Journal of Diabetes Science and Technology
`Volume 2, Issue 6, November 2008
`© Diabetes Technology Society
`
`~
`
`COMMENTARY
`
`United States Patient Preference and Usability for the New Disposable
`Insulin Device Solos tar® versus Other Disposable Pens
`
`Jerome S. Fischer, M.D.,1 Steven V. Edelman, M.D.,2 and Sherwyn L. Schwartz, MD., P.A.1
`
`Abstract
`
`The uptake of insulin pen use has been slow in the United States, despite their advantages over the vial/
`syringe. We present results of a United States subset of 150 patients with type 1/type 2 diabetes, who were
`enrolled in an open-label study, that assessed usability, pen features, and patient preferences for four prefilled
`insulin pens: SoloSTAR®, FlexPen®, Lilly disposable pen, and a prototype, Pen X. Overall, the SoloSTAR
`and FlexPen were more user-friendly; 95 and 88% of patients, respectively, completed the steps correctly
`(without safety/attach-needle step-deemed independent of device) versus the Lilly disposable pen (60%)
`and Pen X (61%; all p < 0.05). The SoloSTAR was rated highest most frequently for pen feature comparisons.
`Results suggest that the SoloSTAR and FlexPen could potentially facilitate insulin use in the United States.
`
`J Diabetes Sci Technol 2008;2(6):1157-1160
`
`Commentary
`
`I n the United States, the prevalence of diabetes has
`been estimated at 7% of the population (20.8 million
`individuals) and the majority have type 2 diabetes
`mellitus (T2DM).1
`
`Insulin pens have the potential to enhance initiation and
`acceptance of insulin use among patients with diabetes.
`Compared with vial and syringes, insulin pens offer
`substantial improvements in compliance, freedom, and
`flexibility for all insulin-using patients. 2 Insulin pens
`may also provide more accurate dosing, which could
`improve blood glucose control and long-term outcomes, 3
`along with increased adherence and reduced therapy
`costs.4 Furthermore, compared with vial and syringes,
`
`a clear preference for pen devices has been shown5- 7;
`in addition, prefilled, disposable insulin pens offer the
`advantage of simplicity, require minimal training, and
`do not necessitate the installation of new cartridges.
`Insulin pens may also provide greater protection from
`the heat and light, with fewer units of insulin being
`exposed to the environment compared with a vial and
`syringe. Despite these advantages, the uptake of insulin
`pen devices in the United States has been slow. 8
`
`A recent multinational trial involving 510 patients in France,
`Germany, Japan, and the United States,
`investigated
`patient acceptability of a new 3.0-ml prefilled, disposable
`insulin pen [SoloSTAR® (sanofi-aventis, Paris, France)]
`
`Author Affiliations: 1Diabetes and Glandular Disease Research Associates, Inc., San Antonio, Texas, and 2University of California, San Diego
`Veterans Affairs Medical Center, San Diego, California
`
`Abbreviations: (OAD) oral antidiabetic drug, (SD) standard deviation, (TlDM) type 1 diabetes rnellitus, (T2DM) type 2 diabetes rnellitus
`
`Keywords: disposable pen, FlexPen, insulin device, Lilly disposable pen, SoloSTAR, United States
`
`Corresponding Author: Sherywn L. Schwartz, M.D., P.A., Diabetes and Glandular Disease Research Associates, Inc., 5107 Medical Drive,
`San Antonio, TX 78229-4801; email address slschwartz@dgdclinic.com
`
`1157
`
`Sanofi Exhibit 2126.001
`Mylan v. Sanofi
`IPR2018-01675
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`

`

`United States Patient Preference and Usability for the New Disposable Insulin Device SoloSTAR® versus Other Disposable Pens
`
`Fischer
`
`compared with two currently available prefilled pens
`[Novolog® FlexPen®
`(Novo Nordisk A/S, Bagsvaerd,
`Denmark) and Lilly disposable pen (Eli Lilly and Company,
`Indianapolis, IN)] and a prototype-prefilled pen (Pen X)
`in patients with type 1 diabetes mellitus (TlDM) or
`T2DM.9 Pen X was an alternative pen concept that was in
`development, but was subsequently discontinued based
`on technical and user feedback, including the results of
`this study. The study was conducted as part of the sanofi(cid:173)
`aventis development program for SoloSTAR, which is
`used to deliver insulin glargine (LANTUS®; sanofi-aventis,
`Paris, France) and insulin glulisine (Apidra®; sanofi-aventis,
`Paris, France). This article presents results from the
`United States subset of patients enrolled in this study,
`which assessed the usability, specific pen features, and
`patient preferences for
`the SoloSTAR, FlexPen, Lilly
`disposable pen, and Pen X.
`
`Patients with T1DM/T2DM (duration ::c:2 years) were
`included in the study: insulin-naive patients with T2DM
`receiving oral antidiabetic drugs (OADs) and insulin(cid:173)
`experienced patients with T1DM/T2DM receiving insulin
`via a reusable or disposable pen, or a vial and syringe.
`Patients were aged between 11 and 85 years with a
`similar distribution of males and females. The study also
`included cohorts of patients with diabetes with dexterity
`problems and visual impairments.
`
`The trial consisted of qualitative, quantitative, face-to-face,
`1-hour interviews conducted in patients with diabetes,
`which were carried out by independent moderators, as
`described in more detail elsewhere.9 Respondents were
`asked to prepare each pen (SoloSTAR, FlexPen, Lilly
`disposable pen, and Pen X) for injection and inject into
`a receptacle; independent moderators recorded the extent
`to which the respondents completed each step correctly.
`A user's manual was present for each pen; however,
`respondents were not required to use this; this was to
`mimic everyday practice, in that the patient was able to
`choose if he/she wanted to read the manual. Moderators
`did not provide assistance or training throughout the
`study and no other
`training materials were made
`available. Respondents were not blinded to the make/
`manufacturer of the pens, but were not informed of
`who sponsored the study. All respondents provided
`written, informed consent and signed a confidentiality
`agreement before taking part in the study. Respondents
`were recruited locally using research databases at each
`study site.
`
`The study was divided into two sections; the first
`section examined the usability of the pens with the
`following steps: getting started and removing the cap;
`
`attaching a needle; activating the dose-knob setting;
`setting and delivering a safety dose; dialing a 40-unit
`dose; and delivering that dose. Subanalyses were also
`performed for the following groups of patients: age
`(11-15 years and ::c:60 years), current therapy (insulin users
`versus OAD users), previous pen use, and self-reported
`disability status (visual disorders not fully corrected
`by glasses; any problems with manual dexterity). The
`second section consisted of a competitive assessment and
`respondents evaluated 14 key features (Table 1) using
`a five-point scale. Respondents were asked to rank the
`pens in order based on their overall pen preference. For
`both sections, a Latin-square design (four versions) was
`used to balance the order in which pens were given to
`the patients. Significance testing among the pens was
`conducted by two-, three-, and four-way x,2 analysis on
`the patient population as a whole; no significance testing
`was performed on the subanalysis groups, such as elderly
`patients or patients with manual or visual impairments.
`
`Of the 510 patients included in the study, 150 were
`from the United States (across 10 centers), of whom 45%
`had TlDM and 55% had T2DM. There was an equal
`distribution of male (47%) and female (53%) patients, the
`mean [standard deviation (SD)] age was 42 (21) years,
`and the mean (SD) duration of diabetes was 10 (9) years.
`Regarding the usability assessment, in the overall group,
`a greater proportion of patients completed the steps
`correctly (without the safety step or attach-needle step,
`which were deemed independent of the device) with the
`SoloSTAR (95%; p < 0.05) and FlexPen (88%; p < 0.05) versus
`both the Lilly disposable pen (60%) and Pen X (61%).
`
`In the subanalysis of patients aged ::c:60 years (n = 41),
`the SoloSTAR and FlexPen demonstrated
`similar
`usability (proportion of patients completing the steps
`correctly without the safety or attach-needle step), with
`a trend for greater usability with the SoloSTAR (98% vs
`83%, respectively), and greater usability versus the Lilly
`disposable pen (46%) or Pen X (44%). In patients aged
`11-15 years (n = 35), a similar trend was observed
`(SoloSTAR: 97%; FlexPen: 89%; Lilly disposable pen: 63%;
`Pen X: 66%). With regard to younger patients, the lower
`insulin doses used typically in children are measured
`more easily with pen devices. 3 The fact that the majority
`of older and younger patients in our study completed the
`steps correctly with both the SoloSTAR and the FlexPen
`suggests that these difficult-to-treat age groups would
`benefit from either device in terms of increased accuracy
`of insulin dosing. Furthermore, the ease of use of these
`insulin pens could reduce the social impact and the
`many challenges of diabetes in young patients.3
`
`J Diabetes Sci Technol Vol 2, Issue 6, November 2008
`
`1158
`
`www.iournalofdst.om
`
`Sanofi Exhibit 2126.002
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`IPR2018-01675
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`

`

`United States Patient Preference and Usability for the New Disposable Insulin Device SoloSTAR® versus Other Disposable Pens
`
`Fischer
`
`In diabetes patients with visual impairments [n = 27;
`including glaucoma (8), cataracts (6),
`retinopathy (6),
`macular degeneration (4), another reason (4)] or dexterity
`impairments (n = 22; including neuropathy (7), rheumatoid
`arthritis (4), osteoarthritis (4), another reason (9)], the
`proportion of patients completing the assessed steps
`again correctly demonstrated a trend similar to that
`observed in the other subgroups: SoloSTAR: 96 and 91%;
`FlexPen: 85 and 77%; Lilly disposable pen: 52 and 46%;
`and Pen X: 48 and 46%;
`for visual and dexterity
`impairment, respectively. The fact that the vast majority
`of both visually and dexterity-impaired patients were able
`to complete all steps correctly using the SoloSTAR and
`FlexPen is important; self-management can prove difficult
`and, as such, injection devices with easily readable dose
`scales and easy-to-handle dose selectors are preferred
`for those patients in whom coordination or vision is
`compromised.
`
`As expected, pen-experienced patients found all pens
`easier to operate compared with pen-naive patients, with
`the SoloSTAR (98% vs 89%, respectively) and FlexPen (93%
`vs 82%, respectively) being very usable in both groups.
`
`SoloSTAR was rated "best" most frequently by the
`patients for pen feature comparisons, including 3 out of
`4 attributes relating to the design and esthetics of the
`pen and 9 out of 10 attributes relating to the usability of
`the pen (Table 1).
`
`Regarding injection performance, the SoloSTAR was
`preferred by a significantly greater number of patients
`as their first choice (65%) compared with the other pens
`assessed (FlexPen: 15%; Lilly disposable pen: 15%; Pen X:
`5%; p < 0.05). A significantly higher proportion of
`patients expressed an overall preference for the SoloSTAR
`(55%) versus the FlexPen (28%; p < 0.05) and the Lilly
`disposable pen (17%; p < 0.05).
`
`The results of this study, obtained in patients from the
`United States, demonstrate that, as observed in the
`multinational trial,9 the SoloSTAR and FlexPen were
`associated with comparable usability. Importantly, the
`findings also demonstrate the suitability of both the
`SoloSTAR and the FlexPen in a wide range of patients with
`diabetes, including both elderly and younger patients and
`those with visual and dexterity impairments. Of note,
`if reading of the pen user manual had been mandatory,
`the percentage of patients completing the steps correctly
`may have been different; however, lack of providing
`training and allowing patients to choose whether or not
`to read the manual was to stimulate real life.
`
`Table 1.
`Evaluation of Four Prefilled Insulin Pen Devices by
`Patients with Type 1 or Type 2 Diabetes Mellitusa
`
`Evaluation of pen features:
`percentage of time rated as
`"best"
`
`SoloSTAR® FlexPen®
`A
`B
`
`Lilly'
`C
`
`Pen X
`D
`
`Design/esthetics
`
`Exterior design and styling
`
`Size and portability
`
`How well the cap fits onto
`the pen
`
`Tactile feel
`
`Easy/intuitive to figure out
`
`Easy to set dose
`
`Easy to read that you have
`set the exact dose
`
`Easy to correct dose if
`overdialed
`
`41C,D
`
`47C,D
`
`45D
`
`47B,C,D
`
`Usability
`
`50B,C,D
`
`57B,C,D
`
`48B,C,D
`
`34D
`
`35D
`
`35
`
`23
`
`25
`
`26
`
`23
`
`55B,C,D
`
`31C
`
`Auditory feedback
`
`40C,D
`
`39C,D
`
`Requires low numbers of
`turns to set 40 units
`
`How far the dose button
`sticks out (40 units)
`
`Effort it takes to inject
`40 units
`
`Easy to determine the entire
`dose delivery
`
`Easy to determine the
`amount left in the cartridge
`
`45B,D
`
`39B,D
`
`53B,C,D
`
`55B,C,D
`
`49B,D
`
`27
`
`19
`
`17
`
`27
`
`26
`
`25
`
`28
`
`49D
`
`13
`
`18
`
`15
`
`21
`
`20
`
`12
`
`32D
`
`47B,D
`
`17
`
`27
`
`35
`
`13
`
`15
`
`23
`
`22
`
`11
`
`16
`
`19
`
`24
`
`15
`
`12
`
`9
`
`3
`
`15
`
`19
`
`a Pen feature comparison: percentage of time that the pens were rated
`as "best" by patients using the SoloSTAR, FlexPen, Lilly disposable
`pen, and Pen X (n = 150). Letters denote statistical significance
`versus the corresponding letter, at p < 0.05. Respondents selected
`the one pen they considered "best" on each attribute. Row
`percentages may add to >100%, as some respondents could not
`select one pen as "best," but instead opted for "ties."
`b Lilly disposable pen.
`
`Given that the obstacles of initiation of insulin therapy
`include the fear of self-injection2 and that, compared
`with a vial and syringe, a clear preference for pens has
`been shown across all age groups, 5- 7 advances in diabetes
`therapy should be aimed at providing diabetes patients
`with
`the most efficient, convenient, and adaptable
`treatment. Accordingly, a well-accepted insulin device
`will likely improve compliance and, consequently, result
`in better adherence to treatment,4 improved glycemic
`control, and a
`reduced
`risk of
`long-term diabetes(cid:173)
`associated complications,3,8
`in addition
`to
`reducing
`therapy costs.4 Acceptance of, and adherence to, insulin
`
`J Diabetes Sci Technol Vol 2, Issue 6, November 2008
`
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`
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`

`United States Patient Preference and Usability for the New Disposable Insulin Device SoloSTAR® versus Other Disposable Pens
`
`Fischer
`
`3. 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.
`
`4. Lee WC, Balu S, Cobden D, Joshi AV, Pashas CL. Medication
`adherence and the associated health-economic impact among
`patients with type 2 diabetes mellitus converting to insulin pen
`therapy: an analysis of third-party managed care claims data. Clin
`Ther. 2006;28(10):1712-25.
`
`5. Bohannon NJ, Ohannesian JP, Burdan AL, Holcombe JH, Zagar A.
`Patient and physician satisfaction with the Humulin/Humalog Pen,
`a new 3.0-mL prefilled pen device for insulin delivery. Clin Ther.
`2000;22(9):1049-67.
`
`6. Korytkowski M, Bell D, Jacobsen C, Suwannasari R. A multicenter,
`randomized, open-label, comparative, two-period crossover trial of
`preference, efficacy, and safety profiles of a prefilled, disposable
`pen and conventional vial/syringe for insulin injection in patients
`with type 1 or 2 diabetes mellitus. Clin Ther. 2003;25(11):2836-48.
`
`7. Shelmet J, Schwartz S, Cappleman J, Peterson G, Skovlund S,
`Lytzen L, Nicklasson L, Liang J, Lyness W; InnoLet Study Group.
`Preference and resource utilization in elderly patients: InnoLet
`versus vial/syringe. Diabetes Res Clin Pract. 2004;63(1):27-35.
`
`8. Da Costa S, Brackenridge B, Hicks D. A comparison of insulin pen
`use in the United States and the United Kingdom. Diabetes Educ.
`2002;28(1):52-6, 59-60.
`
`9. 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.
`
`10. Arslanoglu I, Saka N, Bundak R, Giinoz H, Darendeliler F. A
`comparison of the use of premixed insulins in pen-injectors
`with conventional patient-mixed insulin treatment in children
`and adolescents with IDDM. Is there a decreased risk of night
`hypoglycemia? J Pediatr Endocrinol Metab. 2000;13(3):313-8.
`
`injectors versus
`11. Lteif AN, Schwenk WF. Accuracy of pen
`insulin syringes in children with type 1 diabetes. Diabetes Care.
`1999;22(1):137-40.
`
`12. de Luis DA, Aller R, Cuellar L, Terroba MC, Ovalle HF, Izaola 0,
`Romero E. Effect on quality of life with a new insulin injection
`device in elderly patients with diabetes mellitus type 2. J Diabetes
`Complications. 2004;18(4):216-9.
`
`13. Albano S. Assessment of quality of treatment in insulin-treated
`patients with diabetes using a pre-filled insulin pen. The ORBITER
`Study Group. Acta Biomed. 2004;75(1):34-9.
`
`14. Lassmann-Vague V. Hypoglycaemia in elderly diabetic patients.
`Diabetes Metab. 2005;3l(Spec No 2):5S53-5S7.
`
`15. Rosenstock J. Management of type 2 diabetes mellitus in the
`elderly: special considerations. Drugs Aging. 2001;18(1):31-44.
`
`16. American Diabetes Association. Insulin administration. Diabetes
`Care. 2004;27(Suppl l):S106-S7.
`
`treatment regimens is more likely to occur if pen devices
`are easy to use and offer effective delivery of insulin
`with minimal discomfort.6 In many patients, particularly
`those who have visual and/or dexterity impairments7
`or are young10,11 or elderly,7,12,13 insulin devices have
`been demonstrated to improve the accuracy of insulin
`administration and adherence compared with the vial
`and syringe. In the elderly population, who are very
`susceptible to the debilitating effects of hypoglycemia,14,15
`along with the greater prevalence of comorbidities, such
`as visual and/or manual disorders,7,12,13 making insulin
`administration easier and simpler will likely promote
`self-care in this population, as advocated by the American
`Diabetes Association.16
`
`Overall, our findings provide evidence that the SoloSTAR
`was preferred by more patients in this study and that
`the SoloSTAR and FlexPen are particularly user-friendly
`and acceptable prefilled insulin pen devices that offer
`promising alternatives to the vial and syringe for the
`initiation and administration of insulin in the treatment of
`diabetes in the United States. Further studies comparing
`the SoloSTAR with other commercially available pens on
`the market, such as the Humalog KwikPen™, would be
`of interest.
`
`Funding:
`
`This study was supported by sanofi-aventis.
`
`Acknowledgments:
`
`This study was performed for sanofi-aventis by an independent
`research company (DataTactics, Inc., Bala Cynwyd, PA). Editorial
`support for this article was provided by the Global Publications group
`of sanofi-aventis.
`
`Disclosure:
`
`Steven Edelman has received honoraria for advisory work for
`sanofi-aventis, has acted as a consultant for Novo Nordisk and Eli Lilly,
`is a member of the Taking Control Of Your Diabetes board of directors,
`and volunteers for the American Diabetes Association and the Juvenile
`Diabetes Research Foundation. Jerome Fischer and Sherwyn Schwartz
`have conducted research on behalf of sanofi-aventis; Eli Lilly;
`Novo Nordisk; and Becton, Dickinson and Company.
`
`References:
`
`1. American Diabetes Association, Diabetes statistics [cited 2006 Feb
`8]. Available from: http:Uwww.diabetes.org/diabetes-statistics.isp.
`
`2. Summers KH, Szeinbach SL, Lenox SM. Preference for insulin
`delivery systems among current insulin users and nonusers. Clin
`Ther. 2004;26(9):1498-505.
`
`J Diabetes Sci Technol Vol 2, Issue 6, November 2008
`
`1160
`
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