ORIGINAL RESEARCH

Using Patient Feedback to Optimize the Designof a Certolizumab Pegol Electromechanical Self-Injection Device: Insights from Human Factors Studies

Barbara Domanska . Oliver Stumpp . Steven Poon . Serkan Oray .

Irina Mountian . Clovis Pichon

Received: September 29, 2017 / Published online: December 8, 2017� The Author(s) 2017. This article is an open access publication

ABSTRACT

Introduction: We incorporated patient feed-back from human factors studies (HFS) in thepatient-centric design and validation of ava�,an electromechanical device (e-Device) for self-injecting the anti-tumor necrosis factor cer-tolizumab pegol (CZP).Methods: Healthcare professionals, caregivers,healthy volunteers, and patients with rheuma-toid arthritis, psoriatic arthritis, ankylosingspondylitis, or Crohn’s disease participated in

11 formative HFS to optimize the e-Devicedesign through intended user feedback; ninestudies involved simulated injections. Forma-tive participant questionnaire feedback wascollected following e-Device prototype han-dling. Validation HFS (one EU study and one USstudy) assessed the safe and effective setup anduse of the e-Device using 22 predefined criticaltasks. Task outcomes were categorized as ‘‘fail-ures’’ if participants did not succeed withinthree attempts.Results: Two hundred eighty-three participantsentered formative (163) and validation (120)HFS; 260 participants performed one or moresimulated e-Device self-injections. Designchanges following formative HFS includedalterations to buttons and the graphical userinterface screen. All validation HFS participantscompleted critical tasks necessary for CZP dosedelivery, with minimal critical task failures (12of 572 critical tasks, 2.1%, in the EU study, and2 of 5310 critical tasks, less than 0.1%, in the USstudy).Conclusion: CZP e-Device development wasguided by intended user feedback through HFS,ensuring the final design addressed patients’needs. In both validation studies, participantssuccessfully performed all critical tasks,demonstrating safe and effective e-Device self-injections.Funding: UCB Pharma.

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Electronic supplementary material The onlineversion of this article (https://doi.org/10.1007/s12325-017-0645-1) contains supplementary material, which isavailable to authorized users.

B. Domanska (&) � S. PoonUCB Pharma, Slough, UKe-mail: barbara.domanska@ucb.com

O. Stumpp � C. PichonUCB Pharma, Bulle, Switzerland

S. OrayUCB Pharma, Braine l’Alleud, Belgium

I. MountianUCB Pharma, Brussels, Belgium

Adv Ther (2018) 35:100–115

https://doi.org/10.1007/s12325-017-0645-1

Keywords: Anti-tumor necrosis factor;Biological disease-modifying antirheumaticdrug; Certolizumab pegol; Electromechanicalinjection device; e-Device; Human factorsstudies; Self-injection

Plain Language Summary: Plain languagesummary available on the journal website.

PLAIN LANGUAGE SUMMARY

Aims of the Study: People living with long-term diseases caused by inflammation, such asrheumatoid arthritis, often use medication thatmust be injected under the skin. The aim of thisresearch was to use patient feedback to helpdesign a new, patient-friendly electromechani-cal injection device (e-Device).How the Research was Carried Out: Peoplewho regularly use injection devices, such asdoctors, patients, and patients’ carers, wereasked to take part in this research. The researchwas carried out in two stages. In the first part,participants were given an early version of thee-Device and asked for their opinions on thedesign. Their feedback was then used to makethe design more patient friendly. Once the ini-tial design was set, participants used the e-De-vice to inject a fake skin pad. Any feedbackreceived was used to further improve the design.In the second part, the design of the e-Devicewas checked to make sure users could safely set-up and use the e-Device. Two studies were car-ried out to check this, one in America and theother in Europe. Participants were providedwith an instruction booklet and were notallowed to ask for additional help or advicefrom the people doing the research.What we Found: Feedback from the 163 peoplewho participated in the first part of the researchled to important changes to the design of thee-Device. For example, the buttons were chan-ged to make them easier for patients to push,and the instructions on the screen were madeclearer. After these design changes were made120 people tested the final e-Device. This part ofthe study confirmed that everyone could safelyuse the e-Device. Doctors could safely set up thee-Device, and everyone taking part could safelyperform a pretend injection.

INTRODUCTION

Anti-tumor necrosis factors (anti-TNFs) can bean effective treatment option for a number ofchronic inflammatory diseases, includingrheumatoid arthritis (RA), ankylosingspondylitis (AS), psoriatic arthritis (PsA), andCrohn’s disease (CD).

Certolizumab pegol (CZP) is an Fc-free,PEGylated anti-TNF [1], delivered subcuta-neously, often by self-injection. Self-adminis-tration of subcutaneous injections can bebeneficial to patients, as this can increaseindependence, and offer greater flexibility inthe timing of injections [2, 3]. However, sub-optimal treatment adherence can reduce theclinical benefits of anti-TNF therapy [4]. Treat-ment adherence is influenced by multiple fac-tors. Many patients with RA, AS, PsA, or CD facebarriers to safe self-injection, including needlephobia, problems with manual dexterity, painlinked to joint swelling in the hands, and a lackof confidence in the self-injection process [5–8].As a number of factors affecting treatmentadherence are associated with treatment deliv-ery [3], optimizing device design can provide anopportunity to improve adherence, enhance thepatient experience, and aid disease manage-ment. Self-injection devices can be designedspecifically to meet patients’ unmet needs andprovide flexibility and control for treatmentadministration, with additional features such asinjection reminders to aid scheduling, promot-ing ease of use [2, 3].

Currently, CZP is administered via a pre-filled syringe (PFS) or prefilled pen (PFP) [1].Patients, together with healthcare professionals(HCPs), can select a device best suited to theirneeds, taking into account factors such as avisible versus hidden needle, and the control ofinjection speeds using manual versus auto-matic injection devices. For example, in astudy in patients with RA, participants com-pared several designs of PFPs and identified theability to hold the grip securely, reassurance ofmedication delivery, an easy activationmethod, and a cap that is easy to remove asthe most important design features for self-in-jection devices [9].

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Human factors studies (HFS) are designed tocollect feedback from intended users on devicedesign and user interface, and to eliminate ormitigate any potential use-related hazards [10].HFS are used to observe patients’ interactionswith devices and iteratively improve devicedesign by listening to patient feedback. A reviewof medical device usability testing methodshighlighted the value of HFS as part of a patient-centric design process, with user-feedback-leddesign more likely to result in patient satisfac-tion and correct use of the final device [11].Furthermore, these studies form part of the USAFDA’s requirements to validate the usability andsafety of medical devices [10, 12, 13], and helpto demonstrate conformance with requirementsof EU and international regulatory authorities,such as the European Parliament and Council ofthe European Communities’ medical devicesdirectives and the International Electrotechni-cal Commission [13–15].

Here, we report the results from formativeand validation HFS conducted across the UKand USA to support the development of ava�,an electromechanical injection device (e-De-vice) designed for self-injection of CZP.Through interaction with patients across severalindications, healthy volunteers, HCPs, andcaregivers, we sought to ensure the develop-ment and the safe and effective use of the newe-Device and hence to further widen the devicechoices available for patients receiving CZPtherapy. Responses from intended users wereused to develop, improve, and validate the finaldesign of the CZP e-Device, including but notlimited to the device itself, its packaging, andinstructional materials for use of the e-Device.The ava� e-Device was recently approved forCZP administration in the EU [1].

METHODS

A comprehensive series of 13 HFS (11 formativestudies, 1 EU validation study, and 1 US vali-dation study) were used to guide the develop-ment of the e-Device and validate the finalversion for use. The studies enrolled a mixtureof HCPs, caregivers, healthy volunteers, andpatients.

The initial prototype CZP e-Device wasdesigned in collaboration with OXO (New York,NY, USA), with use of feedback from RA patientsand HCPs. Users recommended a simple andintuitive graphical user interface (GUI), leadingto the development of on-screen, step-by-stepself-injection guidance. This initial prototypewas designed to automatically direct the userthrough the entire injection process, includinginserting the dose-dispenser cartridge (DDC),performing the injection, and DDC disposal. Askin sensor on the device was included soinjection could be initiated only when thee-Device was placed in full contact with theskin, and to ensure that the needle would befully retracted and hidden from the user whennot in use. A scroll wheel allowed the choice ofthe speed of the injection (four speeds between7 and 18 s), with additional control provided bya pause button to stop the injection at any time.

This OXO-designed prototype e-Device wasthen refined and validated with use of feedbackfrom 13 HFS, performed by independent humanfactors specialists. Eleven formative HFS wereused to iteratively refine the e-Device; the firsttwo formative studies were led by SmartDesign(Barcelona, Spain), the third, fourth, and ninthformative studies were run by UCB Celltech(Slough, UK), and the remaining formative andvalidation studies were performed by MedicalDevice Usability Ltd (Cambridge, UK). The EUand US validation HFS included intended usersto assess the final design.

According to the label recommendations,CZP regimens are initiated with an initial load-ing dose consisting of 400 mg at weeks 0, 2, and4 followed by a maintenance dose of either200 mg every other week or 400 mg every4 weeks [1]. For the HFS involving injections, nomedications were administered. Instead, simu-lated self-injections were administered with useof an artificial skin pad attached to the patient’supper thigh or abdomen. The validation stud-ies’ test environments simulated either a homeenvironment (for patients and caregivers) or anoffice environment (for HCPs).

Simulated injections were performed in nineof the 11 formative studies and both of the vali-dation studies. After each simulated injection, amoderator asked open-ended questions to

102 Adv Ther (2018) 35:100–115

understand the participants’ experiences. Useerrors and feedback were recorded by observationof participants during the simulated injections orby knowledge tests; these included asking whowould set up the e-Device, what dose of medica-tion the participant would inject, and what theparticipant should do to confirm that the dose hasbeen successfully delivered. Following each for-mative study, participant questionnaire feedbackwas used to continually improve the design of thee-Device and user interface.

Participants

HCPs, caregivers, healthy volunteers (bothinjection-naıve and injection-experienced heal-thy volunteers), and patients with RA, CD, AS, orPsA were enrolled in the formative and valida-tion studies; participants reflected the intendedusers of the device and were recruited via phoneand e-mail screeners. Participants aged 18 yearsor older were included if they were caregiverswho administered subcutaneous injections for apatient with RA, AS, PsA, or CD; HCPs currentlyin practice for at least 2 years, and treating atleast one RA, CD, AS, and/or PsA patient,administering a total of four or more injectionsper month; and patients with an active diagno-sis of RA, AS, PsA, or CD as confirmed by aphysician letter, and currently receiving anymedication for these conditions. There were nofurther eligibility criteria for healthy volunteersother than no involvement with the develop-ment of the e-Device. Full eligibility criteria foreach individual study are described in Table S1.

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 all par-ticipants for their being included in the studies.In compliance with the FDA human factorsguidelines [12], 15 participants from each dis-tinct user group (HCPs, caregivers, RA patients,PsA patients, AS patients, and CD patients) wererecruited for the US validation study. For the EUvalidation study, 15 participants with RA and 15HCPs were recruited [13].

Formative Studies

Eleven formative studies (studies 1–10 and study12) were conducted between March 2011 andDecember 2015 in the UK (London, Slough,Cambridge, and Stockport) and the USA (Balti-more, MA; Houston, TX; Los Angeles, CA;Englewood, NJ; and Miami, FL). The first for-mative study used the OXO-designed prototype.The following three formative studies iterativelyupdated the design of this prototype, incorpo-rating feedback from healthy volunteers, HCPs,and patients with RA. The final e-Device designdeveloped following the fourth formative studywas used in the seven remaining formativestudies. Intended users provided feedback fol-lowing the HCP setup and simulated use of thee-Device in response to moderator questions,and healthy volunteers assessed the ease ofinterpreting injection logs. Details of all e-Devicecomponents evaluated are shown in Table 1.

Validation Studies

An EU and a US validation study were under-taken to validate the safe and effective use ofthe final CZP e-Device, but with CZP replacedby sorbitol in the DDCs. All simulated scenariosreflected the expected use of the e-Device.Twenty-two tasks considered critical for safeand effective administration were evaluated inboth validation studies (Table S2), either byobservation during simulated injection on anartificial skin pad or by a knowledge test. Pre-defined criteria determined whether a partici-pant successfully completed the tasks associatedwith safe and effective use of the CZP e-Device.Successful task completion was recorded if theparticipant could achieve the successful out-come of that task, or could answer a knowledgequestion correctly. For a task to be classified assuccessful, the participant had to complete itwithin three attempts. Task outcomes werereported as ‘‘successes’’ (completed the taskwithout mistakes), ‘‘successes with difficulties’’(completed the task within three attempts), or‘‘failures’’ (did not succeed within threeattempts). Any critical task failures were asses-sed by a moderator in a posttask interview to

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Table1

Evaluationof

electrom

echanicalinjectiondevice

(e-D

evice)

user

interfaceelem

ents

DDC

dose-dispenser

cartridge,HCPhealthcare

professional,IFU

instructions

foruse

aNocriticaluser

tasksdepend

onusingthelog.Forthisreason,the

injectionlogwas

notevaluatedin

study13.

104 Adv Ther (2018) 35:100–115

determine whether the failure was caused by/linked to the design of the e-Device.

EU Validation StudyThe EU validation study (study 11) was under-taken in the UK after the first ten formativestudies had been completed, and the design wasimproved and finalized with use of patientfeedback. The objective was to verify thatuntrained participants could understand theinstructions for use (IFU), GUI, and e-Devicetraining materials to perform all critical taskssafely and effectively without prior training.

Patients performed simulated CZP loadingdose self-injections using an artificial skin padattached to the intended injection site (ab-domen/thigh) and determined the next sched-uled injection date. HCPs were asked to set upCZP loading dose and maintenance dose regi-mens on the e-Device, and perform simulatedpatient injections. After the simulated injec-tion, each participant had a 120-min interviewwith a human factors specialist.

US Validation StudyThe US validation study (study 13) used thefinal e-Device design; participants were not

Table 2 Validation study participants

AS ankylosing spondylitis, CD Crohn’s disease, CG caregiver, HCP healthcare professional, NA not applicable, NR notreported, PsA psoriatic arthritis, RA rheumatoid arthritisa ‘‘White’’ is composed of ‘‘white’’, ‘‘white other’’, ‘‘white British’’, and ‘‘white American’’.b ‘‘Other’’ is composed of ‘‘African American’’, ‘‘Southeast Asian/Middle Eastern’’, ‘‘Indian/Pakistani/Middle Eastern’’,‘‘Mexican/Hispanic/Latino’’, ‘‘black/African/Caribbean’’, ‘‘other (not stated)’’, ‘‘black’’, and ‘‘Asian’’.c Levels of disease severity were self-reported by patients.d Injection responses are not mutually exclusive.

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given any training and had only the associatedpackaging, labeling, and instructional materialsfor guidance. The study was undertaken todemonstrate that all intended users couldeffectively and safely use the device, and thatHCPs could both effectively and safely set upthe e-Device, and show others how to use it.Each participant attended two separate 90-mininterviews with a human factors specialist, witha simulated injection at each interview, and a2-week period between the interviews, reflect-ing the most commonly expected dosing inter-val for CZP.

RESULTS

Patient Disposition and BaselineCharacteristics

Overall, 283 participants (HCPs, caregivers,healthy volunteers, and patients with RA, CD,AS, or PsA) were enrolled in the formative studies(Tables S3, S4) and validation studies (Table 2).Participants were representative of intendedusers of the e-Device. Across all studies, 260 par-ticipants performed at least one simulated self-injection with the e-Device (Fig. 1). No needle-stick injuries occurred during any study, and allparticipants could successfully and safely com-plete an injection procedure.

Formative Studies with Early Prototypes

The first four formative studies with prototypesinvolved 17 healthy volunteers, 5 HCPs, 1caregiver, and 28 RA patients (Table S3; studies1–4). These studies tested the simulated injec-tion, interpretation of the IFU, and use of theDDC. Step-by-step instructions were providedby the GUI to guide patients in the correct useof the e-Device throughout the injection pro-cess, and a training cartridge was available forparticipants to practice the injection procedure.Key findings included the existence of use errorswith DDC insertions and recognition that thetraining cartridge aided the operation andunderstanding of the device, and would bevaluable for inclusion with the final e-Device.

Changes to the device’s design, includingalterations to button locations, GUI screen fea-tures, and task descriptions, were made to pre-vent these use errors (all outcomes andsubsequent design feature changes are summa-rized in Table 3).

Formative Studies with Fully FunctioningDevices

The final design of the e-Device was used in theremaining seven formative studies and is pre-sented in Fig. 2. These studies included 18

Fig. 1 Participant injection summaries for a formativestudies and b validation studies. AS ankylosing spondylitis,CD Crohn’s disease, CGs caregivers, HCPs healthcareprofessionals, IE injection-experienced, IN injection-naıve,PsA psoriatic arthritis, RA rheumatoid arthritis

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Table 3 Key findings of formative studies

CGs caregivers, DDC dose-dispenser cartridge, e-Device electromechanical injection device, GUI graphical user interface,HCP healthcare professional, IFU instructions for use

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healthy volunteers, 25 HCPs, 35 RA patients, 7AS patients, 8 CD patients, 8 PsA patients, and11 caregivers (Table S4; studies 5–10 and 12). Inaddition to features analyzed in studies 1–4,these studies tested device charging, injectionlogs, and GUI alarms. Key findings includeduser difficulties interpreting the injection logand HCP difficulties with the device setup; thesefindings and their resulting design modifica-tions are summarized in Table 3.

Validation Studies

Thirty participants were enrolled in the EUvalidation study (Table 2): 15 patients with RAand 15 HCPs who treat RA patients. Overall, 60simulated injections were performed. Amongthe HCPs tested, only one failure to set up thee-Device correctly was recorded, which was dueto poor understanding of English (Fig. 3a).

Despite some difficulties, all other HCPs couldset up the e-Device correctly.

All 30 participants in the EU validation studysuccessfully completed all the tasks required tosafely and effectively administer a full loadingdose within three attempts. Failures werereported in four of 285 critical tasks (1.4%)performed by HCPs and eight of 287 criticaltasks (2.8%) performed by patients. Failure tocorrectly dispose of used DDCs in the sharps bin(critical task number 20, CT20) accounted forseven of the failures (five patients and twoHCPs); all seven participants stated this was dueto their assuming the DDC would be reusedwithin the test scenario and that they would usea sharps bin in daily practice. Other reasons forfailure included the following: one patient andone HCP stated they would inject a syringewhich had cloudy contents (CT06), twopatients did not correctly describe how to clean

Fig. 2 a Final certolizumab pegol (CZP) electromechanical injection device (e-Device) and dose-dispenser cartridge(DDC), and b key features of the e-Device. GUI graphical user interface, HCP healthcare professional. (From [1])

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the e-Device (CT21), and one HCP had a poorunderstanding of English, resulting in a failureto configure the e-Device (CT02). Successes withdifficulty reported by HCPs (n = 26) andpatients (n = 14) were most commonly due toan inability to find the information in the IFU(Fig. 4). The device was temporarily positioned

upside down by one HCP and one patient, butthis was quickly rectified and did not impact ondrug delivery (Table 4); these were thereforeclassified as successes with difficulty. Patientscommented positively on the user-friendlinessof the final GUI (‘‘I like that it shows you how toinject’’; ‘‘Told me what to do when I had a dif-ficulty’’) and general ease of understanding theGUI instructions (’’Bright screen with easywriting’’; ‘‘Good diagrams for people whereEnglish is not first language’’).

Ninety participants were enrolled in the USvalidation study (Table 2). Overall, difficultieswere reported in 57 of 5310 critical tasks(1.1%). No remaining use errors occurred thatwere unexplained or unexpected (Table 4).There were two critical task failures (less than0.1%): one HCP failed to set up the e-Devicewith a maintenance dose of 200 mg threetimes, and one patient held the device upsidedown four times before completing the taskcorrectly after reading the IFU. In both cases,the participants were aware that they were notperforming the task correctly, and eventuallycompleted it successfully; as both took three ormore attempts to complete the task, these taskswere classified as failures. Critical tasksinvolving difficulties or failures are summa-rized in Fig. 5.

DISCUSSION

Although efficacy and safety are central con-siderations when one is selecting treatmentoptions, patient attitudes toward differentmethods of administration are an importantconsideration as well. Patients often have apreference for specific devices or administrationmethods that are influenced by personal prior-ities such as preferring fewer injection steps orbeing reassured that the injection was com-pleted successfully [16–18]. Aligning the injec-tion device to patients’ preferences provides anopportunity to improve the treatment experi-ence, which has the potential to promotetreatment adherence [3]. The importance ofpatient choice when selecting treatmentoptions for chronic inflammatory disease washighlighted in two ethnographic studies

Fig. 3 a 1/15 EU HCPs failed to set up the e-Device withMD1; this was due to poor understanding of English; thisHCP was not involved in the remaining e-Device set-uptasks, resulting in n=14 HCPs in the LD then MD2,MD1, and MD2 task groups. b 1/15 US HCPs failed toset up MD1 due to confusion over the meaning of thepharmacy label; the HCP correctly set MD but alsoincluded the LD 3 times before succeeding with the taskon the 4th attempt. HCP: healthcare professional; LDloading dose; MD1 maintenance dose 1 (200 mg everyother week); MD2 maintenance dose 2 (400 mg every 4weeks)

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examining the patient experience of self-injec-tion that interviewed self-injection device users,and concluded that patients with more treat-ment options and a deeper disease understand-ing were more likely to have a better self-injection experience [19].

The HFS reported here used feedback fromhealthy volunteers and intended users todevelop a new patient-centric e-Device for self-injection of CZP. HCPs configured the dosageregimen and intended users followed on-screenguidelines to perform their injections. Both the

Fig. 4 Summary of critical task failures and difficulties (EU validation study). DDC dose-dispenser cartridge, e-Device,electromechanical injection device, HCP healthcare professional, RA rheumatoid arthritis

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screen design and the GUI text were optimizedin response to user feedback during 11 forma-tive studies. Key design changes included mov-ing the screen viewing angle to reflect typicaluse, altering the GUI color scheme to improvelegibility, and text simplification.

In the final US validation study, there weretwo critical task failures (less than 0.1% of allcritical tasks). However, user feedback suggestedthat had this happened outside a study envi-ronment, users would be fully aware that theyhad not completed the task successfully and theGUI would guide them toward safe use. Patientsholding the device in the incorrect orientationis a known problem with self-injection devices[9, 20]. All US validation study participantsdemonstrated safe use, and no participant acti-vated the device upside down. In all cases whereparticipants initially placed the device upsidedown, the GUI and the user manual instructedthem to correct the orientation of the devicebefore beginning the injection procedure,allowing the injection to be completedsuccessfully.

Rates of adherence to biologic therapy can besuboptimal; in a retrospective study of 53,477self-injecting patients with RA, AS, or PsA, only37% were adherent during their first year of useof a new anti-TNF agent [21]. RebiSmart�

(Merck, Zug, Switzerland) is an electronicinjection device for use by multiple sclerosispatients. It was the first electromechanicalautoinjector for multiple sclerosis patients [22],and has reported adherence rates of 95% acrossa median drug exposure period when the deviceis used for 979 days [23–25]. There is evidencesuggesting that technologized injection devicesmay increase the rates of adherence to use ofbiologics. For example, a study assessing thegolimumab SmartJect� autoinjection device inRA patients reported that 91.7% of patientscompleted 6 months of treatment [26].

An electromechanical autoinjector currentlyin development for use with etanercept,another tumor necrosis factor inhibitor used totreat chronic rheumatological conditions,highlighted the importance of incorporatingpatient feedback into the design of an injectiondevice [16]. A real-world study comparingpatient preferences of an etanercept PFP withthe electromechanical autoinjector reportedthat the etanercept PFP was preferred bypatients, as it had fewer steps and patientsexperienced less injection site discomfort orpain [16]. In previous studies with the anti-TNFadalimumab, many RA patients reported apreference for a PFP over a PFS, due to the use ofa hidden needle in the PFP [27]. The CZP

Table 4 Key findings of validation studies

GUI graphical user interface, HCP healthcare professional, NA not applicable

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e-Device avoids many limitations often associ-ated with self-injection devices through theincorporation of patient feedback during eachstage of device development. Patients with painand reduced dexterity can find it difficult to gripdevices securely [8, 28]. The e-Device wasdesigned to reduce these difficulties,

incorporating a large, nonslip hand grip andlarge buttons. The IFU was updated in responseto early patient concerns with IFU legibility.

Response to anti-TNF treatment can be reli-ably predicted from patients’ disease activityfollowing 3 months of therapy [29], and sotreat-to-target guidance suggests that treatment

Fig. 5 Critical task failures and difficulties [US validation study]. AS ankylosing spondylitis; CD Crohn’s disease; DDCdose-dispenser cartridge; CG caregiver; HCP healthcare professional; PsA psoriatic arthritis; RA rheumatoid arthritis

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should be adjusted at least every 3 months untilthe desired treatment target is reached [30].However, this guidance does not differentiatebetween no response to treatment for noneffi-cacy reasons or nonadherence. The CZP e-De-vice automatically generates an electronicinjection log, providing quantifiable compli-ance and adherence data that can be used byboth patients and HCPs as a disease manage-ment tool to improve treatment decisions.

HFS are limited by their simulated nature;full clinical studies are required to assess com-mon concerns with self-injection such as painlevels and self-injection anxiety. In addition,participants may also perform the self-injectionprocess differently when being observed in anHFS environment rather than in day-to-day lifeat home or in the office, even when theselocations are simulated within the HFS; one EUvalidation study patient stated that the diffi-culties this patient had may be related to studyanxiety: ‘‘Under the circumstances I was prob-ably panicking, unfamiliar with everything, lotsof information. At home [I] would be fine.’’There are also several limitations associatedwith the design of the e-Device. The e-Device isbattery operated and is relatively large com-pared with alternative devices such as a PFP or aPFS, which may affect travel and generalportability. However, the e-Device needs to beused only one or two times a month, so this islikely to cause only minimal disruption topatients.

CONCLUSIONS

User involvement in medical device design andtesting provides a valuable means of ensuringthat devices accurately meet patients’ needs anddesires, and helps to minimize any potentialreasons for injection failure. HFS are particularlyimportant, as intended user feedback can beboth collected and acted on in accordance withstrict US and EU guidelines to validate a device’susability and safety [10, 12, 13].

In this study, intended user feedback wascollected across 11 formative studies in the UKand the USA and was used to develop andimprove the patient-centric design of the

e-Device, and minimize use error. The EU andUS validation HFS confirmed that intendedusers of the final, optimized e-Device couldsafely and effectively perform self-injectionswith the e-Device without training.

ACKNOWLEDGEMENTS

UCB Pharma sponsored the study and thedevelopment of the manuscript and reviewedthe text to ensure that from the UCB Pharmaperspective, the data presented in the publica-tion are scientifically, technically, and medi-cally supportable, that they do not contain anyinformation that has the potential to damagethe intellectual property of UCB Pharma, andthat the publication complies with applicablelaws, regulations, guidelines, and good industrypractice. Article processing charges were fundedby UCB Pharma. All authors had full access toall of the data in this study and take completeresponsibility for the integrity of the data andaccuracy of the data analysis. All named authorsmeet the International Committee of MedicalJournal Editors (ICMJE) criteria for authorshipfor this article, take responsibility for theintegrity of the work as a whole, and have givenfinal approval for the version to be published.The authors thank the patients, the investiga-

tors, and their teams who participated in thisstudy in addition to OXO (New York, NY, USA)for their assistance in developing the elec-tromechanical injection device, and bothSmartDesign (Barcelona, Spain) and MedicalDevice Usability Ltd (Cambridge, UK) for sup-port with conducting a number of the HFS. Theauthors also acknowledge Debbie Nixon fromUCB Pharma (UK) for publication coordinationand Aimee Hall and Simon Foulcer from Cost-ello Medical Consulting (UK) for medical writ-ing and editorial assistance in preparing themanuscript for publication, based on theauthors’ input and direction.

Data Availability. The datasets generatedand/or analyzed during the current study areavailable from the corresponding author onreasonable request.

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Disclosures. B. Domanska is an employee ofUCB Pharma. O. Stumpp is an employee of UCBPharma. S. Poon is an employee of UCB Pharma.S. Oray is an employee of UCB Pharma.I. Mountian is an employee of UCB Pharma.C. Pichon is an employee of UCB Pharma.

Compliance with Ethics Guidelines. Thestudy protocol was not submitted for priorapproval by an ethics committee as the study’sscope falls outside the requirements for priorethical review; no type of clinical interventionwas tested, and participants were asked to per-form simulated self-injections on a fake skininjection pad. All procedures followed were inaccordance with the ethical standards of theresponsible committee on human experimen-tation (institutional and national) and with theHelsinki Declaration of 1964, as revised in 2013.Informed consent was obtained from all par-ticipants in the study.

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 non-commercial use, distribution, and reproductionin any medium, provided you give appropriatecredit to the original author(s) and the source,provide a link to the Creative Commons license,and indicate if changes were made.

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