WO2021170641A1

WO2021170641A1 - Add-on dose logging device with dose guidance functionality

Info

Publication number: WO2021170641A1
Application number: PCT/EP2021/054539
Authority: WO
Inventors: Blake Matsuzaki
Original assignee: Novo Nordisk A/S
Priority date: 2020-02-25
Filing date: 2021-02-24
Publication date: 2021-09-02

Abstract

An add-on device for mounting on a drug delivery device, the add-on device comprising sensor means adapted to measure a property indicative of the amount of drug expelled from the drug delivery device, a display, and processor means and associated memory adapted to store in the memory expelled dose amount values and blood glucose (BG) values based on received BG data. The memory comprises instructions that, when executed by the processor means, calculate a dose recommendation value based on stored dose and BG log data, and control the display to communicate to a user a BG value and a calculated dose recommendation value based thereon.

Description

ADD-ON DOSE LOGGING DEVICE WITH DOSE GUIDANCE FUNCTIONALITY

The present invention generally relates to systems and devices adapted to provide dose rec ommendations (dose guidance) based on dose and blood glucose data for a subject in treat ment for a diabetic condition.

BACKGROUND OF THE INVENTION

In the disclosure of the present invention reference is mostly made to the treatment of diabetes by delivery of insulin, however, this is only an exemplary field of use for the present invention.

It has been estimated that around 422 million adults worldwide were living with diabetes in 2014, representing an increase in prevalence of 3.8% from 1980 in the adult population. The majority of these cases represent type 2 diabetes (T2D) and reflect the increased prevalence of risk factors, which include an aging population, the current obesity epidemic, and lifestyle factors such as an unhealthy diet, physical inactivity, and smoking. Patients with T2D have an increased risk of cardiovascular and cerebrovascular morbidity and mortality, as well as other diabetes-associated complications such as visual impairment, renal failure, and lower-limb am putations. Achieving and maintaining glycemic control reduces the long-term risk of microvas- cular complications, however, despite the availability of detailed management guidelines and a wide range of treatment options, almost half of patients with diabetes in the USA fail to achieve adequate glycemic control, defined by a glycated hemoglobin A1c (HbAi_c) level < 7%.

T2D is a progressive disease; as b-cell function declines, escalation of treatment with oral anti diabetes drugs (OADs) becomes less effective, and ultimately insulin therapy becomes a major means of controlling hyperglycemia.

Data from clinical studies evaluating the safety and efficacy of basal insulins in insulin-naive patients provides the basis for recommendations regarding treatment initiation and titration. Key head-to-head studies of insulin initiation vary in terms of treatment goals and schedules. In addition to clinical trials, a number of studies have been performed to evaluate different basal insulin algorithms, with varying numbers of steps, different step sizes (i.e. , magnitude of increase or decrease in insulin dose), and different titration frequencies, ranging from daily to weekly. Considering the data altogether, most trials used a basal insulin starting dose of 10 U/day, with the majority using an FPG (fasting plasma glucose) target of approximately 100 mg/dL. Most algorithms used weekly or 3-day dose adjustments and titrated insulin on the basis of a mean value from more than one and generally two to three FPG levels over the previous days. Insulin dose steps varied, with some studies using simple 2-U steps and others smaller or larger steps based on blood glucose levels [Advances in Therapy volume 36, pages 1031-1051(2019)].

As an example, one type of initial insulin therapy for Type 2 diabetics is to use once-daily injections with a long-acting insulin such as Levemir® from Novo Nordisk, often in combination with oral antidiabetic agents. However, to be successful, insulin therapy requires timely and appropriate titration of dosages. For example, in combination with oral antidiabetic agents it is recommended to initiate Levemir® treatment with once daily administration at a dose of 10 U or 0.1-0.2 U/kg. The dose of Levemir® should then be titrated based on individual patients' needs, e.g. based on average (3-7 measurements) self-measured pre-breakfast blood glucose (BG) values. For example, for a calculated value of >10.0 mmol/L it is recommended to adjust the Levemir® dose with +8 units, for a calculated value of 9.1-10.0 mmol/L it is recommended to adjust the Levemir® dose with +6 units, for a calculated value of 8.1-9.0 mmol/L it is recom mended to adjust the Levemir® dose with +4 units, for a calculated value of 7.1-8.0 mmol/L it is recommended to adjust the Levemir® dose with +2 units, and for a calculated value of 6.1- 7.0 mmol/L it is recommended to adjust the Levemir® dose with +2 units. If one BG measure ment is 3.1-4.0 mmol/L it is recommended to adjust the Levemir® dose with -2 units, and if one BG measurement is <3.1 mmol/L it is recommended to adjust the Levemir® dose with -4 units. The calculation of the average pre-breakfast BG values as well as the resulting Levemir® dose adjustments may either be performed by the patient him/herself or by a doctor/nurse based on BG values supplied by the patient. As appears, such a regimen is both time-consum ing as well as prone to mistakes. This said, self-titration regimens are considered to facilitate empowerment of patients, allowing them to become more involved in their treatment which may then result in improved glycaemic control.

Although plasma glucose values are about 11% higher than those of whole blood glucose values when the hematocrit is normal, the term “blood glucose” is often used as a general term.

Correspondingly, devices and systems have been provided in which recommendations are generated based on self-measured BG values by a pre-programmed algorithm, e.g. corre sponding to the relatively simple titration regimen described above. Indeed, much more so phisticated algorithms can be implemented taking into account e.g. patient characteristics and other variable inputs, see e.g. US 2009/0253970. The algorithm may be in the form of software adapted to run on different platforms, e.g. PC, PDA or smartphone, or it may be impeded in a device such as a blood glucose meter (BGM), see e.g. US 2010/0016700. WO 2010/098931 discloses a drug delivery pen provided with a processor and an accelerometer whereby use of the pen can be detected, the information being used to guide a patient to use the pen correctly. WO 2005/046559 discloses a system adapted to detect and store information relating to use of drug delivery pen.

WO 2014/111337 discloses an add-on device for mounting on a pen drug delivery device which may be provided with sensors enabling the device to determine the size of delivered insulin doses as well as the latest BGM reading of the patient’s blood. The add-on device may be adapted to display or transmit stored log data. Together with logged data additional data such as a medical practitioner’s name a recommended amount of dose to be administered may be stored.

US 2016/0000998 discloses a glucagon administration system comprising a controller device controlling operation of a glucagon pump. The controller may be adapted to receive blood glucose values from an external glucose monitoring device. Based on available data patient data, e.g. blood glucose data, the controller is adapted to calculate a recommended dose of glucagon to be infused.

Although such automatically generated recommendations may be of great help to both medical staff and patients, the recommendations may be wrong if they are based on incorrect assump tions, especially that the patient follows the regimen as prescribed.

Having regard to the above, it is an object of the present invention to provide systems, devices and methods supporting cost-effective optimization and control of patient self-titration of a medical regimen. It is a further object of the invention to provide systems, devices and methods supporting cost-effective and user-friendly calculation of meal-related bolus dose amounts.

DISCLOSURE OF THE INVENTION

In the disclosure of the present invention, embodiments and aspects will be described which will address one or more of the above objects or which will address objects apparent from the below disclosure as well as from the description of exemplary embodiments.

Today the traditional standard of care is to have a BGM device and an injection device for treatment of diabetes. These two different devices from two different manufactures are not intended to work together. Blood glucose levels (BGLs) and dose amounts should be associ ated with one another to provide meaning to the user and provide the health care professional (HCP) insight to better treatments. Device-to-device information sharing becomes a techno logical and usability challenge. For example, handling two different devices creates more user steps and inconvenience. Currently there are no good logging systems that associate BGLs with injection amounts. User studies have shown that patients do not see value in logging injections. Patient really care about blood glucose levels. Injection amounts are not an indica tion of how well a patient is doing. BGLs equal results, injections do not.

Dose guidance may be useful for e.g. users new to insulin. It is necessary to build up to the optimal dose amount in a controlled regimen to reduce dangerous hypoglycaemic events. This is often referred to as titrating. Current options for dose guidance require several different de vices or system to share information and add to the complexity to the treatment of diabetes e.g. injection device, BGM or CGM device, a user interface and information processor, e.g. mobile phone app and/or cloud server with imbedded algorithms. All of these devices are sep arate and often made by different companies. Device-to-device information sharing becomes a technological and usability challenge. Not having control over all systems can lead to serious patient safety events when providing dose guidance. Have to rely on multiple devices and systems to receive dose guidance. It is difficult to digitally share the data between devices and systems.

Thus, based on the above analysis and considerations the present inventors have realized that just because data and information are available it does not in the real world provide patients with a solution to the problem of providing dose guidance in a form and configuration that will actually be used. Correspondingly, having identified this root course to the problem of making dose guidance not just theoretically available but also an attractive and easy to use possibility, the present invention provides an integrated device which brings together all the necessary components in an integrated and easy-to-use configuration.

Thus, in a first aspect of the invention an add-on device adapted to be releasably mounted on a drug delivery device is provided, the drug delivery device comprising a housing, a rug-filled cartridge or means for receiving a drug-filled cartridge, and drug expelling means comprising dose setting means allowing a user to set a dose amount of drug to be expelled, as well as release means actuatable to allow the drug expelling means to expel a set dose amount. The add-on device comprises an add-on housing adapted to be releasably attached to the drug delivery device housing, first sensor means adapted to measure a property of the drug expel ling means indicative of the amount of expelled drug, a display, and processor means and associated memory. The processor means and associated memory are adapted to store in the memory expelled dose amount values based on data received from the first sensor means, thereby creating a dose log comprising a plurality of determined dose amount values and as sociated time stamps, and store in the memory blood glucose (BG) values based on received BG data, thereby creating a BG log comprising a plurality of BG values and associated time stamps. The memory comprises instructions that, when executed by the processor means, calculate a dose recommendation value based on stored dose log data and BG log data, and control the user communication means to communicate to a user a BG value and a calculated dose recommendation value based thereon.

By the above arrangement a cost-effective and user-friendly add-on device for a drug delivery device is provided assuring to a high degree that data relevant for calculation of recommended dose amounts of drugs is collected and used in an optimal way.

More specifically, the incorporation of a BGM in an add-on device (and/or adaptation for re ceiving CGM data) reduces components and user steps and associate injections and BGLs providing an incentive to use and meaning to the user and thus eliminates or reduces need to communicate digital information between multiple devices and systems. Further, by displaying recommended dose amounts directly and in the immediate vicinity of the drug delivery device dose setting means (e.g. a pen dose dial), a strong incentive to use the recommendation is provided. Correspondingly, displaying a recommended dose size next to the actual means for setting a given dose (e.g. the pen dose dial in combination with the scale drum dose size indicator window) reduces the risk of errors and mistakes when setting the recommended dose.

In an exemplary embodiment the add-on device comprises second sensor means adapted to receive a blood sample and measure a property indicative of a blood glucose (BG) value for the blood sample, i.e. a BGM. The processor means is adapted to determine and store in the memory BG values based on data received from the second sensor means.

The processor means may be adapted to determine a most-recent BG value from a received blood sample and control the display to display the most-recent BG value. When it is deter mined, based on pre-set conditions stored in memory, that the user is in need for receiving an amount of drug: calculate and control the display to display a dose recommendation value based on BG log data and dose log data. The pre-set conditions could be in the form of time- slots, e.g. a morning time slot for a titration regimen or mealtime slots for calculation of a bolus amount. The pre-set conditions could also specify unscheduled activities, e.g. reminders in case a given event is not detected such as a titration dose in the morning or a meal dose at a mealtime, or BG values outside a given pre-defined range. In this way the user will automati cally be presented to dose recommendations when needed, the add-on device serving as a BGM for the remaining time.

Alternatively or in addition, the add-on device may comprise wireless receiver means adap ted to receive BG data (e.g. from an external CGM device), the processor means being adapted to store in the memory BG values based on the received BG data. The processor means may be adapted to display the most-recent BG value to display recent BG values as a function of time. When it is determined, based on pre-set conditions stored in memory, that the user is in need for receiving an amount of drug, the processor is adapted to calculate and control the display to display a dose recommendation value based on BG log data and dose log data. The pre-set conditions may correspond to the above-described conditions. Addition ally, the pre-set conditions could be based on trend analysis of received BG data.

In a specific embodiment the add-on device comprises a motorized drive mechanism adapted to engage the drug delivery device dose setting means, wherein the processor means is adapted to control the motorized drive mechanism corresponding to a calculated or an adjusted calculated dose recommendation.

The drug expelling means in the drug delivery device on which the add-on device is adapted to be mounted, may comprise an indicator adapted to rotate during expelling of a dose amount, the amount of rotation being indicative of the size of the expelled dose amount. Correspond ingly, the first sensor means may be operatable to detect the amount of rotation of the indicator during expelling of a dose amount.

In a second aspect of the invention an assembly comprising a drug delivery device as de scribed above and an add-on device as described above is provided. In such an assembly the drug expelling means may comprise an indicator adapted to rotate during expelling of a dose amount, the amount of rotation being indicative of the size of the expelled dose amount, the indicator comprising one or more dipole magnets. Correspondingly, the first sensor means comprises one or more magnetometers adapted to determine magnetic field values from the one or more dipole magnets, and the processor means is configured to determine on the basis of measured values from the plurality of magnetometers a rotational position and/or a rotational movement of the indicator. In a further aspect of the invention a unitary drug delivery device is provided, comprising a drug-filled cartridge or means for receiving a drug drug-filled cartridge, drug expelling means comprising dose setting means allowing a user to set a dose amount of drug to be expelled, and release means actuatable to allow the drug expelling means to expel a set dose amount, first sensor means adapted to measure a property of the drug expelling means indicative of the amount of expelled drug, a display, as well as processor means and associated memory. The processor means and associated memory is adapted to store in the memory expelled dose amount values based on data received from the first sensor means, thereby creating a dose log comprising a plurality of determined dose amount values and associated time stamps, and store in the memory blood glucose (BG) values based on received BG data, thereby cre ating a BG log comprising a plurality of BG values and associated time stamps. The memory comprises instructions that, when executed by the processor means, calculate a dose recom mendation value based on stored dose and BG log data, and control the display to communi cate to a user a BG value and a calculated dose recommendation value based thereon.

The unitary device may be provided with wireless receiver means adapted to receive BG data, or it may comprise second sensor means adapted to receive a blood sample and measure a property indicative of a BG value for the blood sample, the processor means being adapted to determine and store in the memory BG values based on data received from the second sensor means.

In exemplary embodiments, the unitary device may comprise the same further features as described above for the add-on embodiment of the invention.

When it is defined that the processor means is adapted to provide a given functionality, this includes set-ups in which the actual instructions for performing the functionality are stored in the memory and subsequently executed by the processor means.

In a specific embodiment the unitary device comprises a motorized drive mechanism, wherein the processor means is adapted to control the motorized drive mechanism corresponding to a calculated or an adjusted calculated dose recommendation.

In an exemplary embodiment the drug expelling means comprises an indicator adapted to rotate during expelling of a dose amount, the amount of rotation being indicative of the size of the expelled dose amount, wherein the first sensor means is operatable to detect the amount of rotation of the indicator during expelling of a dose amount. As used herein, the term "insulin" is meant to encompass any drug-containing flowable medi cine capable of being passed through a delivery means such as a cannula or hollow needle in a controlled manner, such as a liquid, solution, gel or fine suspension, and which has a blood glucose controlling effect, e.g. human insulin and analogues thereof as well as non-insulins such as GLP-1 and analogues thereof. In the description of the exemplary embodiments ref erence will be made to the use of insulin.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following the invention will be further described with reference to the drawings, wherein fig. 1A shows a pen device, fig. 1B shows the pen device of fig. 1A with the pen cap removed, fig. 2 shows in an exploded view the components of the pen device of fig. 1A, figs. 3A and 3B show in sectional views an expelling mechanism in two states, figs. 4A and 4B respectively show an exemplary drug delivery device and a corresponding add-on device adapted to be mounted thereon, figs. 5A and 5B respectively show an exemplary drug delivery device and a corresponding add-on dose recommendation device adapted to be mounted thereon, figs. 6A-6G show a series of display screen shots corresponding to an exemplary use of the add-on dose recommendation device of figs. 5A and 5B, and fig. 7 shows an exemplary combined recommendation and motorized drug delivery device.

In the figures like structures are mainly identified by like reference numerals.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

When in the following terms such as “upper” and “lower”, “right” and “left”, “horizontal” and “vertical” or similar relative expressions are used, these only refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only. When the term member or element is used for a given component it generally indicates that in the described embodiment the component is a unitary component, however, the same member or element may alternatively comprise a number of sub-components just as two or more of the described components could be provided as unitary components, e.g. manufactured as a single injection moulded part. The term “as sembly” does not imply that the described components necessarily can be assembled to provide a unitary or functional assembly during a given assembly procedure but is merely used to describe components grouped together as being functionally more closely related.

Before turning to embodiments of the present invention perse, an example of a prefilled drug delivery and a logging device adapted to be mounted thereon will be described, such devices providing the basis for the exemplary embodiments of the present invention. Although the pen- formed drug delivery device 100 shown in figs. 1-3 may represent a “generic” drug delivery device, the actually shown device is a FlexTouch® prefilled drug delivery pen as manufactured and sold by Novo Nordisk A/S, Bagsvasrd, Denmark.

The pen device 100 comprises a cap part 107 and a main part having a proximal body or drive assembly portion with a housing 101 in which a drug expelling mechanism is arranged or inte grated, and a distal cartridge holder portion in which a drug-filled transparent cartridge 113 with a distal needle-penetrable septum is arranged and retained in place by a non-removable cartridge holder attached to the proximal portion, the cartridge holder having openings allowing a portion of the cartridge to be inspected as well as distal coupling means 115 allowing a needle assembly to be releasably mounted. The cartridge is provided with a piston driven by a piston rod forming part of the expelling mechanism and may for example contain an insulin, GLP-1 or growth hormone formulation. A proximally arranged rotatable dose setting member 180 with a number of axially oriented grooves 188 serves to manually set a desired dose of drug shown in display window 102 and which can then be expelled when the button 190 is actuated. The dose setting member 180 has a generally cylindrical outer surface (i.e. the dose setting member may be slightly tapered) which in the shown embodiment is textured by com prising a plurality of axially oriented fine grooves to improve finger grip during dose setting. The window is in the form of an opening in the housing surrounded by a chamfered edge portion 109 and a dose pointer 109P, the window allowing a portion of a helically rotatable indicator member 170 (scale drum) to be observed. Depending on the type of expelling mech anism embodied in the drug delivery device, the expelling mechanism may comprise a spring as in the shown embodiment which is strained during dose setting and then released to drive the piston rod when the release button is actuated. Alternatively the expelling mechanism may be fully manual in which case the dose member and the actuation button move proximally during dose setting corresponding to the set dose size, and then is moved distally by the user to expel the set dose, e.g. as in a FlexPen® manufactured and sold by Novo Nordisk A/S.

Although fig. 1 shows a drug delivery device of the prefilled type, i.e. it is supplied with a pre mounted cartridge and is to be discarded when the cartridge has been emptied, in alternative embodiments the drug delivery device may be designed to allow a loaded cartridge to be re placed, e.g. in the form of a “rear-loaded” drug delivery device in which the cartridge holder is adapted to be removed from the device main portion, or alternatively in the form of a “front- loaded” device in which a cartridge is inserted through a distal opening in the cartridge holder which is non-removable attached to the main part of the device.

As the invention relates to electronic circuitry adapted to interact with a drug delivery device, an exemplary embodiment of such a device will be described for better understanding of the invention.

Fig. 2 shows an exploded view of the pen-formed drug delivery device 100 shown in fig. 1. More specifically, the pen comprises a tubular housing 101 with a window opening 102 and onto which a cartridge holder 110 is fixedly mounted, a drug-filled cartridge 113 being arranged in the cartridge holder. The cartridge holder is provided with distal coupling means 115 allowing a needle assembly 116 to be releasable mounted, proximal coupling means in the form of two opposed protrusions 111 allowing a cap 107 to be releasable mounted covering the cartridge holder and a mounted needle assembly, as well as a protrusion 112 preventing the pen from rolling on e.g. a table top. In the housing distal end a nut element 125 is fixedly mounted, the nut element comprising a central threaded bore 126, and in the housing proximal end a spring base member 108 with a central opening is fixedly mounted. A drive system comprises a threaded piston rod 120 having two opposed longitudinal grooves and being received in the nut element threaded bore, a ring-formed piston rod drive element 130 rotationally arranged in the housing, and a ring-formed clutch element 140 which is in rotational engagement with the drive element (see below), the engagement allowing axial movement of the clutch element. The clutch element is provided with outer spline elements 141 adapted to engage correspond ing splines 104 (see fig. 3B) on the housing inner surface, this allowing the clutch element to be moved between a rotationally locked proximal position, in which the splines are in engage ment, and a rotationally free distal position in which the splines are out of engagement. As just mentioned, in both positions the clutch element is rotationally locked to the drive element. The drive element comprises a central bore with two opposed protrusions 131 in engagement with the grooves on the piston rod whereby rotation of the drive element results in rotation and thereby distal axial movement of the piston rod due to the threaded engagement between the piston rod and the nut element. The drive element further comprises a pair of opposed circum ferentially extending flexible ratchet arms 135 adapted to engage corresponding ratchet teeth 105 arranged on the housing inner surface. The drive element and the clutch element comprise cooperating coupling structures rotationally locking them together but allowing the clutch element to be moved axially, this allowing the clutch element to be moved axially to its distal position in which it is allowed to rotate, thereby transmitting rotational movement from the dial system (see below) to the drive system. The interaction between the clutch element, the drive element and the housing will be shown and described in greater detail with reference to figs. 3A and 3B.

On the piston rod an end-of-content (EOC) member 128 is threadedly mounted and on the distal end a washer 127 is rotationally mounted. The EOC member comprises a pair of op posed radial projections 129 for engagement with the reset tube (see below).

The dial system comprises a ratchet tube 150, a reset tube 160, a scale drum 170 with an outer helically arranged pattern forming a row of dose indicia, a user-operated dial member 180 for setting a dose of drug to be expelled, a release button 190 and a torque spring 155 (see fig. 3). The dial member is provided with a circumferential inner teeth structure 181 en gaging a number of corresponding outer teeth 161 arranged on the reset tube, this providing a dial coupling which is in an engaged state when the reset tube is in a proximal position during dose setting and in a disengaged state when the reset tube is moved distally during expelling of a dose. The reset tube is mounted axially locked inside the ratchet tube but is allowed to rotate a few degrees (see below). The reset tube comprises on its inner surface two opposed longitudinal grooves 169 adapted to engage the radial projections 129 of the EOC member, whereby the EOC can be rotated by the reset tube but is allowed to move axially. The clutch element is mounted axially locked on the outer distal end portion of the ratchet tube 150, this providing that the ratchet tube can be moved axially in and out of rotational engagement with the housing via the clutch element. The dial member 180 is mounted axially locked but rota tionally free on the housing proximal end, the dial ring being under normal operation rotationally locked to the reset tube (see below), whereby rotation of the dial ring results in a corresponding rotation of the reset tube 160 and thereby the ratchet tube. The release button 190 is axially locked to the reset tube but is free to rotate. A return spring 195 provides a proximally directed force on the button and the thereto mounted reset tube. The scale drum 170 is arranged in the circumferential space between the ratchet tube and the housing, the drum being rotationally locked to the ratchet tube via cooperating longitudinal splines 151 , 171 and being in rotational threaded engagement with the inner surface of the housing via cooperating thread structures 103, 173, whereby the row of numerals passes the window opening 102 in the housing when the drum is rotated relative to the housing by the ratchet tube. The torque spring is arranged in the circumferential space between the ratchet tube and the reset tube and is at its proximal end secured to the spring base member 108 and at its distal end to the ratchet tube, whereby the spring is strained when the ratchet tube is rotated relative to the housing by rotation of the dial member. A ratchet mechanism with a flexible ratchet arm 152 is provided between the ratchet tube and the clutch element, the latter being provided with an inner circumferential teeth structures 142, each tooth providing a ratchet stop such that the ratchet tube is held in the position to which it is rotated by a user via the reset tube when a dose is set. In order to allow a set dose to be reduced a ratchet release mechanism 162 is provided on the reset tube and acting on the ratchet tube, this allowing a set dose to be reduced by one or more ratchet increments by turning the dial member in the opposite direction, the release mechanism being actuated when the reset tube is rotated the above-described few degrees relative to the ratchet tube.

Having described the different components of the expelling mechanism and their functional relationship, operation of the mechanism will be described next with reference mainly to figs. 3A and 3B.

The pen mechanism can be considered as two interacting systems, a dose system and a dial system, this as described above. During dose setting the dial mechanism rotates and the tor sion spring is loaded. The dose mechanism is locked to the housing and cannot move. When the push button is pushed down, the dose mechanism is released from the housing and due to the engagement to the dial system the torsion spring will now rotate back the dial system to the starting point and rotate the dose system along with it.

The central part of the dose mechanism is the piston rod 120, the actual displacement of the plunger being performed by the piston rod. During dose delivery, the piston rod is rotated by the drive element 130 and due to the threaded interaction with the nut element 125 which is fixed to the housing, the piston rod moves forward in the distal direction. Between the rubber piston and the piston rod, the piston washer 127 is placed which serves as an axial bearing for the rotating piston rod and evens out the pressure on the rubber piston. As the piston rod has a non-circular cross section where the piston rod drive element engages with the piston rod, the drive element is locked rotationally to the piston rod, but free to move along the piston rod axis. Consequently, rotation of the drive element results in a linear forwards movement of the piston. The drive element is provided with small ratchet arms 134 which prevent the drive element from rotating clockwise (seen from the push button end). Due to the engagement with the drive element, the piston rod can thus only move forwards. During dose delivery, the drive element rotates anti-clockwise and the ratchet arms 135 provide the user with small clicks due to the engagement with the ratchet teeth 105, e.g. one click per unit of insulin expelled. Turning to the dial system, the dose is set and reset by turning the dial member 180. When turning the dial, the reset tube 160, the EOC member 128, the ratchet tube 150 and the scale drum 170 all turn with it due to the dial coupling being in the engaged state. As the ratchet tube is connected to the distal end of the torque spring 155, the spring is loaded. During dose set ting, the arm 152 of the ratchet performs a dial click for each unit dialled due to the interaction with the inner teeth structure 142 of the clutch element. In the shown embodiment the clutch element is provided with 24 ratchet stops providing 24 clicks (increments) for a full 360 degrees rotation relative to the housing. The spring is preloaded during assembly which enables the mechanism to deliver both small and large doses within an acceptable speed interval. As the scale drum is rotationally engaged with the ratchet tube, but movable in the axial direction and the scale drum is in threaded engagement with the housing, the scale drum will move in a helical pattern when the dial system is turned, the number corresponding to the set dose being shown in the housing window 102.

The ratchet 152, 142 between the ratchet tube and the clutch element 140 prevents the spring from turning back the parts. During resetting, the reset tube moves the ratchet arm 152, thereby releasing the ratchet click by click, one click corresponding to one unit IU of insulin in the described embodiment. More specifically, when the dial member is turned clockwise, the reset tube simply rotates the ratchet tube allowing the arm of the ratchet to freely interact with the teeth structures 142 in the clutch element. When the dial member is turned counter-clockwise, the reset tube interacts directly with the ratchet click arm forcing the click arm towards the centre of the pen away from the teeth in the clutch, thus allowing the click arm on the ratchet to move “one click” backwards due to torque caused by the loaded spring.

To deliver a set dose, the push button 190 is pushed in the distal direction by the user as shown in fig. 3B. The dial coupling 161 , 181 disengages and the reset tube 160 decouples from the dial member and subsequently the clutch element 140 disengages the housing splines 104. Now the dial mechanism returns to “zero” together with the drive element 130, this leading to a dose of drug being expelled. It is possible to stop and start a dose at any time by releasing or pushing the push button at any time during drug delivery. A dose of less than 5 IU normally cannot be paused, since the rubber piston is compressed very quickly leading to a compres sion of the rubber piston and subsequently delivery of insulin when the piston returns to the original dimensions. The EOC feature prevents the user from setting a larger dose than left in the cartridge. The EOC member 128 is rotationally locked to the reset tube, which makes the EOC member rotate during dose setting, resetting and dose delivery, during which it can be moved axially back and forth following the thread of the piston rod. When it reaches the proximal end of the piston rod a stop is provided, this preventing all the connected parts, including the dial member, from being rotated further in the dose setting direction, i.e. the now set dose corresponds to the remaining drug content in the cartridge.

The scale drum 170 is provided with a distal stop surface 174 adapted to engage a corre sponding stop surface on the housing inner surface, this providing a maximum dose stop for the scale drum preventing all the connected parts, including the dial member, from being ro tated further in the dose setting direction. In the shown embodiment the maximum dose is set to 80 I U. Correspondingly, the scale drum is provided with a proximal stop surface adapted to engage a corresponding stop surface on the spring base member, this preventing all the con nected parts, including the dial member, from being rotated further in the dose expelling direc tion, thereby providing a “zero” stop for the entire expelling mechanism.

To prevent accidental over-dosage in case something should fail in the dialling mechanism allowing the scale drum to move beyond its zero-position, the EOC member serves to provide a security system. More specifically, in an initial state with a full cartridge the EOC member is positioned in a distal-most axial position in contact with the drive element. After a given dose has been expelled the EOC member will again be positioned in contact with the drive element. Correspondingly, the EOC member will lock against the drive element in case the mechanism tries to deliver a dose beyond the zero-position. Due to tolerances and flexibility of the different parts of the mechanism the EOC will travel a short distance allowing a small “overdose” of drug to be expelled, e.g. 3-5 IU of insulin.

The expelling mechanism further comprises an end-of-dose (EOD) click feature providing a distinct feedback at the end of an expelled dose informing the user that the full amount of drug has been expelled. More specifically, the EOD function is made by the interaction between the spring base and the scale drum. When the scale drum returns to zero, a small click-arm 106 on the spring base is forced backwards by the progressing scale drum. Just before “zero” the arm is released and the arm hits a countersunk surface on the scale drum.

The shown mechanism is further provided with a torque limiter in order to protect the mecha nism from overload applied by the user via the dial member. This feature is provided by the interface between the dial member and the reset tube which as described above are rotation- ally locked to each other. More specifically, the dial member is provided with circumferential inner teeth structure 181 engaging a number of corresponding outer teeth 161 , the latter being arranged on a flexible carrier portion of the reset tube. The reset tube teeth are designed to transmit a torque of a given specified maximum size, e.g. 150-300 Nmm, above which the flexible carrier portion and the teeth will bend inwards and make the dial member turn without rotating the rest of the dial mechanism. Thus, the mechanism inside the pen cannot be stressed at a higher load than the torque limiter transmits through the teeth.

Turning to figs. 4A and 4B an exemplary embodiment of an add-on dose logging device 300 adapted to be mounted on a pen-formed drug delivery device 200 is shown, the pen device essentially corresponding to a FlexTouch® prefilled drug delivery pen with the shown add-on dose logging device being branded as “Dialoq®”. The add-on device 300 comprises a housing portion 385 adapted to be mounted axially and rotationally locked on the drug delivery housing via releasable coupling means 386, the housing being provided with a window 370 allowing the pen scale drum 270 to be observed during dose setting. The add-on device comprises a rotatable dose setting member 380 which during dose setting is coupled to the pen dose setting member 280 such that rotational movement of the add-on dose setting member in either direc tion is transferred to the pen dose setting member. The add-on device further comprises a dose release member 390 which can be moved distally to thereby actuate the pen release member 290.

In order to determine the size of an expelled dose amount of drug, the pen device may be provided with magnetic identifiers adapted to rotate during dose expelling and the add-on de vice may correspondingly be provided with sensor circuitry allowing the amount of rotation to be captured and thereby the expelled dose size to be determined. A number of embodiments based on this concept is disclosed and described in detail in WO 2019/162235 which is hereby incorporated by reference.

In summary, the add-on device disclosed in WO 2019/162235 comprises an outer assembly being releasably attachable to the drug delivery device housing, and an inner assembly. The outer assembly comprises an add-on dose setting member 380, and an add-on release mem ber 390 axially moveable relative to the add-on dose setting member between a dose setting state and a dose expelling state. The inner assembly comprises an inner dose setting member adapted to engage the dose setting member 280, sensor means adapted to detect the amount of rotation of the indicator during expelling of a dose amount, and an actuator coupled to the add-on release member and being axially moveable between a proximal position and a distal position relative to the inner dose setting member, the actuator being adapted to engage and actuate the pen device release member 290 when moved distally. The sensor circuitry, e.g. in the form of an electronic module, may form part of the actuator (and thus move axially there with) and be coupled non-rotationally to the inner dose setting member to prevent rotation during dose expelling. The sensor circuitry will typically be activated from a sleep state when the user actuates and axially moves the add-on release member 390. The determined dose size (or data on basis of which a dose size can subsequently be calculated) will be stored together with a time stamp and, if detected, a drug type identifier in a log memory. The content of the log memory may then be transmitted by NFC, Bluetooth® or other wireless means to an external device, e.g. a smartphone, which has been paired with the add-on logging device. Correspondingly, the shown add-on logging device comprises no means for displaying log data.

Further sensor means may be provided allowing the type of the device to be recognized, e.g. a light emitter and a colour sensor adapted to determine the colour of the pen release member 290, the colour serving as an identifier for the drug type contained in the prefilled pen device.

Having described the working principles of a mechanical drug delivery device and an add-on dose logging device, embodiments of the present invention will be described.

Turning to fig. 5 an exemplary embodiment of a dose recommendation (or guidance) add-on device 400 releasably mounted on a pen-formed drug delivery device 200 is shown. The drug delivery device corresponds to the drug delivery device 200 shown in fig. 4A and comprises a housing, a drug-filled cartridge, drug expelling means comprising dose setting means 280 (see fig. 4A) allowing a user to set a dose amount of drug to be expelled, and release means 290 (see fig. 4A) actuatable to allow the drug expelling means to expel a set dose amount.

The add-on dose recommendation device 400 is based on the design of the add-on logging device shown in fig. 4B and thus comprises an outer assembly being releasably attachable to the drug delivery device housing, and an inner assembly. The outer assembly comprises a housing 485 with a window 470 for the pen scale drum, an add-on dose setting member 480, and an add-on release member 490 axially moveable relative to the add-on dose setting mem ber between a dose setting state and a dose expelling state. The inner assembly comprises an inner dose setting member adapted to engage the dose setting member 280 (e.g. via the axially oriented grooves 288), first sensor means adapted to detect the amount of rotation of the indicator during expelling of a dose amount, and an actuator coupled to the add-on release member 490 and being axially moveable between a proximal position and a distal position relative to the inner dose setting member, the actuator being adapted to engage and actuate the pen device release member 290 when moved distally. The sensor circuitry, e.g. in the form of an electronic module, may form part of the actuator (and thus move axially therewith) and be coupled non-rotationally to the inner dose setting member to prevent rotation during dose expelling. The sensor circuitry will typically be activated from a sleep state when the user ac tuates and axially moves the add-on release member 490.

The add-on dose recommendation device 400 additionally comprises user communication means in the form of a display 410, e.g. LCD or OLED, and a processor and associated memory adapted to determine and store in the memory expelled dose amount values based on data received from the first sensor means, thereby creating a dose log comprising a plurality of determined dose amount values and associated time stamps, and store in the memory blood glucose (BG) values based on received BG data, thereby creating a BG log comprising a plu rality of BG values and associated time stamps. The memory comprises instructions that, when executed by the processor, can calculate a dose recommendation value based on stored dose log and BG log data. The processor is adapted to control the user display to communicate to a user a BG value and a calculated dose recommendation value based thereon. The calculated dose recommendation may be in respect of a meal related bolus injection or an injection with a long or ultra-long acting insulin, e.g. during a titration regimen. In the shown embodiment the add-on dose recommendation device comprises second sensor means comprising a strip port 420 adapted to receive a corresponding strip with a blood sample and measure a property indicative of a blood glucose (BG) value for the blood sample, the processor being adapted to determine and store in the memory BG values based on data received from the second sensor means.

Alternatively or in addition, the add-on dose recommendation device may be provided with a wireless receiver adapted to receive BG data from a skin-mounted continuous blood glucose meter (CGM) upon which data a recommend dose can be calculated. For a titration regimen the algorithm may be based on BG input in the form of values representing a titration glucose level value (TGL) which traditionally would be in the form of a fasting BG value taken manually by the patient in the morning, e.g. using a build-in strip port 420. Alternatively, a TGL value may be determined based on CGM data. For example, a daily TGL may be determined as the lowest BG average for a sliding window of a predetermined amount of time, e.g. 60, 120 or 180 minutes, across the BG values for the corresponding day, see e.g. WO 2020/002428. As indicated above, the add-on logging device 300 on which the add-on dose recommendation device 400 is based is designed without a display, the content of the log memory being trans mitted by wireless means to an external device. To avoid redesign of the dose logging means the log data may be transmitted wirelessly to corresponding receiver circuitry associated with the processor. Indeed, the first sensor means will typically also comprise some kind of proces sor circuitry.

Alternatively, the dose sensor circuitry may be redesigned and integrated in the non-moving electronic circuitry associated with the above-described processor, memory and display, e.g. by means of wired communication. As the add-on dose recommendation device 400 is pro vided with a display 410, the first sensor means based on magnetometers and a magnet ar ranged in the drug delivery device may be replaced by fully external sensor means such as optically based sensor means adapted to determine an expelled dose based on observation of the moving scale drum 270, such sensor means typically covering the scale drum and thus necessitating an additional display, see e.g. WO 2013/120776 and WO 2015/110520 disclos ing add-on dose logging devices based on OCR of the scale drum.

In a further alternative embodiment, the add-on dose recommendation device may be provided with a drive arrangement adapted to engage and rotate the pen dose setting means 280, this allowing a calculated recommended dose to be set (i.e. dialled) automatically. To adjust such an automatically set dose the add-on dose recommendation device may be provided with but ton means (e.g. virtual buttons provided by the display) allowing the dose to be adjusted up or down. Release of the set dose may be controlled by a switch controlled e.g. by a proximally arranged dose release button resembling a traditional pen release button 290.

In the following with reference to figs. 6A-6G a first use scenario for an exemplary embodiment of an add-on dose recommendation device of the type shown in fig. 5B will be described.

The user activates the add-on dose recommendation device, e.g. by pressing the release but ton 490 or alternatively a button (not shown) on the display 410 which turns on the display asking the user whether he or she wants to dial a dose or initiate a dose recommendation calculation by inserting a BG test strip (fig. 6A). If a test strip (of the kind designed to receive a blood sample on the “outer” end of the strip) is inserted in the strip port 420 the user is prompted to apply a blood sample on the free proximal end of the inserted test strip (fig. 6B). Alternatively a test strip with a blood sample applied on the distal test strip end is inserted in the strip port 420. After a blood sample has been applied the user starts BG determination, e.g. by pressing button or the display screen, and BG determination will start. During determination a “wait” symbol may be displayed after which the test result is displayed, e.g. a BG value of 196 mg/DI as shown in fig. 6C. When the user removes the test strip from the strip port a dose recom mendation may be calculated and displayed. Calculating and displaying a recommendation may be done if no dose amount has been determined within a given amount of time, this to prevent overdosing. In this way the add-on device can be used as a conventional BGM. In the shown example the user is informed that a titration dose is increased by two IU of insulin to a total of 18 IU (fig. 6D). The user may accept the recommendation by e.g. pushing a button or adjust the dose using corresponding buttons on the device housing or directly on the display. The latter may be the case if the user is aware of additional data that may or should influence the dose, e.g. a hypoglycaemic event. When the dose has been accepted the user is prompted to set the recommended/adjusted dose using the add-on dose setting dial 480, e.g. 18 Ul as shown in fig. 6E and thereafter push the add-on dose release button 490 to expel the set dose, this also initiating the dose logging circuitry. During dose expelling this may be indicated on the display as shown in fig. 6F. When the out-dosing has finished (or has been paused) the expelled amount is displayed and stored in the memory. In case an expelling event is paused the add-on device may be set up to combine two expelled doses (i.e. a split dose) within a given amount of time as a single combined dose which may then be indicated on the display. In case the expelled dose differs from the dose previously accepted by the user, the user may be prompted with an “injected dose differs from accepted dose” notification on the display. The logged dose amount data, the logged BG data and the calculated/adjusted dose recommen dation data may be transmitted to an external device, e.g. a smartphone, for subsequent presentation as well as analysis. The add-on device may also allow stored data to be viewed directly on the display 410.

In a second use scenario, the add-on device may be set up for calculating a recommended meal bolus of insulin. When the device is turned on the user can request a bolus to be calcu lated. The bolus may be calculated based on a pre-set number of carbs shown in the display and determined by the time of the day or the user may enter a value or adjust the shown value. The display may prompt the user to determine a new BG value before a recommendation is calculated.

In an alternative embodiment the exemplary embodiment of an add-on dose recommendation device of the type shown in fig. 5B is provided with wireless communication means allowing BG data to be received from a skin-mounted CGM device and shown on the display. The add- on device may or may not be provided with a build-in BGM. In the latter case the device may be adapted to receive BG data wirelessly from an external BG meter.

Corresponding to the above-described use scenarios an add-on device provided with CGM display functionality may provide dose recommendations according to the user’s regimen, however, as the add-on device continuously receives CGM data it may be set-up to function primarily as a display device, i.e. show the current BG value optionally together with composite data, e.g. BG graphs, trend indicators or warnings. The display may be always on, wake up when the device is moved or when a button or the display is activated.

When requested by the user or when entering a given time range, the display may show a calculated dose recommendation and/or request additional input from the user. If needed re minders or alarms may be sounded. As any injected (i.e. expelled) amount of drug is automat ically registered, a dose recommendation system is provided which provides the user with BG information and dose recommendations with only a minimum of involvement required by the user. The add-on device may be provided with wireless communication means allowing data to be transmitted to an external device, e.g. a smartphone could be set-up to fully or partly mirror the add-on display.

In an alternative embodiment (not shown) the add-on device comprises a motorized drive mechanism adapted to engage the drug delivery device dose setting means (e.g. via grooves 188), wherein the processor means is adapted to control the motorized drive mechanism cor responding to a calculated or an adjusted calculated dose recommendation. In this way a mo torized drug delivery assembly is provided offering essentially the same functionality as the motorized drug delivery device shown in fig. 7.

Turning to fig. 7 an embodiment of a drug delivery device according to a further aspect of the present invention is shown.

More specifically, fig. 7 shows a motorized drug delivery device in which the expelling mecha nism is provided by a processor-controlled motorized drive mechanism, this allowing dose set ting to be controlled in the electronic domain. The motorized drug delivery device 500 is adapted to receive a cylindrical drug cartridge with an axially displaceable piston having a proximal surface allowing a piston driver forming part of the expelling mechanism to engage the piston. The cartridge may for example contain a drug in the form of an insulin. The cartridge may be provided with distal coupling means in the form of a needle hub mount. More specifically, the drug delivery device comprises a cap part 501 and a main portion 502 forming an interior in which a drug expelling mechanism and associated controller electronics as well as a rechargeable energy source (battery) is arranged. The distal main portion com prises a front-loaded cartridge holder compartment 513 adapted to receive a drug-filled trans parent cartridge through a distal opening, a received cartridge being retained in place by a distal cartridge holder locking assembly. The device further comprises a display 510 as well as user input means. In the shown embodiment the user input means is in the form of a com bined dial member 580 which via a decoder allows the user to set a dose and control operation of the device via rotational and axial movement of the dial member. Such a motorized drug delivery device is well known perse, see e.g. WO 2015/121494.

However, corresponding to the above-described exemplary embodiment of an add-on dose logging device 300, the motorized drug delivery device 500 is provided with a processor and associated memory adapted to determine and store in the memory expelled dose amount val ues based on data received from the electronic motor controller, thereby creating a dose log comprising a plurality of determined dose amount values and associated time stamps, and store in the memory blood glucose (BG) values based on received BG data, thereby creating a BG log comprising a plurality of BG values and associated time stamps. The memory com prises instructions that, when executed by the processor, calculate a dose recommendation value based on stored dose log and BG log data. The processor is adapted to control the user display to communicate to a user a BG value and a calculated dose recommendation value based thereon. The calculated dose recommendation may be in respect of a meal related bolus injection or an injection with a long or ultra-long acting insulin, e.g. during a titration regimen. In the shown embodiment the add-on dose recommendation device comprises sec ond sensor means comprising a strip port 520 adapted to receive a corresponding strip with a blood sample and measure a property indicative of a blood glucose (BG) value for the blood sample, the processor being adapted to determine and store in the memory BG values based on data received from the second sensor means.

Alternatively or in addition, the motorized dose recommendation and drug delivery device may be provided with a wireless receiver adapted to receive BG data from a skin-mounted contin uous blood glucose meter (CGM) upon which data a recommend dose can be calculated.

In use, the motorized dose recommendation and drug delivery device essentially functions in the same way as the add-on device mounted on a pen device as described with reference to e.g. figs. 6A-6G, with the main difference that dose setting and dose capture work as an inte grated part of the electronically controlled motor device.

In the above description of the preferred embodiment, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present specification.

Claims

1. An add-on device (400) adapted to be releasably mounted on a drug delivery device (200), the drug delivery device comprising: a housing, a drug-filled cartridge or means for receiving a drug-filled cartridge, drug expelling means comprising: dose setting means (280) allowing a user to set a dose amount of drug to be expelled, and release means (290) actuatable to allow the drug expelling means to expel a set dose amount, the add-on device comprising: an add-on housing (485) adapted to be releasably attached to the drug delivery device housing, first sensor means adapted to measure a property of the drug expelling means indic ative of the amount of expelled drug, a display (410), processor means and associated memory adapted to: store in the memory expelled dose amount values based on data received from the first sensor means, thereby creating a dose log comprising a plurality of de termined dose amount values and associated time stamps, and store in the memory blood glucose (BG) values based on received BG data, thereby creating a BG log comprising a plurality of BG values and associated time stamps, wherein the memory comprises instructions that, when executed by the processor means, cal culate a dose recommendation value based on stored dose and BG log data, and control the display to display a BG value and a calculated dose recommendation value based thereon.

2. An add-on device as in claim 1, comprising: second sensor means (420) adapted to receive a blood sample and measure a prop erty indicative of a BG value for the blood sample, wherein the processor means is adapted to determine and store in the memory BG values based on data received from the second sensor means.

3. An add-on device as in claim 2, wherein: the processor means is adapted to: determine a most-recent BG value from a received blood sample, control the display to display the most-recent BG value, and when it is determined, based on pre-set conditions stored in memory, that the user is in need for receiving an amount of drug: calculate and control the display to display a dose recommendation value based on BG log data and dose log data.

4. An add-on device as in claim 1, comprising wireless receiver means adapted to re ceive BG data, the processor means being adapted to store in the memory BG values based on the received BG data.

5. An add-on device as in claim 4, wherein: the processor means is adapted to: display the most-recent BG value, and when it is determined, based on pre-set conditions stored in memory, that the user is in need for receiving an amount of drug: calculate and control the display to display a dose recommendation value based on BG log data and dose log data.

6. An add-on device as in claim 5, wherein the received BG data is CGM data.

7. An add-on device as in claim 6, wherein the processor means is adapted to control the display to display BG data as a function of time.

8. An add-on device as in any of claims 1-7, comprising: wireless transmitter means adapted to transmit dose amount values and/or BG values to an external device.

9. An add-on device as in any of claims 1-8, comprising a motorized drive mechanism adapted to engage the drug delivery device dose setting means, wherein: the processor means is adapted to control the motorized drive mechanism corre sponding to a calculated or an adjusted calculated dose recommendation.

10. An add-on device as in any of claims 1-9, the drug expelling means comprising: an indicator (160) adapted to rotate during expelling of a dose amount, the amount of rotation being indicative of the size of the expelled dose amount, and wherein the first sensor means is operatable to detect the amount of rotation of the indicator during expelling of a dose amount.

11. An assembly comprising a drug delivery device (200) as defined in claim 1 and an add-on device (400) as defined in any of claims 1-10.

12. An assembly (200, 400) as in claim 11 , wherein: the drug expelling means comprises an indicator (160) adapted to rotate during ex pelling of a dose amount, the amount of rotation being indicative of the size of the expelled dose amount, the indicator comprising one or more dipole magnets, the first sensor means comprises one or more magnetometers adapted to determine magnetic field values from the one or more dipole magnets, and the processor means is configured to determine on the basis of measured values from the one or more magnetometers a rotational position and/or a rotational movement of the indi cator.

13. A unitary drug delivery device (500), comprising. a drug-filled cartridge or means for receiving a drug drug-filled cartridge, drug expelling means comprising dose setting means allowing a user to set a dose amount of drug to be expelled, and release means actuatable to allow the drug expelling means to expel a set dose amount, first sensor means adapted to measure a property of the drug expelling means indic ative of the amount of expelled drug, a display, and processor means and associated memory adapted to: store in the memory expelled dose amount values based on data received from the first sensor means, thereby creating a dose log comprising a plurality of de termined dose amount values and associated time stamps, and store in the memory blood glucose (BG) values based on received BG data, thereby creating a BG log comprising a plurality of BG values and associated time stamps, wherein the memory comprises instructions that, when executed by the processor means, cal culate a dose recommendation value based on stored dose and BG log data, and control the display to communicate to a user a BG value and a calculated dose recommendation value based thereon.

14. A unitary drug delivery device as in claim 13, comprising: second sensor means (520) adapted to receive a blood sample and measure a prop erty indicative of a BG value for the blood sample, wherein the processor means is adapted to determine and store in the memory BG values based on data received from the second sensor means.

15. A unitary drug delivery device as in claim 13, comprising: wireless receiver means adapted to receive BG data, the processor means being adapted to store in the memory BG values based on the received BG data.

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