ORIGINAL RESEARCH

Patient and Healthcare Professionals Preferencefor Brenzys vs. Enbrel Autoinjector for RheumatoidArthritis: A Randomized Crossover Simulated-UseStudy

Marc Egeth . Jennifer Soosaar . Peter Nash . Denis Choquette .

Ricardo Infante . Dena Rosen Ramey . Sevag Sahakian .

Angela Lai . Jin Ju Kim . David Wu

Received: February 3, 2017 / Published online: April 17, 2017� The Author(s) 2017. This article is an open access publication

ABSTRACT

Introduction: Brenzys was developed as anetanercept biosimilar of Enbrel. The aim of thisstudy was to assess preference and perceivedease of use for the new Brenzys autoinjectorcompared to the currently available marketedEnbrel MYCLIC autoinjector (Australia) and

Enbrel SureClick autoinjector (Canada) for thetreatment of rheumatoid arthritis (RA). BecauseRA affects manual dexterity, ease of use of anautoinjector is a particularly important consid-eration in developing effective self-delivery oflong-term courses of therapy.Methods: Patients (N = 191) reporting a diag-nosis of RA and nurses and rheumatologists(N = 90) with experience managing RA wereshown how to use Brenzys and Enbrel autoin-jectors (in counterbalanced order between par-ticipants), then they used each autoinjector byinjecting into a pad simulating skin, and com-pleted a questionnaire. Study sessions tookplace in Australia and Canada.

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Electronic supplementary material The onlineversion of this article (doi:10.1007/s12325-017-0523-x)contains supplementary material, which is available toauthorized users.

M. Egeth (&) � J. SoosaarCore Human Factors, Inc., Bala Cynwyd, PA, USAe-mail: egeth@corehf.com

P. NashDept of Medicine, University of Queensland,Sunshine Coast, QLD, Australia

D. ChoquetteInstitut de recherche en rhumatologie de Montreal,CHUM ( Notre-Dame), Universite de Montreal,Montreal, Canada

R. InfanteMedical Affairs, Merck & Co., Inc., Kenilworth, NJ,USA

D. R. RameyCenter for Observational & Real World Evidence,Merck & Co., Inc., Kenilworth, NJ, USA

S. SahakianMedical Affairs, Merck Canada Inc., Kirkland,Quebec, Canada

A. LaiMedical Affairs, MSD Australia, Macquarie Park,NSW, Australia

J. J. KimMSD Korea Ltd., Mapo-GU, Seoul, Korea

D. WuMerck & Co., Inc., Kenilworth, NJ, USA

Adv Ther (2017) 34:1157–1172

DOI 10.1007/s12325-017-0523-x

Results: A binomial test showed that signifi-cantly more patients indicated that the Brenzysautoinjector was easier to use than the Enbrelautoinjector (79% reporting Brenzys easier touse; p\0.001, two-sided, 95% CI [73%, 85%]).In addition, significantly more nurses andrheumatologists with experience managing RAalso indicated that the Brenzys autoinjector waseasier to use (86%; p\0.001, two-sided, 95% CI[77%, 92%) and that they would recommendthe buttonless Brenzys autoinjector over theEnbrel autoinjector to patients (83%; p\0.001,two-sided, 95% CI [74%, 90%]). Almost allpatients who reported past experience using anEnbrel autoinjector (N = 17) reported on thebasis of using the two devices in the study thatthey would prefer to switch their device to theBrenzys autoinjector rather than continue theircourse of therapy using the Enbrel autoinjector(16/17, 94%, 95% CI [71%, 100%]).Conclusion: On the basis of the study results,the Brenzys autoinjector was rated statisticallysignificantly easier to use, and was overall pre-ferred by patients and healthcare professionalswith experience managing RA patients.Funding: Merck & Co., Inc.

Keywords: Autoinjector; Biosimilar; Enbrel;Etanercept; Human factors; Medical device;Patients; Preferences; Rheumatoid arthritis;Simulated use

INTRODUCTION

Effective biologics have been developed formanagement of rheumatoid arthritis (RA) usingself-injection devices; however, detrimentaleffects of RA on manual dexterity can makeself-injection an especially difficult procedurefor patients to complete. Injection devices thatare easier to use therefore have the potential to

decrease pain and increase long-term RA ther-apy adherence and effectiveness. Merck & Co.,Inc. Kenilworth, NJ, USA, in collaboration withSamsung Bioepis, has been developing theBrenzys autoinjector to deliver a biosimilar ofetanercept (Enbrel). The Brenzys autoinjectorwas designed to be easy for patients, includingthose with arthritis. For example, the Brenzysautoinjector was designed to have no pushbutton requiring the thumb (the user justpresses it onto skin); it allows one-handeddelivery; it has a large, easy-to-grip cap; and itprovides visual and auditory confirmation thatthe injection is complete. Compared to theEnbrel autoinjector (‘‘MYCLIC’’ in Australia,‘‘SureClick’’ in Canada), it has fewer steps forinjection (Fig. 1).

However, to date there has been no empiricalvalidation of the Brenzys autoinjector as a rel-atively easily usable option for RA patients. Thecurrent study was designed to provide data froman unbiased, counterbalanced crossover trial inwhich patients and healthcare professionals(HCPs) with experience managing RA (nursesand rheumatologists) injected both devices(into a pad representing skin) and reported onoverall preference and ease of use (Fig. 2).

There have been several studies comparingpatient perspectives on alternative injectiondevices. For example Berteau et al. [1], studyinghealthy subjects matched by demographics tobe representative of RA patients, investigatedpatient preference for an autoinjector comparedto a syringe and found an overall preference forthe autoinjector. Schiff et al. [2] asked RApatients, caregivers, and HCPs to compare use ofthe Abatacept autoinjector to autoinjectors theyhad previously had experience with, withAbatacept performing favorably. Thakur et al.[3] assessed European nurses’ preferences for atraining version of the Benepali autoinjectorcompared to the Enbrel autoinjector, finding

Fig. 1 BRENZYS autoinjector

1158 Adv Ther (2017) 34:1157–1172

that Benepali, which is the same as the Brenzysautoinjector, was generally preferred (86% ofnurses estimated that their patients would pre-fer the Benepali autoinjector to the Enbrelautoinjector) (Fig. 3).

To conduct a study comparing patient andHCP preferences and perspectives on ease of useof the Brenzys autoinjector compared to Enbrelautoinjectors, we first developed and validated aquestionnaire to assess autoinjector preferenceamong RA patients and HCPs in Australia andCanada. We then enrolled 191 patients and 90HCPs in Australia and Canada, who were blin-ded to the study sponsor, into a preferencestudy. We presented each participant with bothdevices, in counterbalanced order between par-ticipants (approximately half of each groupreceived the Brenzys autoinjector first, and halfreceived the Enbrel autoinjector first). Partici-pants received a demonstration of how to useeach device, and then used each device. Afterthey used both devices, participants were pre-sented with a brief paper-and-pencil question-naire. The questionnaire instructed participantsto select an answer for each question. A bino-mial test was used to determine if the nullhypothesis (i.e., there is no population-levelpreference for one device over another) shouldbe rejected.

METHODS

A primary concern of this research project wasin maintaining fairness in the process of testinguser preferences between autoinjectors, in par-ticular given that the study sponsor is thedeveloper of one of the autoinjectors (Brenzys).

Questionnaire Development

Because no previous autoinjector-comparisonmethod has been validated among our intendedstudy populations (patients and HCPs in Aus-tralia and Canada), we first conducted an initialqualitative questionnaire development andvalidation phase. To design an initial question-naire, the coauthors worked with subject matterexperts at Merck & Co., Inc., Kenilworth, NJ,

USA to outline a list of aspects of use that mightdiffer between the Brenzys and Enbrel autoin-jectors. This list was turned into a forced-choicequestionnaire that was then translated intoFrench Canadian and reviewed by linguisticexperts with respect to potential word choiceissues in French Canadian, Canadian English,and Australian English. A single ‘‘English’’ ver-sion and a single ‘‘French’’ version of the ques-tionnaire resulted from this initial process.

Following initial drafting of the question-naire, a total of 35 research participants (pa-tients and HCPs) in Australia, English-speakingCanada, and French-speaking Canada partici-pated in one-on-one moderated sessions. Eachparticipant was presented with training versionsof the autoinjectors and were given demon-strations of how to use the training devices.Participants then simulated use of the autoin-jector training device into an injection pad.Presentation of the devices was counterbal-anced between participants. Following use ofthe second device, participants completed thewritten questionnaire. After completing thequestionnaire, participants were interviewedin-depth regarding their experience with andunderstanding of the questionnaire.

All participants in this development phase(35/35, 100%) indicated the same overall pref-erence for one device over the other in thewritten questionnaire as during the subsequentverbal interview. Furthermore, none of thequestionnaire items led more than one partici-pant to respond differently on the writtenquestionnaire as during the subsequent verbalinterview. This process gave us confidence thatthe paper-and-pencil questionnaire could cap-ture overall preference between the twoautoinjectors when compared to the gold stan-dard of an in-person discussion with a person—in other words, the personal interview could bedispensed with, and the questionnaire alonecould be used to learn about users’ preferences.

Modifications were made to the question-naire on the basis of a few issues encountered byparticipants. These changes were not validatedempirically with additional study participants,but translations of changes were vetted by ateam of translation experts familiar with localvernacular.

Adv Ther (2017) 34:1157–1172 1159

Compliance with Ethics Guidelines

All procedures followed were in accordancewith the ethical standards of the responsiblecommittee on human experimentation (insti-tutional and national) and with the HelsinkiDeclaration of 1964, as revised in 2013.Informed consent was obtained from allpatients for being included in the study.

Questionnaire Deployment (Testing)

Study PopulationTo represent actual users, the study populationin each country (Australia and Canada) inclu-ded individuals from two defined user groupswho met the following criteria: (1) patients withRA, including both autoinjector-naive andautoinjector-experienced; and (2) HCPs withexperience managing patients with RA, includ-ing both nurses and rheumatologists. Partici-pants provided written consent beforeparticipating in the study and were compen-sated for their time with an honorarium.

Target Sample SizeOn the basis of estimates that a true 60% and65% population-level preference amongpatients and HCPs, respectively, for one deviceover another would be meaningful, a minimumsample size of 188 patients and 80 HCPs wascalculated to have 80% power to detect truepopulation-level preferences for one device overthe other.

Study Procedures and AssessmentsEach study session employed the followingprocedure over the course of the sessions lastingup to 30 min; there were no delays plannedbetween the items listed below:• Moderator verbally confirmed participant’s

consent to participate in the study, previ-ously provided on an informed consentform.

• Moderator reviewed inclusion/exclusion cri-teria with participants.

• Moderator assigned participants to counter-balancing condition (which device to receivefirst).

• Moderator briefly showed how to use thefirst autoinjector.

• Participant used the first autoinjector toinject medication into an injection pad.

• Moderator briefly showed how to use thesecond autoinjector.

• Participant used the second autoinjector toinject medication into an injection pad.

• Participant completed paper-and-pencilquestionnaire; for each item below, thequestionnaire instructed the participant tocircle either ‘‘The first one I used’’ or ‘‘Thesecond one I used’’.• Overall, which autoinjector do you

prefer?• Which one is easier to use?• Which autoinjector was better at indicat-

ing that a full dose was actuallyadministered?

• Which autoinjector’s cap was easier toremove?

• Which autoinjector was easier to use toadminister the dose?

• [Patients only]: Which autoinjectorwould you recommend to others?

• [HCP only]: Which autoinjector wouldyou recommend to patients?

• [HCP only]: Which autoinjector do youthink would be easier to teach patientshow to use?

• [Enbrel autoinjector-experienced patientsonly]: If you could use either autoinjectorto continue your treatment for rheuma-toid arthritis, which one would youchoose?

• Moderator reviewed completed question-naire to make sure responses were legibleand no responses were missing. In caseswhere participants would not provide ananswer, saying the devices were similar,moderators encouraged participants to thinkmore fully to find some way to differentiate.If participants would still not choose, theiranswer was coded as ‘‘same’’ and werereported but excluded from analysis ofpreferences.Note that one additional questionnaire item

(‘‘Which autoinjector’s label was easier to read’’)was initially planned but not completedbecause the Brenzys autoinjectors were

1160 Adv Ther (2017) 34:1157–1172

unlabeled. Also note that the Enbrel MYCLICautoinjectors available in Australia and used inthe study had a dark blue plunger, while theEnbrel SureClick autoinjectors available inCanada and used in the study had a yellowplunger.

A binomial test was planned to identify sta-tistical significance (p\0.05), separately forpatients and for HCPs, for each questionnaireitem (except for the item intended for Enbrelautoinjector-experienced patients only, owingto the lower sample size for that item.) Therewas no correction for multiple comparisonsbecause the number of planned comparisonswas small, all comparisons would be presented,and questionnaire items are not independent ofeach other (all being related to ease of use andoverall preference) making the use of a correc-tion factor potentially misleading. To mitigatefor issues related to multiple statistical com-parisons, we encourage attention to the overallpattern of results rather than to results of anyone statistical test. Responses broken down byadditional subgroups (e.g., patients with andwithout limitations in hand function) aredepicted without significance tests.

RESULTS

The study was conducted from May to June2016 at research centers in Sydney, Australia;Melbourne, Australia; Brisbane, Australia; Tor-onto, Canada; and Montreal, Canada. A total of191 patients reporting a diagnosis of RA and 90HCPs with experience managing RA patientsparticipated.

Overall, participants were more likely toindicate preferring Brenzys autoinjector thanEnbrel autoinjector for all questionnaire items.Details of participant demographics andresponses are shown below.

Participant Demographics

The mean age of patient participants was52 years old and the majority of them arefemale which is consistent with the general RApatient demographic and included participantswith (18%) and without (82%) autoinjector

experience for RA. Most participants reporteddifficulty with use of their hands due to RA(92%) (Table 1).

HCP participants included 59 nurses and 31rheumatologists who have experience manag-ing patients with RA (Table 2).

Questionnaire Items

Note throughout this section that sample sizesof less than 191 (patients) and 90 (HCPs) indi-cate participants who responded ‘‘same’’ or‘‘both’’ on a questionnaire item.

For all survey items, patients were signifi-cantly more likely to indicate a preference forBrenzys autoinjector than Enbrel autoinjector.In the overall patient sample, the weakest pref-erence was for cap removal (60.0% preferringBrenzys autoinjector), and the strongest prefer-ence was in indicating which autoinjector is‘‘easier to use’’ (79.1% preferring Brenzysautoinjector) (Table 3).

HCPs were also significantly more likely toindicate a preference for Brenzys autoinjectorthan Enbrel autoinjector on all survey itemsexcept for cap removal. The strongest prefer-ence was in indicating which autoinjectorwould be easier to teach to patients (87.8%preferring Brenzys autoinjector) (Table 4).

Four additional ad hoc two-sided binomialtests were carried out, for overall preference forBrenzys vs. Enbrel among patients and HCPsconsidered separately in each country. Asshown in Table 5, all four of these groups werestatistically more likely to indicate an overallpreference (all p\0.001) for Brenzysautoinjector.

Tables 6, 7, 8, and 9 provide questionnaireresponses broken down by demographic sub-groups. Statistical tests were not applied.

In this study, it appears that most Canadianand Australian subgroups (i.e., by age, gender,experience with autoinjector, dexterity, etc.)were each independently more likely to preferthe Brenzys autoinjector to the Enbrel autoin-jector on all survey items. These subgroupanalyses demonstrated consistency in the pref-erence for the Brenzys autoinjector across dif-ferent subpopulations.

Adv Ther (2017) 34:1157–1172 1161

DISCUSSION

The results from this study suggest that RApatients and HCPs would significantly preferthe Brenzys autoinjector over the Enbrelautoinjector when choosing their injectiondevice for their RA treatment. In addition, theywould also be more likely to recommend theBrenzys autoinjector to their peers andpatients. Subgroup analyses also indicate that amajority of English-Canadian, French-Cana-dian, and Australian RA patients and HCPshave an overall preference for the Brenzysautoinjector including patients with and

without limitations in hand function, patientswith and without previous autoinjector expe-rience, male and female, different age groups,nurses, and rheumatologists.

Almost all RA patient participants whohad past experience with the Enbrel autoin-jector indicated that they would prefer to usethe Brenzys autoinjector. Participants wereselected to be representative of real-worldusers, leading to the conclusion that RApatients and HCPs with experience managingRA would prefer and/or recommend theBrenzys autoinjector over the Enbrelautoinjector.

Table 1 Patient participant demographics

Demographics Australia Canada (English) Canada (French) TotalPatients with RA (N5 90) (N5 77) (N5 24) (N5 191)

Gender

Female 59 (65.6%) 55 (71.4%) 15 (62.5%) 129 (67.5%)

Average age (years) 52.5 51.7 50.9 52

Age (years)

18–39 15 (16.7%) 14 (18.2%) 10 (41.7%) 39 (20.4%)

40–49 18 (20.0%) 23 (29.9%) 0 (0.0%) 41 (21.5%)

50–59 25 (27.8%) 18 (23.4%) 5 (20.8%) 48 (25.1%)

60–69 25 (27.8%) 15 (19.5%) 6 (25.0%) 46 (24.1%)

70? 7 (7.8%) 7 (9.1%) 3 (12.5%) 17 (8.9%)

Autoinjector experience for rheumatoid arthritis

Naive 74 (82.2%) 64 (83.1%) 19 (79.2%) 157 (82.2%)

Injection experience other than rheumatoid arthritis

Naive 84 (93.3%) 70 (90.9%) 21 (87.5%) 175 (91.6%)

Dexteritya

Difficulty 89 (98.9%) 69 (89.6%) 19 (79.2%) 177 (92.7%)

a Participants were asked the following question, and those who indicated anything other than ‘‘none of the above’’ wereconsidered to have difficulty with dexterity:With regard to your hands, wrists, and fingers, which if any of the following do you have on a regular basis?(a) Significant hand weakness making it difficult to hold heavy objects(b) Significant pain making it difficult to move your hands or grasp objects(c) Limited dexterity making it difficult to pick up, hold, and/or manipulate small objects (i.e., coins, buttons, pencils, etc.)(d) Limited range of motion making it difficult to fully open or close your hand or rotate your wrists(e) Deformities in the joints of your hands causing your fingers/thumbs to twist(f) None of the above

1162 Adv Ther (2017) 34:1157–1172

In the questionnaire development and vali-dation phase of this study, some patient andHCP participants reported during interviews

that injecting with the Enbrel autoinjectorcould be painful for patients with limitations inhand function because of the button press

Table 2 HCP participant demographics

Demographics Australia Canada (English) Canada (French) TotalHCPs (n5 39) (n5 36) (n5 15) (n5 90)

Gender

Female 30 (76.9%) 25 (69.4%) 13 (86.7%) 68 (75.6%)

Average age (years) 46.0 52.3 46.7 48.7

Age, years (avg. age)

18–39 11 (28.2%) 3 (8.3%) 6 (40.0%) 20 (22.2%)

40–49 12 (30.8%) 10 (27.8%) 3 (20.0%) 25 (27.8%)

50–59 15 (38.5%) 15 (41.7%) 2 (13.3%) 32 (35.6%)

60–69 1 (2.6%) 6 (16.7%) 3 (20.0%) 10 (11.1%)

70? 0 (0%) 2 (5.6%) 1 (6.7%) 3 (3.3%)

Position

Nurse 30 (76.9%) 17 (47.2%) 12 (80.0%) 59 (65.6%)

Rheumatologist 9 (23.1%) 19 (52.8%) 3 (20.0%) 31 (34.4%)

Table 3 Patient questionnaire results

Patients

N Prefer Brenzys 95% CI p value

Overall, which autoinjector do you prefer? 191 142 (74.3%) [67.5%, 80.3%] \0.001

Which autoinjector is easier to use? 191 151 (79.1%) [72.5%, 84.6%] \0.001

Which autoinjector was better at indicating that a full

dose was actually administered?

188 119 (63.3%) [55.9%, 70.1%] \0.001

Which autoinjector’s cap was easier to remove? 190 114 (60.0%) [52.5%, 67.0%] \0.05

Which autoinjector was easier to use to administer the dose? 191 150 (78.5%) [72.0%, 84.1%] \0.001

Which autoinjector would you recommend to others? 191 141 (73.8%) [66.9%, 79.9%] \0.001

[Enbrel autoinjector-experienced only]: If you could use

either autoinjector to continue your treatment for rheumatoid

arthritis, which one would you choose?

17 16 (94.1%) [71.3%, 99.8%] N/Aa

a Not tested because of sample size

Adv Ther (2017) 34:1157–1172 1163

which requires thumb use, and commentedthat the buttonless Brenzys autoinjector wouldwork better for patients with RA who might

have limitations in hand function. Thakur et al.[3] similarly found preferences for a new etan-ercept autoinjector based on a buttonless

Fig. 2 Forest plot of patient preference

Table 4 HCP questionnaire results

HCP

N PreferBrenzys

95% CI p value

Overall, which autoinjector do you prefer? 90 72 (80.0%) [70.2%,

87.6%]

\0.001

Which autoinjector is easier to use? 90 77 (85.6%) [76.5%,

92.0%]

\0.001

Which autoinjector was better at indicating that a full dose was

actually administered?

87 67 (77.0%) [66.7%,

85.3%]

\0.001

Which autoinjector’s cap was easier to remove? 87 48 (55.2%) [44.1%,

65.8%]

Not significant

(p = 0.053)

Which autoinjector was easier to use to administer the dose? 90 76 (84.4%) [75.2%,

91.2%]

\0.001

Which autoinjector would you recommend to patients? 89 74 (83.1%) [73.7%,

90.2%]

\0.001

Which autoinjector do you think would be easier to teach patients

how to use?

90 79 (87.8%) [79.1%,

93.7%]

\0.001

1164 Adv Ther (2017) 34:1157–1172

design. In addition to confirming relative easeof use to perform the actual injection with theBrenzys autoinjector, the current study alsofound that patients prefer the Brenzys capremoval (cap removal also requiring manualdexterity). The Brenzys dose feedback mecha-nism (plunger visible in a window) indicating acomplete dose was also overall preferred toEnbrel’s.

Nurses and rheumatologists in the currentstudy indicated that they would recommendthe Brenzys rather than Enbrel autoinjector topatients, and also indicated that they thoughtthe Brenzys autoinjector would be easier toteach to patients than to the Enbrel

autoinjector. An autoinjector that is simpler tolearn and easier to use has the potential toreduce time taken in training sessions and hasthe potential to improve long-term adherenceto, and thereby effectiveness of, a course oftherapy. Further research would be needed toassess actual impacts of such a preferred deviceon adherence, safety, effectiveness, and health-care costs.

Limitations

Participants injected into an injection pad,rather than into themselves, and only once

Table 5 Overall preference (questionnaire item 1), patients and HCPs in Australia and Canada

RA patients HCPs (nurses and rheumatologists)

N % preferring Brenzys overall p value N % preferring Brenzys overall p value

Australia 90 83.3 \0.001 39 85.0 \0.001

Canada 101 66.3 \0.001 51 76.5 \0.001

Fig. 3 Forest plot of HCP preference

Adv Ther (2017) 34:1157–1172 1165

Table6

Questionn

aire

item

sby

demograph

icbreakdow

n,AustraliaRA

patients

Australia

Overall

preference

Easeof

use

Indicating

full

dose

administered

Easeof

cap

removal

Easeof

administration

Recom

mendto

others

[IfEnb

reluser]

Deviceto

continue

treatm

ent

Patientswith

RA

(n5

90)

(n5

90)

(n5

90)

(n5

90)

(n5

90)

(n5

90)

(n5

6)

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

Gender

Female

5983.1

5986.4

5972.9

5959.3

5989.8

5984.7

4100.0

Male

3183.9

3190.3

3187.1

3167.7

3187.1

3183.9

2100.0

Age

(years)

18–3

915

66.7

1580.0

1580.0

1560.0

1586.7

1566.7

1100.0

40–4

918

88.9

1894.4

1866.7

1866.7

1888.9

1888.9

3100.0

50–5

925

80.0

2584.0

2572.0

2560.0

2584.0

2580.0

1100.0

60–6

925

92.0

2592.0

2592.0

2564.0

2596.0

2596.0

0NA

70?

785.7

785.7

771.4

757.1

785.7

785.7

1100.0

Autoinjectorexperience

forrheumatoidarthritis

Naive

7479.7

7485.1

7478.4

7459.5

7486.5

7481.1

0NA

Experienced

16100

16100

1675

1675

16100

16100

6100

Injectionexperience

otherthan

rheumatoidarthritis

Naive

8483.3

8488.1

8477.4

8461.9

8488.1

8483.3

5100.0

Experienced

683.3

683.3

666.7

666.7

6100.0

6100.0

1100.0

Dexterity

Diffi

culty

8983

8988

8978

8962

8989

8984

6100

Nodifficulty

1100

1100

1100

1100

1100

1100

0NA

Patientsoverall

preference

9083.3

9087.8

9077.8

9062.2

9088.9

9084.4

6100.0

1166 Adv Ther (2017) 34:1157–1172

Table7

Questionn

aire

item

sby

demograph

icbreakdow

n,Australia(H

CPs)

Australia

Overall

preference

Easeof

use

Indicating

full

dose

administered

Easeof

cap

removal

Easeof

administration

Recom

mendto

patients

Easierto

teachto

patients

Healthcare

profession

als

(n5

39)

(n5

39)

(n5

39)

(n5

38)

(n5

39)

(n5

39)

(n5

39)

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

N%

preference

forBrenzys

Gender

Female

3083.3

3083.3

3080.0

3056.7

3090.0

3086.7

3093.3

Male

988.9

988.9

988.9

862.5

977.8

988.9

988.9

Age

(years)

18–3

911

90.9

1190.9

1190.9

1154.5

1181.8

1190.9

11100.0

40–4

912

75.0

1275.0

1275.0

1258.3

1283.3

1283.3

1283.3

50–5

915

86.7

1586.7

1580.0

1464.3

1593.3

1586.7

1593.3

60–6

91

100.0

1100.0

1100.0

10.0

1100.0

1100.0

1100.0

70?

0NA

0NA

0NA

0NA

0NA

0NA

0NA

Position

Nurse

3083.3

3083.3

3086.7

3056.7

3086.7

3086.7

3093.3

Rheum

atologist

988.9

988.9

966.7

862.5

988.9

988.9

988.9

HCPoverall

preference

3985

3985

3982

3858

3987

3987

3992

Adv Ther (2017) 34:1157–1172 1167

Table8

Questionn

aire

item

sby

demographicbreakdow

n,CanadaRA

patients

Canada

Overallpreference

Easeof

use

Indicating

full

dose

administered

Easeof

cap

removal

Easeof

administration

Recom

mendto

others

[IfEnb

reluser]

Deviceto

continue

treatm

ent

Patientswith

RA

(n5

101)

(n5

101)

(n5

98)

(n5

100)

(n5

101)

(n5

101)

(n5

11)

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

Gender

Female

7064.3

7070.0

6749.3

7055.7

7068.6

7061.4

475.0

Male

3171.0

3174.2

3151.6

3063.3

3171.0

3171.0

7100.0

Age

(years)

18–3

924

50.0

2466.7

2437.5

2441.7

2458.3

2445.8

475.0

40–4

923

78.3

2382.6

2369.6

2263.6

2382.6

2378.3

2100.0

50–5

923

82.6

2382.6

2050.0

2373.9

2382.6

2378.3

2100.0

60–6

921

57.1

2157.1

2142.9

2152.4

2157.1

2157.1

2100.0

70?

1060.0

1060.0

1050.0

1060.0

1060.0

1060.0

1100.0

Autoinjectorexperience

forrheumatoidarthritis

Naive

8362.7

8366.3

8046.3

8252.4

8366.3

8362.7

0NA

Experienced

1883.3

1894.4

1866.7

1883.3

1883.3

1872.2

1190.9

Injectionexperience

otherthan

rheumatoidarthritis

Naive

9168.1

9171.4

8951.7

9157.1

9171.4

9165.9

1090.0

Experienced

1050.0

1070.0

966.7

966.7

1050.0

1050.0

1100.0

Dexterity

Diffi

culty

8867.0

8871.6

8648.8

8858.0

8868.2

8865.9

1190.9

Nodifficulty

1361.5

1369.2

1258.3

1258.3

1376.9

1353.8

0NA

1168 Adv Ther (2017) 34:1157–1172

instead of repeatedly over the course of therapy.It is possible that long-term use or use intoactual skin may yield different patterns ofpreferences, although there is no specific reasonthat this would be the case.

The Brenzys autoinjector was preferred byparticipants, but it was not in the scope of thecurrent study to record and analyze use errors,so the preference for ease of use of the Brenzysautoinjector or the Enbrel autoinjector is notequivalent to an assessment of safe and effectiveuse of either device.

Patient dexterity and difficulties with dex-terity were self-assessed, but not independentlyverified.

The study was conducted in Australia andCanada. Users in other locations might havedifferent impressions of the autoinjectors,although there is no specific reason we know ofthat this would be the case.

CONCLUSIONS

RA patients and nurses and rheumatologistswith experience managing RA patients indi-cated an overall preference for using the Brenzysautoinjector, rather than the Enbrel autoinjec-tor, after using both devices. The preferenceextended to various aspects of use, teaching,and recommendations participants would maketo others. Both HCPs and patients were morelikely to indicate that they would recommendto others the Brenzys autoinjector rather thanthe Enbrel autoinjector. Owing to the design ofthe study, we expect that readers can use thisdata to understand the experiences of real--world users using devices. The study allows us toinfer that real-life users, including RA patientswith limitations in hand function, would have abetter injection experience were they to use theBrenzys autoinjector rather than the Enbrelautoinjector. DiMatteo [4] and Mohr et al. [5]found that difficulty injecting can lead toincreased and unnecessary pain, lack of adher-ence, and increased overall treatment costs. Inlight of the importance of ease of use and pref-erence by patients and providers, healthcarestakeholders (patients, lay caregivers, nurses,doctors, payers, policy makers, etc.) can useT

able8

continued

Canada

Overallpreference

Easeof

use

Indicating

full

dose

administered

Easeof

cap

removal

Easeof

administration

Recom

mendto

others

[IfEnb

reluser]

Deviceto

continue

treatm

ent

Patientswith

RA

(n5

101)

(n5

101)

(n5

98)

(n5

100)

(n5

101)

(n5

101)

(n5

11)

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

Patients

overall

preference

101

66.3

101

71.3

9850.0

100

58.0

101

69.3

101

64.4

1190.9

Adv Ther (2017) 34:1157–1172 1169

Table9

Questionn

aire

item

sby

demographicbreakdow

n,CanadaHCPs

Canada

Overallpreference

Easeof

use

Indicating

full

dose

administered

Easeof

cap

removal

Easeof

administration

Recom

mendto

patients

Easierto

teach

topatients

Healthcare

profession

als

(n5

51)

(n5

51)

(n5

48)

(n5

49)

(n5

51)

(n5

50)

(n5

51)

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

N% preference

forBrenzys

Gender

Female

3876.3

3886.8

3672.2

3751.4

3884.2

3778.4

3884.2

Male

1376.9

1384.6

1275.0

1258.3

1376.9

1384.6

1384.6

Age

(years)

18–3

99

55.6

977.8

955.6

955.6

966.7

955.6

955.6

40–4

913

84.6

1392.3

1376.9

1346.2

1392.3

1283.3

1392.3

50–5

917

82.4

1782.4

1566.7

1650.0

1788.2

1788.2

1788.2

60–6

99

88.9

9100.0

8100.0

875.0

988.9

988.9

9100.0

70?

333.3

366.7

366.7

333.3

333.3

366.7

366.7

Position

Nurse

2969.0

2982.8

2766.7

2853.6

2979.3

2871.4

2979.3

Rheum

atologist

2286.4

2290.9

2181.0

2152.4

2286.4

2290.9

2290.9

HCPoverall

preference

5176.5

5186.3

4872.9

4953.1

5182.4

5080.0

5184.3

1170 Adv Ther (2017) 34:1157–1172

evidence from this study to assist their deci-sion-making when selecting Brenzys or Enbrelfor RA management.

ACKNOWLEDGEMENTS

This study was commissioned by Merck & Co.,Inc., Kenilworth, NJ, USA. Article processingcharges were funded by Merck & Co. Thanks toRenna Patel, Jinan Liu, and Girish Prajapati. Allauthors had full access to all of the data in thisstudy and take complete responsibility for theintegrity of the data and accuracy of the dataanalysis. All named authors meet the Interna-tional Committee of Medical Journal Editors(ICMJE) criteria for authorship for this manu-script, take responsibility for the integrity of thework as a whole, and have given final approvalfor the version to be published. Merck and Co,Inc. (‘‘Merck’’) hired Core Human Factors, Inc.(‘‘Core’’), an independent research group, todesign, conduct, and write up a study compar-ing use of Brenzys autoinjector to Enbrelautoinjector in Australia and Canada. Merckhad a hypothesis that Brenzys was easier to usethan Enbrel owing to its one-press form factor.Merck commented on and approved researchdesigns throughout the research process. Theresulting study design compared the twoautoinjectors in an unbiased way on the factorshypothesized (described in the paper ashypotheses) to favor Brenzys. Researchers fromCore moderated sessions or independentlymanaged non-English-speaking moderators tointerview study participants, gathered the data,and conducted the analyses. Other co-authorsinclude employees either at Merck or at Core, aslisted in affiliations. The results seem to theauthors to be valid and to represent the contri-bution to developments in therapy as describedin the paper including the conclusions.

Disclosures. Marc Egeth is an employee ofCore Human Factors Inc, an independentresearch company engaged by (paid by) Merckand Co. to design and conduct the study. Jen-nifer Soosaar is an employee of Core HumanFactors Inc, an independent research company

engaged by (paid by) Merck and Co. to designand conduct the study. Peter Nash is a priorpaid consultant of Merck & Co., not paid withrespect to the current research. Denis Cho-quette is a prior paid consultant of Merck & Co.,not paid with respect to the current research.Ricardo Infante is an employee of Merck & Co.Dena Rosen Ramey is an employee of Merck &Co. Sevag Sahakian is an employee of Merck &Co. Angela Lai is an employee of Merck & Co.Jin Ju Kim is an employee of Merck & Co. DavidWu is an employee of Merck & Co.

Compliance with Ethics Guidelines. Allprocedures followed were in accordance withthe ethical standards of the responsible com-mittee on human experimentation (institu-tional and national) and with the HelsinkiDeclaration of 1964, as revised in 2013.Informed consent was obtained from allpatients for being included in the study.

Data Availability. The datasets analyzedduring the current study are available from thecorresponding author on reasonable request.

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommer-cial use, distribution, and reproduction in anymedium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.

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