Journal of Diabetes Science and Technology
`Volume 3, Issue 6, November 2009
`© Diabetes Technology Society
`
`ORIGINAL ARTICLES
`
`Usability, Participant Acceptance, and Safety of a Prefilled
`Insulin Injection Device in a 3-Month Observational Survey
`in Everyday Clinical Practice in Australia
`
`John Carter, M.B.B.S., B.Sc. (Med), MD., FRACP,1,2 Jonathan Beilin, Ph.D., M.B.B.S., FRACP,3
`Adam Morton, M.B.B.S. (Hons), FRACP,4 and Mario De Luise, Ph.D., M.B.B.S., B.Sc. (Med)., FRACP5
`
`Abstract
`
`Background:
`SoloSTAR® (SOL; sanofi-aventis, Paris, France) is a prefilled insulin pen device for the injection of insulin
`glargine and insulin glulisine. This is the first Australian survey to determine its usability, participant
`acceptance, and safety in clinical practice.
`
`Methods:
`A 3-month, nonrandomized, noncomparative, observational survey in Australia was conducted in individuals
`with diabetes. Participants were given SOL pens containing glargine, the instruction leaflet, and a toll-free helpline
`number. Training was offered to all participants. Safety data, including product technical complaints (PTCs), were
`gathered from ongoing feedback given by the participant or health care professional (HCP) and by independent
`interviews conducted 6-10 weeks after study start.
`
`Results:
`Some 2674 people consented to take part across 93 sites (150 HCPs), and 2029 participated in interviews. Of these,
`52.6% had type 1 diabetes, 16.3% had manual dexterity problems, and 15.5% had poor eyesight not corrected by
`glasses. At the time of interview, 96.8% of participants were still using SOL. None of the eight PTCs reported
`were due to technical defects; most were related to handling errors. Some 62 participants reported 77 adverse
`events; none were related to a PTC. The vast majority of participants (95.4%) were "very satisfied" or "satisfied"
`with using SOL, and 89.7% of the participants had no questions or concerns using SOL on a daily basis.
`Similar positive findings were reported by participants with manual or dexterity impairments.
`
`Conclusions:
`In this survey of everyday clinical practice, SOL had a good safety profile and was very well accepted by
`participants.
`
`J Diabetes Sci Technol 2009;3(6):1425-1438
`
`Author Affiliations: 'Concord and Hornsby Hospitals, Hornsby, New South Wales, Australia; 2University of Sydney, New South Wales, Australia;
`3Royal Perth Hospital, Perth, Western Australia, Australia; 4Mater Hospital, Brisbane, Queensland, Australia; and 5Austin Hospital, Heidelberg,
`Victoria, Australia
`
`Abbreviations: (AE) adverse event, (CI) confidence interval, (FP) FlexPen, (HCP) health care professional, (NGFP) Next Generation FlexPen,
`(PTC) product technical complaint, (SOL) SoloSTAR
`
`Keywords: clinical practice, diabetes, insulin glargine, safety, SoloSTAR
`
`Corresponding Author: John Carter, M.D., FRACP, Concord and Hornsby Hospitals, 39 Palmerston Road, Hornsby, NSW 2077, Australia;
`email address icarter@bigpond.net.au
`
`1425
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`Mylan v. Sanofi
`IPR2018-01675
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`

`

`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Carter
`
`Introduction
`
`I nsulin pens have had a significant impact on the
`treatment of diabetes. Compared with a vial and syringe,
`they offer substantial advantages in terms of compliance,
`social acceptability, and flexibility for patients using
`insulin and have been shown to be preferred by both
`people with diabetes and the health care professionals
`(HCPs) who treat them.1- 4 Since the first insulin pen was
`introduced in 1985, ongoing developments in technology
`have led to more advanced devices that offer larger
`maximum doses, smaller dose increments, and improved
`dose features, such as lower injection force and ease of
`identifying the insulin.5- 7
`
`SoloSTAR® (SOL) is a new prefilled insulin pen device
`developed for the administration of either insulin glargine
`(LANTUS®) or insulin glulisine (Apidra®; all sanofi-aventis,
`Paris, France). The SOL pen can be set in 1 U increments,
`similar to other devices, and is capable of delivering a
`maximum dose of 80 U, which is a larger dose volume
`compared with other commonly used disposable pen
`devices. SoloSTAR has a different pen body color for
`each insulin-gray for insulin glargine and blue for
`insulin glulisine. In addition, the insulin glulisine pen
`has a tactile differentiation of a raised ring on the dose
`button besides other differentiation features, including
`different colors in the labels and packaging.
`
`The aim of this survey was to evaluate the safety,
`usability, and acceptance of SOL in a clinical setting and
`focuses on the administration of insulin glargine with
`SOL.
`
`Participants and Methods
`
`Objectives
`The primary objective of this survey was to monitor SOL
`in actual everyday use in order to collect information
`on real use experience and detect any product technical
`complaints (PTCs), safety issues, or problems related to
`its use. This survey was designed to monitor the device
`and not
`the
`insulin. Secondary objectives
`included
`participant satisfaction with the use of the pen. This was
`a 3-month, prospective, observational survey based in
`Australia and was conducted between November 2006
`and February 2007.
`
`antidiabetes agents or people considered by their health
`care provider to be candidates for initiation of injectable
`insulin therapy were invited to participate in the survey.
`Exclusion criteria included current addiction or current
`alcohol/drug abuse; diagnosis of dementia; severe visual
`or dexterity impairment; mental condition rendering
`the person unable to understand the nature, scope, and
`possible consequences of the survey; or any person
`deemed by the investigator as potentially uncooperative.
`Potential participants who met the inclusion criteria were
`identified by their HCP, and the program was explained
`to them at either the next routine clinic visit or by
`telephone. Participants were informed that they would
`be required to report and keep records of any apparently
`broken or not properly
`functioning devices and
`participate in a 10 min telephone interview. All potential
`participants were clearly informed that participation
`was entirely voluntary and that they would continue to
`receive the best standard of care available, even if they
`chose not to participate. Those who were interested were
`then asked to sign an information sheet, which further
`described the program. The survey was conducted in
`accordance with the Declaration of Helsinki. Health
`care professionals who participated in the survey were
`reimbursed for costs associated with administration of
`the survey.
`
`Survey Design
`At the start of the observation period, participants
`were given SOL pens containing insulin glargine, the
`instruction leaflet, and a toll-free helpline number, which
`was operated by an independent agency. At this time,
`participants were also offered training by the HCPs
`on how to use SOL. Participants used SOL for 6-10
`weeks and were asked to report any issues that they
`experienced during this time. At 6-10 weeks after initial
`use, participants were contacted to take part in a 10 min
`telephone survey (Appendix 1) to collect information on
`any problems experienced with SOL. Participants were
`also asked to rate their experience with SOL, including
`aspects of use. To maintain participant confidentiality,
`all telephone contact with participants was managed
`through an
`independent customer
`service group
`(lnternational'M SOS) specializing in medical assistance.
`
`Participants
`People with type 1 or type 2 diabetes with past or
`current use of injectable insulin or other prescribed
`
`Statistical Analysis
`No comparisons were performed, and descriptive
`data are provided. Events are presented as number of
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
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`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Carter
`
`participants and percentages with exact 95% confidence
`intervals (Cls; binomial distribution, as assessed by
`the Clopper-Pearson algorithm). All analyses were
`performed using SAS version 8.2 (SAS Inc., Cary, NC).
`An estimated sample size of 2000 participants was
`determined by taking into account potential device and
`handling problems, which were derived from already
`marketed insulin pen devices in terms of occurrence
`rate. In addition, the minimum sample size allowed the
`detection (with 95% confidence) of potential pen issues
`that occur at a rate of 0.005% or handling problems
`occurring at a rate of 0.0035%, based on an estimated
`6 weeks of use, involving 10,000 pens and >105,000
`injections.
`
`Results
`
`Participant Characteristics and Disposition
`A total of 2674 people agreed to participate in this
`observational
`survey of everyday clinical practice,
`which was conducted across 93
`sites,
`involving
`150 HCPs
`(Appendix 2). Health care professionals
`were a
`combination of primary care physicians,
`endocrinologists/diabetologists, and diabetes educators.
`Twenty participants withdrew consent prior
`to
`the
`survey; therefore, 2654 people used SOL. At 6-10 weeks
`after initial use of SOL, 2029 people provided feedback
`during solicited interviews. Participant characteristics
`and demographics are summarized in Table 1.
`
`Table 1.
`Characteristics and Demographics of the Participants, Collected from Spontaneous Interviews Conducted after
`6-10 Weeks of SOL Use in the Overall Survey Population and in Specified Subgroups Of Participants, Including
`Diabetes Type, Prior Device Experience, Visual/Manual Impairments and Participant Age
`Self-reported
`impairments
`
`Diabetes type
`
`Prior device experience
`
`Participant age
`
`Overall
`population
`(n = 2029)
`
`Age (years) a
`
`50.5 ± 16.1
`
`Females/males(%)
`Type 1/2 diabetes(%)
`Never used an
`injection pen (%)
`Satisfied with using
`SOL(%)
`Very satisfied
`Satisfied
`Neutral
`Unsatisfied
`Very unsatisfied
`Participants without
`concerns/questions/
`issues(%)
`Questions raised
`during interviews(%)
`Needle attachment
`Dose dialing
`Injecting
`Reading anything
`on the pen
`Removing bubbles
`Continuing to use
`SOL after the end of
`survey period (%)
`
`49/51
`54/46
`
`10
`
`74
`21
`3
`<1
`1
`
`90
`
`<1
`3
`4
`
`<1
`
`<1
`
`97
`
`a Mean ± standard deviation.
`
`Type 1
`(n = 1067)
`42.6
`± 15.4
`49/51
`100
`
`Type 2
`(n = 926)
`59.3
`± 11.6
`48/52
`100
`
`Na:rve
`(n = 194)
`55.8
`± 16.4
`46/54
`29/71
`
`Experienced
`(n = 1834)
`
`50.0 ± 16.0
`
`49/51
`56/44
`
`Visual
`(n = 170)
`60.4
`± 13.2
`57/43
`42/58
`
`Manual
`(n = 130)
`60.8
`± 12.9
`58/42
`34/66
`
`<18 years 2:70 years
`(n = 21)
`(n = 230)
`14.9
`75.0
`± 3.0
`± 4.4
`43/57
`48/52
`100/0
`22/78
`
`5
`
`15
`
`100
`
`0
`
`8
`
`8
`
`24
`
`16
`
`74
`22
`3
`<1
`<1
`
`90
`
`<1
`3
`4
`
`1
`
`<1
`
`97
`
`75
`20
`3
`<1
`1
`
`90
`
`<1
`3
`5
`
`<1
`
`<1
`
`97
`
`77
`21
`1
`1
`
`<1
`
`92
`
`<1
`3
`3
`
`<1
`
`0
`
`96
`
`74
`21
`3
`<1
`1
`
`89
`
`<1
`3
`4
`
`<1
`
`<1
`
`97
`
`72
`19
`5
`<1
`2
`
`88
`
`2
`5
`4
`
`<1
`
`0
`
`98
`
`78
`18
`2
`<1
`2
`
`91
`
`<1
`2
`5
`
`1
`
`0
`
`76
`19
`5
`0
`0
`
`86
`
`5
`5
`0
`
`0
`
`5
`
`95
`
`100
`
`77
`19
`3
`<1
`<1
`
`94
`
`<1
`2
`2
`
`0
`
`0
`
`97
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
`1427
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`

`Carter
`
`guide booklet, and 12.6% (n = 256) received no training
`(multiple answers were allowed). The median age was
`42 years for participants with type 1 diabetes and 60
`years for participants with type 2 diabetes. Overall,
`16.3% (n = 329/2024) of participants had manual dexterity
`problems, 15.5% (n = 314/2023) had poor eyesight not
`corrected by glasses, and 12.1% (n = 245/2022) had other
`disabilities considered unrelated to the ability to use
`SOL.
`
`(n = 1962/2027) of
`At the time of interview, 96.8%
`participants were still using SOL. Of the participants
`who discontinued use of SOL, 17 (0.8%) ceased use
`SOL 1-6 days prior to interview, 19 (0.9%) 2-4 weeks
`previously, 16
`(0.8%) 3-4 weeks previously, and 13
`(0.6%) 5-6 weeks previously; reasons for discontinuation
`were not recorded. In total, 21.2% (n = 430/2028) were
`using insulin glargine as the only insulin, and 78.8%
`(n = 1598/2028) reported that they were using insulin
`glargine plus one or more other insulin product.
`The mean duration of SOL use prior to the interviews
`was 60.5 ± 15.7 days.
`
`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Similar numbers of participants with type 1 and type 2
`diabetes were included in the survey,
`the majority
`had used a pen device in the past, and 9.6% of the
`participants (n = 194/2029) reported no prior experience
`of using insulin devices. Training was offered to all
`participants, and 87%
`(n = 1770/2029) were
`trained.
`Training by one-to-one demonstration was carried out
`in 74%
`(n = 1501) of participants, 12.5%
`(n = 253) of
`participants were trained using a group demonstration,
`36.1% (n = 732) received both demonstration and a user
`guide booklet, 32.1% (n = 651) were trained with the user
`
`Table 2.
`Adverse Events Reported
`
`AE
`
`Nonserious
`
`Serious
`
`Total
`
`Injection-site reaction
`
`33
`
`Hypoglycemia
`
`Dizziness
`
`Swelling
`
`Abdominal pain
`
`Pain
`
`Headache
`
`Hyperglycemia
`
`Nausea
`
`Rhinorrhea
`
`Drug exposure during
`pregnancy
`
`Back pain
`
`Cystitis
`
`7
`
`3
`
`2
`
`2
`
`2
`
`2
`
`3
`
`2
`
`2
`
`2
`
`1
`
`-
`
`1
`
`1
`
`-
`
`1
`
`-
`
`-
`
`-
`
`-
`
`-
`
`-
`
`-
`
`-
`
`34
`
`8
`
`3
`
`3
`
`2
`
`2
`
`2
`
`3
`
`2
`
`2
`
`2
`
`1
`
`1
`
`Product Technical Complaints
`A total of eight problems were considered to be PTCs,
`of which seven were reported during the solicited
`interviews. In three instances, the pens jammed; in two
`instances, the pens leaked; in two instances, the pens
`were hard to push; and in one instance, the pen or plunger
`was reported as "faulty." Investigations were performed
`according to standard methods, and results were logged
`into the PTC database. None of the PTCs were due to
`a technical defect, and five PTCs were considered to be
`related to handling errors by the participants. The eight
`participants who reported a PTC rated their satisfaction
`with SOL to be either "very satisfied" (n = 6) or "satisfied"
`(n = 2).
`
`Safety
`A total of 77 adverse events (AEs) were reported by 62
`people, none of which were related to a PTC. The most
`commonly reported AEs were injection-site reactions,
`hypoglycemia, dizziness, and hyperglycemia (Table 2).
`The reported rate of occurrence for injection-site reactions
`was 1.7% based on the number of enrolled participants.
`Injection site reactions are expected and are a listed event
`for insulin glargine. No AE was considered to be related
`to the SOL pen. There were four cases of serious AEs,
`none of which were related to a PTC. The majority of
`these events were most likely related to the participants'
`underlying diabetes or other confounding factors.
`
`Deatha
`
`Diarrhea
`
`Drug ineffective
`
`Emotional disorder
`
`Hunger
`
`Hypotension
`
`Kidney infection
`
`Loss of consciousness
`
`Edema peripheral
`
`Renal dysfunction
`
`Respiratory disorder
`
`Visual acuity reduced
`
`Total
`
`-
`
`1
`
`1
`
`1
`
`1
`
`-
`
`-
`
`-
`
`-
`
`-
`
`1
`
`1
`
`67
`
`1
`
`1
`
`-
`
`-
`
`-
`
`-
`
`1
`
`1
`
`1
`
`1
`
`1
`
`-
`
`-
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`1
`
`10
`
`77
`
`a This participant had long-standing medical history of renal
`and heart failure. Death was considered due to these
`conditions and not related to the use of SOL.
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
`1428
`
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`100
`
`90
`
`70
`
`60
`
`~ 80
`,,,
`'E
`~ ·c:;
`t:
`~ 50
`0
`§
`40
`~ 30
`C. e 20
`
`Carter
`
`74.4
`
`21.0
`
`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Acceptance
`Overall, the large majority (n = 1934/2028; 95.4%) of
`participants reported that they were either "satisfied" or
`"very satisfied" with using SOL (Figure 1). When the
`participants were asked to report on the occurrence of
`any issue or question during the 6-10 weeks period of
`SOL use, the majority of participants (n = 1820/2029; 89.7%;
`95% CI: 88.3, 91.0%) reported that they experienced none
`with using SOL on a daily basis. This was consistent
`between those participants who were device nai"ve
`(n = 179/194; 92.3%; 95% CI: 87.6, 95.6%) and
`those
`who had previously used a device (n = 1641/1834; 89.5%;
`95% CI: 88.0, 90.8%) and between people with type 1
`diabetes (n = 957/1067; 89.7%; 95% CI: 87.7, 91.5%) and
`type 2 diabetes (n = 830/926; 89.6%; 95% CI: 87.5, 91.5%;
`Table 1). Similar findings were also reported by participants
`with manual or dexterity impairments and by young
`and elderly participants (Table 2). A small proportion of
`participants suggested aspects that could be improved,
`including injection (n = 86/2029; 4.2%; 95% CI: 3.4, 5.2%),
`dialing a dose (n = 65/2029; 3.2%; 95% CI: 2.5, 4.1%), reading
`anything on the pen (n = 16/2029; 0.8%; 95% CI: 0.5, 1.3%),
`attaching a needle (n = 13/2029; 0.6%; 95% CI: 0.4, 1.1%),
`removing air bubbles (n = 7/2029; 0.3%; 95% CI: 0.1, 0.7%),
`or something else (n = 21/2029; 1.0%).
`
`that they were
`Of the 32 participants who reported
`"unsatisfied" or "very unsatisfied," only seven subsequently
`provided further comments, of which four were related
`to injecting and one each of dialing a dose, attaching a
`needle, and reading anything on the pen.
`
`Discussion
`
`In this survey of everyday clinical practice, SOL had
`a good safety profile and was very well accepted by
`participants with a low incidence of participant-reported
`questions or concerns during use, confirming
`its
`convenience in everyday practice. The results from this
`observational survey support the findings of Haak and
`colleagues that SOL demonstrates high patient usability and
`high patient preference in people with diabetes.8
`
`Although patients with type 1 diabetes must accept
`the need for
`insulin from diagnosis, patients with
`type 2 diabetes are often resistant to the addition of
`insulin to their regimen of oral antidiabetes agents.9,10
`Delaying insulin therapy in type 2 diabetes may lead to
`deleterious effects on glycemic control and, as a result,
`increase the risk of diabetes-specific complications, such as
`retinopathy, nephropathy, and neuropathy.11 Insulin pens
`have the potential to help patients overcome barriers to
`
`0..
`
`10
`
`1.1
`
`0.5
`
`3.1
`
`Very unsatisfied
`
`Unsatisfied
`
`Neutral
`
`Satisfied
`
`Very satisfied
`
`Participant-reported level of satisfaction
`
`Figure 1. Participant satisfaction with SOL (percent ± 95% confidence
`bounds).
`
`the initiation of insulin, such as fear of needles, social
`acceptability, and the inconvenience of a vial and syringe.4
`
`The number of participants with type 1 versus type 2
`diabetes who reported no concerns with using SOL on a
`daily basis and were either "satisfied" or "very satisfied"
`with the device were similar in this survey; a very small
`proportion of participants reported SOL as "acceptable,"
`"poor," or "very poor." These positive experiences with
`SOL suggest that it may be a very convenient and useful
`tool in overcoming some of the barriers associated with
`the initiation of insulin in patients with type 2 diabetes
`and encouraging earlier use.
`
`In the population of people included in this survey, only
`a small percentage were device nai"ve. Further studies in
`this group, and in insulin-nai"ve subjects, would help to
`strengthen this hypothesis. Nevertheless, results from
`this population of people, the majority of whom had
`type 2 diabetes, confirms the results given by Haak and
`colleagues8 that SOL is rated positively by people with
`no experience of using insulin pen devices.
`
`In addition, results of participants who were device nai"ve
`were similar to those in people who were experienced
`with devices. Of particular interest, the majority of
`people who had no experience of insulin devices had
`no problems using SOL and were either "satisfied" or "very
`satisfied" with the device. This ease of initiation with
`SOL could be expected to translate to benefits in everyday
`clinical practice for both people with diabetes and their
`HCPs. These findings were also consistent among the
`participants with manual or visual dexterity impairments
`and among the young and elderly participants.
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
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`

`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Carter
`
`The results of this survey, which suggest that SOL was easy
`to use since the majority of device-nai"ve participants
`were "satisfied" or "very satisfied," are consistent with a
`laboratory-based study where the injection force of SOL
`was compared with FlexPen (FP) and Next Generation
`FlexPen (NGFP). A realistic dispense rate (6 U/s, constant
`volume flow
`rate) was used. The mean± standard
`deviation plateau dispense force for each pen to dispense
`60 U at a rate of 6 U/s was 7.15 ± 0.69 N for SOL versus
`12.51 ± 0.96 N
`for FP and 9.72 ± 0.72 N for NGFP.
`This finding mirrors the study by Clarke and Spollett,
`who also reported lower injection force dynamics for SOL
`versus FP.6 Although it is unknown whether this lower
`injection force of SOL compared with other available pens
`on the market is clinically significant, it may potentially
`be of benefit for those who have limited levels of manual
`dexterity.
`
`Information regarding the likelihood of participants
`continuing using SOL as part of their daily management
`of diabetes was not captured in this survey. Nevertheless,
`a high proportion of patients (over 95%) were still using
`SOL at the time of the interview. Unfortunately, reasons
`for discontinuation were not recorded; however, it seems
`probable
`that participants may have stopped using
`SOL owing to therapy changes, for example, a change
`in insulin regimen or a switch to oral therapy, or the
`participant preferred other pen devices. It would be of
`further interest to investigate the continuation rates of
`SOL use after the survey was conducted, as this would
`provide valuable information on the longer-term impact
`of SOL.
`
`One of the main limitations of surveys is that participants
`may not feel comfortable in reporting negative feedback,
`especially as the participants were invited to participate
`in the survey by their HCP, which may have introduced
`some bias to the results; re-interviewing participants could
`help to overcome this problem. We endeavored to minimize
`this effect by ensuring all telephone contact and data
`collection was mediated through an independent agency
`providing anonymity from
`the HCPs and sponsor.
`Nevertheless, the results of this survey of people with
`type 1 or type 2 diabetes were consistent with the
`previously reported findings for 65 of the 150 HCPs
`involved in managing the participants. Indeed, 85% of
`the HCPs reported that SOL had made it easier to train
`people to use the device, while 98% reported that it
`was quicker to train participants.12 Such findings from
`people with diabetes who use the device described
`in the present report and those findings reported for
`the prescribing HCPs demonstrate the ease of use
`
`and indicate the potential saving of resources used in
`training people how to use the device.
`
`Finally, it would be of interest to repeat this observation
`in a larger population of people with no prior experience of
`using insulin and insulin devices, given the increasing
`prevalence of type 2 diabetes13 and the known benefit of
`adding insulin to existing therapy versus intensification
`of oral therapy.14 As this was an observational study,
`further randomized trials with a crossover design that
`compare SOL with other available devices in a clinical
`setting could be performed; however, participants may
`compare the type of insulin given, which may confound
`the results.
`
`Conclusions
`
`In this noninterventional, observational survey of everyday
`clinical practice, SOL was well accepted by participants
`with both type 1 and type 2 diabetes, with the majority
`of participants reporting that they were either very
`satisfied or satisfied with the device. SoloSTAR also had
`a good safety profile. Most of the PTCs reported were likely
`due to participant handling errors and not to technical
`deficiencies. This is the first survey to demonstrate the
`high usability, high participant acceptance, and safety of
`SOL in everyday clinical practice. Further comparative
`studies and follow-up surveys conducted in the clinical
`practice setting would be of interest to confirm the
`findings presented here.
`
`Funding:
`
`This survey was funded by sanofi-aventis.
`
`Acknowledgements:
`
`Editorial support for this article was provided through the global
`publications group of sanofi-aventis. We thank all the investigators for
`their commitment to this survey.
`
`Disclosures:
`
`Carter has received financial support from sanofi-aventis, Novo Nordisk,
`and Lilly to attend congresses. De Luise has received financial support to
`attend endocrine/diabetes congresses from sanofi-aventis, Novo-Nordisk,
`Lilly, GSK, and Bayer. Beilin has received financial support from GSK,
`Novo Nordisk, and sanofi-aventis to attend congresses. The sponsor
`coordinated the study and monitored the investigator sites. Data
`processing and statistical analyses were performed by StatProcess.
`International SOS collected the data and managed participant contact.
`The authors had access to the data and final responsibility for the
`decision to submit for publication.
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
`1430
`
`www.iournalofdst.om
`
`Sanofi Exhibit 2118.006
`Mylan v. Sanofi
`IPR2018-01675
`
`

`

`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Carter
`
`References:
`
`1. Bohannon NJ. Insulin delivery using pen devices. Simple-to-use
`tools may help young and old alike. Postgrad Med. 1999;106(5):57-8,
`61-4, 68.
`
`2. Graff MR, McOanahan MA. Assessment by patients with diabetes
`mellitus of two insulin pen delivery systems versus a vial and
`syringe. Clin Ther. 1998;20(3):486-96.
`
`3. Klonoff DC. The pen is mightier than the needle (and syringe).
`Diabetes Technol Ther. 2001;3(4):631-3.
`
`4. Summers KH, Szeinbach SL, Lenox SM. Preference for insulin
`delivery systems among current insulin users and nonusers. Clin
`Ther. 2004;26(9):1498-505.
`
`5. Clarke A, Dain MP. Dose accuracy of a reusable insulin pen using
`a cartridge system with an integrated plunger mechanism. Expert
`Opin Drug Deliv. 2006;3(5):677-83.
`
`6. Clarke A, Spollett G. Dose accuracy and injection force dynamics
`of a novel disposable insulin pen. Expert Opin Drug Deliv.
`2007;4(2):165-74.
`
`7. Robertson KE, Glazer NB, Campbell RK. The latest developments
`in insulin injection devices. Diabetes Educ. 2000;26(1):135-8, 141-6,
`149-52.
`
`8. Haak T, Edelman S, Walter C, Lecointre B, Spollett G. Comparison
`of usability and patient preference for the new disposable insulin
`device Solostar versus Flexpen,
`lilly disposable pen, and a
`prototype pen: an open-label study. Clin Ther. 2007;29(4):650-60.
`
`9. Peyrot M, Rubin RR, Lauritzen T, Skovlund SE, Snoek FJ,
`Matthews DR, Landgraf R, Kleinebreil L, International DAWN
`Advisory Panel. Resistance to insulin therapy among patients and
`providers: results of the cross-national Diabetes Attitudes, Wishes,
`and Needs (DAWN) study. Diabetes Care. 2005;28(11):2673-9.
`
`10. Polansky WH, Fisher L, Guzman S, Villa-Caballero L, Edelman SV.
`Psychological insulin resistance in patients with type 2 diabetes:
`the scope of the problem. Diabetes Care. 2005;28(10):2543-5.
`
`11. Golden SH, Selvin E, Cunningham KE. Glycaemic status and
`cardiovascular disease in type 2 diabetes mellitus: re-visiting
`glycated haemoglobin targets for cardiovascular disease prevention.
`Diabetes Obes Metab. 2007;9(6):792-8.
`
`12. Carter J, Roberts A. Usability of a pre-filled insulin injection device
`in a 3-month observational survey of everyday clinical practice in
`Australia. Curr Med Res Opin. 2008;24(10):2741-9.
`
`13. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence
`of diabetes: estimates for the year 2000 and projections for 2030.
`Diabetes Care. 2004;27(5):1047-53.
`
`14. Gerstein HC, Yale JF, Harris SB, Issa M, Stewart JA, Dempsey E.
`A randomized trial of adding insulin glargine vs. avoidance of
`insulin in people with Type 2 diabetes on either no oral glucose(cid:173)
`lowering agents or submaximal doses of metformin and/or
`sulphonylureas. The Canadian INSIGHT
`(Implementing New
`Strategies with Insulin Glargine for Hyperglycaemia Treatment)
`Study. Diabet Med. 2006;23(7):736-42.
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
`1431
`
`www.iournalofdst.om
`
`Sanofi Exhibit 2118.007
`Mylan v. Sanofi
`IPR2018-01675
`
`

`

`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Carter
`
`Appendix 1: Survey Questions
`
`C:
`0
`:.;::;
`Ul
`Q)
`:::l
`0
`
`_!_ Participant Profile
`1.1 Age
`
`1.2 Diabetes
`
`1.3 Who gives you the
`injection?
`
`1.4 Have you used an
`injection pen before
`SoloSTAR?
`
`1.5 How many types
`of insulin do you
`currently use?
`
`1.6 How many types of
`injections devices do
`you currently use?
`
`1.7 Do you have any
`disability or other
`restrictions?
`
`CJ
`Fl
`
`~
`
`Type 1
`Type 2
`
`Self
`Parent
`Spouse
`Nurse/ carer
`Other
`
`1 other
`2 other
`3 or more
`Never
`
`LANTUS only
`LANTUS + 1 other
`LANTUS + 2 other
`LANTUS + 3 or
`more
`
`SoloSTAR only §
`
`SoloSTAR + 1 other
`SoloSTAR + 2 other
`
`CJ go to 1.8
`
`None
`Poor eyesight not corrected by
`glasses
`
`Manual dexterity problems, e.g.,
`arthritis, neuropathy
`
`Other (specify): CJ
`
`Mild
`Moderate
`Severe
`
`Mild
`Moderate
`Severe
`
`Mild
`Moderate
`Severe
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
`1432
`
`www.iournalofdst.om
`
`Sanofi Exhibit 2118.008
`Mylan v. Sanofi
`IPR2018-01675
`
`

`

`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Carter
`
`1.8 Did you start using
`SoloSTAR the day you
`received your supply?
`
`Yes
`
`C:) goto 1.9
`
`1 day later ~
`Give date of starting I
`
`2 days later
`3 days later
`4 or more days
`later
`
`No
`
`SoloSTAR
`
`C:J go to 1.10
`Stopped 1 - 6 r7
`days ago
`Stopped 1 - 2 C:J
`weeks ago
`C:J
`Stopped 3 - 4
`weeks ago
`C:J
`Stopped 5 - 6
`weeks ago
`
`1.9 Are you still using
`SoloSTAR?
`
`Yes
`
`No
`
`1.10 How many SoloSTAR
`pens have you used
`already?
`
`Free text
`
`2 Technical pen handling aspects
`2.1 What is your current
`daily dose of
`LANTUS?
`
`Free text
`
`2.2 How often do you use
`a new needle?
`
`2.3 How often do you do
`the safety test?
`
`Before every
`injection
`Every second day
`Every third day
`Between 4-5 days
`Between 6-7 days
`Other. Please
`specify
`
`Before every
`injection
`Every second day
`Once a week
`With each new pen
`Only when there are
`air bubbles in the
`reservoir
`Never
`Other. Please
`specify
`
`2.4 What brand of needles
`are you using with
`SoloSTAR?
`
`BD
`Novo
`Braun
`
`J Diabetes Sci Technol Vol 3, Issue 6, November 2009
`
`1433
`
`www.iournalofdst.om
`
`Sanofi Exhibit 2118.009
`Mylan v. Sanofi
`IPR2018-01675
`
`

`

`Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device
`in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
`
`Carter
`
`__lJ Pen Issue-core question
`3.1 Did you have any
`problems where you
`thought something
`was not working
`properly or you
`thought something
`was broken on the
`pen?
`
`3.1.1
`
`No
`
`CJ
`go to 4
`
`3.1.2
`
`Yes (one at a time)
`
`3.1.2.1
`
`When
`
`a
`
`b
`
`C
`
`With
`attaching
`a needle?
`
`With
`dialing a
`dose?
`
`With
`injecting?
`
`d
`With
`reading
`anything
`on the
`pen?
`
`e
`
`Other
`(please
`specify)?
`
`3.1.2.2
`
`How frequently
`
`3.1.2.3
`
`Extent of
`problem
`
`3.1.3 Did you tell anyone?
`3.1.3.1
`
`Yes
`
`Within 1 week of
`usina SoloSTAR
`Between 2 - 4
`weeks of