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WO2025172500A1 - Method for determining the dose capturing accuracy - Google Patents

Method for determining the dose capturing accuracy

Info

Publication number
WO2025172500A1
WO2025172500A1 PCT/EP2025/053969 EP2025053969W WO2025172500A1 WO 2025172500 A1 WO2025172500 A1 WO 2025172500A1 EP 2025053969 W EP2025053969 W EP 2025053969W WO 2025172500 A1 WO2025172500 A1 WO 2025172500A1
Authority
WO
WIPO (PCT)
Prior art keywords
dose
test
drug
dosage size
delivered
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2025/053969
Other languages
French (fr)
Inventor
Stephan Riedel
Christian Rehbein
Rene STAMPFER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi SA
Original Assignee
Sanofi SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi SA filed Critical Sanofi SA
Publication of WO2025172500A1 publication Critical patent/WO2025172500A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • G16H20/17—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/60—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
    • G16H40/63—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3125—Details specific display means, e.g. to indicate dose setting
    • A61M2005/3126—Specific display means related to dosing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/50—General characteristics of the apparatus with microprocessors or computers
    • A61M2205/52—General characteristics of the apparatus with microprocessors or computers with memories providing a history of measured variating parameters of apparatus or patient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically

Definitions

  • the disclosure generally relates to methods for determining and investigating the dose capturing accuracy of electronic dose capturing system(s).
  • Drug delivery devices e.g. insulin pens
  • DA dosing accuracy
  • ISO Norms e.g. ISO 11608
  • Dosing accuracy is usually measured in the laboratory and describes the deviation between a set drug dose of a drug, e.g. insulin, and the delivered drug dose.
  • the dose recording accuracy (also called dose capturing accuracy (DCA)) instead may indicate the accuracy of an electronic dose capturing system to capture a set drug dose, e.g. a drug dose being delivered.
  • DA dosing accuracy
  • the electronic dose capturing system may be configured to capture a dosage size of a drug dose delivered from a drug delivery device, e.g. to electronically capture a dosage size of a drug dose delivered from a drug delivery device.
  • the drug delivery device may comprise a device dose indicator.
  • the device dose indicator may be configured to provide a dose indication indicative of the dosage size of a set drug dose and/or of a delivered drug dose.
  • drug dose or just “dose” will be used in the following for both cases, e.g. the drug dose comprising a real drug or the drug dose comprising another fluid.
  • delivering a drug dose of a specific dosage size as indicated by the device dose indicator may also be disclosed as "delivering a set drug dose”.
  • the method may further comprise the step of capturing the dosage size of the delivered dose using the electronic dose capturing system.
  • the method may further comprise the step of determining whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator, e.g. the set drug dose and/or the delivered drug dose.
  • the dosage size(s) may for example be given in International Units (IU).
  • Capturing the dosage size of the delivered dose may comprise measuring mechanical movement of a component of the drug delivery device, the component being directly or indirectly linked with the dispensing of the drug dose, and optionally giving a visual display of the value on the electronic dose capturing system.
  • the electronic dose capturing system may be configured to capture the dosage size by capturing the movement of the component of the drug delivery device, the movement may be indicative for the amount of drug delivered while the element is moving.
  • the electronic dose capturing system may comprise at least one sensor configured to capture the movement of a component of the drug delivery device involved in the dispensing of the drug dose, the movement being indicative for the amount of drug delivered while the element is moving.
  • the at least one sensor may be one or more of an optical sensor, a magnetic sensor, a capacitive sensor and a mechanical sensor.
  • Differences between the dose indication and the captured drug dose may for example occur due to incorrect or imprecise capturing by the electronic dose capturing system. Differences between the dose indication and the captured drug dose, may for example be due to the electronic dose capturing system capturing additional movement of the component of the drug delivery device being directly or indirectly linked with the dispensing of the drug dose. The additional movement may be incorrectly identified by the electronic dose capturing unit as an additional drug dose being dispensed, although the additional movement of the component did not correspond to an additional drug dose being dispensed.
  • the electronic dose capturing system may be configured to capture the dosage size through capturing of the axial and/or rotational movement of the plunger of a drug delivery device.
  • the plunger may however, after having expelled the set drug still move, e.g. rotate or axially move, for a predetermined distance.
  • This additional movement may be (sometimes) captured by the electronic dose capturing system as an additional drug dose having being expelled, thereby creating a difference between the dose indication and the captured drug dose.
  • the dose dialing element may not return to its zero-dose position, but may, instead, return to an intermediate position indicative of the difference between the set dose and the delivered dose. If for example, a set dosage size of ten drug doses was set, but only a dosage size of seven drug doses was dispensed, the dialing element may return from a set dose position indicating ten doses, to an intermediate position indicating three drug doses.
  • the determination may be performed on a first dosage size of the set drug dose, the first dosage size being less than or equal to a threshold dosage size. Additionally or alternatively the determination, e.g. whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator, may be performed on a second dosage size of the set drug dose, the second dosage size being greater than or equal to a threshold dosage size. According to at least one embodiment, the second dosage size 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 times greater than the first dosage size.
  • the tests may comprise determining the dose capturing accuracy of an electronic dose capturing system of at least one test system according to the method of the first aspect of this disclosure and/or any of its embodiments.
  • the tests may comprise determining the dose capturing accuracy of electronic dose capturing systems of a set of test system.
  • the drug delivery devices and the electronic dose capturing systems of different test systems of the set of test systems may have identical configuration. Identical configuration may imply that the same type of drug delivery device is used and/or that the same type of electronic dose capturing system may be used with the drug delivery device.
  • compiling test data and/or evaluating test data may comprise the quantification of the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test.
  • compiling the test data further comprises the step of gathering at least one of, more of or all of following data to be used as test data:
  • the set dosage size of the delivered drug dose may for example be the dosage size of the drug dose that was selected in the dial-member.
  • the captured dosage size may be the dosage size captured by the electronic dosage capturing system (s).
  • test user specific use data may comprise at least one of, more of, or all of following information:
  • test system specific data may comprise at least one of, more of, or all of following information:
  • the test data is derived or derivable from at least seven tests carried out respectively on at least one test system, e.g. on three test systems.
  • evaluating the test data comprises performing analysis on the compiled test data. The analysis may be for example statistical analysis.
  • Figure 2 is a schematic view of an exemplary embodiment of steps of the method according to the first aspect
  • Figure 7 shows an exemplary embodiment of the step of evaluating the compiled test data.
  • the electronic dose capturing system can easily be installed on the injection device, and can easily be removed through application of a removal force between the electronic dose capturing system and the injection device in an axial direction.
  • the electronic dose capturing system is manipulated by the user in order to effect operation of the injection device.
  • the electronic dose capturing system when installed monitors quantities and times of medicament delivery from the injection pen.
  • Medicament quantities can be transmitted to an external device, e.g. to a smartphone, and/or displayed on a display of the electronic dose capturing system.
  • an external device e.g. to a smartphone
  • the electronic dose capturing system By providing the electronic dose capturing system with push-fit features, it can be located onto and used with a series of different drug delivery devices and thus monitor a user's medicament treatment over multiple devices. Moreover, this can be achieved without impeding normal use of the injection device and without obscuring a dosage window, e.g. a device dose indicator of the injection device.
  • FIG. 1a is an exploded view of a medicament delivery device.
  • the medicament delivery device is an injection device 1, such as the one disclosed in the patent application WO 2004/078239 A1.
  • the injection device 1 of Figure 1a is a pre-filled, disposable injection pen that may comprise a housing 10 comprising an insulin container 14, to which a needle 15 can be affixed. The needle is protected by an inner needle cap 16 and either an outer needle cap 17 or an alternative cap 18.
  • the dosage knob 12 is turned to its initial position, in an axial movement, that is to say without rotation, while the number sleeve 70 is rotated to return to its initial position, e.g. to a zero-dose position, e.g. to display a dose of zero units.
  • Injection device 1 may be used for several injection processes until either the insulin container 14 is empty or the expiration date of the medicament in the injection device 1 (e.g. 28 days after the first use) is reached.
  • injection device 1 before using injection device 1 for the first time, it may be necessary to perform a so-called "prime shot” to remove air from insulin container 14 and needle 15, for instance by selecting two units of insulin and pressing injection button 11 while holding injection device 1 with the needle 15 upwards.
  • a so-called "prime shot” to remove air from insulin container 14 and needle 15, for instance by selecting two units of insulin and pressing injection button 11 while holding injection device 1 with the needle 15 upwards.
  • the ejected amounts substantially correspond to the injected doses, so that, for instance the amount of medicament ejected from the injection device 1 is equal to the dose received by the user. Nevertheless, differences (e.g. losses) between the ejected amounts and the injected doses, e.g. the dosing accuracy, may need to be taken into account.
  • Figure 1b is a perspective view of one end (e.g. proximal end) of the injection device 1 of Figure 1a when an electronic dose capturing system 20 according to an example embodiment is attached.
  • the electronic dose capturing system 20 may include a housing 21 and an end plate 22 with an optional display 22a.
  • the electronic dose capturing system 20 may take one of a number of different forms.
  • the drug delivery device 1 may be an injection device, e.g. the injection pen shown in the Figure 1a, e.g. an injector pen 1 as the one disclosed in WO 2004/078239 A1.
  • different drug delivery device e.g. different injection pen as shown in Figure 1a
  • Figure 1a and 1 b therefore illustrates that the method according to the disclosure may be performed with different drug delivery devices (and different electronic dose capturing systems 20).
  • a test user 2 of the device sets a dosage size of a drug dose 200, e.g. by dialing the dosage size in the device dose indicator, which e.g. may comprise a dialing member or may comprise turning a knob as described in relation to Figure 1a.
  • the device dose indicator 210 may be a mechanical device dose indicator.
  • the drug dose may then be delivered 220, e.g. on an injection pad (not shown).
  • the method may be performed either with a real drug, e.g. insulin, or with a drug substitute, e.g. a fluid having similar characteristics as the drug usually used.
  • An electronic dose capturing system may then be configured to capture the dosage size of the delivered drug dose 230.
  • the difference between the captured dosage size of the electronic dose capturing system and the dosage size set on the device dose indicator 240 may then imply the dose capturing accuracy, DCA (also called dose recording accuracy DRA in other figures, e.g. Figure 8).
  • DCA also called dose recording accuracy DRA in other figures, e
  • Such a difference may influence the trust a patient will have with respect to the drug delivery device. Furthermore, the difference might result in the patient deciding to deliver to himself an additional dose of the drug (if for example the dosage size captured by the electronic dose capturing system is lower than the set dosage size, thereby creating the false impression that less drug was delivery than the one intended) or to wait longer than necessary to deliver a new dose (if for example the dose capturing system captured a higher dosage size as the set dosage size, thereby creating the false impression that more drug was delivered as the one set). Both cases can result in extreme dangerous situations for a patient.
  • the specific dosage size to be delivered may be set.
  • Setting the specific dosage size may comprise dialing the dosage size (given in International Units, IU) on a dialing sleeve of a dialing member or by, e.g. turning a knob on one end (e.g. proximal end) of the device as explained in relation to Figure 1a and 1b.
  • the step may however be dispensed as part of the method, as the method may start with a drug delivery device in which the specific dosage size of the drug dose is already set.
  • the specific dosage size may be delivered.
  • the delivery may occur on an injection pad, as the method may be non-therapeutical.
  • the device dose indicator of the drug delivery device may comprise and/or show a dose indication.
  • the dose indication may be indicative of a dosage size of a drug dose that was set and/or of a drug dose that was delivered.
  • the device dose indicator may correspond and/or comprise the dialing member of the drug delivery device.
  • the dosage size of the delivered dose may be captured, e.g. by an electronic dose capturing system of the drug delivery device.
  • Capturing the dosage size of the delivered dose may comprise measuring mechanical movement of a component of the drug delivery device, the component being directly or indirectly linked with the dispensing of the drug dose, and optionally giving a visual display of the value.
  • the electronic dose capturing system may be configured to capture the dosage size by capturing the movement of the component of the drug delivery device, the movement may be indicative for the amount of drug delivered while the element is moving.
  • the movement may be, for example, an axial and/or rotational movement of the component, e.g. of a plunger, a sleeve, and/or a collar.
  • Axial movement of the component, e.g. of the plunger, of a specific distance may for example correspond to a specific dosage size e.g. 5 mm axial movement of the plunger may correspond to one III.
  • rotational movement of the component, e.g. of the plunger, of specific degrees may correspond to a specific dosage size, e.g. 6 degree rotation of the plunger may correspond to one IU.
  • the method may comprise the step of checking if the add-on device is mounted properly.
  • the method may comprise the step of, if at any stage during any step of the method the add-on module is demounted, remounting the add-on module on the drug delivery device and repeating the steps of the method. Repeating might comprise starting the method from the beginning, e.g. by setting the dose and/or dispensing the specific dosage size of the drug dose.
  • Figure 4 shows a schematic overview of a method according to an exemplary embodiment of the second aspect.
  • test data may be compiled.
  • the test data may be derived from tests carried out by n test users of a group of test users comprising n test users.
  • the tests may comprise determining the dose capturing accuracy of an electronic dose capturing system of at least one test system (e.g. as shown in this figure of x test systems) according to the method of the first aspect and/or any of its embodiments, e.g. according to the method of Figure 3, e.g. by performing at least steps S1 to S4.
  • each test user TU_1 to TU_n may be provided with x numbers of test systems, e.g. test system 1 , TS_1 to test system x, TS_x.
  • Each test system may comprise a drug delivery device and an electronic dose capturing system.
  • the drug delivery devices and the electronic dose capturing systems of different test systems of the set of test systems may have identical configuration, e.g. the may all have the same type of drug delivery device and the same type of electronic dose capturing system, e.g. an injection pen and a cCap as shown and described in Figure 1 and/or Figure 2.
  • a test user 1 may perform z tests (z being a natural number, e.g. 7), e.g. test x_1 to test x_z, on the x-th test system, e.g. test system x, TS_x.
  • the test data obtained by each of the z test may then be compiled 1100.
  • test 1 and test system 2 of test user 1 at least two test, e.g. test 1_2 and test 2_3, may be equal with respect to the specific dosage size of the drug dose used in the tests, e.g. used for steps S1 and/or S2.
  • test 3_5 of test user 1 and test 1_3 of test user 2 may be equal with respect to the specific dosage size of the drug dose used in the tests, e.g. used for steps S1 and/or S2.
  • a dosage size being smaller than a predetermined dosage size, e.g. 10 III, and 50% are done with a dosage size being larger than the predetermined dosage size, e.g. 10 IU.
  • a predetermined dosage size e.g. 10 III
  • 50% are done with a dosage size being larger than the predetermined dosage size, e.g. 10 IU.
  • Different percentages are however also envisaged, e.g. depending whether test data should be compiled focused on some more specific dosage sizes.
  • test systems for different test users may have identical configuration, e.g. test system 1 of test user 1 has identical configuration to test system 1 of test user 3.
  • Identical configuration may mean that the type of the drug delivery device and/or of the electronic dose capturing system is substantially identical.
  • the numbers a, b, z may be equal to each other, equal to some of each other or different to each other.
  • a may be equal to b which may be equal to z which may be equal to at least seven, i.e. for each test system, seven tests would be performed.
  • test users It has proven advantageous to have at least 16 test users, as this value of test users provide sufficient relevant data, e.g. for an evaluation of the test data, e.g. a statistical evaluation of the test data, without requiring too much operational expense.
  • the disclosure is not limited to this value, and also with less or more test user the compiled test data and evaluated test data may result significant, e.g. depending on other parameters. Due to fatigue and deconcentrating of the test user, each test user may perform less than 45 test, e.g. less than 15 test per test system. The disclosure is however not limited to less than 45 tests per user.
  • test data 1000 of all the test may be compiled and may form compiled test data 1100.
  • the compiled test data 1100 may also comprise the quantification of the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test, e.g. determined in step S4 of each test.
  • the quantification of the difference may however, additionally or alternatively be comprised in the step of evaluating the test data.
  • the compiled test data may comprise the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test, e.g. determined in step S4 of each test.
  • the evaluation of the compiled test data may comprise quantifying the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test.
  • the selected dosage size may vary between each or at least some of the tests, in order to investigate the dose capturing accuracy of electronic dose capturing systems at different dosage sizes and in the evaluation stage to evaluate if a correlation exists between the dosage size used and the dose capturing accuracy.
  • the captured dosage size may comprise the dosage size data captured by the electronic dose capturing system.
  • the difference determined during the performance of the method of the first aspect may also be quantified and the quantification may be gathered as test data and may be comprised in the compiled test data and/or may be evaluated in the step of evaluating the test data.
  • the hand used by the test user may be relevant in order to assess, if the accuracy changes between left-handers and/or right-handers.
  • the same may hold for the finger, e.g. the finger used for delivery a drug dose.
  • the finger e.g. the finger used for delivery a drug dose.
  • the drug delivery device is usually held with the whole hand, e.g. remaining for fingers grab the housing of the drug delivery device.
  • the force applied by the hand acting on the drug delivery device while pressing the injection button e.g. the radially inward force acting on the housing of the drug delivery device, may interfere with the capturing of the dose by the electronic dose capturing system thereby creating a difference between the dose indication and the captured drug dose.
  • Test system specific data from each test system may comprise at least, one of, more of, or all of following information:
  • test system 1 e.g. test system 1;
  • the test user specific personal data may comprise at least, one of, more of, or all of following information:
  • test user(s) e.g. type of diabetes.
  • test user specific personal data may be anonymised in order e.g. to fulfil data security requirements.
  • Figure 5 shows an exemplary embodiment of a test data compiling data sheet, e.g. a data sheet used for compiling the test data of one test user, e.g. of test user 1 , P01.
  • Figure 6 shows an exemplary embodiment of specific elements of the step of compiling test data for several test users, e.g. for 20 test users, PA-01 to PA-20. Only the test data specific to the difference (or the quantification) of the difference between the captured dosage size and the dose indication provided by the device dose indicator is shown in this Figure, however also other test data may be added to the table.
  • Different test user performed the tests on different days as can be seen in the table. However all users may perform the test on the same day, and the disclosure is not limited to multiday tests.
  • test system 1 denoted with “V3-Z”
  • test system 2 denoted with “V3-X”
  • test system 3 denoted with “V3-C”.
  • the test system may be different with respect to each other.
  • no difference between the captured dosage size and the dose indication provided by the device dose indicator may have been determined.
  • the value therefore corresponds both to the set dosage size of the drug dose and to the captured dosage size.
  • the set dosage size and the captured dosage size may correspond to 6.
  • the first value may correspond to the set dosage size, while the second value may correspond to the captured dosage size.
  • the values may identify is given:
  • test system 1 V3-Z, of test user 6, PA-06, "56»inc" is shown.
  • the value “inc” may stand for "injection incomplete”, meaning that, in this case, the set dosage size was set to 56 and was delivered, but the electronic dose capturing system although recognizing that a delivery was done did not capture a dose size.
  • the value "7»m" is shown in the seventh test of test system 3, V3-C, of test user 14, PA-14.
  • This may stand for "missing data", meaning that the test user has set a dosage size of a drug dose, e.g. seven, delivered the dosage size but the electronic dose capturing system shows no entry and no delivery.
  • a dosage size of a drug dose e.g. seven
  • the electronic dose capturing system shows no entry and no delivery.
  • about 50% of the tests are done with a first dosage size, the dosage size being smaller than a predetermined dosage size, e.g. a threshold dosage size, e.g. 10 IU, and 50% are done with a second dosage size, the dosage size being larger than the predetermined dosage size, e.g. than the threshold dosage size, e.g. 10 IU.
  • Pattern coding (as such) of the table provided in Figure 6 has proven particularly advantageous, as it may permit an automatic evaluation of the test data by optical devices.
  • Figure 7 shows an exemplary embodiment of the step of evaluating the compiled test data, e.g. the test data of Figure 6.
  • evaluating the compiled test data may comprise the step of analysing, e.g. in absolute numbers and/or in percentage, Tot., the quantification of the difference between the captured dosage size and the dose indication provided by the device dose indicator with respect to all test and/or with respect to the test with less than a predetermined dose, e.g. less than 10 III, and with respect to the test with more than a predetermined dose, e.g. more than 10 IU.
  • the colour coding may be equal to the colour coding of the compiled test data (see e.g. Figure 6).
  • the evaluation in percentage may be done with respect to all test in which a dosage size of a drug dose was set and in which the electronic dose capturing system captured a dosage.
  • Tests in which data was missing 504, the injection was incomplete 502 and/or ghost data 500 may be analysed as such, with respect to all tests, e.g. with respect to the sum 506 of "injection incomplete 502 and missing dose (e.g. ghost data 500 and/or missing data 504), but may not be considered in the evaluation with respect to the difference between the captured dosage size and the dose indication provided by the device dose indicator, see, e.g. row 508 "n without "injection incomplete", and missing data.
  • the evaluation may comprise evaluating in absolute numbers and/or in percentage, Tot., in how many tests the difference between the captured dosage size and the dose indication provided by the device dose indicator, is one dose, e.g. deviations of +1 or -1 dose, or that the difference is two dose, e.g. deviations of +2 or -2 doses, or that the difference is greater than 2 dose, e.g. deviations of +3 or more dose or of -3 or more dose.
  • Figure 8 shows a poster giving some further information regarding some exemplary embodiments of the first and/or second aspect of the method.
  • Features described in the poster may be used to further describe embodiments of the first aspect and/or second aspect of the disclosure.
  • Features described in the poster may also be used as claim subject matter.
  • the poster 100 may comprise an introduction section 110.
  • the section may read: "Insulin management can be challenging, e.g. to keep track on daily dosing. Digital solutions might alleviate the burden of those documentations.
  • Connected caps (cCaps) are currently available for disposable insulin pens as part of the digital diabetes management offerings.
  • Literature indicates that the User Experience (UX) and performance of cCaps based on Dose Recording Accuracy (DRA) is crucial in the onboarding phase for acceptance".
  • the introduction session may also define an objective 110a, for example: "1 st time evaluation of UX on Look & Feel, Handling, and DRA in the onboarding phase into digital diabetes management (mgt.) with marketed insulin pens, dedicated cCaps and apps.”
  • an objective 110a for example: "1 st time evaluation of UX on Look & Feel, Handling, and DRA in the onboarding phase into digital diabetes management (mgt.) with marketed insulin pens, dedicated cCaps and apps.”
  • Box 110b may show possible ecosystems that might comprise pen, cap and app.
  • the pen on the left might be the pen described in WO 2004/078239 A1, comprising a smart-add on, on its distal end.
  • the pen in the middle may be the "Tempo-Pen” with a "Tempo-Button”.
  • the pen on the right might be the Flex-Touch comprising the "Mallya”. Please note that marketed products might be Registered or protected via Trademark in specific countries. All three pens might be connected to a smartphone via Bluetooth.
  • a method section 120 may be provided.
  • the method section may comprise a subsection "Lab Setting with Randomized Testing" 120a.
  • the subsection 120a may disclose in bullet points:
  • the graph visible in the poster represents: cCaps 120b in a randomized order.
  • Digital diabetes Management pen, cap, app
  • look & feel and handling 120c and DRA 120d and a questionnaire for evaluation of UX 120e.
  • Section 130 may disclose:
  • Section 140 may instead disclose some possible results.
  • the section may show:
  • the intuitive mounting, the dialing and the injection may represent handling steps in setup.
  • The" Drives 2 nd UX for Users" 150 may disclose:
  • the diary data 150b may include date, time, dosage and medication.
  • Box 150c represents an example of Health2Sync Diary.
  • the user may have primed Medication Toujeo-Priming at 15:12 and may have medicated with Toujeo on 15:13, e.g. after lunch.
  • Section 160 may disclose information of patient perspective in digital diabetes management. It may dislcose:
  • the drug container may be or may include a dualchamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber.
  • the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body.
  • the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing.
  • analogue and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue.
  • the added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues.
  • Insulin analogues are also referred to as "insulin receptor ligands".
  • the term ..derivative refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids.
  • one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.
  • insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N- palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-g
  • GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211 , CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1 , ZYD-1, GSK-237
  • hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
  • Gonadotropine Follitropin, Lutropin, Choriongonadotropin, Menotropin
  • Somatropine Somatropin
  • Desmopressin Terlipressin
  • Gonadorelin Triptorelin
  • Leuprorelin Buserelin
  • Nafarelin Nafarelin
  • Goserelin Goserelin.
  • an example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.
  • antibody refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen.
  • the antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement.
  • the antibody has reduced or no ability to bind an Fc receptor.
  • the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region.
  • the term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).
  • TBTI tetravalent bispecific tandem immunoglobulins
  • CODV cross-over binding region orientation
  • fragment refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen.
  • Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments.
  • Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and immunoglobulin single variable domains. Additional examples of antigen-binding antibody fragments are known in the art.
  • SMIP small modular immunopharmaceuticals
  • immunoglobulin single variable domain (ISV), interchangeably used with “single variable domain”, defines immunoglobulin molecules wherein the antigen binding site is present on, and formed by, a single immunoglobulin domain.
  • immunoglobulin single variable domains are capable of specifically binding to an epitope of the antigen without pairing with an additional immunoglobulin variable domain.
  • the binding site of an immunoglobulin single variable domain is formed by a single heavy chain variable domain (VH domain or VHH domain) or a single light chain variable domain (VL domain).
  • VH domain or VHH domain single heavy chain variable domain
  • VL domain single light chain variable domain
  • An immunoglobulin single variable domain can be a heavy chain ISV, such as a VH (derived from a conventional four-chain antibody), or VHH (derived from a heavy-chain antibody), including a camelized VH or humanized VHH.
  • the immunoglobulin single variable domain may be a (single) domain antibody, a "dAb” or dAb or a Nanobody® ISV (such as a VHH, including a humanized VHH or camelized VH) or a suitable fragment thereof.
  • Nanobody® is a registered trademark of Ablynx N.V.]; other single variable domains, or any suitable fragment of any one thereof.
  • VHH domains also known as VHHs, VHH antibody fragments, and VHH antibodies, have originally been described as the antigen binding immunoglobulin variable domain of “heavy chain antibodies” (i.e. , of “antibodies devoid of light chains”; Hamers-Casterman et al. 1993 (Nature 363: 446-448).
  • VHH domain has been chosen in order to distinguish these variable domains from the heavy chain variable domains that are present in conventional 4- chain antibodies (which are referred to herein as “VH domains”) and from the light chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “VL domains”).
  • VHH domains For a further description of VHH’s, reference is made to the review article by Muyldermans 2001 (Reviews in Molecular Biotechnology 74: 277-302).
  • CDR complementarity-determining region
  • framework region refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding.
  • framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.
  • antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
  • Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.
  • An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needlebased injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems.
  • the container may be a replaceable container or an integrated non-replaceable container.
  • a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
  • Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
  • a single-dose container system may involve a needle-based injection device with a replaceable container.
  • each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).
  • a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container.
  • each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation).
  • each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

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Abstract

A method for determining the dose capturing accuracy of an electronic dose capturing system is provided, wherein the electronic dose capturing system is configured to electronically capture a dosage size of a drug dose delivered from a drug delivery device. The drug delivery device may comprise a device dose indicator, the device dose indicator being configured to provide a dose indication indicative of a dosage size of a set drug dose and/or of a delivered drug dose. The method may comprise the steps of - delivering a dose of a specific dosage size as indicated by the device dose indicator from the drug delivery device and - capturing the dosage size of the delivered dose using the electronic dose capturing system and - determining whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator.

Description

Title
Method for determining the dose capturing accuracy
Technical field
The disclosure generally relates to methods for determining and investigating the dose capturing accuracy of electronic dose capturing system(s).
Background
Drug delivery devices, e.g. insulin pens, must maintain dosing accuracy (DA) according to ISO Norms, e.g. ISO 11608 in case of insulin pens. Dosing accuracy is usually measured in the laboratory and describes the deviation between a set drug dose of a drug, e.g. insulin, and the delivered drug dose.
Summary
The dose recording accuracy (DRA) (also called dose capturing accuracy (DCA)) instead may indicate the accuracy of an electronic dose capturing system to capture a set drug dose, e.g. a drug dose being delivered.
While users of the drug delivery device do not notice the dosing accuracy (DA), he/she is confronted with the DCA. The user knows or sees what his/her set drug dose is and what the captured drug dose shows. High deviations can therefore lead to uncertainty and, if necessary also lead to mishandling. Mishandling could cause the user to give themselves an additional injection in the event of a dose deviation, e.g. if the captured drug dose is less than the set drug dose, which might correspond to hazard of an overdose. Frequent small dose variations can also affect user satisfaction.
An object of the present disclosure is therefore to provide a method for determining the dose capturing accuracy (also called dose recording accuracy) of an electronic dose capturing system and a method for investigating the dose capturing accuracy of an electronic dose capturing system. The object is achieved by the method according to claim 1 and/or the method according to claim 9, respectively. Exemplary embodiments are provided in the dependent claims.
According to a first aspect of the present disclosure a method for determining the dose capturing accuracy of an electronic dose capturing system is provided. The electronic dose capturing system may be configured to capture a dosage size of a drug dose delivered from a drug delivery device, e.g. to electronically capture a dosage size of a drug dose delivered from a drug delivery device.
The drug delivery device may comprise a device dose indicator. The device dose indicator may be configured to provide a dose indication indicative of the dosage size of a set drug dose and/or of a delivered drug dose.
The method may comprise the step of delivering a drug dose of a specific dosage size as indicated by the device dose indicator from the drug delivery device. The delivery of the drug dose according to the present disclosure may not be therapeutic, e.g. the delivery of the drug dose may not occur on a patient but e.g. on an injection pad. In some embodiments the drug may be a real drug, e.g. a medicament such as insulin as e.g. commercially available for its use in drug delivery devices, in particular injection devices. The drug used in a drug dose may not be a real drug, e.g. it may be water or any other composition resembling the drug dose, e.g. having similar fluid characteristics as a drug, e.g. similar viscosity.
For sake of simplicity, the term "drug dose" or just "dose" will be used in the following for both cases, e.g. the drug dose comprising a real drug or the drug dose comprising another fluid. Furthermore, in this disclosure, delivering a drug dose of a specific dosage size as indicated by the device dose indicator, may also be disclosed as "delivering a set drug dose".
According to at least one embodiment the method may further comprise the step of capturing the dosage size of the delivered dose using the electronic dose capturing system. The method may further comprise the step of determining whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator, e.g. the set drug dose and/or the delivered drug dose. The dosage size(s) may for example be given in International Units (IU).
Capturing the dosage size of the delivered dose may comprise measuring mechanical movement of a component of the drug delivery device, the component being directly or indirectly linked with the dispensing of the drug dose, and optionally giving a visual display of the value on the electronic dose capturing system. For example, the electronic dose capturing system may be configured to capture the dosage size by capturing the movement of the component of the drug delivery device, the movement may be indicative for the amount of drug delivered while the element is moving.
The movement may be an axial and/or rotational movement of the component, e.g. of a plunger, a sleeve, and/or a collar. Axial movement of the component, e.g. of the plunger, of a specific distance may for example correspond to a specific dosage size e.g. 5 mm axial movement of the plunger may correspond to one III. Similarly, rotational movement of the component, e.g. of the plunger, of specific degrees may correspond to a specific dosage size, e.g. 6-degree rotation of the plunger may correspond to one IU. The axial length and/or the degrees of rotation are not limited to the one disclosed here and may for example depend on the drug delivery device used.
According to at least one embodiment the electronic dose capturing system may comprise at least one sensor configured to capture the movement of a component of the drug delivery device involved in the dispensing of the drug dose, the movement being indicative for the amount of drug delivered while the element is moving. The at least one sensor may be one or more of an optical sensor, a magnetic sensor, a capacitive sensor and a mechanical sensor.
The device dose indicator in particular may be a mechanical device dose indicator, e.g. a device dose indicator which functions mechanically, e.g. through a number sleeve rotating. The difference between the captured dosage size and the dose indication provided by the device dose indicator may for example arise when the mechanically set dosage size and/or delivered dosage size is incorrectly measured by an electronic component, such as the electronic dose capturing system.
If the device dose indicator is instead electronic, then usually the drug delivery device does not require the electronic dose capturing system, because in such a case the dose indication of the device dose indicator would already be in electronic form and may immediately be used as indication of the captured dosage size of the delivered drug dose. The disclosure, however is not limited to mechanical device dose indicators, as drug delivery devices may comprise both an electronic device dose indicator and an electronic dose capturing system, e.g. being configured to capture a delivered drug dose by measuring mechanical movement of a component of the drug delivery device, the component being directly or indirectly linked with the dispensing of the drug dose, as foe example explained above.
Differences between the dose indication and the captured drug dose may for example occur due to incorrect or imprecise capturing by the electronic dose capturing system. Differences between the dose indication and the captured drug dose, may for example be due to the electronic dose capturing system capturing additional movement of the component of the drug delivery device being directly or indirectly linked with the dispensing of the drug dose. The additional movement may be incorrectly identified by the electronic dose capturing unit as an additional drug dose being dispensed, although the additional movement of the component did not correspond to an additional drug dose being dispensed.
For example, the electronic dose capturing system may be configured to capture the dosage size through capturing of the axial and/or rotational movement of the plunger of a drug delivery device. The plunger may however, after having expelled the set drug still move, e.g. rotate or axially move, for a predetermined distance. This additional movement may be (sometimes) captured by the electronic dose capturing system as an additional drug dose having being expelled, thereby creating a difference between the dose indication and the captured drug dose.
According to at least one embodiment, the method may further comprise the step of, prior to delivering the dose of a specific dosage size, setting the specific size of the drug dose to be delivered.
According to at least one embodiment, setting the specific drug dose to be delivered may comprise dialing the drug dose to be delivered on a dose dialing element of the drug delivery device.
According to at least one embodiment, the dose dialing element may be or may comprise the device dose indicator. The dose dialing element may be configured to be displaced from a set dose position to a zero-dose position after the set drug dose has been delivered. The dose dialing element may for example be rotated to a set dose position corresponding to a set dosage size of a drug dose to be delivered. After delivery of the complete set dose, the dose dialing element may be configured to return to its zero-dose position.
If, however, e.g. less than the set dose is delivered, the dose dialing element may not return to its zero-dose position, but may, instead, return to an intermediate position indicative of the difference between the set dose and the delivered dose. If for example, a set dosage size of ten drug doses was set, but only a dosage size of seven drug doses was dispensed, the dialing element may return from a set dose position indicating ten doses, to an intermediate position indicating three drug doses.
The dose position of the device dose indicator corresponding to a set drug dose and/or delivered drug dose, e.g. the set dose position, the zero-dose position, any intermediate dose position and/or a maximum dose position (identifying the maximum dose that may be delivered), may be visible to the user of a drug delivery device, e.g. through a dialing sleeve with numbers, e.g. displaying the dosage size, e.g. in International Units, on it.
According to at least one embodiment, the method may further comprise the step of determining if the dose dialing element has returned from its set-dose position to its zero-dose position after the set dose has been delivered, e.g. in order to capture if the whole dosage size was delivered, and/or to an intermediate dose position.
According to at least one embodiment, the electronic dose capturing system may be integrated into a drug delivery system comprising the drug delivery device and the electronic dose capturing system. The electronic system may be fixedly integrated into the drug delivery device, e.g. not removable from the drug delivery device.
According to at least one embodiment, the electronic dose capturing system is comprised in an add-on module configured to be permanently or releasable mounted on the drug delivery device. The add-on module may for example be an add-on module as the one disclosed in WO 2016/198516 A1.
According to at least one embodiment, the method comprises the step of, prior to delivering a drug dose and/or prior to setting a dosage size, checking whether the add-on module is correctly mounted of the drug delivery device.
According to at least one embodiment the method may comprise the step of, if at any stage during any step of the method the add-on module is demounted, remounting the add-on module on the drug delivery device and repeating the steps of the method. Repeating might comprise starting the method from the beginning, e.g. by setting the dose and/or dispensing the specific dosage size of the drug dose.
According to at least one embodiment the determination, e.g. determining whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator, may be performed on a first dosage size of the set drug dose, the first dosage size being less than or equal to a threshold dosage size. Additionally or alternatively the determination, e.g. whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator, may be performed on a second dosage size of the set drug dose, the second dosage size being greater than or equal to a threshold dosage size. According to at least one embodiment, the second dosage size 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 times greater than the first dosage size.
According to at least one embodiment, the method may further comprise the step of quantifying the differences between the captured dosage size and the dose indication provided by the device dose indicator. In this case, the difference might be given in International Units. The quantification of the difference may help in better investigating, e.g. analyzing, the dose capturing accuracy of the electronic dose capturing system.
According to at least one embodiment, the drug delivery device is a single-use drug delivery device or a disposable drug delivery device or a reusable drug delivery device. According to at least one embodiment, the drug delivery device is an injector, e.g. a pen-type injector and autoinjector. The drug delivery device may in particular be a drug delivery device in which the dispensing operation is executed mechanically.
According to at least one embodiment, if during delivery of a set drug dose the needle of the drug delivery device is determined to be blocked and/or to be bent, the needle may be unblocked and/or replaced and the steps of the method may be repeated, e.g. from the start.
According to at least one embodiment, the electronic dose capturing system comprises a transmitter unit, the transmitter unit being configured to transmit the captured dosage size of the drug dose to an external device configured to record and/or reproduce the captured dosage size. The electronic dose capturing system may have Bluetooth® communication and/or near field communication (NFC) circuits for proximity-based pairing and connectivity with the external device for real-time or deferred transfer of captured data to the external device.
According to at least one embodiment, the external device is any one of: a mobile device, e.g. a smartphone, a wearable device, e.g. a smartwatch, a computing device, a tablet, a pc, a laptop.
The captured dosage size of the drug dose may then for example be displayed on the external device, e.g. on an app of a smartwatch, on a computer program of a pc, on the smart watch, etc.
According to a second aspect of the disclosure, a method for investigating the dose capturing accuracy of electronic dose capturing systems is provided. The method may be for investigating inter-use variability of the dose capturing accuracy of electronic dose capturing systems, e.g. how the dose capturing accuracy varies depending for example on parameters linked to a user of the drug delivery device, e.g. a user of the electronic dose capturing system. The method may comprise compiling test data derived or derivable from tests carried out by test users of a group of test users.
The tests may comprise determining the dose capturing accuracy of an electronic dose capturing system of at least one test system according to the method of the first aspect of this disclosure and/or any of its embodiments.
Each test system may comprise a drug delivery device and the electronic dose capturing system. The method of the second aspect may also comprise the step of evaluating the test data.
According to at least one embodiment, the tests may comprise determining the dose capturing accuracy of electronic dose capturing systems of a set of test system. The drug delivery devices and the electronic dose capturing systems of different test systems of the set of test systems may have identical configuration. Identical configuration may imply that the same type of drug delivery device is used and/or that the same type of electronic dose capturing system may be used with the drug delivery device.
According to at least one embodiment, the set of test system may comprise at least three test systems. According to at least one embodiment the method may comprise determining the dose capturing accuracy of an electronic dose capturing system of at least three test systems according to the method of the first aspect of this disclosure and/or any of its embodiments.
According to at least one embodiment, compiling test data and/or evaluating test data may comprise the quantification of the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test.
According to at least one embodiment compiling the test data further comprises the step of gathering at least one of, more of or all of following data to be used as test data:
- set dosage size of delivered drug dose,
- captured dosage size,
- error test data indicative of problems during the carrying out of the test,
- test user specific use data from each test user of the group test users,
- test system specific data from each test system,
- test user specific personal data. The set dosage size of the delivered drug dose may for example be the dosage size of the drug dose that was selected in the dial-member.
The captured dosage size may be the dosage size captured by the electronic dosage capturing system (s).
Error test data may include any data indicative of an error in performing the method of the first and/or of the second aspect. Error data may for example include: information regarding the blocking of the needle, e.g. what dosage size was selected when the needle was blocked; information about bending of the needle, e.g. the age group of the test user that bent the needle and/or the hand used by the test user; and/or information about improper demounting of an addon comprising the electronic dose capturing system, etc. .
According to at least one embodiment, the test user specific use data may comprise at least one of, more of, or all of following information:
- experience level of each test user with respect to usage of the drug delivery device,
- hand used by each test user to hold the drug delivery device during delivery of the drug dose,
- finger used by each test user to deliver the drug dose,
- experience of each test user with respect to different drug delivery system,
- maximum ever delivered dosage size by each test user.
According to at least one embodiment, the test system specific data may comprise at least one of, more of, or all of following information:
- type and/or model of drug delivery device used in the test system,
- type and/or model of electronic dose capturing system and/or add on device used in the test system,
- specific dosage size of the drug dose delivered in each test.
According to at least one embodiment the test user specific personal data may comprise at least one of, more of, or all of following information:
- age of test user and/or average age of all test users,
- gender of test user(s),
- diseases of test user(s).
According to at least one embodiment, the test data is derived or derivable from at least seven tests carried out respectively on at least one test system, e.g. on three test systems. According to at least one embodiment, evaluating the test data comprises performing analysis on the compiled test data. The analysis may be for example statistical analysis.
We note that features described above and below in conjunction with different embodiments or aspects can be combined with one another, even if such a combination is not explicitly disclosed herein above or below. Further features, advantages and expediencies of the disclosure and, particularly, of the proposed concepts will become apparent from the following description of the exemplary embodiments in conjunction with the drawings.
Further scope of applicability of the present disclosure will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating exemplary embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description.
Brief Description of the Drawings
The present disclosure will become more fully understood from the detailed description given below and the accompanying drawings, which are given by way of illustration only, and do not limit the present disclosure, and wherein:
Figure 1a shows an exemplary embodiment of a drug delivery device to which an electronic dose capturing system may be attachable;
Figure 1b shows a perspective view of one end of the drug delivery device of Figure 1a when an electronic dose capturing system according to an exemplary embodiment is attached.
Figure 2 is a schematic view of an exemplary embodiment of steps of the method according to the first aspect;
Figure 3 is a schematic flow diagram of some steps of an exemplary embodiment of the method of the first aspect;
Figure 4 is a schematic view of some steps an exemplary embodiment of the method of the second aspect.
Figure 5 shows a schematic exemplary embodiment of a data sheet used for compiling and/or evaluating the test data from exemplary embodiments of the methods. Figure 6 shows some exemplary embodiments of compiled test data according to an exemplary embodiment of the methods.
Figure 7 shows an exemplary embodiment of the step of evaluating the compiled test data.
Figure 8 shows a poster giving some further information regarding some exemplary embodiments of the first and/or second aspect of the method.
The present Figure 1a shows a drug delivery device e.g. an injection device, such as a pen injector, to which an electronic dose capturing system 20 is attachable to a proximal end, such as to fit the injector device like a cap (see e.g. Figure 1b). The electronic dose capturing system 20 may be configured such that it can be push-fitted over a dosage knob or dose dialing knob of the injection device. In particular, a first portion of the electronic dose capturing system includes a cavity that receives the dosage knob, and includes a deformable inner surface such as to provide a tight fit over the dosage knob and/or has features that mate closely with external features of the dosage knob. Through the push-fit features, the electronic dose capturing system can easily be installed on the injection device, and can easily be removed through application of a removal force between the electronic dose capturing system and the injection device in an axial direction. When installed, the electronic dose capturing system is manipulated by the user in order to effect operation of the injection device. The electronic dose capturing system when installed monitors quantities and times of medicament delivery from the injection pen.
Medicament quantities can be transmitted to an external device, e.g. to a smartphone, and/or displayed on a display of the electronic dose capturing system. By providing the electronic dose capturing system with push-fit features, it can be located onto and used with a series of different drug delivery devices and thus monitor a user's medicament treatment over multiple devices. Moreover, this can be achieved without impeding normal use of the injection device and without obscuring a dosage window, e.g. a device dose indicator of the injection device.
In the following, embodiments of the present invention will be described with reference to an insulin injection device. The present invention is however not limited to such application and may equally well be deployed with injection devices that eject other medicaments or drug delivery devices that deliver other medicaments. Figure 1a is an exploded view of a medicament delivery device. In this example, the medicament delivery device is an injection device 1, such as the one disclosed in the patent application WO 2004/078239 A1. The injection device 1 of Figure 1a is a pre-filled, disposable injection pen that may comprise a housing 10 comprising an insulin container 14, to which a needle 15 can be affixed. The needle is protected by an inner needle cap 16 and either an outer needle cap 17 or an alternative cap 18. An insulin dose to be ejected from injection device 1 can be programmed, or 'dialed in' by turning a dosage knob 12, and a currently programmed dose is then displayed via device dose indicator 13, for instance in multiples of units. For example, where the injection device 1 is configured to administer human insulin, the dosage may be displayed in so-called International Units (IU), wherein one IU is the biological equivalent of about 45.5 micrograms of pure crystalline insulin (1/22 mg). Other units may be employed in injection devices for delivering analogue insulin or other medicaments. It should be noted that the selected dose may equally well be displayed differently than as shown in device dose indicator 13 in Figure 1a.
The device dose indicator 13 may be in the form of an aperture in the housing 10, which permits a user to view a limited portion of a number sleeve 70 that may be configured to move when the dosage knob 12 is turned, to provide a visual indication of a currently set dose, e.g. a set specific dosage size of a drug dose. The dosage knob 12 may be rotated on a helical path with respect to the housing 10 when turned during setting. The device dose indicator 13 may be and/or comprise the number sleeve 70.
In this example, the dosage knob 12 includes one or more formations 71a, 71b, 71c to facilitate attachment of the electronic dose capturing system.
The injection device 1 may be configured so that turning the dosage knob 12 causes a mechanical click sound to provide acoustical feedback to a user. The number sleeve 70 mechanically interacts with a piston in insulin container 14. When needle 15 is stuck into a skin portion of a patient or in an injection pad, and then injection button 11 is pushed, the insulin dose displayed in device dose indicator 13 will be ejected from injection device 1. When the needle 15 of injection device 1 remains for a certain time in the skin portion or the injection pad after the injection button 11 is pushed, a high percentage of the dose is actually injected into the patient's body or the injection pad. Ejection of the insulin dose may also cause a mechanical click sound, which is however different from the sounds produced when using dosage knob 12.
In this embodiment, during delivery of the insulin dose, the dosage knob 12 is turned to its initial position, in an axial movement, that is to say without rotation, while the number sleeve 70 is rotated to return to its initial position, e.g. to a zero-dose position, e.g. to display a dose of zero units. Injection device 1 may be used for several injection processes until either the insulin container 14 is empty or the expiration date of the medicament in the injection device 1 (e.g. 28 days after the first use) is reached.
Furthermore, before using injection device 1 for the first time, it may be necessary to perform a so-called "prime shot" to remove air from insulin container 14 and needle 15, for instance by selecting two units of insulin and pressing injection button 11 while holding injection device 1 with the needle 15 upwards. For simplicity of presentation, in the following, it will be assumed that the ejected amounts substantially correspond to the injected doses, so that, for instance the amount of medicament ejected from the injection device 1 is equal to the dose received by the user. Nevertheless, differences (e.g. losses) between the ejected amounts and the injected doses, e.g. the dosing accuracy, may need to be taken into account.
Figure 1b is a perspective view of one end (e.g. proximal end) of the injection device 1 of Figure 1a when an electronic dose capturing system 20 according to an example embodiment is attached. The electronic dose capturing system 20 may include a housing 21 and an end plate 22 with an optional display 22a. The electronic dose capturing system 20 may take one of a number of different forms.
As can be seen in Figure 2 the drug delivery device 1 may be an injection device, e.g. the injection pen shown in the Figure 1a, e.g. an injector pen 1 as the one disclosed in WO 2004/078239 A1. However, different drug delivery device, e.g. different injection pen as shown in Figure 1a, may be used, e.g. the Fiasp® Flextouch® pen, and/or the Basaglar® pen. Figure 1a and 1 b therefore illustrates that the method according to the disclosure may be performed with different drug delivery devices (and different electronic dose capturing systems 20).
The electronic dose capturing system may be configured to be releasable attachable to the drug delivery device, e.g. in the form of an add-on module, e.g. in the form of a connected cap (cCaps) as described in relation to Figure 1a and 1 b. In other embodiments, the drug delivery device may be a reusable drug delivery device and the electronic dose capturing system may be configured to be permanently attached to the drug delivery device.
A test user 2 of the device, e.g. usually a patient or a healthcare, sets a dosage size of a drug dose 200, e.g. by dialing the dosage size in the device dose indicator, which e.g. may comprise a dialing member or may comprise turning a knob as described in relation to Figure 1a. The device dose indicator 210 may be a mechanical device dose indicator. The drug dose may then be delivered 220, e.g. on an injection pad (not shown). The method may be performed either with a real drug, e.g. insulin, or with a drug substitute, e.g. a fluid having similar characteristics as the drug usually used. An electronic dose capturing system may then be configured to capture the dosage size of the delivered drug dose 230. The difference between the captured dosage size of the electronic dose capturing system and the dosage size set on the device dose indicator 240 may then imply the dose capturing accuracy, DCA (also called dose recording accuracy DRA in other figures, e.g. Figure 8).
Such a difference may influence the trust a patient will have with respect to the drug delivery device. Furthermore, the difference might result in the patient deciding to deliver to himself an additional dose of the drug (if for example the dosage size captured by the electronic dose capturing system is lower than the set dosage size, thereby creating the false impression that less drug was delivery than the one intended) or to wait longer than necessary to deliver a new dose (if for example the dose capturing system captured a higher dosage size as the set dosage size, thereby creating the false impression that more drug was delivered as the one set). Both cases can result in extreme dangerous situations for a patient.
Figure 3 shows a schematic flow diagram of some steps of an exemplary embodiment of the method of the first aspect, e.g. a method for determining the drug capturing accuracy of an electronic dose capturing system.
According to a step S1 the specific dosage size to be delivered may be set. Setting the specific dosage size may comprise dialing the dosage size (given in International Units, IU) on a dialing sleeve of a dialing member or by, e.g. turning a knob on one end (e.g. proximal end) of the device as explained in relation to Figure 1a and 1b. The step may however be dispensed as part of the method, as the method may start with a drug delivery device in which the specific dosage size of the drug dose is already set.
According to a further step S2, the specific dosage size may be delivered. The delivery may occur on an injection pad, as the method may be non-therapeutical. The device dose indicator of the drug delivery device may comprise and/or show a dose indication. The dose indication may be indicative of a dosage size of a drug dose that was set and/or of a drug dose that was delivered. The device dose indicator may correspond and/or comprise the dialing member of the drug delivery device.
According to an even further step, S3 the dosage size of the delivered dose may be captured, e.g. by an electronic dose capturing system of the drug delivery device. Capturing the dosage size of the delivered dose may comprise measuring mechanical movement of a component of the drug delivery device, the component being directly or indirectly linked with the dispensing of the drug dose, and optionally giving a visual display of the value. For example, the electronic dose capturing system may be configured to capture the dosage size by capturing the movement of the component of the drug delivery device, the movement may be indicative for the amount of drug delivered while the element is moving.
The movement may be, for example, an axial and/or rotational movement of the component, e.g. of a plunger, a sleeve, and/or a collar. Axial movement of the component, e.g. of the plunger, of a specific distance may for example correspond to a specific dosage size e.g. 5 mm axial movement of the plunger may correspond to one III. Similarly, rotational movement of the component, e.g. of the plunger, of specific degrees may correspond to a specific dosage size, e.g. 6 degree rotation of the plunger may correspond to one IU.
A further step of the method, S4, comprises determining whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator. Such a difference may for example occur when the plunger, e.g. after delivery of a set dosage size of a drug dose, continues to rotate for a predetermined amount of degrees. This rotation may be captured by an electronic dose capturing system and may be considered as a further unit of drug dose being delivered. The captured dosage size by the electronic dose capturing system may therefore not coincide with the dose indication provided by the device dose indicator, e.g. the set drug dose. The difference may also be quantified. The quantification may be useful for evaluating test data as will explained later.
The determination may be performed on a first dosage size of the set drug dose, the first dosage size being less than or equal to a threshold dosage size and/or on a second dosage size of the set drug dose, the second dosage size being greater than or equal to a threshold dosage size. The second dosage size may for example be three times greater than the first dosage size.
If the electronic dose capturing system is configured or comprised in an add-on device, the method may comprise the step of checking if the add-on device is mounted properly. The method may comprise the step of, if at any stage during any step of the method the add-on module is demounted, remounting the add-on module on the drug delivery device and repeating the steps of the method. Repeating might comprise starting the method from the beginning, e.g. by setting the dose and/or dispensing the specific dosage size of the drug dose. Figure 4 shows a schematic overview of a method according to an exemplary embodiment of the second aspect.
Investigating the dose capturing accuracy DCA of the electronic dose capturing system may be achieved through the exemplary embodiment of the method shown in Figure 4. According to this embodiment test data may be compiled. The test data may be derived from tests carried out by n test users of a group of test users comprising n test users. The tests may comprise determining the dose capturing accuracy of an electronic dose capturing system of at least one test system (e.g. as shown in this figure of x test systems) according to the method of the first aspect and/or any of its embodiments, e.g. according to the method of Figure 3, e.g. by performing at least steps S1 to S4.
In this exemplary embodiment, each test user TU_1 to TU_n may be provided with x numbers of test systems, e.g. test system 1 , TS_1 to test system x, TS_x. Each test system may comprise a drug delivery device and an electronic dose capturing system. The drug delivery devices and the electronic dose capturing systems of different test systems of the set of test systems may have identical configuration, e.g. the may all have the same type of drug delivery device and the same type of electronic dose capturing system, e.g. an injection pen and a cCap as shown and described in Figure 1 and/or Figure 2.
A test user 1 , TU_1 , may perform a tests (a being a natural number, e.g. 7), e.g. test 1_1 to test 1_a, on the first test system, e.g. test system 1 , TS_1. The test data obtained by each of the a test may then be compiled 1100.
A test user 1 , TU_1 , may perform b tests (b being a natural number, e.g. 7), e.g. test 1_1 to test 1 _b, on the second test system, e.g. test system 2, TS_2. The test data obtained by each of the b test may then be compiled 1100.
A test user 1 , TU_1 , may perform z tests (z being a natural number, e.g. 7), e.g. test x_1 to test x_z, on the x-th test system, e.g. test system x, TS_x. The test data obtained by each of the z test may then be compiled 1100.
The steps performed by the test users, e.g. steps S1 to S4, may differ from each other with respect of the specific dosage size in steps S1 and/or S2.ln other words, different test users may perform at least some tests with different dosage sizes of the drug dose. In the same test system of one user, e.g. test system 1 , TS_1 , of test user 1 , TU_1 , the tests may all differ with respect to the specific dosage size of the drug dose, e.g. used for steps S1 and/or S2.
In different test systems of one test user, e.g. test system 1 and test system 2 of test user 1 , at least two test, e.g. test 1_2 and test 2_3, may be equal with respect to the specific dosage size of the drug dose used in the tests, e.g. used for steps S1 and/or S2.
Different tests of different test users, e.g. test 3_5 of test user 1 and test 1_3 of test user 2, may be equal with respect to the specific dosage size of the drug dose used in the tests, e.g. used for steps S1 and/or S2.
In some embodiments about 50% of the tests are done with a dosage size being smaller than a predetermined dosage size, e.g. 10 III, and 50% are done with a dosage size being larger than the predetermined dosage size, e.g. 10 IU. Different percentages are however also envisaged, e.g. depending whether test data should be compiled focused on some more specific dosage sizes.
In certain embodiments, the test systems for different test users may have identical configuration, e.g. test system 1 of test user 1 has identical configuration to test system 1 of test user 3. Identical configuration may mean that the type of the drug delivery device and/or of the electronic dose capturing system is substantially identical.
One exemplary embodiment may for example comprise three test systems, e.g. x=3. It was found that using at least three test systems offers enough information for a significant evaluation of test data, e.g. a statistical significant investigation of the drug capturing accuracy of electronic dose capturing systems.
The numbers a, b, z, may be equal to each other, equal to some of each other or different to each other. In one example a may be equal to b which may be equal to z which may be equal to at least seven, i.e. for each test system, seven tests would be performed.
In total for a test user 1, test data from (a+b+...+z) tests may be compiled. For a test group of test users n, test data from n*(a+b+...+z) tests may be compiled. It has proven advantageous for the evaluation of the test data if the number of tests per test system performed by each test user is the same, e.g. the numbers a, b, z being the same for each test user. According to one embodiment (e.g. as shown in Figure 6), twenty test users (n=20) are provided with three test systems (x=3) and perform seven tests (a=b=z=7). In this embodiment a total of 420 tests are performed and the test data may be compiled and evaluated.
It has proven advantageous to have at least 16 test users, as this value of test users provide sufficient relevant data, e.g. for an evaluation of the test data, e.g. a statistical evaluation of the test data, without requiring too much operational expense. The disclosure, however is not limited to this value, and also with less or more test user the compiled test data and evaluated test data may result significant, e.g. depending on other parameters. Due to fatigue and deconcentrating of the test user, each test user may perform less than 45 test, e.g. less than 15 test per test system. The disclosure is however not limited to less than 45 tests per user.
The test data 1000 of all the test may be compiled and may form compiled test data 1100.
The compiled test data 1100 may also comprise the quantification of the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test, e.g. determined in step S4 of each test. The quantification of the difference may however, additionally or alternatively be comprised in the step of evaluating the test data. For example, the compiled test data may comprise the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test, e.g. determined in step S4 of each test. The evaluation of the compiled test data may comprise quantifying the differences between the captured dosage size and the dose indication provided by the device dose indicator for each test.
Compiling the test data 1100 may further comprise the step of gathering at least one of, more of or all of following data to be used as test data:
- set dosage size indicated by the device dose indicator
- captured dosage size
- quantification of the differences between the captured dosage size and the set dosage size indicated by the device dose indicator;
- error test data indicative of problems during the carrying out of the tests.
- user specific use data from each test user of the group test users
- test system specific data from each test system;
- test user specific personal data.
As mentioned, the selected dosage size may vary between each or at least some of the tests, in order to investigate the dose capturing accuracy of electronic dose capturing systems at different dosage sizes and in the evaluation stage to evaluate if a correlation exists between the dosage size used and the dose capturing accuracy.
The captured dosage size, may comprise the dosage size data captured by the electronic dose capturing system.
The difference determined during the performance of the method of the first aspect, may also be quantified and the quantification may be gathered as test data and may be comprised in the compiled test data and/or may be evaluated in the step of evaluating the test data.
Error test data may include any data indicative of an error in performing the method of the first and/or for the second aspect. Error data may for example include: information regarding the blocking of the needle, e.g. what dosage size was selected when the needle was blocked; information about bending of the needle, e.g. the age group of the test user that bent the needle and/or the hand used by the test user; information about unproper demounting of an add-on comprising the electronic dose capturing system; information regarding test protocols not being properly executed by the test users, etc.
Test user specific use data from each test user of the group test users may comprise at least, one of, more of, or all of following information:
- experience level of each test user with respect to usage of the drug delivery device,
- hand used by each test user to hold the drug delivery device during delivery of the drug dose,
- finger used by each test user to deliver the drug dose,
- experience of each test user with respect to different drug delivery system,
- maximum ever delivered dosage size by each test user.
The hand used by the test user may be relevant in order to assess, if the accuracy changes between left-handers and/or right-handers. The same may hold for the finger, e.g. the finger used for delivery a drug dose. For example, when using the thumb to deliver a drug dose, e.g. when pressing the injection button 11 (of Figure 1) with the thumb, the drug delivery device is usually held with the whole hand, e.g. remaining for fingers grab the housing of the drug delivery device. The force applied by the hand acting on the drug delivery device while pressing the injection button, e.g. the radially inward force acting on the housing of the drug delivery device, may interfere with the capturing of the dose by the electronic dose capturing system thereby creating a difference between the dose indication and the captured drug dose.
Such an interference may for example be caused by a relative movement of the electronic dose capturing system with respect to the drug delivery device or e.g. by an additional movement of a component of the drug delivery device (caused by the grabbing), this additional movement being identified by the electronic dose capturing system as being indicative of a further dose having been delivered (although no such does was delivered).
It may therefore be advantageous to include the finger used for dispensing drug dose and/or the hand used for dispensing a drug dose in the test user specific use data, for example to asses if the dose capturing accuracy is dependent on the finger and/or hand used.
The experience level of each test user, e.g. with respect to usage of drug delivery devices and/or with respect to use of different drug delivery system, may be enumerated by a respective value. The maximum ever dosage size dispensed by each test user may be used to determine if there is a correlation between dosage capturing accuracy of the electronic systems and specific dosage sizes, the specific dosage size being in the range of used dosage sizes by the test users or being outside of the range, e.g. higher than the maximum ever dosage size dispensed by the test user.
Data that has no intrinsic number value, e.g. experience level may be given value data based on predetermined scales, e.g. no experience may be given the value 0, while daily experience may be given the value 10.
Test system specific data from each test system, e.g. test system 1, may comprise at least, one of, more of, or all of following information:
- type and/or model of drug delivery device used in the test system, e.g. test system 1;
- type and/or model of electronic dose capturing system and/or add on device used in the test system, e.g. the one used in Figure 1 ;
- specific dosage size of the drug dose delivered in each test, which as mentioned may vary between tests in a test system and between test in different test systems.
The test user specific personal data may comprise at least, one of, more of, or all of following information:
- age of test user and/or average age of all test users;
- gender of test user(s);
- diseases of test user(s), e.g. type of diabetes.
The test user specific personal data may be anonymised in order e.g. to fulfil data security requirements. Figure 5 shows an exemplary embodiment of a test data compiling data sheet, e.g. a data sheet used for compiling the test data of one test user, e.g. of test user 1 , P01.
As can be seen from Figure 5, the data sheet of this embodiment is configured to compile data from three test systems, e.g. test system 1, 2, and 3 (TS_1, TS_2, TS_3, respectively). For each test system, seven tests are performed. The set dosage sizes, DD, and the captured dosage size, RD, may be compiled in the first and in the second column respectively. Any relevant observation may be added in the observation column, OBS., e.g. any test error data.
A further example of relevant information that might be added to the observation list, e.g. relevant information that might be gathered for the step of compiling the test data, is whether an unexpected feedback signal of the electronic dose capturing system mis perceived. As mentioned with respect to Figure 1 , the drug delivery device and/or the electronic dose capturing system may be configured to generate a feedback signal, e.g. when delivery is completed. If this signal is generated earlier than when the actual delivery is completed a test user might have slightly released the drug delivery device during injection and thereby influenced the dose recording accuracy of the electronic dose capturing system. As such it may prove relevant to gather that information as well.
On top of the data sheet, 50, following data may gathered: the anonymised name of the participant, the date of the test the start time and the end time of the test(s), the device type, e.g. which test system, e.g. which drug delivery device and/or which electronic dose capturing system is used, and the finger used for the injections, e.g. if thumb or index finger was used. The data sheet is however not limited to these information and more or less data may be gathered and recorded on the data sheet.
Figure 6 shows an exemplary embodiment of specific elements of the step of compiling test data for several test users, e.g. for 20 test users, PA-01 to PA-20. Only the test data specific to the difference (or the quantification) of the difference between the captured dosage size and the dose indication provided by the device dose indicator is shown in this Figure, however also other test data may be added to the table.
Different test user performed the tests on different days as can be seen in the table. However all users may perform the test on the same day, and the disclosure is not limited to multiday tests.
Three different test systems are shown in this Figure, test system 1, denoted with "V3-Z"; test system 2, denoted with "V3-X" and test system 3, denoted with "V3-C". The test system may be different with respect to each other. In the cells where a single value is shown, no difference between the captured dosage size and the dose indication provided by the device dose indicator may have been determined. The value therefore corresponds both to the set dosage size of the drug dose and to the captured dosage size. For example, in the first test of test system V3-Z for test user 1 , PA-01 , the set dosage size and the captured dosage size may correspond to 6.
In the cells where a first value is given followed by a second value, the first value may correspond to the set dosage size, while the second value may correspond to the captured dosage size. In the following, some examples of what the values may identify is given:
In the second test of test system 2, V3-X, for test user 1 , PA-01 , the set dosage size was 51 , but the electronic dose capturing system may only have captured a dosage size of 49.
In the second test of test system 1 , V3-Z, for test user 5, PA-05, the set dosage size was 47, but the electronic dose capturing system may have captured an additional dosage size, so a dosage size of 48.
In the first test of test system 1 , V3-Z, of test user 6, PA-06, "56»inc" is shown. The value "inc" may stand for "injection incomplete", meaning that, in this case, the set dosage size was set to 56 and was delivered, but the electronic dose capturing system although recognizing that a delivery was done did not capture a dose size.
In the fourth test of test system 3, V3-C, of test user 16, PA-16, the value "33»29+4R" is shown. This may mean that the set dosage size was set to 33 and that when the dosage was delivered the device dose indicator was showing still four doses left (corresponding to the "4R") and the electronic dose capturing system captured a dosage size of 29. The value in the electronic dose capturing system, in such a case may be deemed correct.
In the fourth test of test system 3, V3-C, of test user 14, PA-14, the value "1G" is shown. This may stand for "ghost data", meaning that one dosage size was not delivered but the electronic dose capturing system has captured a dose by mistake.
In the seventh test of test system 3, V3-C, of test user 14, PA-14, the value "7»m" is shown. This may stand for "missing data", meaning that the test user has set a dosage size of a drug dose, e.g. seven, delivered the dosage size but the electronic dose capturing system shows no entry and no delivery. Preferably, about 50% of the tests are done with a first dosage size, the dosage size being smaller than a predetermined dosage size, e.g. a threshold dosage size, e.g. 10 IU, and 50% are done with a second dosage size, the dosage size being larger than the predetermined dosage size, e.g. than the threshold dosage size, e.g. 10 IU.
The colour or pattern coding and/or use of codes and abbreviations, e.gg 33»29+4R, G, 7»m, 56»inc, may not be limited to the one shown in the table and may be modified. The legend (reproduced here below) in the figure further describes what each abbreviation may mean (as also disclosed above).
The legend mentions an App, e.g. the app in which the captured dosage size by the electronic dose capturing unit is reproduced. The disclosure is however not limited to this and the entries of the captured dosage size(s) can also or only be reproduced on the electronic dose capturing system itself, e.g. on a display as shown in Figure 2.
Pattern coding (as such) of the table provided in Figure 6 however has proven particularly advantageous, as it may permit an automatic evaluation of the test data by optical devices.
Figure 7 shows an exemplary embodiment of the step of evaluating the compiled test data, e.g. the test data of Figure 6.
As can be seen from Figure 7, evaluating the compiled test data may comprise the step of analysing, e.g. in absolute numbers and/or in percentage, Tot., the quantification of the difference between the captured dosage size and the dose indication provided by the device dose indicator with respect to all test and/or with respect to the test with less than a predetermined dose, e.g. less than 10 III, and with respect to the test with more than a predetermined dose, e.g. more than 10 IU. The colour coding may be equal to the colour coding of the compiled test data (see e.g. Figure 6).
The evaluation in percentage may be done with respect to all test in which a dosage size of a drug dose was set and in which the electronic dose capturing system captured a dosage. Tests in which data was missing 504, the injection was incomplete 502 and/or ghost data 500, may be analysed as such, with respect to all tests, e.g. with respect to the sum 506 of "injection incomplete 502 and missing dose (e.g. ghost data 500 and/or missing data 504), but may not be considered in the evaluation with respect to the difference between the captured dosage size and the dose indication provided by the device dose indicator, see, e.g. row 508 "n without "injection incomplete", and missing data.
The evaluation may comprise evaluating in absolute numbers and/or in percentage, Tot., in how many tests the difference between the captured dosage size and the dose indication provided by the device dose indicator, is one dose, e.g. deviations of +1 or -1 dose, or that the difference is two dose, e.g. deviations of +2 or -2 doses, or that the difference is greater than 2 dose, e.g. deviations of +3 or more dose or of -3 or more dose.
Figure 8 shows a poster giving some further information regarding some exemplary embodiments of the first and/or second aspect of the method. Features described in the poster may be used to further describe embodiments of the first aspect and/or second aspect of the disclosure. Features described in the poster may also be used as claim subject matter.
The poster 100 may comprise an introduction section 110. The section may read: "Insulin management can be challenging, e.g. to keep track on daily dosing. Digital solutions might alleviate the burden of those documentations. Connected caps (cCaps) are currently available for disposable insulin pens as part of the digital diabetes management offerings. Literature indicates that the User Experience (UX) and performance of cCaps based on Dose Recording Accuracy (DRA) is crucial in the onboarding phase for acceptance".
The introduction session may also define an objective 110a, for example: "1st time evaluation of UX on Look & Feel, Handling, and DRA in the onboarding phase into digital diabetes management (mgt.) with marketed insulin pens, dedicated cCaps and apps."
Box 110b may show possible ecosystems that might comprise pen, cap and app. The pen on the left might be the pen described in WO 2004/078239 A1, comprising a smart-add on, on its distal end. The pen in the middle may be the "Tempo-Pen" with a "Tempo-Button". The pen on the right might be the Flex-Touch comprising the "Mallya". Please note that marketed products might be Registered or protected via Trademark in specific countries. All three pens might be connected to a smartphone via Bluetooth. Next to the introduction section 110, a method section 120 may be provided. The method section may comprise a subsection "Lab Setting with Randomized Testing" 120a. The subsection 120a may disclose in bullet points:
• 30 people with T1D or T2D (18-63 years).
• Simulation of the onboarding phase with setup of each system, injection according to the IFU, DRA, and evaluation of UX by patients.
• To measure DRA 16 people, perform 15 injections at predetermined doses with each cCap into a cushion.
• Evaluation of UX with a questionnaire - based on 5-point Likert scales.
The graph visible in the poster, represents: cCaps 120b in a randomized order. Digital diabetes Management (pen, cap, app) which comprises look & feel and handling 120c and DRA 120d; and a questionnaire for evaluation of UX 120e.
Underneath the "Lab Setting with randomized Testing 120a" a section "Definition of a DRA Test Method" 130 is provided. Section 130 may disclose:
130a - Pen dialled & injected dosage;
130b - cCap measured & processed of data;
130c - App displayed dosage, date and time;
130d - Comparison of data;
130e - Randomized testing;
130e1 - Minimum number of injection n= 180, reflecting 3 month of usage;
130f - DRA classification;
130g - Injection incomplete;
130h - Ghost data;
130i - Missing data.
Section 140 may instead disclose some possible results. The section may show:
• 140a "Setup of System Drives 1st UX for Users. Smart add-on scores better in Look & Feel (p < 0,001), Dialing, and Injection (p < 0,01) by patients vs. TempoButton and Mallya. TempoButton scores higher in Intuitive Mounting vs. Smart add-on (p < 0,05) & Mallya (p < 0,01). Mean subject evaluation of UX of cCaps".
The mean subject evaluation of UX of cCaps may be shown further below in section 140 and may disclose:
• 140b - the results for the SoloSmart;
• 140c - the results for the TempoButton;
• 140d - the results for the Mallya; • 140e to 140i - Very Bad, Bad, Neutral, Good and Very Good, respectively;
• 140j - Look & Feel;
• 140k - Intuitive mounting;
• 1401 - Dialing;
• 140m - Injection.
The intuitive mounting, the dialing and the injection may represent handling steps in setup.
The" Drives 2nd UX for Users" 150, may disclose:
150a - "The DRA - dialed & injected dose vs. displayed - is similar for all the tested digital diabetes management systems. The displayed data in the diary functions of glooko and Health2Sync is comparable".
The diary data 150b may include date, time, dosage and medication.
Box 150c represents an example of Health2Sync Diary. In this example on a normal weekday, the user may have primed Medication Toujeo-Priming at 15:12 and may have medicated with Toujeo on 15:13, e.g. after lunch.
Section 160 may disclose information of patient perspective in digital diabetes management. It may dislcose:
• "Dosage, time, date, and medication is evaluated as added value by patients".
• "Patients assessed the DRA - as key performance indicator of the tested digital diabetes mgt. systems - as acceptable".
• "To support patients, further information beyond IFU is recommended".
Section 170 may disclose discussion points, such as:
"New DRA Test Method proposal reflects simulation of critical 1st 3 months of usage.
If one of the ecosystem components (pen, cCap & app) fails, the overall acceptance and UX by patients is poor in general".
In section 180 a conclusion may be given. The conclusion may disclose:
• Patients evaluate dosage, time, date, and medication as added value to support insulin management.
• The device, e.g. the cCap as disclosed in of WO 2004/078239, being the smallest device, scored better vs. Tempo and Mallya, on UX for people with T 1 &T2 diabetes.
• Digital diabetes support sounds promising. Onboarding to the ecosystem is a critical step, which requires support beyond the IFU. The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.
As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.
The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., shorter long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C). In some instances, the drug container may be or may include a dualchamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body. The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis of many different types of medical disorders.
Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (antidiabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.
Examples of APIs for the treatment and/or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term ..derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide. Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.
Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N- palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega- carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(w- carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(w-carboxyheptadecanoyl) human insulin.
Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC- 1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211 , CM-3, GLP-1 Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1 , ZYD-1, GSK-2374697, DA-3091 , MAR-701 , MAR709, ZP- 2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA- 15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide- XTEN and Glucagon-Xten.
An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrom.
Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate. The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigenbinding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).
The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that still comprises at least a portion of a full- length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and immunoglobulin single variable domains. Additional examples of antigen-binding antibody fragments are known in the art.
The term “immunoglobulin single variable domain” (ISV), interchangeably used with “single variable domain”, defines immunoglobulin molecules wherein the antigen binding site is present on, and formed by, a single immunoglobulin domain. As such, immunoglobulin single variable domains are capable of specifically binding to an epitope of the antigen without pairing with an additional immunoglobulin variable domain. The binding site of an immunoglobulin single variable domain is formed by a single heavy chain variable domain (VH domain or VHH domain) or a single light chain variable domain (VL domain). Hence, the antigen binding site of an immunoglobulin single variable domain is formed by no more than three CDRs. An immunoglobulin single variable domain (ISV) can be a heavy chain ISV, such as a VH (derived from a conventional four-chain antibody), or VHH (derived from a heavy-chain antibody), including a camelized VH or humanized VHH. For example, the immunoglobulin single variable domain may be a (single) domain antibody, a "dAb" or dAb or a Nanobody® ISV (such as a VHH, including a humanized VHH or camelized VH) or a suitable fragment thereof. [Note: Nanobody® is a registered trademark of Ablynx N.V.]; other single variable domains, or any suitable fragment of any one thereof.
“VHH domains”, also known as VHHs, VHH antibody fragments, and VHH antibodies, have originally been described as the antigen binding immunoglobulin variable domain of “heavy chain antibodies” (i.e. , of “antibodies devoid of light chains”; Hamers-Casterman et al. 1993 (Nature 363: 446-448). The term “VHH domain” has been chosen in order to distinguish these variable domains from the heavy chain variable domains that are present in conventional 4- chain antibodies (which are referred to herein as “VH domains”) and from the light chain variable domains that are present in conventional 4-chain antibodies (which are referred to herein as “VL domains”). For a further description of VHH’s, reference is made to the review article by Muyldermans 2001 (Reviews in Molecular Biotechnology 74: 277-302).
For the term “dAb’s” and “domain antibody”, reference is for example made to Ward et al. 1989 (Nature 341: 544), to Holt et al. 2003 (Trends Biotechnol. 21: 484); as well as to WO 2004/068820, WO 2006/030220, WO 2006/003388. It should also be noted that, although less preferred in the context of the present invention because they are not of mammalian origin, single variable domains can be derived from certain species of shark (for example, the so-called “IgNAR domains”, see for example WO 2005/18629).
The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.
Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab). Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.
Those of skill in the art will understand that modifications (additions and/or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.
An example drug delivery device may involve a needle-based injection system as described in Table 1 of section 5.2 of ISO 11608-1 :2014(E). As described in ISO 11608-1 :2014(E), needlebased injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.
As further described in ISO 11608-1 :2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).
As further described in ISO 11608-1 :2014(E), a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). As also described in ISO 11608-1:2014(E), a single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

Claims

Claims
1. A method for determining the dose capturing accuracy of an electronic dose capturing system (20), wherein the electronic dose capturing system (20) is configured to electronically capture a dosage size of a drug dose delivered from a drug delivery device (1), wherein the drug delivery device (1) has a device dose indicator, the device dose indicator (13) being configured to provide a dose indication indicative of a dosage size of a set drug dose and/or of a delivered drug dose, the method comprising:
- delivering (S2) a drug dose of a specific dosage size as indicated by the device dose indicator (13) from the drug delivery device (1) and
- capturing (S3) the dosage size of the delivered dose using the electronic dose capturing system (20) and
- determining (S4) whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator (13).
2. The method according to claim 1 , comprising, prior to delivering the drug dose of a specific dosage size, setting (S1) the specific size of the drug dose to be delivered.
3. The method according to claim 2 wherein setting the specific drug dose to be delivered comprises dialing the drug dose to be delivered on a dose dialing element (12) of the drug delivery device (1), wherein the dose dialing element (12) is or comprises the device dose indicator (13).
4. The method according to claim 3, wherein the dose dialing element (12) is configured to be displaced from a set dose position to a zero-dose position after the set drug dose has been delivered, the method further comprising the step of determining if the dose dialing element (12) has returned to its zero-dose position after the set dose has been delivered.
5. The method according to any one of the preceding claims, wherein the electronic dose capturing system (20) comprises at least one sensor configured to capture movement of an element of the drug delivery device involved in the dispensing of the drug dose, the movement being indicative for the amount of drug delivered while the element is moving.
6. The method according to any one of the preceding claims, wherein the specific dosage size is a first dosage size of the set drug dose, the first dosage size being less than or equal to a threshold dosage size and/or wherein the specific dosage size is a second dosage size of the set drug dose, the second dosage size being greater than or equal to a threshold dosage size.
7. The method according to any one of the preceding claims, further comprising the step of quantifying the differences between the captured dosage size and the dose indication provided by the device dose indicator (13).
8. The method according to any one of the preceding claims, wherein the drug delivery device (1) is a single use drug delivery device (1) or a disposable drug delivery device (1) or a reusable drug delivery device, e.g. a pen-type injector (1).
9. A method for investigating the dose capturing accuracy of electronic dose capturing systems (20), the method comprising:
- Compiling (110) test data derived or derivable from tests carried out by test users of a group of test users, wherein the tests comprise determining the dose capturing accuracy of an electronic dose capturing system (20) of at least one test system according to the method of claims 1 to 8, wherein each test system comprises a drug delivery device (1) and the electronic dose capturing system (20), and
- evaluating the test data.
10. The method according to claim 9 wherein the tests comprise determining the dose capturing accuracy of electronic dose capturing systems (20) of a set of test system, wherein the drug delivery devices (1) and the electronic dose capturing systems (20) of different test systems of the set of test systems have identical configuration.
11. The method according to any one of claims 9 to 10, wherein evaluating test data comprises the quantification of the differences between the captured dosage size and the dose indication provided by the device dose indicator (13) for each test.
12. The method according to any one of claims 9 to 11 , wherein compiling (1100) the test data further comprises the step of gathering at least one of, more of or all of following data to be used as test data: - selected dosage size of delivered drug dose,
- captured dosage size,
- quantification of the differences between the captured dosage size and the dose indication provided by the device dose indicator (13) for each test,
- error data indicative of problems during the carrying out of the test,
- test user specific use data from each test user of the group test users,
- test system specific data from each test system,
- test user specific personal data.
13. The method according to claim 12, wherein the test user specific use data comprise at least, one of, more of, or all of following information:
- experience level of each test user with respect to usage of the drug delivery device (1),
- hand used by each test user to hold the drug delivery device (1) during delivery of the drug dose,
- finger used by each test user to deliver the drug dose,
- experience of each test user with respect to different drug delivery system,
- maximum ever delivered dosage size by each test user.
14. The method according to any one of claims 12 to 13, wherein the test system specific data comprise at least, one of, more of, or all of following information:
- type and/or model of drug delivery device used in the test system,
- type and/or model of electronic dose capturing system (20) and/or add on device used in the test system,
- specific dosage size of the drug dose delivered in each test.
15. The method according to any one of claims 9 to 14, wherein evaluating the test data comprises performing statistical analysis on the compiled test data.
16. A method for determining the dose capturing accuracy of an electronic dose capturing system (20), wherein the electronic dose capturing system (20) is configured to electronically capture a dosage size of a drug dose delivered from a drug delivery device (1), wherein the drug delivery device (1) has a device dose indicator, the device dose indicator (13) being configured to provide a dose indication indicative of a dosage size of a set drug dose and/or of a delivered drug dose, the method comprising:
- setting (S1) the specific size of the drug dose to be delivered
- delivering (S2) a drug dose of a specific dosage size as indicated by the device dose indicator (13) from the drug delivery device (1) and - capturing (S3) the dosage size of the delivered dose using the electronic dose capturing system (20) and
- determining (S4) whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator (13), wherein setting the specific drug dose to be delivered comprises dialing the drug dose to be delivered on a dose dialing element (12) of the drug delivery device (1), wherein the dose dialing element (12) is or comprises the device dose indicator (13), wherein the dose dialing element (12) is configured to be displaced from a set dose position to a zero-dose position after the set drug dose has been delivered, the method further comprising the step of determining if the dose dialing element (12) has returned to its zero-dose position after the set dose has been delivered.
17. A method for investigating the dose capturing accuracy of electronic dose capturing systems (20), the method comprising:
- compiling (1100) test data derived or derivable from tests carried out by test users of a group of test users, wherein the tests comprise determining the dose capturing accuracy of an electronic dose capturing system (20) of at least one test system according to following steps
- delivering (S2) a drug dose of a specific dosage size as indicated by a device dose indicator (13) of the drug delivery device (1) and
- capturing (S3) the dosage size of the delivered dose using the electronic dose capturing system (20) and
- determining (S4) whether there is a difference between the captured dosage size and the dose indication provided by the device dose indicator (13); and,
- evaluating the test data, wherein compiling (1100) the test data further comprises the step of gathering test user specific use data from each test user of the group test users, wherein the test user specific use data comprise at least, one of, more of, or all of following information: hand used by each test user to hold the drug delivery device (1) during delivery of the drug dose, and/or finger used by each test user to deliver the drug dose.
PCT/EP2025/053969 2024-02-14 2025-02-14 Method for determining the dose capturing accuracy Pending WO2025172500A1 (en)

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