Upload
sheila-m
View
214
Download
1
Embed Size (px)
Citation preview
Review
Assessment of Patient-Reported Outcomes of InsulinPen Devices Versus Conventional Vial and Syringe
Cliff Molife, M.P.H.,1 Lauren J. Lee, Pharm.D., M.S.,1 Lizheng Shi, Ms.Pharm., Ph.D.,2
Monika Sawhney, M.S.W.,2 and Sheila M. Lenox, R.D., M.S., C.D.E.1
Abstract
Patient-reported outcomes (PROs) associated with insulin therapy are potentially important determinants ofadherence to diabetes management programs. This article reviews published evidence of PROs over the past 3decades in patients with type 1 diabetes (T1D) and=or type 2 diabetes (T2D) who used vial and syringe forinsulin delivery compared to those who used insulin pens. Based on predetermined selection criteria, articleswere identified through a search of primary sources published from January 1980 to February 2008. Twoindependent reviewers determined study eligibility and performed a detailed evaluation of the articles that metthe selection criteria. Of the 124 articles screened, 41 met selection criteria. Approximately 75% of the selectedarticles were published between 1990 and 2008, and a majority (78%) of the research studies was conductedoutside the United States. Most (>75%) of the studies evaluated male and female patients with T1D and=or T2Dand mean ages around 45 years. Studies used varied comparative study designs with follow-up periods rangingfrom 2 weeks to 5 years. The PROs assessed in these articles included preference, acceptability, treatmentsatisfaction, ease of use, convenience, injection pain, handling, and dosing. Most articles (n¼ 36) showed morefavorable PROs for insulin pen users compared to vial and syringe users. These findings have potential clinicaland policy implications for patients, diabetes care providers, and=or payers to make evidence-based decisionsregarding ways to facilitate initiation and management of insulin therapy.
Introduction
Optimal diabetes management through improvedglycemic control has been shown to reduce the risk of
developing diabetes-related microvascular complications.1,2
Evidence supports that direct medical costs associated withtreatment of type 2 diabetes (T2D) are significantly higherfor persons who have poor glycemic control as compared tothose who have optimal glycemic control.3 It is estimated thatthe majority of patients with T2D do not achieve optimalglycemic control (e.g., glycosylated hemoglobin <7%, as re-commended by the American Diabetes Association).4,5 Mul-tiple daily insulin injections are often recommended byhealthcare providers to improve glycemic control. Increasedtreatment burden for patients on multiple daily insulininjections may occur when using vial and syringe. Non-adherence to insulin treatment, due to factors related to in-jection therapy, is a potential contributing factor for thesuboptimal diabetes management trend.5,6 In certain studies,
the use of vial and syringes has been reported to be cumber-some and inconvenient, and for some patients, it was sociallystigmatizing or fear inducing.7
Patient self-management is a critical factor in achievingoptimal diabetes management.4 Some self-management ortherapy effects are known only to the patient (e.g., injectionpain); hence, perspectives of patients on related outcomes andburden of self-management are critical to investigate. Nu-merous studies have examined patient preference and otherpatient-reported outcomes (PROs) associated with the use ofvarious insulin delivery devices. Reviews of these studieshave consistently concluded that among patients with dia-betes, an overall greater preference and acceptance for insulinpen devices exist compared to conventional vial and sy-ringe.8–13 However, these reviews were conducted with afocus on specific insulin pen devices (e.g., NovoPen� [NovoNordisk A=S, Copenhagen, Denmark]). The objective of thisreview was to conduct a comprehensive systematic litera-ture search and report the comparative PRO data between all
1Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, Indianapolis.2Tulane University, Health Systems Management, New Orleans, Louisiana.
DIABETES TECHNOLOGY & THERAPEUTICSVolume 11, Number 8, 2009ª Mary Ann Liebert, Inc.DOI: 10.1089=dia.2009.0007
529
insulin pen devices and conventional vial and syringe in di-abetes patients of all ages.
Methods
Primary sources comparing insulin pens with vial and sy-ringe published from January 1980 to February 2008 weregathered from MEDLINE, EMBASE, CINAHL, CochraneDatabases, Cochrane Central Register of Controlled Trials,Cochrane Database of Systematic Reviews, and Database ofAbstracts of Reviews of Effects. In MEDLINE, EMBASE, andCINAHL, ‘‘insulin,’’ ‘‘pen,’’ ‘‘syringe,’’ and PROs (i.e., ‘‘satis-faction,’’ ‘‘acceptance,’’ ‘‘quality of life’’ (QoL), ‘‘preference,’’‘‘convenience,’’ and ‘‘pain’’) were utilized as the main keywords for the searches. Subject headings (e.g., MeSH) for‘‘insulin’’ and ‘‘diabetes’’ were combined with key words (andvariants) for ‘‘pen,’’ ‘‘vial,’’ or ‘‘syringe’’ and subject headingsand=or key words for the aforementioned PROs. Similarkeyword searches were conducted in the Cochrane databasesand the Database of Abstracts of Reviews of Effects to identifyrelevant systematic reviews. To maximize the search andmitigate potential publication bias, the following additionalsources were explored: doctoral theses, non–peer-reviewedjournals, references listed in reviews and=or primary sources,and meeting abstracts dated within the past 2 years found onthe websites of the American Diabetes Association and theEuropean Association for the Study of Diabetes.
Articles meeting the following selection criteria were in-cluded: (1) the study incorporated a comparative study designof insulin pen use versus vial and syringe use; (2) the studyincluded approaches to control for confounding and othertypes of potential bias; (3) the full text of the article included afull description of the study design, methods used to measureand assess PROs, and results; (4) the publication was writtenin English (translated non-English studies were included); (5)study subjects were children, adolescents, and=or adults withtype 1 diabetes (T1D) and=or T2D who, during the course ofthe study, used insulin pen devices and=or vial and syringe;and (6) the study evaluated patient preference and=or otheraforementioned PROs as either a primary or secondary ob-jective. In order to avoid bias in the selection of articles, twoindependent reviewers (C.M. and L.S.) determined study el-igibility. Any discrepancies between two independent re-viewers were resolved via adjudication and a third reviewer(M.S.) when necessary. Lastly, a data summary table (Table 1)was created to summarize the main study attributes (e.g.,study design, country, PROs, results) from each publication.Data within the summary table were reviewed for accuracyby two independent reviewers (L.S. and M.S.).
Results
Literature search
The database search yielded 124 publications, which in-cluded six review articles. Application of selection criteriaresulted in a total of 50 primary source articles by bothreviewers. Discrepancies between the two independent re-viewers were primarily associated with study design. Afterresolution of these discrepancies, 41 articles met the selectioncriteria and were included in this review. As shown in Table 1,these studies used a wide range of comparative study de-signs with varied follow-up periods ranging from 2 weeks to 5
years. Approximately 75% of the articles were published be-tween 1990 and 2008. A majority (78%) of the research studieswas conducted outside the United States. Most (>75%) of thestudies evaluated male and female patients with diabeteswith mean ages around 45 years. Some of the studies evalu-ated children with diabetes who were as young as 8 years oldand elderly patients as old as 79 years old.17,24,25,40
The objective(s) of some studies included a comparison of‘‘safety’’ and=or ‘‘efficacy’’ profiles between insulin penand vial and syringe use.14,16–19,21–27,30–41,43,44,46–49,51–54 Tobe consistent with our objective, the current review solelyfocused on PRO data. A majority (>90%) of these studiesmeasured PROs as a primary objective (see Table 1 for de-tails). Studies included in the current review did not provideexplicit conceptual and=or operational definitions of PROs,but, overall, PROs were measured using self-reported ques-tionnaires. The studies either measured the PRO directly orindirectly through specified PRO indicators. For example,depending on the study, ‘‘preference’’ was measured eitherdirectly by asking patients which delivery device they pre-ferred or indirectly via preference indicators such as ‘‘will-ingness to continue’’ or ‘‘recommend insulin pen use.’’ Insulinpen devices used by studies in the current review included theHumulin=Humalog� pen (Eli Lilly and Co., Indianapolis, IN),HumaPen� Ergo (Eli Lilly and Co.), NovoPen, NovoLet�
(Novo Nordisk A=S), BD� pens (Becton Dickinson, FranklinLakes, NJ), InnoLet� (Novo Nordisk A=S), Insuject� (NovoNordisk A=S), FlexPen� (Novo Nordisk A=S), and Optipen�
(sanofi-aventis, Paris, France).
Preference
Twenty-nine articles assessed preference as a primary PROmeasure.14,15,17–20,23–28,32–35,37–40,43–51 In 28 of these studies,the majority (>66%) of patients preferred insulin pen devicesover vial and syringe, or they chose and=or were willing tocontinue treatment with insulin pen devices instead of vialand syringe.14,15,17–20,23–28,32,34,35,37–40,43–51 For example, inone head-to-head study by Jorgensen et al.34 (1988), 48 out of50 patients with T1D reported a greater preference for theinsulin pen over vial and syringe. In a study by Bohannon andOhannesian20 (2000), 74% of 315 diabetes patients preferredthe pen to vial and syringe. Similar results were found inprospective studies in which patients reported greater pref-erence with their use of insulin pens when compared to theirprevious experience with using vial and syringe.20,38,50,51 Onestudy found similar preference profiles between insulin penand vial and syringe use.33
Acceptability
Twelve studies assessed acceptability,18,19,23,26,27,32,33,38,40,41,46,47
and in 10 of them (*80%), the majority (>75%) of patientsreported greater acceptance of the insulin pen devices com-pared to vial and syringe.19,23,26,27,32,38,40,41,46,47 For example,in a prospective study that included 100 patients with T1D orT2D, a significantly higher acceptance rate was found whenpatients switched from using vial and syringe to insulin pens(P< 0.01).41 Two studies did not report greater acceptabilitywith pen devices than vial and syringe.18,33 Hung and Wang33
(1992) measured insulin delivery, privacy, and dosage accu-racy as indicators of acceptability in a study that yieldedmixed results with regard to acceptability: in this study, 78%
530 MOLIFE ET AL.
Ta
bl
e1.
Su
mm
ar
yT
ab
le
fo
rP
RO
s
PR
Ore
sult
s(m
ethod
ofas
sess
men
t)e,f
Ref
eren
ce(y
ear)
Fu
ndin
gso
urc
eaC
oun
try
Sam
ple
size
(dia
bete
sty
pe)
bS
tudy
des
ign
c
PR
Om
easu
red
aspri
mar
yor
seco
ndar
yob
ject
ived
Met
hod
ofP
RO
asse
ssm
ent
(val
idat
ion
stat
us)
eF
lexib
ilit
yA
ccep
tabi
lity
Tre
atm
ent
sati
sfac
tion
Pre
fere
nce
QoL
Eas
eof
use
Con
ven
ien
cean
dhan
dli
ng=
dos
ing
Pai
n
Alb
ano
14
(200
4)N
DIt
aly
1,62
2(D
TN
)P
rosp
ecti
ve,
mu
ltic
ente
r,si
ng
leg
rou
pp
re–p
ost
stu
dy
wit
hP
IUC
PD
TS
Q(V
)þ
(DT
SQ
)þ
(DT
SQ
)þ
(DT
SQ
)
An
der
son
and
Bar
net
t15
(199
4)
ISU
nit
edK
ing
do
m1,
016
(DT
N)
Pro
spec
tiv
e,o
pen
,m
ult
icen
ter,
sin
gle
gro
up
stu
dy
wit
hP
IUC
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
An
der
son
and
Wik
by
16
(199
7)
NIS
Sw
eden
65(T
ID)
Ret
rosp
ecti
ve
coh
ort
anal
ysi
s
PQ
Lsc pac
kag
e(V
SN
)
�(Q
Lsc
pac
kag
e)
Ars
lan
og
luet
al.1
7
(200
0)N
DT
urk
ey20
(T1D
)R
and
om
ized
cro
sso
ver
tria
l
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)þ
(Qai
re)
þ(Q
aire
)
Bar
net
tet
al.1
8
(199
6)IS
Un
ited
Kin
gd
om
93(T
2D)
Ran
do
miz
edcr
oss
ov
ertr
ial
PW
BQ
(V),
SO
TQ
(V),
IDA
Q(V
)
�(I
DA
Q)
�(S
OT
Q)þ
(ID
AQ
)�
(WB
Q)
Ber
ger
etal
.19
(198
5)IS
Den
mar
k16
(T1D
)R
and
om
ized
cro
sso
ver
tria
l
SQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
þ(Q
aire
)
Bo
han
no
nan
dO
han
nes
ian
20
(200
0)
ISU
nit
edS
tate
s31
5 (bo
th)
Pro
spec
tiv
e,o
pen
-lab
el,
mu
ltic
ente
r,si
ng
leg
rou
pp
re–p
ost
stu
dy
wit
hP
IUC
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Bu
yss
chae
rtet
al.2
1
(198
8)N
DB
elg
ium
10(T
1D)
Pro
spec
tiv
e,si
ng
leg
rou
pp
re–p
ost
stu
dy
PC
SIQ
(VS
N),
MH
LC
Q(V
SN
),H
DR
S(V
SN
)
�(C
SIQ
,M
HL
CQ
,H
DR
S)
Ch
ante
lau
etal
.22
(199
7)IS
Ger
man
y77
(T1D
)P
rosp
ecti
ve
coh
ort
stu
dy
PD
CC
TQ
(VS
N)
�(D
CC
TQ
)
Ch
enet
al.2
3
(199
9)N
IST
aiw
an19
(bo
th)
Op
en,
ran
do
miz
ed,
con
tro
lled
two
-per
iod
cro
sso
ver
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Co
rsi
etal
.24
(199
7)N
DIt
aly
21(T
2D)
Ran
do
miz
edcr
oss
ov
ertr
ial
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
þ(Q
aire
)
(con
tin
ued
)
531
Ta
bl
e1.
(C
on
tin
ue
d)
PR
Ore
sult
s(m
ethod
ofas
sess
men
t)e,f
Ref
eren
ce(y
ear)
Fu
ndin
gso
urc
eaC
oun
try
Sam
ple
size
(dia
bete
sty
pe)
bS
tudy
des
ign
c
PR
Om
easu
red
aspri
mar
yor
seco
ndar
yob
ject
ived
Met
hod
ofP
RO
asse
ssm
ent
(val
idat
ion
stat
us)
eF
lexib
ilit
yA
ccep
tabi
lity
Tre
atm
ent
sati
sfac
tion
Pre
fere
nce
QoL
Eas
eof
use
Con
ven
ien
cean
dhan
dli
ng=
dos
ing
Pai
n
Co
scel
liet
al.2
5
(199
5)N
DIt
aly
60(B
oth
)R
and
om
ized
,tw
o-p
erio
dcr
oss
ov
er
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
þ(Q
aire
)
Du
nb
aret
al.2
6
(199
4)N
DIr
elan
d27
(T1D
)R
and
om
ized
,o
pen
-lab
el,
two
-per
iod
,cr
oss
ov
er
SQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
En
gst
rom
27
(199
0)N
DS
wed
en40
(T1D
)R
and
om
ized
cro
sso
ver
tria
l
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Fo
xet
al.2
8
(200
2)IS
Un
ited
Kin
gd
om
86(T
2D)
Mu
ltic
ente
r,o
pen
,ra
nd
om
ized
,co
mp
arat
ive
stu
dy
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Gra
ffan
dM
cCla
nah
an29
(199
8)
ISU
nit
edS
tate
s50
7(b
oth
)P
rosp
ecti
ve,
mu
ltic
ente
r,si
ng
leg
rou
pp
re–p
ost
stu
dy
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Han
asan
dL
ud
vig
sso
n30
(199
7)
ND
Sw
eden
158
(T1D
)C
ross
-sec
tio
nal
stu
dy
PQ
aire
(VS
N)
þ(Q
aire
)
Ho
utz
ager
set
al.3
1
(198
9)IS
Th
e Net
her
lan
ds
16(T
1D)
Op
en,
ran
do
miz
edcr
oss
ov
er
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Ho
utz
ager
set
al.3
2
(198
9)IS
Th
e Net
her
lan
ds
16(T
1D)
Op
en,
ran
do
miz
edcr
oss
ov
er
PQ
aire
(VS
N)þ
(Qai
re)
Hu
ng
and
Wan
g33
(199
2)N
DT
aiw
an18
(bo
th)
Ran
do
miz
ed,
cro
sso
ver
tria
l
PQ
aire
(VS
N)
�(Q
aire
)�
(Qai
re)
þ(Q
aire
)�
(Qai
re)
Jorg
ense
net
al.3
4(1
988)
ND
Den
mar
k50
(T1D
)O
pen
,ra
nd
om
ized
,cr
oss
ov
ertr
ial
PQ
aire
(VS
N)
þ(Q
aire
)
Kad
iri
etal
.35
(199
8)IS
Mo
rocc
o96
(T2D
)R
and
om
ized
,o
pen
-lab
el,
two
-per
iod
cro
sso
ver
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
þ(Q
aire
)
Ko
len
do
rfet
al.3
6(1
988)
ND
Den
mar
k19
(T1D
)R
and
om
ized
,cr
oss
ov
ertr
ial
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)þ
(Qai
re)
Ko
rytk
ow
ski
etal
.37
(200
3)IS
Un
ited
Sta
tes
121
(bo
th)
Mu
ltic
ente
r,ra
nd
om
ized
,o
pen
-lab
el,
two
-per
iod
cro
sso
ver
PP
PQ
(VS
N),
DT
SQ
(V)�
(DT
SQ
)�
(DT
SQ
)þ
(PP
Q)
�(D
TS
Q)
532
Mar
tin
etal
.38
(199
9)IS
Un
ited
Kin
gd
om
286
(bo
th)
Pro
spec
tiv
e,o
pen
-lab
el,
mu
ltic
ente
r,si
ng
leg
rou
pst
ud
yw
ith
PIU
C
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Mu
rray
etal
.39
(198
8)N
DIr
elan
d78
(T1D
)C
on
tro
lled
,ra
nd
om
ized
tria
l
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
O’H
agan
and
Gre
ene4
0
(199
3)
ISS
cotl
and
40(T
1D)
Op
en,
ran
do
miz
ed,
two
-per
iod
cro
sso
ver
stu
dy
SQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Ro
we
etal
.41
(199
2)N
DU
nit
edK
ing
do
m10
0(b
oth
)P
rosp
ecti
ve,
op
en,
sin
gle
gro
up
stu
dy
wit
hP
IUC
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Ru
bin
and
Pey
rot4
2
(200
8)
ISU
nit
edS
tate
s60
0(b
oth
)C
ross
-sec
tio
nal
stu
dy
PQ
aire
(VS
N)
�(Q
aire
)
Sau
rbre
yet
al.4
3
(198
5)N
DD
enm
ark
16(D
TN
)R
and
om
ized
,cr
oss
ov
ertr
ial
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Sch
ust
eret
al.4
4(1
998)
NIS
Un
ited
Sta
tes
93(T
1D)
Pro
spec
tiv
e,ra
nd
om
ized
con
tro
lled
tria
l
SO
bse
rvat
ion
by
DN
Es,
Qai
re(V
SN
)
þ(O
bse
rvat
ion
by
DN
Es,
Qai
re)
þ(O
bse
rvat
ion
by
DN
Es,
Qai
re)
Sch
war
tzet
al.4
5(2
007)
ISU
nit
edS
tate
s60
(T2D
)S
ing
lece
nte
r,ra
nd
om
ized
,o
pen
lab
el,
two
-per
iod
cro
sso
ver
PP
HR
Q(V
SN
)þ
(PH
RQ
)þ
(PH
RQ
)þ
(PH
RQ
)
Sh
elm
etet
al.4
6(2
004)
ISU
nit
edS
tate
s79
(Bo
th)
Mu
ltic
ente
r,ra
nd
om
ized
,o
pen
-lab
el,
two
-per
iod
cro
sso
ver
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
þ(Q
aire
)
Sm
all
etal
.47
(198
8)N
DS
cotl
and
37(T
1D)
Ran
do
miz
edco
ntr
oll
edtr
ial
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Sp
ijk
eret
al.4
8(1
986)
ND
Th
e Net
her
lan
ds
21(T
1D)
Ran
do
miz
ed,
two
-per
iod
cro
sso
ver
stu
dy
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
Sto
ckl
etal
.49
(200
7)IS
Un
ited
Sta
tes
260
(T1D
)P
rosp
ecti
ve,
ran
do
miz
ed,
two
-lab
el,
cro
ss-o
ver
PID
PQ
(V),
ITS
Q(V
)þ
(IT
SQ
)þ
(ID
PQ
)þ
(ID
PQ
)þ
(ID
PQ
)
Sto
cks5
0(2
001)
ISA
ust
rali
a70
(bo
th)
Pro
spec
tiv
e,o
pen
,m
ult
icen
ter,
sin
gle
gro
up
stu
dy
wit
hP
IUC
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
(con
tin
ued
)
533
Ta
bl
e1.
(C
on
tin
ue
d)
PR
Ore
sult
s(m
ethod
ofas
sess
men
t)e,f
Ref
eren
ce(y
ear)
Fu
ndin
gso
urc
eaC
oun
try
Sam
ple
size
(dia
bete
sty
pe)
bS
tudy
des
ign
c
PR
Om
easu
red
aspri
mar
yor
seco
ndar
yob
ject
ived
Met
hod
ofP
RO
asse
ssm
ent
(val
idat
ion
stat
us)
eF
lexib
ilit
yA
ccep
tabi
lity
Tre
atm
ent
sati
sfac
tion
Pre
fere
nce
QoL
Eas
eof
use
Con
ven
ien
cean
dhan
dli
ng=
dos
ing
Pai
n
Su
cic
etal
.51
(200
2)IS
Cro
atia
330
(bo
th)
Pro
spec
tiv
e,o
pen
-lab
el,
mu
ltic
ente
r,si
ng
leg
rou
pst
ud
yw
ith
PIU
C
PA
FQ
(VS
N)
þ(A
FQ
)þ
(AF
Q)
Tal
lro
thet
al.5
2
(198
9)N
DS
wed
en18
(T1D
)R
and
om
ized
,tw
o-p
erio
dcr
oss
ov
er
PM
AC
L(V
SN
),E
DT
Q(V
SN
),Q
aire
(VS
N)
�(M
AC
L,
ED
TQ
,Q
aire
)
Wik
by
etal
.53
(199
8)N
DS
wed
en56
(T1D
)P
rosp
ecti
ve,
sin
gle
gro
up
stu
dy
PM
SR
Q(V
SN
),B
asic
Qo
Las
sess
men
tp
ack
age
(VS
N)
þ(M
SR
Q,
Bas
icQ
oL
asse
ssm
ent
pac
kag
e)
Wil
ket
al.5
4
(200
2)IS
Un
ited
Sta
tes
23(T
1D)
Pro
spec
tiv
e,si
ng
leg
rou
pst
ud
yw
ith
PIU
C
PQ
aire
(VS
N)
þ(Q
aire
)þ
(Qai
re)
aIS
,in
du
stry
spo
nso
red
(fin
anci
alfu
nd
ing
fro
ma
ph
arm
aceu
tica
lco
mp
any
was
spec
ifica
lly
dis
clo
sed
inth
ep
ub
lica
tio
n.)
;N
IS,
no
n–i
nd
ust
rysp
on
sore
d(p
ub
lica
tio
nci
ted
no
n-p
har
mac
euti
cal
com
pan
yas
the
fun
din
gso
urc
e;d
rug
pro
du
ctan
d=o
rd
eliv
ery
dev
ice
may
hav
eb
een
sup
pli
ed);
ND
,st
ud
ysp
on
sor
info
rmat
ion
no
td
iscl
ose
d(p
ub
lica
tio
nd
idn
ot
cite
any
spec
ific
fin
anci
alfu
nd
ing
info
rmat
ion
;o
ther
form
so
fsu
pp
ort
no
tsp
ecifi
edas
fin
anci
alsu
pp
ort
,in
clu
din
gd
rug
pro
du
ctan
d=o
rd
eliv
ery
dev
ice,
may
hav
eb
een
sup
pli
ed).
bT
1D,
typ
e1
dia
bet
es;
T2D
,ty
pe
2d
iab
etes
;b
oth
,T
1Dan
dT
2D;
DT
N,
dia
bet
esty
pe
no
tsp
ecifi
ed.
c PIU
C,
pre
vio
us
insu
lin
del
iver
yd
evic
eu
sed
asco
mp
arat
or
(at
stu
dy
com
ple
tio
n,
par
tici
pan
tsw
ere
ask
edto
reca
llan
dco
mp
are
exp
erie
nce
sw
ith
the
insu
lin
del
iver
yd
evic
eu
sed
du
rin
gth
est
ud
yto
thei
rp
rev
iou
sin
suli
nd
eliv
ery
dev
ice)
.dP
,P
RO
mea
sure
das
ap
rim
ary
ob
ject
ive;
S,
PR
Om
easu
red
asa
seco
nd
ary
ob
ject
ive.
eA
FQ
,A
ccep
tab
ilit
yan
dF
un
ctio
nal
ity
Qu
esti
on
nai
re;
CS
IQ,
Co
op
ersm
ith
Sel
f-E
stee
mIn
ven
tory
Qu
esti
on
nai
re;
DC
CT
Q,
Dia
bet
esC
om
pli
cati
on
sC
on
tro
lT
rial
Qo
LQ
ues
tio
nn
aire
;D
NE
,d
iab
etes
nu
rse
edu
cato
r;D
TS
Q,D
iab
etes
Tre
atm
ent
Sat
isfa
ctio
nQ
ues
tio
nn
aire
;E
DT
Q,
Ex
per
ien
ceo
fD
iab
etes
Tre
atm
ent
Qu
esti
on
nai
reu
sin
gV
AS
;H
DR
S,
Th
eH
amil
ton
Dep
ress
ion
Rat
ing
Sca
le;
IDA
Q,
Insu
lin
Del
iver
yA
ccep
tab
ilit
yQ
ues
tio
nn
aire
;ID
PQ
,In
suli
nD
eliv
ery
Sy
stem
Pre
fere
nce
Qu
esti
on
nai
re;
ITS
Q,
Insu
lin
Tre
atm
ent
Sat
isfa
ctio
nQ
ues
tio
nn
aire
;M
AC
L,
Mo
od
Ad
ject
ive
Ch
eck
list
;M
HL
CQ
,M
ult
i-d
imen
sio
nal
Hea
lth
Lo
cus
of
Co
ntr
ol
Qu
esti
on
nai
re;
MS
RQ
,M
od
ified
So
cial
Rea
dju
stm
ent
Rat
ing
Qu
esti
on
nai
re;
PH
RQ
,P
refe
ren
ce,
Pat
ien
tH
and
lin
g,
and
Res
ou
rce
Uti
liza
tio
nQ
ues
tio
nn
aire
;P
PQ
,P
atie
nt
Pre
fere
nce
Qu
esti
on
nai
re;
Qai
re,
qu
esti
on
nai
rew
ho
sen
ame
was
un
spec
ified
;Q
Lsc
,Q
ual
ity
of
Lif
e:st
atu
san
dch
ang
e;Q
oL
,q
ual
ity
of
life
;S
OT
Q,
Sat
isfa
ctio
no
fT
reat
men
tQ
ues
tio
nn
aire
;V
,v
alid
ated
;V
AS
,V
isu
alA
nal
og
Sca
le;
VS
N,
val
idat
ion
stat
us
no
tsp
ecifi
ed;
WB
Q,
Wel
l-b
ein
gQ
ues
tio
nn
aire
.f þ
,p
enis
mo
refa
vo
rab
leth
anv
ial=
syri
ng
e;�
,v
ial=
syri
ng
eis
mo
refa
vo
rab
leth
anp
en;�
,n
od
iffe
ren
ceo
rm
ixed
resu
lts
bet
wee
np
enan
dv
ial=
syri
ng
e.
534
of the patients rated the insulin pen device as quicker than vialand syringe with regard to insulin delivery. Whereas 50% ofpatients reported more privacy when using the pen devicethan vial and syringe, the remaining 50% reported no differ-ence.33
Pain
Pain was measured as a PRO in nine stud-ies.17,19,24,25,29,30,33,35,36 All but one study reported the majority(>50%) patients experiencing less pain while using a pendevice than vial and syringe: in the study by Hung andWang33 (1992), the majority of patients (i.e., approximately67%) reported no difference in pain between the insulin pendevice and vial and syringe. In a study by Graff and McCla-nahan29 (1998), 507 participants with T1D or T2D were eval-uated, and 90% of them reported ‘‘little or no pain’’ with theinsulin pen device, whereas 62% reported ‘‘moderate tosevere’’ pain with vial and syringe.
QoL
Three36,49,53 of the eight studies16,18,21,22,36,49,52,53 that eval-uated QoL as a PRO found a greater improvement in QoLamong diabetes patients who used insulin pen devices com-pared to those who used vial and syringe. In contrast, studiesby Barnett et al.18 (1996), Chantelau et al.22 (1997), and An-derson and Wikby16 (1997) found no statistically significantdifferences with regards to QoL after using an insulin pendevice compared to vial and syringe. Studies by Buysschaertet al.21 (1988) and Tallroth et al.52 (1989) yielded mixed results.Tallroth et al.52 (1989) found no differences regarding moodand well-being, but showed that treatment using the insulinpen device resulted in increased experiences of freedom andflexibility in meal times.
Satisfaction
Five14,39,41,49,51 of the seven14,18,37,39,41,49,51 studies thatevaluated patient satisfaction with insulin pen devices com-pared to vial and syringe found that the majority (>76%) ofpatients reported higher treatment satisfaction from usinginsulin pen devices. For example, in a randomized, multi-center, two-period, crossover study by Stockl et al.49 (2007)with a sample of 260 T1D or T2D patients, patients had sig-nificantly greater treatment satisfaction (P< 0.0001) from us-ing the insulin pen device than the conventional vial andsyringe. Conversely, studies by Barnett et al.18 (1996) andKorytkowski et al.37 (2003), with samples of 93 and 121, re-spectively, found no statistically significant differences(P< 0.05) in treatment satisfaction between insulin pen deviceand vial and syringe use.
Convenience, handling, dosing, and ease of use
Ten studies evaluated convenience15,17,29,33,36,37,42,43,49,54
and two others evaluated handling and dosing associatedwith the delivery device.45,46 Eight of the 10 studies reportedthat the majority (56–100%) patients found insulin pendevices to be more convenient than vial and sy-ringe.15,17,29,33,36,43,49,54 In a study by Graff and McClanahan29
(1998), ease of use, facilitation of compliance, and quickness ofuse were used as indicators for convenience; in this study, themajority (86%) of the patients found insulin pen devices to be
easier to use than vial and syringe, 77% reported that pendevices facilitated compliance with their regimen, and 86%considered the pen devices quicker to use than vial and sy-ringe. A study by Korytkowski et al.37 (2003) found no sta-tistically significant difference in convenience between pendevices and vial and syringe. Schwartz et al.45 (2006) andShelmet et al.46 (2004) each conducted studies to evaluate PROassociated with handling and dosing. In a randomized, two-period, crossover study, incorporating a sample of 60 patientswith T2D, Schwartz et al.45 found that 92% of patients con-sidered the insulin pen device to be easier to use, 92% con-sidered handling to be easier, 88% found the insulin pendevice to be more reliable in drawing and dispensing insulin,and there was a significant reduction in overall administrationtime (P< 0.05) compared to vial and syringe.
All nine studies that evaluated ‘‘ease of use’’ found that themajority (�61%) of patients considered the insulin pen de-vices easier to use than vial and syringe.17,20,24,25,28,35,44,46,50
For example, Shelmet et al.46 (2004) reported that 84% of the79 patients with T2D found the insulin pen devices easier touse than the conventional vial and syringe.
Other PROs
Other studies evaluated the following as their primaryPRO: self-reported resource utilization (e.g., number ofphysician visits, hospitalization),45 effects on lifestyle=flexibility,15,29 self-concept,31 anxiety,31 dose-setting confi-dence,40 and overall evaluation.29 Regarding self-reportedresource utilization, studies by Schwartz et al.45 (2006) andShelmet et al.46 (2004) yielded results with patients reportingless nursing assistance with insulin pen devices than vial andsyringe. In a study by Houtzagers et al.32 (1989), patientanxiety, self-concept, and flexibility were found to be im-proved more with insulin pen than vial and syringe. Asso-ciated findings were consistently in favor of the insulin pendevice compared to vial and syringe.31
Discussion
Findings from this review are consistent with previousfindings regarding PROs associated with insulin pen deviceand vial and syringe use.8–13 However, our findings are rel-evant to a wider range of insulin pen devices than previousreviews because we did not limit our search to a particularinsulin pen brand or type. As the current review demon-strates, a strong body of evidence supports that insulinadministration via insulin pen devices is easier, more conve-nient, quicker, and less painful than vial and syringe, and it isassociated with greater patient preference and acceptability.Additionally, patients with diabetes are more satisfied withusing insulin pen devices and consider insulin pen devicesless conspicuous and more socially acceptable. These resultsare understandable considering insulin pen devices possess avariety of features, including dial-a-dose mechanism, half-unit dosing, memory of dose, time, and date of previousdoses, audible clicks, clear dial showing the selected dose, andportability.8,9,55
A variety of barriers to optimal diabetes managementhave been shown to be associated with insulin injectiontherapy. Insulin injection is perceived to be painful, and painhas been shown to be a significant barrier in adhering to
PATIENT-REPORTED OUTCOMES OF PEN VERSUS VIAL 535
insulin regimens.9,17,19,24,25,29,30,33,35,36,56 Thus, the evidence inthe current review, demonstrating that insulin pen devicesgenerally facilitate less painful injections than vial and sy-ringe, is especially important. The current review also sup-ports that some patients with diabetes consider insulin pendevices to be more socially acceptable than vial and syringe,29
which may mitigate another barrier for adults and adolescentswho may feel more conspicuous carrying and using a vial andsyringe in public places. It has been reported that 60–80% ofpatients who use vial and syringe for insulin administrationincorrectly administer insulin because of timing and dosingerrors.57,58 Population subgroups at potential risk of dosingerrors include the elderly (>60 years), who represent ap-proximately 50% of all patients with diabetes in the UnitedStates,59 patients who are visually and physically impaired,children, adolescents, and their caregivers who may need tomeasure small doses.
Continuing refinement of insulin delivery devices (e.g.,pens, pumps) aim to improve glycemic control by facilitatingadherence to complex and sometimes intensive insulin ther-apy regimens.20 In a study by Vijan et al.60 (2005) that exam-ined patients’ views of the burden of diabetes therapy, itwas found that patients viewed insulin injection and self-monitoring of blood glucose as very burdensome. Patients’views of burden were the strongest consistent independentpredictor of self-rated levels of adherence to therapy, as wellas willingness to accept insulin therapy. Insights from theHealth Belief Model61,62 indicate that patients with diabeteswill more likely engage in optimal diabetes management be-haviors, such as adherence to prescribed insulin regimens, ifthe perceived threat of diabetes and benefits of adherence arehigh enough when balanced against barriers of engaging inthis behavior. In light of this, minimizing aforementionedbarriers to adherence (e.g., pain) via insulin delivery deviceattributes favored by patients, as evidenced by associatedPROs, may potentially increase patients’ self-efficacy and thelikelihood of adhering to prescribed insulin regimens.
Although this review employed approaches to mitigatebias (e.g., publication and study selection bias), some limita-tions are noteworthy. A majority (72%) of the examinedstudies was conducted before 2000, and some of the studiesexamined older pen devices that have been discontinued orwere never marketed. However, because findings were rep-licated in more recent studies, the potential for misclassifica-tion bias is minimal. Second, examined studies were notblinded; however, the sample was as unbiased as could beachieved in studies of this nature. Thirdly, because several ofthe examined studies had short follow-up periods (range,3–12 weeks), there may not have been sufficient time or op-portunity to examine any significant changes associated withPROs. In addition, some studies examined small sample sizes(i.e., <30 participants); therefore, interpretation of thesestudies’ findings may be limited. Last, studies varied widelyin the type and validation status of PRO questionnaires used,limiting our ability to make consistent comparisons acrossstudies.
Conclusions
Insulin pen devices are a preferred and more acceptableinsulin delivery system compared to conventional vial andsyringe. Additionally, insulin pen devices offer greater con-
venience, flexibility, treatment satisfaction, ease of use, per-ceived dosing accuracy, and self-efficacy and less pain, socialstigma, and insulin administration time, compared to vial andsyringe. These findings support how insulin pen device usecan potentially improve adherence to insulin therapy regi-mens. Diabetes care providers, patients, and payers can allcontribute to reducing barriers associated with conventionalinsulin therapy by incorporating favorable components (e.g.,well-accepted insulin delivery device) into diabetes manage-ment programs, practice, and=or protocols.
Acknowledgments
We thank Philip Walker for his assistance in literaturesearch. This review was financially supported by Eli Lilly andCompany.
Author Disclosure Statement
C.M., L.J.L., and S.M.L. are employees of Eli Lilly andCompany. L.S. and M.S. declare no competing financial in-terests.
References
1. The effect of intensive treatment of diabetes on the devel-opment and progression of long-term complications ininsulin-dependent diabetes mellitus. The Diabetes Controland Complications Trial Research Group. N Engl J Med1993;329:977–986.
2. Intensive blood-glucose control with sulphonylureas or in-sulin compared with conventional treatment and risk ofcomplications in patients with type 2 diabetes. UK Pro-spective Diabetes Study Group. UK Prospective DiabetesStudy (UKPDS) 33. Lancet 1998;352:837–853.
3. Oglesby AK, Secnik K, Barron J, Al Zakwani I, Lage MJ: Theassociation between diabetes related medical costs and gly-cemic control: a retrospective analysis. Cost Eff Resour Alloc2006;4:1.
4. Norris SL, Lau J, Smith SJ, Schmid CH, Engelgau MM: Self-management education for adults with type 2 diabetes: ameta-analysis of the effect on glycemic control. DiabetesCare 2002;25:1159–1171.
5. Spellman CW: Insulin therapy for maximal glycemic controlin type 2 diabetes mellitus. J Am Osteopath Assoc 2007;107:260–269.
6. Hunt LM, Valenzuela MA, Pugh JA: NIDDM patients’ fearsand hopes about insulin therapy: the basis of patient reluc-tance. Diabetes Care 1997;20:292–298.
7. Da Costa S, Brackenridge B, Hicks DA: Comparison of in-sulin pen use in the United States and the United Kingdom.Diabetes Educ 2002;28:52–60.
8. Korytkowski M, Niskanen L, Asakura T: FlexPen: addres-sing issues of confidence and confidence and convenience ininsulin delivery. Clin Ther 2005;27(Suppl B):S89–S100.
9. Rex J, Jensen KH, Lawton SA: A review of 20 years’ expe-rience with the NovoPen family of insulin injection devices.Clin Drug Invest 2006;26:367–401.
10. Fleming DR: Mightier than the syringe. Am J Nurs 2000;100(11):44–48.
11. Flood T: Advances in insulin delivery systems and devices:beyond the vial and syringe. Insulin 2006;1:99–108.
12. Funnell MM: Quality of life and insulin therapy in type 2diabetes mellitus. Insulin 2008;3:31–36.
536 MOLIFE ET AL.
13. Piscopo MA, Chiesa G, Bonfanti R, Viscardi M, Meschi F,Chiumello G: Quality of life and new devices in the man-agement of type 1 diabetes in children and adolescents. ActaBiomed 2003;74(Suppl 1):21–25.
14. 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;75:34–39.
15. Anderson DM, Barnett AH: A multicenter study of B-D(Becton Dickinson) pen as a delivery system for human in-sulin. Pract Diabetes 1994;11:36–38.
16. Anderson PO, Wikby A: Pen injection and change in meta-bolic control and quality of life in insulin dependent diabetesmellitus. Diabetes Res Clin Pract 1997;36:169–172.
17. Arslanoglu I, Saka N, Bundak R, Gunoz H, Darendeliler F: Acomparison of the use of premixed insulins in pen-injectorswith conventional patient-mixed insulin treatment in chil-dren and adolescents with IDDM. Is there a decreased risk ofnight hypoglycemia? J Pediatr Endocrinol Metab 2000;13:313–318.
18. Barnett AH, Bowen JD, Burden AC: Multicentre study toassess quality of life and glycaemic control of type 2 diabeticpatients treated with insulin compared with oral hypogly-caemic agents. Pract Diabetes Int 1996;13:179–183.
19. Berger AS, Saurbrey N, Kuhl C, Villumsen J: Clinical expe-rience with a new device that will simplify insulin injections.Diabetes Care 1985;8:73–76.
20. Bohannon NJV, Ohannesian JP: Patient and physician sat-isfaction with the HUMULIN=HUMALOG Pen, a new3.0mL prefilled pen device for insulin delivery. Clin Ther2000;22:1049–1067.
21. Buysschaert M, Janne P, Mpoy M, Reynaert C, PirsonF, Cassiers L, Lambert AE: Metabolic and psychologicalevolution of insulin dependent diabetic patients during a6 months insulin-pen treatment. Diabetes Metab 1988;14:75–79.
22. Chantelau E, Schiffers T, Schutze J, Hansen B: Effect ofpatient-selected intensive insulin therapy on quality of life.Patient Educ Couns 1997;30:167–173.
23. Chen HS, Hwu CM, Ching FK, Kwok CF, Yang HJ, ShihKC, Lin BJ, Ho LT: Clinical response and patient acceptanceof a prefilled, disposable insulin pen injector for insulin-treated diabetes. Zhonghua Yi Xue Za Zhi (Taipei) 1999;62:455–460.
24. Corsi A, Torre E, Coronel G, Ghisoni G, Carboni G, DeCastro A, Comaschi M: Pre-filled insulin pen in newlyinsulin-treated diabetic patients over 60 years old. DiabetesNutr Metabol Clin Exp 1997;10:78–81.
25. Coscelli C, Lostia S, Lunetta M, Nosari I, Coronel GA: Safety,efficacy, acceptability of a pre-filled insulin pen in diabeticpatients over 60 years old. Diabetes Res Clin Pract 1995;28:173–177.
26. Dunbar JM, Madden PM, Gleeson DT, Fiad TM, McKennaTJ: Premixed insulin preparations in pen syringes maintainglycemic control and are preferred by patients. DiabetesCare 1994;17:874–878.
27. Engstrom LHK: Insulin pen for administration of isophaneinsulin. Pract Diabetes 1990;7:162–164.
28. Fox C, McKinnon C, Wall A, Simon AL: Ability to handle,and patient preference for, insulin delivery devices in visu-ally impaired patients with type 2 diabetes. Pract DiabetesInt 2002;19:104–107.
29. Graff MR, McClanahan MA: Assessment by patients withdiabetes mellitus of two insulin pen delivery systems versusa vial and syringe. Clin Ther 1998;8:486–496.
30. Hanas R, Ludvigsson J: Experience of pain from insulin in-jections and needle phobia in young patients with IDDM.Pract Diabetes Int 1997;14:95–99.
31. Houtzagers CM, Visser AP, Berntzen PA, van der Stap H,van Maarschalkerweerd WW, Heine RJ, van der Veen EA:Multiple daily insulin injections improve self-confidence.Diabet Med 1989;6:512–519.
32. Houtzagers CM, Berntzen PA, van der Stap H, van Maar-schalkerweerd WW, Lanting P, Boen Tan I, Heine RJ, vander Veen EA: Efficacy and acceptance of two intensifiedconventional insulin therapy regimens: a long-term cross-over comparison. Diabetes Med 1989;6:416–421.
33. Hung CT, Wang FF: Pen injector for insulin-requiring dia-betic patients. J Formos Med Assoc 1992;91:1026–1029.
34. Jorgensen J, Flyvbjerg A, Jorgensen JT, Sorensen SS, Jo-hansen BR, Christiansen JS: NPH insulin administration bymeans of a pen injector. Diabet Med 1988;5:574–576.
35. Kadiri A, Chraibi A, Marouan F, Ababou MR, El Guermai N,Wadjinny A, Kerfati A, Douiri M, Bensouda JD, Belkhadir J,Arvanitis Y: Comparison of NovoPen 3 and syringes=vialsin the acceptance of insulin therapy in NIDDM patients withsecondary failure to oral hypoglycaemic agents. DiabetesRes Clin Pract 1998;41:15–23.
36. Kolendorf K, Beck-Nielsen H, Oxenboll B: Clinical experi-ence with NovoPen II and insulin Protaphane HM Penfill.Postgrad Med J 1988;64(Suppl 3):14–16.
37. Korytkowski M, Bell D, Jacobsen C, Suwannasari R: Amulticenter, randomized, open-label, comparative, two-period crossover trial of preference, efficacy, and safetyprofiles of a prefilled, disposable pen and conventional vial=syringe for insulin injection in patients with type 1 or 2 di-abetes mellitus. Clin Ther 2003;25:2836–2848.
38. Martin JM, Llewelyn JA, Ristic S, Bates PC: Acceptabilityand safety of a new 3.0ml re-usable insulin pen (HumaPen)in clinical use. Diabetes Nutr Metab Clin Exp 1999;12:306–309.
39. Murray DP, Keenan P, Gayer E, Salmon P, Tomkin GH,Drury MI, O’Sullivan DJ: A randomized trial of the efficacyand acceptability of a pen injector. Diabet Med 1988;5:750–754.
40. O’Hagan M, Greene SA: Pre-mixed insulin delivered bydisposable pen in the management of children with diabetes.Diabet Med 1993;10:972–975.
41. Rowe BR, Pizzey M, Barnett AH: A clinical evaluation of theB-D pen. Pract Diabetes 1992;9:138–139.
42. Rubin RR, Peyrot M: Factors affecting use of insulin pens bypatients with type 2 diabetes. Diabetes Care 2008;31:430–431.
43. Saurbrey N, Berger A, Kuhl C: The NovoPen: a practical toolfor simplifying multiple injection insulin therapy. ActaPaediatr Scand Suppl 1985;320:64–65.
44. Schuster MW, Chauhan SP, McLaughlin BN, Perry KG,Morrison JC: Comparison of insulin regimens and admin-istration modalities in pregnancy complicated by diabetes.J Miss State Med Assoc 1998;39:208–212.
45. Schwartz S, Khutoryansky N, Braceras R: Comparison ofresource utilisation, preference and handling of a pre-filledpen and vial=syringe in patients with type 2 diabetes mel-litus. J Clin Res 2007;10:1–10.
46. Shelmet J, Schwartz S, Cappleman J, Peterson G, Skovlund S,Lytzen L, Nicklasson L, Liang J, Lyness W; InnoLet� StudyGroup: Preference and resource utilization in elderly pa-tients: InnoLet� versus vial=syringe. Diabetes Res Clin Pract2003;63:27–35.
PATIENT-REPORTED OUTCOMES OF PEN VERSUS VIAL 537
47. Small M, MacRury S, Boal A: Comparison of conventionaltwice daily subcutaneous insulin administration and amultiple injection regimen (using the NovoPen) in insulin-dependent diabetes mellitus. Diabet Res 1988;8:85–89.
48. Spijker AJ, Hoekstra JBL, Erkelens DW: The insulin pen: anew device for multiple insulin injections. Transplant Proc1986;18:1689–1690.
49. Stockl K, Ory C, Vanderplas A, Nicklasson L, Lyness W,Cobden D, Chang E: An evaluation of patient preference foran alternative insulin delivery system compared to standardvial and syringe. Curr Med Res Opin 2007;23:133–146.
50. Stocks A: HumaPen Ergo: a new 3.0ml reusable insulin penevaluation of patient acceptability. Clin Drug Investig2001;21:319–324.
51. Sucic M, Galic E, Cabrijan T, Ivandic A, Petrusic A, Wyatt J,Mincheva N, Milicevic Z, Malone J: Patient acceptance andreliability of new Humulin=Humalog 3.0 ml prefilled insulinpen in ten Croatian diabetes centers. Med Sci Monit2002;8:P121–P126.
52. Tallroth G, Karlson B, Nilsson A, Agardh CD: The influenceof different insulin regimens on quality of life and metaboliccontrol in insulin-dependent diabetics. Diabetes Res ClinPract 1989;6:37–43.
53. Wikby A, Stenstrom U, Andersson PO, Hornquist J: Meta-bolic control, quality of life, and negative life events: a lon-gitudinal study of well-controlled and poorly regulatedpatients with type 1 diabetes after changeover to insulin pentreatment. Diabetes Educ 1998;24:61–66.
54. Wilk T, Mora PF, Chaney S, Shaw K: Use of an insulin penby homeless patients with diabetes mellitus. J Am AcadNurse Pract 2002;14:372–379.
55. Ignaut DA, Opincar M, Lenox S: FlexPen� and KwikPen�prefilled insulin devices: a laboratory evaluation of ergo-
nomic and injection force characteristics. J Diabetes SciTechnol 2008;2:533–537.
56. Lawton SA: A Practical Guide to Insulin Injection. A Re-source for Diabetes Educators. Bagsværd, Denmark: NovoNordisk A=S, 2000.
57. Newman KD, Weaver MT: Insulin measurement and prep-aration among diabetic patients at a county hospital. NursePract 1994;19:44–45, 48.
58. Coscelli C, Calabrese G, Fedele D, Pisu E, Calderini C, BistoniS, Lapolla A, Mauri MG, Rossi A, Zappella A: Use of premixedinsulin among the elderly. Reduction of errors in patientpreparation of mixtures. Diabetes Care 1992;15:1628–1630.
59. National Diabetes Fact Sheet: General Information and Na-tional Estimate in the United States, 2007. Atlanta: Centersfor Disease Control and Prevention, 2008.
60. Vijan S, Hayward RA, Ronis DL, Hofer TP: The burden ofdiabetes therapy implications for the design of effectivepatient-centered treatment regimens. J Gen Intern Med2005;20:479–482.
61. Becker MH, Malman LA: Sociobehavioral determinants ofcompliance with health and medical care recommendations.Med Care 1975;13:10–24.
62. Rosenstock IM: The health belief model and preventivehealth behavior. Health Educ Monogr 1974;2:354–386.
Address correspondence to:Cliff Molife, M.P.H.
Eli Lilly and CompanyDrop Code 5539
Indianapolis, IN 46285
E-mail: [email protected]
538 MOLIFE ET AL.