system of claim 24, in which the analyte sensor comprises an

episodic analyte monitor and at least one analyte sensing test strip.

28. The drug infusion system of claim 24, in which the system designates a therapy event as Ti where i number of event is a series of integer starting with 1 and records the time duration for each i event.

29. The drug infusion system of claim 28, in which the duration comprises an elapsed time between a time duration recorded for a selected event Ti and a duration recorded as Ti_ Nth +i where i number of event comprises a counter for a most recent therapy event and th comprises a threshold value.

Description:
Infusion Set Replacement Reminder

Inventors:

Cynthia STAR

Luis G. JAHN

PRIORITY

[0001] This application claims the benefits of priority under 35 USC §§ 1 19, 120, or 365 based on prior U.S. Provisional Patent Application S.N. 61/529707 (Attorney Docket No. ANM5255USPSP) filed on August 31, 2011, which application is hereby incorporated by reference as if set forth herein.

BACKGROUND

[0002] Diabetes mellitus is a chronic metabolic disorder caused by an inability of the pancreas to produce sufficient amounts of the hormone drug so that the metabolism is unable to provide for the proper absorption of sugar and starch. This failure leads to hyperglycemia, i.e. the presence of an excessive amount of analyte within the blood plasma. Persistent hyperglycemia has been associated with a variety of serious symptoms and life threatening long term complications such as dehydration, ketoacidosis, diabetic coma, cardiovascular diseases, chronic renal failure, retinal damage and nerve damages with the risk of amputation of extremities. Because healing is not yet possible, a permanent therapy is necessary which provides constant glycemic control in order to always maintain the level of blood analyte within normal limits. Such glycemic control is achieved by regularly supplying external drug to the body of the patient to thereby reduce the elevated levels of blood analyte.

[0003] External drug was commonly administered by means of multiple, daily injections of a mixture of rapid and intermediate acting drug via a hypodermic syringe. While this treatment does not require the frequent estimation of blood analyte, it has been found that the degree of glycemic control achievable in this way is suboptimal because the delivery is unlike physiological drug production, according to which drug enters the bloodstream at a lower rate and over a more extended period of time. Improved glycemic control may be achieved by the so-called intensive drug therapy which is based on multiple daily injections, including one or two injections per day of long acting drug for providing basal drug and additional injections of rapidly acting drug before each meal in an amount proportional to the size of the meal. Although traditional syringes have at least partly been replaced by drug pens, the frequent injections are nevertheless very inconvenient for the patient, particularly those who are incapable of reliably self-administering injections.

[0004] Substantial improvements in diabetes therapy have been achieved by the development of the drug delivery device, relieving the patient of the need for syringes or drug pens and the administration of multiple, daily injections. The drug delivery device allows for the delivery of drug in a manner that bears greater similarity to the naturally occurring physiological processes and can be controlled to follow standard or individually modified protocols to give the patient better glycemic control.

[0005] In addition delivery directly into the intraperitoneal space or intravenously can be achieved by drug delivery devices. Drug delivery devices can be constructed as an implantable device for subcutaneous arrangement or can be constructed as an external device with an infusion set for subcutaneous infusion to the patient via the transcutaneous insertion of a catheter, cannula or a transdermal drug transport such as through a patch. External drug delivery devices are mounted on clothing, hidden beneath or inside clothing, or mounted on the body and are generally controlled via a user interface built-in to the device or on a separate remote device.

[0006] Drug delivery devices have been utilized to assist in the management of diabetes by infusing drug or a suitable biologically effective material into the diabetic patient at a basal rate with additional drug or "bolus" to account for meals or high analyte values, levels or concentrations. The drug delivery device is connected to an infuser, better known as an infusion set by a flexible hose. The infuser typically has a subcutaneous cannula, adhesive backed mount on which the cannula is attached thereto. The cannula may include a quick disconnect to allow the cannula and mount to remain in place on the skin surface of the user while the flexible tubing is disconnected from the infuser.

[0007] Regardless of the type of drug delivery device, blood analyte monitoring is required to achieve acceptable glycemic control. For example, delivery of suitable amounts of drug by the drug delivery device requires that the patient frequently determines his or her blood analyte level and manually input this value into a user interface for the external pumps, which then calculates a suitable modification to the default or currently in-use drug delivery protocol, i.e. dosage and timing, and subsequently communicates with the drug delivery device to adjust its operation accordingly. The determination of blood analyte concentration is typically performed by means of an episodic measuring device such as a hand-held electronic meter which receives blood samples via enzyme-based test strips and calculates the blood analyte value based on the enzymatic reaction.

[0008] In recent years, continuous analyte monitoring has also been utilized with drug delivery devices to allow for closed loop control of the drug(s) being infused into the diabetic patients. Despite the use of either or both of episodic and continuous analyte monitoring, patients often experience erratic blood analyte ("BG") values with the failure of the infusion set line. The cause is believed to be related to the infusion set partially pulling out, partial occlusion of the cannula, extended wear of the infusion set, on-set of a foreign body reaction or infection. At times the infusion set is working well with the patients only occasionally adjusting drug dosage to compensate for error in carbohydrate counting or type of food being consumed, exercise, or other life events that affect drug / carbohydrate metabolism. These changes are done on an infrequent manner. Frequent changes by the patients of drug dosage (basal rates), correction bolus, Drug-Sensitivity-Factor ("ISF") or Drug-to-Carbohydrates ratio ("I:C") or combination thereof are a possible indication of loss of analyte control. It is believed that these events would be an opportunity to remind the patient to check infusion site/infusion set.

SUMMARY OF THE DISCLOSURE

[0009] Applicants have discovered a technique to remind the patient to replace the infusion set by using not the elapsed time since the last infusion set change, but the number of basal changes, correction boluses, drug sensitivity (ISF) changes and drug to carbohydrate ratio (I:C) changes over a defined period of time as an indicator that an infuser set replacement is recommended. This is believed to be important because loss of analyte control can be due to an improperly inserted or damaged infusion set, including a biological response to the infusion set or even the drug being infused therethrough. Thus, the driver for changing the infusion set is not a fixed amount of time since the last infusion set change, but rather, a variable time depending on the nature of the failure.

[0010] In one aspect, a method of reminding users to change a drug infuser connected to a drug delivery device is provided. The method can be achieved by: conducting an analyte measurement of a physiological fluid of a user; determining whether a value related to an analyte measurement is greater than an analyte threshold; in the event the determining step is true, evaluating whether a therapy event has occur and if true, incrementing a therapy event counter by one; querying whether an elapsed time between a duration of a current therapy event from a starting point and a durational threshold is less than a preset time window interval; and in the event the querying step is true, annunciating a reminder to replace the infuser.

[001 1] In another aspect, a method of reminding users to change a drug infuser connected to a drug delivery device is provided. The method can be achieved by: conducting an analyte measurement of a physiological fluid of a user; determining whether a value related to an analyte measurement is greater than an analyte threshold; in the event the determining step is true, evaluating whether a therapy event has occur and if true, incrementing a therapy event counter by one; evaluating whether a difference between a value of a current therapy event counter and a numerical sequence of a prior therapy event added with one is greater or equal to a therapy event threshold; in the event the evaluating step is true, querying whether an elapsed time between a duration of a current therapy event from a starting point and a duration of a prior therapy event from the starting point is less than a preset time window interval; and in the event the querying step is true, annunciating a reminder to replace the infuser.

[0012] In either of the above aspects, the method may include: ascertaining whether the user has previously infused drug to the user subsequent to the determining step; and in the event the ascertaining step is true, setting a drug on board flag as equal to one otherwise setting the drug on board flag as equal to zero. The step of incrementing the therapy event counter may further include recording the number of therapy events (i) and time (Ti) of occurrence of event constituting a therapy event. [0013] In either of the above aspects, the method may further include the steps of: inquiring whether a sum of the number of therapy events and the value of the drug on board flag is greater than a therapy adjustment threshold; and in the event the inquiring step returns a true then performing the querying step.

[0014] In either of the above aspects, the preset time window interval may be about 3 hours; the therapy adjustment threshold may be about four adjustments.

[0015] In either of the above aspects, the method may further include recording a change of the infuser by the user. The incrementing step may include: incrementing a counter (i) by 1 whenever a therapy event occurs; setting the counter (i) equal to the value obtained in the incrementing step; linking a time duration of the therapy event to the counter (i), with the time duration being measured from change of the infuser to the therapy event; defining a durational threshold based on the counter (i) and a threshold value (Nth). The durational threshold may be a time duration linked to a counter value defined by a sum of a difference between the value of the counter and the threshold Nth and one; and the duration of last therapy events is determined by: determining a time duration as linked to a specified value of the counter (T;); calculating the durational threshold (Ti-Nth+i); obtaining a difference between the time duration linked to the specified counter value and the durational threshold.

[0016] In either of the above aspects, the method may further include annunciating to the user a reminder to replace the infuser whenever a time period greater than maximum site duration; the maximum site duration may be about three (3) days; the analyte threshold may be a threshold of about 180 mg of analyte per decilitre of blood.

[0017] In a further aspect, a method of reminding users to change a drug infuser connected to a drug delivery device is provided. The method can be achieved by: conducting an analyte measurement of a physiological fluid of a user; determining whether a value related to the analyte measurement is greater than an analyte threshold; in the event the determining step is false, querying as to whether a total duration of infuser being installed to the drug delivery device is greater than a maximum duration and if true, annunciating a reminder to replace the infuser; in the event the determining step is true, inquiring as to whether drug was previously infused and if true, setting a drug on board flag as equal to one otherwise setting the drug on board flag as equal to zero; recording a number of therapy events and a time associated with such therapy adjustment event; incrementing a therapy event counter upon the recording of the therapy event; investigating whether a sum of the number of therapy adjustment event and other therapy events and a value of the drug on board flag is greater than a therapy adjustment threshold; in case the investigating returns a true, querying whether an elapsed time between a duration of a current therapy event from a starting point and a durational threshold is less than a preset time window interval; and in the event the querying step is true, annunciating a reminder to replace the infuser. This method may further include evaluating whether the user has previously infused drug to the user prior to the starting step; and in the event the evaluating step is true, setting a drug on board flag to one. In this method, the maximum duration may be about 3 days; the preset time window interval may be any value from about one to about four hours. This method may further include recording a change of the infuser by the user. Alternatively, the method may further include annunciating to the user a reminder to replace the infuser whenever a time period greater than a maximum duration is exceeded. Additionally, the method may include incrementing an event number whenever the determining step of the analyte is true and referencing a time to the event number. Also, the method may further include determining whether a sum of the drug on board flag and the number of drug therapy event is greater than a preset event threshold. In the method, the incrementing step may include: incrementing a counter (i) by 1 whenever a therapy event occurs; setting the counter (i) equal to the value obtained in the incrementing step; linking a time duration of the therapy event to the counter (i), with the time duration being measured from change of the infuser to the therapy event; defining a durational threshold based on the counter (i) and a threshold value (Nth).

[0018] In yet another aspect, a drug infusion system is provided that includes an analyte sensor, infuser, drug delivery device, and a controller. The analyte sensor is configured to sense analyte in physiological fluid of a user and provide signals representative of the quantity of analyte in the fluid. The infuser is disposed proximate a body surface of the user, the infuser having an infusion line for delivery of fluid through the infuser. The drug delivery device is configured to deliver a drug to the user through the infusion line, the drug delivery device being controlled based upon control signals provided to a controller. The controller is configured to receive the signals of the analyte sensor and provide control signals to the drug delivery device. The controller is further configured to annunciate a reminder to replace the infuser whenever the signal representative of the analyte amount is greater than a predetermined value and an elapsed time between a duration of a current therapy event and a durational threshold is less than a preset time window interval. In this system, the analyte sensor may be a continuous analyte sensor in wireless communication with the controller. In this system, the drug delivery device may be a drug delivery device in wireless communication with the controller. Also, in this system, the analyte sensor may be an episodic analyte monitor and at least one analyte sensing test strip. In this system, the system may designate a therapy event as Ti where i is a series of integer starting with 1 and records the time duration for each i event. For this system, the duration may be an elapsed time between a time duration recorded for a selected event T; and a duration recorded as T;_ N th +1 where i number of event may be a counter for a most recent therapy event and N th may be a threshold value.

[0019] These and other embodiments, features and advantages will become apparent to those skilled in the art when taken with reference to the following more detailed description of various exemplary embodiments of the invention in conjunction with the accompanying drawings that are first briefly described.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate presently preferred embodiments of the invention, and, together with the general description given above and the detailed description given below, serve to explain features of the invention (wherein like numerals represent like elements).

[0021] Figure 1 illustrates an exemplary embodiment of the diabetic management system.

[0022] Figure 2 illustrates the infusion set for the system of Figure 1.

[0023] Figure 3 illustrates the logic utilized for reminding the user to replace the infusion set in the exemplary system of Figure 1. [0024] Figure 4 illustrates an alternate logic to remind users for the exemplary system of Figure 1.

MODES FOR CARRYING OUT THE INVENTION

[0025] The following detailed description should be read with reference to the drawings, in which like elements in different drawings are identically numbered. The drawings, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of the invention. The detailed description illustrates by way of example, not by way of limitation, the principles of the invention. This description will clearly enable one skilled in the art to make and use the invention, and describes several embodiments, adaptations, variations, alternatives and uses of the invention, including what is presently believed to be the best mode of carrying out the invention.

[0026] As used herein, the terms "about" or "approximately" for any numerical values or ranges indicate a suitable dimensional tolerance that allows the part or collection of components to function for its intended purpose as described herein. In addition, as used herein, the terms "patient," "host," "user," and "subject" refer to any human or animal subject and are not intended to limit the systems or methods to human use, although use of the subject invention in a human patient represents a preferred embodiment. Furthermore, the term "user" includes not only the patient using a drug infusion device but also the caretakers (e.g., parent or guardian, nursing staff or home care employee). The term "drug" may include pharmaceuticals or other chemicals that causes a biological response in the body of a user or patient.

[0027] Figure 1 illustrates a drug delivery system 100 according to an exemplary embodiment. Drug delivery system 100 includes a drug delivery device 102 and a remote controller 104. Drug delivery device 102 is connected to an infusion set 106 via flexible tubing 108.

[0028] Drug delivery device 102 is configured to transmit and receive data to and from remote controller 104 by, for example, radio frequency communication 110. Drug delivery device 102 may also function as a stand-alone device with its own built in controller. In one embodiment, drug delivery device 102 is a drug infusion device and remote controller 104 is a hand-held portable controller. In such an embodiment, data transmitted from drug delivery device 102 to remote controller 104 may include information such as, for example, drug delivery data, blood glucose information, basal, bolus, insulin to carbohydrates ratio or insulin sensitivity factor, to name a few. The controller 104 may be configured to receive continuous analyte readings from a continuous analyte ("CGM") sensor 1 12. Data transmitted from remote controller 104 to drug delivery device 102 may include analyte test results and a food database to allow the drug delivery device 102 to calculate the amount of drug to be delivered by drug delivery device 102. Alternatively, the remote controller 104 may perform dosing or bolus calculation and send the results of such calculations to the drug delivery device. In an alternative embodiment, an episodic blood analyte meter 114 may be used alone or in conjunction with the CGM sensor 112 to provide data to either or both of the controller 102 and drug delivery device 102. Alternatively, the remote controller 104 may be combined with the meter 1 14 into either (a) an integrated monolithic device; or (b) two separable devices that are dockable with each other to form an integrated device. Each of the devices 102, 104, and 1 14 has a suitable microcontroller (not shown for brevity) programmed to carry out various functionalities. For example, a microcontroller can be in the form of a mixed signal microprocessor (MSP) for each of the devices 102, 104, or 1 14. Such MSP may be, for example, the Texas Instrument MSP 430, as described in patent application publication numbers US2010-0332445, and US2008-0312512 which are incorporated by reference in their entirety herein and attached hereto the Appendix of this application. The MSP 430 or the pre-existing microprocessor of each of these devices can be configured to also perform the method described and illustrated herein.

[0029] Drug delivery device 102 may also be configured for bi-directional wireless communication with a remote health monitoring station 116 through, for example, a wireless communication network 118. Remote controller 104 and remote monitoring station 116 may be configured for bi-directional wired communication through, for example, a telephone land based communication network. Remote monitoring station 116 may be used, for example, to download upgraded software to drug delivery device 102 and to process information from drug delivery device 102. Examples of remote monitoring station 1 16 may include, but are not limited to, a personal or networked computer, a personal digital assistant, other mobile telephone, a hospital base monitoring station or a dedicated remote clinical monitoring station.

[0030] Drug delivery device 102 includes processing electronics including a central processing unit and memory elements for storing control programs and operation data, a radio frequency module 116 for sending and receiving communication signals (i.e., messages) to/from remote controller 104, a display for providing operational information to the user, a plurality of navigational buttons for the user to input information, a battery for providing power to the system, an alarm (e.g., visual, auditory or tactile) for providing feedback to the user, a vibrator for providing feedback to the user, a drug delivery mechanism (e.g. a drug pump and drive mechanism) for forcing a drug from a drug reservoir (e.g., a drug cartridge) through a side port connected to an infusion set 106 and into the body of the user.

[0031] Figure 2 illustrates the exemplary infusion set 106 of Figure 1. In this figure, the body 106a of the infusion set 106 is mounted to an adhesive substrate 106b with a cannula 106c mounted to the body 106a of the infuser. The body 106a is in turn in communication with a flexible tubing 108 in which drug is delivered from the drug delivery device 102. A quick- connect 106e may also be provided at the infuser body 106a so that the drug delivery device 102 and associated tubing 108 could be disconnected from the infuser without removal of the cannula from the body of the user. The cannula 106c is mounted to cannula housing portion 106d which is retained to the body 106a by locking band 106e with protrusion 106f and side walls 106g. The cannula may remain in the body after being inserted with a needle that is subsequently removed. In some systems, the cannula should be changed with a particular frequency (every 3 days) to mitigate the risk of clogging. That is, the infusion set must be replaced regularly, usually every 2-3 days. It is believed that drug absorption becomes less effective the longer the duration of the infuser being in place thereby potentially, leading to poorer control of blood analyte. Additional details may be found regarding various infusion sets and associated inserters in U.S. Patent No.'s 7,052,483 and 6,572,586, which are hereby fully incorporated by reference herein and attached to the Appendix. It is noted that the infusion sets are commercially available as the Comfort™ infusion set or Contact™ Detach™ infusion set from Animas Corporation. While only one example of the infuser set is shown and described, it is the intention of the applicants that all types of mechanism that are configured to deliver drug transcutaneously (defined hereto generically as "infuser set" or "infusion device") be useable with applicants' invention, such as, for example, flexible infusers, transdermal type patches or iontophoresis infusing devices.

[0032] Once the new cannula is inserted and the adhesive substrate is attached to the skin of the user, a suitable amount of therapeutic is pumped so that the cannula is filled and ready for delivery to the user. A time stamp in which the cannula fill procedure was performed can be saved to a memory of the drug delivery device 102 or controller 104. Note that the time stamp may be saved to a memory of any of the devices usable with the delivery device 102 that has a memory and a microprocessor. Thereafter, a microprocessor can calculate a number of days in between cannula changes so as to annunciate a reminder to replace the infusion set. As used here, the term "annunciate" or "annunciating" and variations on the root term indicate that an announcement may be provided via text, audio, visual or a combination of all modes of communication on the analyte sensor, drug infusion device, or a remote communication device such as a mobile phone, network server, or remote monitoring system for a user, caretaker (e.g., parents, guardian, nursing staff and the like) or a health care provider.

[0033] Applicants have recognized that while the recommendation for keeping the infusion set in place for 2 to 3 days is fine for certain portions of the diabetic users, there may be instances in which patients often experience erratic blood analyte values associated with the failure of the infusion set line. The cause is believed to be related to many factors, including, for example, the infusion set partially pulling out, partial occlusion of the cannula, extended wear of the infusion set, onset of a foreign body reaction or infection and the like. This invention recognizes that high BG, with attempts by the user to correct high BG by changes in therapy, and being unsuccessful in correcting high BG, are linked to the need to replace the infusion set. In other words, consistently high BG reading s by themselves may be a reflection of meals, incorrect bolus calculation, wrong ISF or ICHO ratio, wrong CHO counting, incorrect basal rate (collectively "therapy events") and clearly indicative of a need to change infusion set. This invention couples high BG with attempts by the user to correct high BG (therapy events) and being unsuccessful to the need of infusion set replacement

[0034] Accordingly, applicants have derived a method to alleviate the issues relating to erratic BG values (whether from the continuous analyte sensor or the episodic sensor) as a result of many factors elucidated above. In this method of reminding users to change a drug infuser connected to a drug delivery device, the method may be achieved by conducting an analyte measurement of a physiological fluid of a user.

[0035] The step of conducting an analyte measurement can be achieved by the use of a blood analyte step strip that has a reagent layer disposed in a reaction chamber of the test strip. The reagent layer may include a suitable enzyme, such as, for example, analyte dehydrogenase (GDH) based on the PQQ co-factor and ferricyanide or alternatively, the enzyme GDH based on the PQQ co-factor may be replaced with the enzyme GDH based on the FAD co-factor. When blood is dosed into a sample reaction chamber of the test strip 115, analyte is oxidized by GDH (OX) and in the process converts GDH (ox) to GDH ( re d), as shown in the chemical transformation shown below. Note that GDH (OX) refers to the oxidized state of GDH, and GDH ( re d) refers to the reduced state of GDH.

D-Analyte + GDH( OX ) -> Gluconic acid + GDH( re d)

[0036] Next, GDH ( re d) is regenerated back to its active oxidized state by ferricyanide (i.e. oxidized mediator or Fe (CN)6 3~ ) as shown in chemical transformation shown below. In the process of regenerating GDH (OX) , ferrocyanide (i.e. reduced mediator or Fe(CN)6 4" ) is generated from the reaction as shown below:

GDH (red ) + 2 Fe(CN) 6 3" - GDH (ox) + 2 Fe(CN) 6 4"

[0037] Alternatively or concurrently, the analyte concentration can be determined by the use of the CG sensor 1 12. The CG sensor 1 12 utilizes amperometric electrochemical sensor technology to measure analyte with three electrodes operably connected to the sensor electronics and are covered by a sensing membrane and a biointerface membrane, which are attached by a clip.

[0038] The top ends of the electrodes are in contact with an electrolyte phase (not shown), which is a free-flowing fluid phase disposed between the sensing membrane and the electrodes. The sensing membrane may include an enzyme, e.g., analyte oxidase, which covers the electrolyte phase. In this sensor, the counter electrode is provided to balance the current generated by the species being measured at the working electrode. In the case of an analyte oxidase based analyte sensor, the species being measured at the working electrode is ¾(¾. Analyte oxidase catalyzes the transformation of oxygen and analyte to hydrogen peroxide and gluconate according to the following reaction:

Analyte+02-> Gluconate+H 2 02 [0039] The change in ¾(¾ can be monitored to determine analyte concentration because for each analyte molecule metabolized, there is a proportional change in the product ¾(¾.

Oxidation of ]¾0 2 by the working electrode is balanced by reduction of ambient oxygen, enzyme generated ¾(¾, or other reducible species at the counter electrode. The H 2 0 2 produced from the analyte oxidase reaction further reacts at the surface of working electrode and produces two protons (2H+), two electrons (2e-), and one oxygen molecule ((¾). A potentiostat is used to measure the electrochemical reaction(s) at the electrode(s) by applying a constant potential between the working and reference electrodes to produce a current value. The current that is produced at the working electrode (and flows through the circuitry to the counter electrode) is proportional to the diffusional flux of ¾(¾. Accordingly, a raw signal may be produced that is representative of the concentration of analyte in the user's body, and therefore may be utilized to estimate a meaningful analyte value. Details of the sensor and associated components are shown and described in US Patent No. 7,276,029, which is incorporated by reference herein and attached to the Appendix. In one embodiment, a continuous analyte sensor from the Dexcom Seven System (manufactured by Dexcom Inc.) can also be utilized with the exemplary embodiment described herein.

[0040] Patients routinely check their blood analyte meter (SMBG) or continuous analyte monitoring system (CGMS) to determine the state of their analyte control. If a patient's analyte level is out of control, i.e. out of the target zone, the patient may change certain parameters or settings related to insulin dosing that impact their glycaemic state as part of their therapy (hereafter designated a patient's "therapy event(s)") including but not limited to a change of basal rate; starting a temporary basal rate; deliver a correction bolus; setting up an extended bolus; changing the I:CHO ratio (drug [insulin] to carbohydrate ratio); changing ISF (drug or insulin sensitivity ratio). Any of these therapy events or small combinations of therapy events routinely takes place due to meal ingestion, exercise, stress, etc. However, the combination of significant number of events (>N th ) as described above over a short amount of time (< At) may be indicative that the infusion site is no longer viable.

[0041] Applicants have recognized that these changes to analyte therapy or "events" can occur at any time. However, time is linear and as such, a time window At for such therapy events moves in time with old events (i.e., earlier events) falling outside the time window At while newer events can also be happening. The problem that applicants have addressed is how to keep accurate track of the numbers of events happening during a moving time window At.

[0042] With reference to Figure 3, applicants have devised a technique to remind patients to change the infusion sets in their diabetes therapeutic delivery system. However, before moving into a detailed discussion of Figure 3, it is worthwhile to discuss the various nomenclatures used in Figure 3.

[0043] In the exemplary Figure 3, the variable "t" represents time and "Τ;" represents a time instance (9:49AM on April 25, 201 1) or a duration from an infuser change event (i.e., a starting point) linked to a specified therapy event designated by a counter "i" where i number of event is an integer. The subscript "i" to the time variable T indicates the event number, thus To is the time at an infuser has been changed, Ti is the time instance at which the first event occurred with respect to the starting time while T 4 is a time or duration of the fourth event as measured to the starting time. Applicants' technique looks for the difference in the subscript indices to understand the number of events, while the variable "T" is used to link the time at which the event took place as compared to the starting time To so as to determine the duration at which the event occurred. For example, with reference to Table 1 , for each event i=l,2,3, 4,

5, 6, 7 ,n there is a corresponding time duration (as measured from To) associated with that event T;= Ti, T 2 , T 3 , T 4 , T 5 , T 6 , T 7 , . . .. T n . Thus, a first therapy event therapy event is recorded as i =1 with a time duration of 3 hours (as measured with respect to To) linked to the event counter and signified by Ti. Similarly, a second therapy event is recorded as i =2 with a time duration T 2 of 5 hours (as measured with respect to To); a third therapy event is recorded as i=3 with a time duration T3 of 6 hours (as measured with respect to To); fourth, fifth and sixth therapy events are recorded as i=4, i=5, and i=6 and each counter is linked to respective time duration (as measured with respect to To). For the fourth through sixth therapy events, the time duration for each therapy event T 4 , T5, and Te occurs at the same duration of 7 hours from the starting time. Finally, a seventh therapy event is recorded as i=7 with a duration T 7 of 8 hours from the starting time. Table 1

[0044] Note that To is the time the infusion set was changed and as such does not constitute an "event." The threshold ΔΤΜΑΧ is a longer durational threshold, on the order of many days as defined by the manufacturer and could be about two to five days. This longer durational threshold is utilized to ensure that the infuser is not in place longer than the manufacturer's recommendation. In addition, if the patient has "drug on board" (signified by IOB >0) while the blood analyte (being measured using an episodic blood analyte meter or SMBG) or analyte level (being measured using a continuous analyte measurement system or CGMS) is greater than the upper blood analyte threshold or BGTH, then it qualifies as an event as well. The system keeps track of this special event for drug on board by using a flag designated as IOB flag. That is, in a situation where the BG value of the patient is greater than BGTH, if the IOB is greater than zero then the IOB flag =l otherwise the IOB flag =0.

[0045] Now that the nomenclatures of Figure 3 have been defined, a discussion of the logic in Figure 3 begins with a recordation of a change to the infusion set in step 302 and the counter i is reset to zero. At step 304, which could occur simultaneously or for a duration after an infusion set change, a blood analyte measurement BG is made. At step 306, this BG value or a value related thereto (e.g., such as an index derived from the measurement) is checked against the upper threshold BGTH- If the BG value is less than or equal to BGTH then the logic flows to step 308. In step 308, if time differential between the current time and the time at which the infusion set was changed (at step 302) is less than or equal to the ΔΤΜΑΧ then the logic returns back to step 304 otherwise if the time differential is greater than ΔΤΜΑΧ then the logic flows to step 322 in which a recommendation for a change in the infusion set is made to the patient.

[0046] Returning to step 306, if the BG value is greater than BGTH then the logic flows to step 310 to determine if the patient has drug in the patient's system (indicated by "IOB") from a recent infusion of drug into the patient's body. If the decision at step 310 returns a false then a flag IOBfi a g is set to zero at step 312 otherwise flag IOB flag is set to 1 at step 314. At step 316, if the system has determined that a therapy event has taken place through a check on the system to see if there has been any action or "event" that could have an impact on the therapy of the patient such as, for example, a change in basal rate, start of a temporary basal rate, deliver of a correction bolus, set up of an extended bolus, change of insulin to carbohydrate ratio, insulin sensitivity ratio or in real-time when both the high glucose (BG>BGth) and one of the therapy events has occurred. If such an event occurred during a system check at step 316 then an event counter i is incremented by one and the counter i is set to this new incremented value. The "event" is also recorded in the form of a duration of the therapy event (as measured from a starting time, e.g., at change of the infusion set) and associated with variable Ti, which represents the duration of time between a start time and the current therapy event i. At step 318, the number of event is checked by summing the number of events "i" with the value of the IOB flag and checking against a threshold number of therapy events th, e.g., if i+IOBfiag > Nth then the number of therapy events has exceed the threshold number of therapy events Nth. That is, in step 308, the logic determines if the number of therapy events is greater than a threshold. If step 318 returns a false then the logic returns to step 304 otherwise the logic moves to step 320, in which a time elapsed for a "duration of last Nth therapy events" based on therapy event counter "i" is calculated and compared to the allowed time window At. The "duration of last Nth therapy events" is the difference in elapsed time "ET" between the time duration (in hour or minute) associated with event counter i represented here as Ti and a durational therapeutic value represented as T (i-Nth+i) where the sum of i- Nth +1 allows for a rolling change in the value of the durational threshold as the number of therapy events accumulate. The logic is only concerned with the last Nth events and the time elapsed between the last Nth events. For example assume i=9 or the ninth event. And assume Nth =4. The logic is concerned not with the time for the 9 th event (Tg) but with the time elapsed between the 9 th and 6 th even i - Nth +1, the time between the last Nth events. In other words, instead of fixing the durational threshold to a time duration that occurred at a fixed event counter value, the durational threshold is allowed for a rolling change as the number of therapy events changes.

[0047] Consequently, in step 320, if an elapsed time ET based on a difference of time duration at the current 1 th number of therapy event and the last Nth therapy events (e.g., ET=T; - T;_Nth+i) is less than At then this means that the th number of therapy events took place in less than the allowed time window At and the logic moves to step 322 otherwise if false the logic returns to step 304. To carry out this logic, the system may utilize a look up table, similar to Table 1, to determine the time duration at event counter "i" and the time duration occurring at a counter value equal to i- N t h +1. For example, assuming that th is set to 4 therapy events and if T; at i=7 in Table 1 then the duration for T 7 is 8 hours and a durational threshold T;_Nth+i based on the value of the current therapy event counter i and a therapy threshold Nth can be determined by referencing the value of subscript (by subtracting the value of Nth from the value of the counter "i" and adding one) to derive the correct event number in which to designate the durational threshold. In this case, the reference counter of the durational threshold T;_Nth+i is 7- 4+1 thereby designating the durational threshold Ti-Nth+i as that duration occurring at the fourth therapy event (T 4 ). Hence, from the look up table, the durational threshold T;_ N th+i is now designated as that of 7 hours. Thus, the elapsed time ET is 8-7 = 1 hours, which is less than the allowed exemplary time threshold At of about 3 hours. Consequently, for this example, step 320 would return as true, and the logic moves to step 322 in which a recommendation to change the infusion set is annunciated to the patient. Thereafter in step 324 a query is provided as to whether the patient has actually changed the infusion set so that a timer may reset to zero. If true in query 324 the logic returns to step 302 otherwise the message in step 322 is repeated. Alternatively, the message in step 322 can be repeated a number of times or the patient may disable the message in step 322. To ensure a full understanding of the technical effect from the underlying logic of Figure 3, applicants describe further details of a first example below.

EXAMPLE 1

[0048] In this first example, it is assumed that BG > BGTH, IOB is not greater than zero (IOBfl a g = 0), ATMAX = a maximum in-dwelling time of the infuser (e.g., 3 days); At = 3 hours; and Nth =4 therapy events. The timing for each particular event is show in Table 2.

Table 2

[0049] From Table 2, all therapy events, as counted by event counter i and the duration of each therapy event is referenced to this counter where Ti (Ti, T 2 , T 3 . . . T n ) are measured from a change of the infuser at start time 0. Since the therapy threshold N t h=4, then the logic needs not look at events 1, 2 or 3 that occurred at times Ti, T2 and T 3 respectively. At the fourth event and thereafter where i > 4, Nth =4 and IOBfl ag =0 the logic condition 318 in Figure 3 (i+IOBfi a g > Nth?) will return as TRUE. Therefore the system would need to evaluate the time elapsed between events (logic step 320 in Figure 3) to understand whether there is a need to issue a recommendation to change the infusion set.

[0050] At the fourth event where i=4, the elapsed time between the last N^ therapy event is calculated using T; - T;_ N th+i. Substituting the known values in the previous equation yields T 4 - T 4 _ 4+ i or T 4 -Ti. Looking at Table 2, the system determines the time of the T 4 event (being at the 7 th hour) and a durational threshold based on the current therapy event being associated with that of the first therapy event (Ti at the 3 rd hour). The elapsed time can be derived from the difference between the duration in question for the fourth therapy event at T 4 = 7 hours and a durational threshold set at Ti = 3 hours where 7-3 is 4hrs, which is greater than At. Since the elapsed time between events at the 4 th event T 4 versus the rolling durational threshold T;_Nth+i is greater than the preset window (At) in step 320, no recommendation was made to the patient and the logic moves to step 304 in Fig. 3.

[0051] Upon evaluation of the fifth event (i=5), the system looks for a durational threshold based on the last Nth event. In this case T; is T5, the fifth event recorded at the 7 th hour and a durational threshold based on the current therapy event counter "i" and a therapy threshold Nth is now T;_Nth+i or T 2 , the second event recorded at the 5 th hour. Therefore, the elapsed time between the last therapy event at i= 5 th event and a durational threshold T;_Nth+i is T5-T2 or 7-5= 2 hours which is less than At (3hrs) in step 320, resulting in a recommendation to change infusion set.

[0052] Similarly, when evaluating the sixth therapy event (i=6), the system looks for the duration based on the last therapy event at i=6 and a durational threshold T;_Nth+i based on the therapy counter i=6 and therapy threshold Nth. In particular, the system determines the elapsed time based on T; - T;_ N th+i or T 6 - T 6 - 4 +i or T 6 - T 3 where the difference from the 7 th hour (at the sixth event Te) and a durational threshold (e.g., T;_Nth+i is set to that of the third therapy event T3 at the 6 hour is equal to (7-6=1) one hour, which is less than At (e.g., ~3hrs) at step 320, thereby resulting in yet another recommendation to change the infuser.

[0053] Finally, when evaluating the seventh therapy event (i=7), the system looks for the duration recorded for the therapy event at i=7 (at T 7 ) and a durational threshold based on the current therapy event counter and a therapy threshold associated with the therapy event counter i=7 and therapy threshold Nth=4 (e.g, Ti-Nth+i). In particular, the system determines the elapsed time based on T; - Ti-Nth+i or T 7 - T 7 _ 4+ i or T 7 - T 4 where the difference from the 9 th hour (at the seventh event T 7 ) and a durational threshold (e.g., Ti-Nth+i is set to that of the fourth therapy event T 4 ) at the 6 th hour is equal to (9-6=3) three hours, which is equal to the threshold At (3hrs) in step 320, resulting in a recommendation to change infusion set. It is noted that while exemplary values are used for the variables described herein, these values are not fixed and different values can be utilized to fit the intended use of a system based on the embodiments described herein.

[0054] Applicants note that the use of the rolling durational threshold Ti-Nth+i allows the system to obtain a durational threshold that changes as function of the latest value of the event counter "i", i.e., at therapy event i=4, the durational threshold is set to Ti or first therapy event recorded at the 3 rd hour; at therapy event i=5, the durational threshold is set to T2 or the second event recorded at the 5 th hour, and at therapy event i=6, the durational threshold is set to the third therapy event T3 recorded at the 6 th hour. In other words, while the durational threshold is set to a fixed number of therapy events from the current therapy event, the number of hours associated with the durational threshold or the therapy event may vary without a fixed relationship. This variation in the number of hours between the durational threshold for therapy events (Ti-Nth+i) from the current therapy event (Τ;) is one of the determining factors in reminding the user to change the infusion set.

[0055] In an alternative embodiment, the logic can be set up to evaluate, among other data, the number of therapy events and the time duration between these events. For this embodiment, as long as the number of therapy events is greater than a threshold and the elapsed time between the therapy events in question is less than preset duration, a reminder to change the infusion set would be provided to the user. Specifically, as shown in Figure 4, a discussion of the logic in Figure 3 begins with a recordation of a change to the infusion set in step 302 and the counter i is reset to zero. At step 304, which could occur simultaneously or for a duration after an infusion set change, a blood analyte measurement BG is made. At step 306, this BG value or a value related thereto (e.g., such as an index derived from the measurement) is checked against the upper threshold BGTH- If the BG value is less than or equal to BGTH then the logic flows to step 308. In step 308, if time differential between the current time and the time at which the infusion set was changed (at step 302) is less than or equal to the ΔΤΜΑΧ then the logic returns back to step 304 otherwise if the time differential is greater than ΔΤΜΑΧ then the logic flows to step 322 in which a recommendation for a change in the infusion set is made to the patient.

[0056] Returning to step 306, if the BG value is greater than BGTH then the logic flows to step 310 to determine if the patient has drug in the patient's system (indicated by "IOB") from a recent infusion of drug into the patient's body. If the decision at step 310 returns a false then a flag IOBfi a g is set to zero at step 312 otherwise flag IOB flag is set to 1 at step 314. At step 316, if the system has determined that a therapy event has taken place through a check on the system to see if there has been any action or "event" that could have an impact on the therapy of the patient such as, for example, a change in basal rate, start of a temporary basal rate, deliver of a correction bolus, set up of an extended bolus, change of insulin to carbohydrate ration or insulin sensitivity ratio. If such an event occurred during a system check at step 316 then an event counter i is incremented by one and the counter i is set to this new incremented value. The "event" is also recorded in the form of a duration of the therapy event (as measured from a starting time, e.g., at change of the infusion set) and associated with variable T;, which represents the duration of time between a start time and the current therapy event i. In step 319, a difference between the number of therapy events ΔΝ is determined based on the current therapy event "i" and a prior "n" therapy event. In the preferred embodiments, ΔΝ = i-n+1. Where ΔΝ is greater than or equal to the threshold number of therapy events Nth, the logic returns a true and moves to step 321. Where ΔΝ is less than the threshold Nth, the logic returns a false and moves to step 308. Assuming that ΔΝ is greater than or equal to Nth, the logic moves to step 321 in which an elapsed time ET between the duration of the current therapy at T; (from starting time To) and the duration of prior therapy (from starting time To) at T n is determined. If the elapsed time (T; - T n ) is less than Δί, the logic moves step 322 in which a recommendation to change the infusion set is annunciated to the patient. Thereafter in step 324 a query is provided as to whether the patient has actually changed the infusion set so that a timer may reset to zero. If true in query 324 the logic returns to step 302 otherwise the message in step 322 is repeated. Alternatively, the message in step 322 can be repeated a number of times or the patient may disable the message in step 322. Applicants note that this embodiment allows for a reminder to change the infusion set whenever (a) BG is greater than a threshold; (b) the difference in the number of therapy events ΔΝ is greater than a preset threshold Nth; and (c) an elapsed time ET between therapy events is less than At. To ensure a complete understanding of the technical effect from the underlying logic of Figure 4, applicants describe details of a second example below.

EXAMPLE 2

[0057] For the entire time in this Example 2, which utilizes the logic of Figure 4, it is assumed that BG > BGTH, It is also assumed that elapsed time ET = Ti-T n is not greater than the preset time window (ET < At) and IOB is not greater than zero (i.e., no drug on board or IOBfi a g = 0) when BG collected from the SMBG or CGMS crosses BG T H, at which point the logic in Figure 4 moves to step 310. The events corresponding to the time slots are provided in Table 3. It is noted that ET=T;-T n is the elapsed time between i th and the prior η Λ event; AN=i- n+1 are the number of events between the i th and n th event; and AN> N th and ET < At then the logic would notify the user for an infusion set change. With the above in mind, we turn to Table 3 and the various scenarios presented below in relation to Table 3.

Table 3

[0058] Events 2 and 1. Referring to Table 3 and Figure 3, step 319, for event 1 and event 2 where AN= n-i +1= 2-1+1 = 2 is not greater or equal to th (where N th =4) resulting in step 319 returning a false. Hence, there is no reminder for the infusion set change in Figure 4 for this instance. [0059] Events 3 and 1. For event 3 and event 1 where ΔΝ= n-i +1 = 3- 1+1 = 3 is not greater or equal to Nth (where N t h=4) and ET= T 3 - Ti< At resulting in step 319 returning a false. Hence, there is no reminder for the infusion set change in Figure 4 for this instance.

[0060] Events 4 and 1. For event 4 and event 1 in step 319 where ΔΝ= n-i +1 = 4-1+1 = 4 is not greater than but it is equal to th (where Nth=4) which returns a true leading to step 321 where ET = T 4 - Ti< At so an infusion change is recommended in step 322.

[0061] Events 9 and 5. For event 9 and event 5 where ΔΝ=η-ί +1 = 9-5+1 = 5 is greater than Nth (where Nth=4) which returns a true leading to step 321 where ET = T9- Ts< At so an infusion set change is recommended in step 322.

[0062] Where a user is primarily (or exclusively) using an episodic blood glucose monitor (e.g., BG meter), a rolling time window may be used in which the logic may look at a time interval (e.g., 4 hours) prior to a recorded glucose measurement. If the number of events is not sufficient for the logic to trigger a reminder, the logic may look at another time interval (e.g., 4 hours) after the recorded measurement. In both of these windows (one window prior to the recorded glucose measurement and one window after the recorded glucose measurement), if the number of events is met as provided in the logic described herein, the reminder is activated to remind the user to replace the infuser. It is noted that in this embodiment, step 306 may not be necessary because the system is looking for therapy events in the first or second time windows to make its determination rather than whether the glucose concentration is greater than a certain threshold. However, step 306 may still be utilized as a high glucose measurement for a user on insulin could indicate that the user is undergoing some event that may need to be checked by reviewing the number of therapy events within a desired time window.

[0063] Where a user is using primarily (or even exclusively) a CGM sensor, which typically measures the glucose level of the user every five (5) minutes, an alternative embodiment is provided in Figure 5. Applicants believe that in applications where many glucose measurements are made over a short time interval such as in CGMS application, this may cause the total number of therapy events to be greater than the threshold N t h and then remain greater than th until the infusion set is changed which could cause the infusion set change reminder to be inactive. In such application, steps 303, 307, 309, 31 1, and 313 may be added to the logic of Figure 3, which for clarity, is provided as Figure 5. In this embodiment, a counter X is set up to keep track of the number of measurements made that are less than or equal to the glucose threshold BGth and under the time limit AT max . Specifically, whenever the infusion set is changed, the counter X is reset to zero at step 303. Where the measurement is less than or equal to BG t h at step 306 and the timer interval is less than AT max at step 308, a counter at step 309 is set up to increment by one. At step 311, the system checks to see if the number of blood measurements is equal to greater than a threshold X t h. If true, then the logic moves to step 313 to reset the counter i to zero whereas if false, the logic returns to step 304. Where the CGM sensor is obtaining a measurement about every 5 minutes, the threshold X t h can be set to 12 so that about an hour (or any desired time interval) may be allowed to elapse as long as the blood glucose value is below a set threshold and the time interval is within time limit ATmax. By virtue of this arrangement, once the glucose level returns to a level below BG t h and remains below BGth for a predetermined time (as set by X and Xth), the event counter is reset to zero so that the number of therapy events does not become greater than threshold th. In the preferred embodiments, the threshold Xth can be about 12.

[0064] Although Figures 3 and 4 are shown separately to distinguish between steps 318 and 320 of Figure 3 and steps 319 and 321 of Figure 4, the steps of Figures 3 and 4 can be combined together into a single flow chart where step 319 follows step 318 and step 321 follows step 320. Alternatively, Figures 4 and 5 may be combinable together into a single flow chart in which step 303 (Fig. 5) follows step 302 (Fig. 4); steps 309, 311, 313 (Fig. 5) follows step 308 (Fig.4) steps 319 (Fig. 4) follows step 318 (Fig. 5), step 321 (Fig. 4) follows step 320 (Fig. 5).

[0065] As shown and described herein, applicants have discovered a method to allow users or others to know when to change an infuser set. The method described herein may be utilized in the system described in relation to Figures 1, 3-5. In this method, certain events are recorded once it has been determined that a certain analyte threshold (BGth) has been breached. The recording of events allows the system carrying out the method to determine the number of events and the timing of events. From the timing of event the system can calculate the elapsed time between events. Using both the number of events and the time elapsed between the maximum allowable events (Nth) the system can determine whether to issue a recommendation. In particular, the method can be achieved by: conducting an analyte measurement of a physiological fluid of a user (e.g., step 304) via an analyte strip measurement or via a continuous analyte measurement; determining whether a value related to an analyte measurement (e.g., the measurement of the analyte or an index derived from the analyte measurement) is greater than an analyte threshold (BG th ) (e.g., step 306); in the event the determining step is true, querying whether an elapsed time between a duration of a current therapy event from a starting point (Τ;) and the durational threshold (Ti-Nth+i ) is less than a preset time window interval (At) (e.g., step 320); and in the event the querying step is true, annunciating a reminder to replace the infuser to the user(s) (e.g., step 322). In a variation of this method, additional steps may be provided in evaluating whether the user has previously infused drug to the user subsequent to the determining step (e.g., step 310); and in the event the evaluating step is true, setting a drug on board flag as equal to one ((e.g., step 314) otherwise setting the drug on board flag as equal to zero (e.g., step 312). Another step that may be provided for this method may include recording a number of event (i) and time (Ti) of occurrence of event constituting a dosing adjustment (e.g., step 316). Applicants note that since the numbers of events is preferably always recorded once BG > BG th , and once the Nth +1 event happens, logic test in step 306 is always TRUE even if the patient has returned to normal glycemia in the mean time. Other steps that may be included are: inquiring whether a sum of the number of events and the value of the drug on board flag is greater than the therapy adjustment threshold ( th ) (e.g., step 318); and in the event the inquiring step returns a true then performing the querying step. Another step that may be included is recording a change of the infuser by the user (e.g., step 324). Yet another step may be annunciating to the user a reminder to replace the infuser whenever a time period greater than maximum site duration (ΔΤΜΑΧ) (e.g., steps 308 and 322). In this method, the preset time window interval (At) may be of any value based on the professional judgment of the health care provider but for the described embodiments, about 3 hours; the therapy adjustment threshold (N th ) may be of any value based on the professional judgment of the health care provider but for the described embodiments, about four adjustments; the maximum site duration may be of any value based on the professional judgment of the health care provider but for the described embodiments, about three (3) days; the analyte threshold (BG th ) may include any threshold based on the professional judgment of the health care provider but for the described embodiments, a threshold of aboutl80 mg of glucose per deciliter of blood. [0066] An alternative method of reminding users to change a drug infuser connected to a drug delivery device is also provided by applicants. The method may be achieved by: conducting an analyte measurement of a physiological fluid of a user; determining whether a value related to the analyte measurement (BG) is greater than an analyte threshold (BG t h); in the event the determining step is false, querying as to whether a total duration (Tj-To) of infuser being installed to the drug delivery device is greater than a maximum duration (ΔΤ ΜΑΧ ) and if true, annunciating a reminder to replace the infuser; in the event the determining step is true, inquiring as to whether drug was previously infused and it is pharmacologically active (IOB) and if true, setting a drug on board flag as equal to one otherwise setting the drug on board flag as equal to zero; recording a number of therapy adjustment event (i) and a time associated with such therapy adjustment event (T;); investigating whether a sum of the number of therapy adjustment event (i) and a value of the drug on board flag (IOBfl ag ) is greater than a therapy adjustment threshold (Nth); hi case the investigating returns a true then querying whether a duration between a last Nth therapy event is less than a preset time window interval (At); and in the event the querying step is true, annunciating a reminder to replace the infuser. The method may further include the steps of evaluating whether the user has previously infused drug to the user prior to the starting step; and in the event the evaluating step is true, setting a drug on board flag to one. Another step may include annunciating to the user a reminder to replace the infuser whenever a time period greater than a maximum duration is exceeded. A further step may include incrementing an event number (i) whenever the determining step of the analyte is true and referencing a time to the event number. Yet another step may include determining whether a sum of the drug on board (IOB) and the number of drug therapy event (i) is greater than a preset event threshold. Additionally, another step may include recording a change of the infuser by the user. Also, in this method, the maximum in-dwelling duration (ΔΤ ΜΑΧ ) may be about three days; and the preset time window interval (At) may be about four hours.

[0067] In particular, the drug infusion system may have an analyte sensor (112 or 114), an infuser 106, a drug delivery device 102, and controller in one of devices 102, 104, or 114. The analyte sensor (which may be a CG sensor 112 or an analyte meter 114) is configured to sense analyte in physiological fluid of a user and provides signals representative of the quantity of analyte in the fluid. The infuser is disposed on a body surface of the user with the infuser having an infusion line for delivery of fluid therethrough. The drug delivery device is configured to deliver a drug to the user through the infusion line. The drug delivery device is controlled based upon control signals provided to a controller. The controller is configured to receive the signals of the sensor (which could be either a SMBG or CGMS or both) and provide control signals to the drug delivery device. In an alternative embodiment, the controller is configured to operate with the drug delivery device to simulate as closely as possible to the pancreas (e.g., an artificial pancreas system). The controller is further configured to annunciate a reminder to replace the infuser whenever the signal representative of the analyte amount is greater than a predetermined value and elapsed time between a duration of a current therapy event from a starting point (Τ;) and a durational threshold based on the current therapy event counter and a therapy threshold (Ti-Nth+i) is less than a preset time window interval (At). The therapy events may include, for example, a drug dosing (oral or intravenous), change in therapy regimen, and change in physiological parameters of the patient. In this system, the analyte sensor may be a continuous analyte sensor in wireless communication with the controller; the drug delivery device comprises a drug delivery device in wireless communication with the controller; or the analyte sensor may be an episodic analyte monitor and at least one analyte sensing test strip. The CG sensor 1 12 or the meter 114 (and associated analyte test strips 115) may provide its signals representative of the analyte (e.g., analyte) to either the controller 104 or the delivery device 102 via a wired or a wireless connection. The drug delivery device 102 may also be connected to the controller 104 via a wired or a wireless connection thereto.

[0068] While the invention has been described in terms of particular variations and illustrative figures, those of ordinary skill in the art will recognize that the invention is not limited to the variations or figures described. In addition, where methods and steps described above indicate certain events occurring in certain order, those of ordinary skill in the art will recognize that the ordering of certain steps may be modified and that such modifications are in accordance with the variations of the invention. Additionally, certain of the steps may be performed concurrently in a parallel process when possible, as well as performed sequentially as described above. Therefore, to the extent there are variations of the invention, which are within the spirit of the disclosure or equivalent to the inventions found in the claims, it is the intent that this patent will cover those variations as well.