Digital Real-world Data Suggest Patient Preference for Tadalafil over Sildenafil in Patients with Erectile Dysfunction

Abstract

Background
Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase-5 inhibitors (PDE5is) used to treat ED.

Objective
This study aimed to evaluate patient data of a large online prescription platform (OPP), specifically analyzing preference for tadalafil over sildenafil.

Design, setting, and participants
Data from a prospectively collected German OPP were retrospectively analyzed. This dataset included patients with a history of taking one or both substances (n = 26 821).

Outcome measurements and statistical analysis
ED patient baseline characteristics were derived from medical questionnaires for PDE5i prescriptions between May 2019 and May 2020. Order behavior was analyzed in patients who ordered both substances over time. We applied Kruskal-Wallis tests, χ² tests, and fisher’s exact tests for statistical analysis.

Results and limitations
Baseline characteristics were comparable for both PDE5is in patients with a median age of 49 yr (sildenafil [interquartile range {IQR} 38–57]; tadalafil [IQR 39–56]), a median body mass index (BMI) of 26 kg/m² (sildenafil [IQR 24.54–29.03]; tadalafil [IQR 24.49–28.69]), ED onset time of >12 mo (sildenafil [87%]; tadalafil [88%]), and the presence of morning erections (sildenafil [62%]; tadalafil [61%]). Tadalafil prescriptions increased significantly from 30% (first order) to 80% (last order) in patients who had already tested both drugs. Patients with age ≤40 yr, BMI ≤25 kg/m², and sustained morning erections preferred tadalafil to sildenafil.

Conclusions
Using database information from an OPP, preference for tadalafil was shown for patients who had tested both PDE5is. This preference was particularly pronounced in patients with age ≤40 yr, BMI ≤25 kg/m², and sustained morning erections. A well-managed OPP can be used for research on more complex health services.

Patient summary
Analysis of large online prescription platforms provide the benefit of identifying young treatment-naïve patients with early-stage disease, which is highlighted by the fact that about two-thirds of our patients analyzed still maintained spontaneous morning erections. Patients who had tested tadalafil once developed preference for this drug.

Full text

Andrology
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction
Moritz
von
Bu
¨ren
a,
*,
Severin
Rodler
b
,
Isabell
Wiesenhu
¨tter
c
,
Florian
Schro
¨der
d
,
Alexander
Buchner
b
,
Christian
Stief
b
,
Christian
Gratzke
a
,
Christian
Wu
¨lfing
e,y
,
Johannes
von
Bu
¨ren
d,y
a
Department
of
Urology,
University
of
Freiburg,
Freiburg,
Germany;
b
Department
of
Urology,
University
of
Munich,
Munich,
Germany;
c
Munich
University
Institute
for
Psychological
Psychotherapy
Training
(MUNIP),
Munich,
Germany;
d
Wellster
Healthtech
Group,
Munich,
Germany;
e
Department
of
Urology,
Asklepios
Klinikum
Altona,
Hamburg,
Germany
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
ava
ilable
at
www.sciencedirect.com
journa
l
homepage:
www.europea
nurology.com/eufocus
Article
info
Article
history:
Accepted
April
23,
2021
Associate
Editor:
Malte
Rieken
Keywords:
Digital
healthcare
Online
prescription
platform
Erectile
dysfunction
Phosphodiesterase-5
inhibitor
Abstract
Background:
Erectile
dysfunction
(ED)
is
a
major
care
problem
worldwide.
Tadalafil
and
sildenafil
are
the
two
most
common
phosphodiesterase-5
inhibitors
(PDE5is)
used
to
treat
ED.
Objective:
This
study
aimed
to
evaluate
patient
data
of
a
large
online
prescription
platform
(OPP),
specifically
analyzing
preference
for
tadalafil
over
sildenafil.
Design,
setting,
and
participants:
Data
from
a
prospectively
collected
German
OPP
were
retrospectively
analyzed.
This
dataset
included
patients
with
a
history
of
taking
one
or
both
substances
(n
=
26
821).
Outcome
measurements
and
statistical
analysis:
EDpatientbaseline characteristicswere
derived
from
medical
questionnaires
for
PDE5i
prescriptions
between
May
2019
and
May
2020.
Order
behavior
was
analyzed
inpatients
who
ordered
both
substances
over
time.
We
applied
Kruskal-Wallis
tests,
x
2
tests,
and
fisher’s
exact
tests
for
statistical
analysis.
Results
and
limitations:
Baseline
characteristics
were
comparable
for
both
PDE5is
in
patients
with
a
median
age
of
49
yr
(sildenafil
[interquartile
range
{IQR}
38–57];
tadalafil
[IQR
39–56]),
a
median
body
mass
index
(BMI)
of
26
kg/m
2
(sildenafil
[IQR
24.54–29.03];
tadalafil
[IQR
24.49–28.69]),
ED
onset
time
of
>12
mo
(sildenafil
[87%];
tadalafil
[88%]),
and
the
presence
of
morning
erections
(sildenafil
[62%];
tadalafil
[61%]).
Tadalafil
prescriptions
increased
significantly
from
30%
(first
order)
to
80%
(last
order)
in
patients
who
had
already
tested
both
drugs.
Patients
with
age
40
yr,
BMI
25
kg/m
2
,
and
sustained
morning
erections
preferred
tadalafil
to
sildenafil.
Conclusions:
Using
database
information
from
an
OPP,
preference
for
tadalafil
was
shown
for
patients
who
had
tested
both
PDE5is.
This
preference
was
particularly
pronounced
in
patients
with
age
40
yr,
BMI
25
kg/m
2
,
and
sustained
morning
erections.
A
well-
managed
OPP
can
be
used
for
research
on
more
complex
health
services.
Patient
summary:
Analysis
of
large
online
prescription
platforms
provide
the
benefit
of
identifying
young
treatment-naïve
patients
with
early-stage
disease,
which
is
highlighted by
the fact that
about
two-thirds
of
our patients
analyzed
still
maintained spontaneous
morning
erections.
Patients
who
had
tested
tadalafil
once
developed
preference
for
this
drug.
©
2021
The
Authors.
Published
by
Elsevier
B.V.
on
behalf
of
European
Association
of
Urology.
This
is
an
open
access
article
under
the
CC
BY-NC-ND
license
(http://creati-
vecommons.org/licenses/by-nc-nd/4.0/).
y
These
authors
contributed
equally.
*
Corresponding
author.
Department
of
Urology,
University
of
Freiburg,
Freiburg,
Germany.
Tel.
+49
761
270
28930;
Fax:
+49
761
270
28960.
E-mail
address:
moritz.bueren@uniklinik-freiburg.de
(M.
von
Büren).
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019
https://doi.org/10.1016/j.euf.2021.04.019
2405-4569/©
2021
The
Authors.
Published
by
Elsevier
B.V.
on
behalf
of
European
Association
of
Urology.
This
is
an
open
access
article
under
the
CC
BY-NC-ND
license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1.
Introduction
Erectile
dysfunction
(ED)
is
a
multidimensional
and
wide-
spread
sexual
malfunction
in
men
[1].
Vascular,
psycholog-
ical,
and
unknown
other
factors
are
associated
with
this
disease
[2].
Treatment
includes
lifestyle
interventions,
pharmacological
treatment
with
phosphodiesterase-5
(PDE5)
inhibitors,
vacuum
erection
devices,
injections,
and
surgical
interventions
[1].
ED
is
associated
with
meta-
bolic
and
cardiovascular
disease,
increase
in
incidence
rates
with
age,
and
cardiovascular
disease
risk
factors
[2].
ED
can
involve
both
physiological
and
psychological
factors.
The
latter
affects
a
more
juvenile
and
potentially
healthier
patient
group
[3].
Sustained
nocturnal
erections
are
the
leading
clinical
factor
to
discriminate
psychological
causes
for
ED
[4].
A
large
previously
unknown
ED
population
that
used
an
online
prescription
platform
(OPP)
to
treat
their
disease
was
epidemiologically
characterized
[5].
Compared
with
the
population
in
approval
studies
[6,7]
and
a
recent
review
comparing
sildenafil
with
tadalafil
[8],
the
group
from
the
OPP
study
is
younger,
mostly
treatment
naïve,
and
not
yet
well
characterized.
Sildenafil
and
tadalafil
are
the
most
common
PDE5
inhi-
bitors
[8].
Sildenafil
showed
a
treatment
success
rate
of
84%,
a
quick
onset
within
30–120
min,
and
an
elimination
half-
life
of
4
h
with
a
maximum
time
of
action
of
12
h
[6,9].
The
tadalafil
treatment
success
rate
was
75%,
with
an
onset
within
approximately
30
min,
a
mean
time
to
maximum
drug
concentration
of
120
min,
and
an
extended
duration
of
action
of
up
to
36
h
[7,10].
Sildenafil
and
tadalafil
showed
similar
results
with
regard
to
efficacy,
tolerability,
and
patient
satisfaction
[8,11,12].
Tadalafil
seemed
to
improve
sexual
confidence
more
effectively
than
sildenafil
in
randomized
controlled
trials
[13–15].
Prospective
studies
showed
a
slight
prefer-
ence
for
tadalafil
over
sildenafil
[16,17].
This
study
aims
to
investigate
whether
data
for
health
services
research
can
be
obtained
by
a
well-managed
OPP
database.
We
hypothesize
tadalafil
to
be
the
preferred
substance
in
this
understudied
population
using
an
OPP
for
medical
treatment.
2.
Patients
and
methods
2.1.
Study
design
This
cross-sectional
study
was
conducted
with
anonymized
data
pro-
vided
by
Wellster
Healthtech
Group,
the
provider
of
“www.gospring.de”,
an
OPP
for
men's
health
[18].
The
OPP
advertised
on
Internet
search
engines,
digital
media,
and
commercial
spots.
Patient
data
were
collected
via
structured
questionnaires
(Supplementary
Tables
1
and
2).
The
patient
was
asked
for
ED
characteristics,
PDE5
inhibitor
contraindica-
tions,
and
possible
medication
interactions.
Physicians
also
considered
cardiovascular
risk
factors
such
as
body
mass
index
(BMI),
nicotine,
and
age
when
deciding
on
a
prescription.
Therapeutic
options
at
the
OPP
included
sildenafil
(25,
50,
and
100
mg)
and
tadalafil
(5,
10,
and
20
mg)
by
patient
choice.
For
other
treatment
options
or
in
the
case
of
contraindications,
patients
were
referred
to
urologists.
After
prescribing,
the
medication
could
be
ordered
from
a
cooperating
online
pharmacy.
Preference
for
one
of
the
PDE5
inhibitors
was
assessed
by
examining
repeat
orders
from
patients
who
had
ordered
both
sildenafil
and
tadalafil
on
a
separate
occasion
(P
2
).
Patients
were
excluded
from
this
cohort
if
the
PDE5
inhibitor
switch
occurred
in
the
most
recent
order.
All
research
was
carried
out
in
accordance
with
the
Code
of
Ethics
of
the
World
Medical
Association
(Declaration
of
Helsinki)
and
its
later
amendments.
Informed
consent
was
received
from
all
patients.
Before
initiation
of
the
study,
the
local
ethics
authority
(Ethikkommission
der
University
of
Freiburg)
revised
the
project
design
and
waived
the
need
for
approval
(reference
number:
21-1002).
2.2.
Setting
OPP’s
service
was
available
only
in
Germany.
The
patient
data
were
collected
between
May
2019
and
May
2020.
Questionnaires
with
at
least
90%
of
questions
answered
were
included.
Patient
data
were
analyzed
at
the
prescription
level,
and
patients
had
the
option
of
ordering
multiple
times
in
a
row.
An
automated
drug
abuse
logic
was
in
place,
so
that
no
more
than
one
tablet
per
day
could
be
ordered,
nor
several
drugs
at
the
same
time.
2.3.
Participants
Male
patients
aged
18
yr
with
self-assessed
ED
were
eligible
for
prescription
evaluation.
Prescriptions
were
issued
only
to
patients
who
regularly
experienced
ED
problems
[19].
2.4.
Statistical
analysis
Descriptive
statistics
were
summarized
as
median
and
interquartile
range
(IQR).
Kruskal-Wallis
tests
were
used
to
examine
the
differences
in
age
and
BMI
scores
by
treatment
category,
as
values
were
not
normally
distributed,
using
the
D’Agostino
and
Pearson
test.
Post
hoc
comparisons
were
performed
using
Dunn’s
multiple
comparison
test.
A
Mann-Whit-
ney
U
test
was
used
to
compare
differences
in
price,
as
values
were
not
normally
distributed.
A
chi-square
test
was
used
for
analysis
of
categori-
cal
variables,
with
the
exception
of
Figures
1
and
2,
and
Supplementary
Figure
1
for
which
the
Fisher’s
exact
test
was
used.
All
p
values
<0.05
were
regarded
as
statistically
significant.
A
Bonferroni
correction
for
multiple
comparisons
was
used
as
statistically
significant
for
Figure
2
and
Supplementary
Figure
1,
with
p
<
0.0125.
All
calculations
were
conducted
by
GraphPad
Prism
software
version
8
(GraphPad
Software,
San
Diego,
CA,
USA).
3.
Results
PDE5
inhibitor
prescriptions
for
26
821
patients
are
shown
in
Table
1
(P
1
).
A
total
of
30
846
(85%)
were
sildenafil,
5043
(14%)
were
tadalafil,
and
the
remaining
516
(1%)
were
“Testkit”
prescriptions.
In
addition,
Table
1
shows
a
subset
of
367
patients
with
1388
prescriptions
(P
2
)
who
had
a
history
with
both
sildenafil
and
tadalafil.
There
were
clini-
cally
significant
differences
in
the
selected
drug
dosages
(chi-square
test,
p
<
0.0001;
Table
1).
In
Table
2,
baseline
characteristics
of
the
sildenafil
cohort
were
comparable
with
those
of
the
tadalafil
cohort
with
a
median
age
of
49
yr
(sildenafil
[IQR
38–57];
tadalafil
[IQR
39–56]),
a
median
BMI
of
26
kg/m
2
(sildenafil
[IQR
24.54–29.03];
tada-
lafil
[IQR
24.49–28.69]),
ED
onset
time
of
>12
mo
(sildenafil
[87%];
tadalafil
[88%]),
and
the
presence
of
morning
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
2
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019

erections
(sildenafil
[62%];
tadalafil
[61%]).
Overall,
baseline
characteristics
of
P
2
were
generally
comparable
with
those
of
P
1
with
a
median
BMI
of
26
kg/m
2
(IQR
23.96–29.05),
ED
onset
time
>12
mo
(88%),
and
presence
of
morning
erec-
tions
(64%).
The
P
2
group
differed
significantly
with
a
median
age
of
48
yr
(comparing
P
1
vs
P
2
in
respective
treatment
groups
based
on
Kruskal-Wallis
tests
with
post
hoc
comparisons
using
Dunn’s
multiple
comparison
test;
p

0.05).
Additionally,
there
were
significant
differences
in
the
consumption
of
nicotine
(chi-square
test,
p
<
0.0321;
Table
2)
and
alcohol
(chi-square
test,
p
<
0.0001;
Supple-
mentary
Table
3)
between
the
groups.
For
sildenafil
and
tadalafil,
higher
dosages
correlated
with
a
larger
pack
size
per
prescription
(Fig.
3A).
The
exception
was
tadalafil
5
mg,
which
is
used
as
a
daily
therapy.
The
most
popular
selection
by
patients
among
sildenafil
and
tadalafil
prescriptions
was
the
pack
size
of
12
(Fig.
3B).
Viagra,
the
original
brand
of
sildenafil,
was
in
greater
demand
than
Cialis
for
tadalafil
(19%
vs
10%;
Fig.
3C).
The
price
per
pill
was
significantly
cheaper
for
tadalafil
at
s5.8
than
for
sildenafil
at
s7.6
(Mann-Whitney
U
test,
p
<
0.0001;
Fig.
3D).
Prescription
frequency
and
sequence
of
P
1
,
P
2
,
and
pre-
scriptions
by
patients
“without
change”
of
medication,
a
subgroup
that
had
experience
with
only
one
type
of
PDE5
inhibitor
in
the
platform's
order
history,
are
shown
in
Figure
4.
In
P
1
,
there
was
a
significant
difference
in
the
relative
prescription
frequency
of
sildenafil
versus
tadalafil
from
order
sequence
“one”
to
“eight”
(chi-square
test,
p
<
0.0001;
Fig.
4A).
Tadalafil
prescriptions
made
up
12%
of
orders
in
prescription
sequence
“one”
compared
with
28%
in
sequence
“eight”.
The
exception
here
were
patients
who
had
a
history
with
one
type
of
PDE5
inhibitor
only,
“without
change”
of
medication.
This
subgroup
made
up
the
majority
of
prescriptions
with
a
total
number
of
31
958,
showing
no
significant
difference
in
the
relative
frequency
of
orders
(tadalafil
vs
sildenafil)
between
prescription
sequences
“one”
and
“eight”
(chi-square
test,
p
=
0.7245;
Fig.
4B).
The
patients’
preference
for
one
type
of
PDE5
inhibitor
was
assessed
in
those
who
had
a
history
with
“both”
sil-
denafil
and
tadalafil
(P
2
;
Figs.
1,
2,
and
4C).
There
was
a
significant
difference
in
the
prescription
frequency
of
sil-
denafil
versus
tadalafil
from
order
sequence
“one”
to
“eight”
(chi-square
test,
p
<
0.0001;
Fig.
4C).
The
relative
frequency
of
tadalafil
prescriptions
increased
from
30%
in
order
sequence
“one”
to
80%
in
sequence
“eight.”
Accordingly,
a
detailed
analysis
revealed
that
there
was
a
significant
dif-
ference
in
the
relative
frequency
of
prescriptions
(tadalafil
and
sildenafil)
before
versus
after
change
of
PDE5
inhibitor
in
P
2
(Fisher’s
exact
test,
p
=
0.0007;
Fig.
1).
The
proportion
of
tadalafil
prescriptions
corresponded
to
45%
before
and
including
the
first
change
of
PDE5
inhibitor,
whereas
the
proportion
increased
to
55%
after
the
change
of
medication.
To
better
understand
the
drivers
behind
this
increase,
the
group
was
divided
according
to
age,
BMI,
or
presence
of
morning
erections.
In
contrast
to
patients
>40
yr
of
age,
or
with
BMI
>25
kg/m
2
,
or
without
morning
erections,
there
was
a
significant
difference
in
the
relative
frequency
of
prescriptions
(tadalafil
and
sildenafil)
before
versus
after
change
of
PDE5
inhibitor
in
patients
with
an
age
of
40
yr
(Fisher’s
exact
test
with
Bonferroni
correction,
p
=
0.0093;
Fig.
2A),
or
a
BMI
of
25
kg/m
2
(Fisher’s
exact
test
with
Bonferroni
correction,
p
=
0.0003;
Fig.
2B),
or
sustained
morning
erections
(Fisher’s
exact
test
with
Bonferroni
cor-
rection,
p
=
0.0001;
Fig.
2C).
The
relative
frequency
of
tada-
lafil
prescriptions
increased
from
45%
before
and
including
the
first
change
of
PDE5
inhibitor
to
59%
after
the
change
of
medication
in
patients
with
sustained
morning
erections.
After
change
of
PDE5
inhibitor,
in
contrast
to
age
and
BMI
(Supplementary
Fig.
1A
and
B),
there
was
a
significant
difference
in
the
relative
frequency
of
prescriptions
in
patients
without
versus
with
sustained
morning
erections
(Fisher’s
exact
test
with
Bonferroni
correction,
p
=
0.0069;
Supplementary
Fig.
1C).
4.
Discussion
This
is
the
largest
study
conducted
among
men
with
ED
using
an
OPP.
It
revealed
baseline
characteristics
of
patients
using
OPPs
for
online
ED
treatment.
Further,
patient
prefer-
ence
for
tadalafil
over
sildenafil
in
a
group
of
men
who
had
a
history
with
“both”
PDE5
inhibitors
was
shown.
Baseline
characteristics
derived
from
PDE5
inhibitor
pre-
scriptions
of
all
patients
of
the
P
1
group
are
comparable
with
those
of
the
P
2
group
that
had
a
history
with
both
sildenafil
and
tadalafil.
The
differences
in
patient
character-
istics
are
statistically
significant
due
to
the
high
number
of
prescriptions
but
are
clinically
irrelevant
(with
the
excep-
tion
of
medication
dosages).
We
realized
that
beneficiaries
of
digital
health
services
are
mainly
treatment
naive
[5],
are
younger
(29,4%
of
our
study
population
is
40
yr,
which
is
Fig.
1
–
Preference
for
tadalafil
over
sildenafil
in
patients
familiar
with
“both”
Drugs.
The
relative
frequency
of
prescriptions
after
PDE5
inhibitor
change
was
defined
as
all
prescriptions
ordered
after
patients
had
taken
both
drugs.
The
relative
frequency
of
prescriptions
before
change
of
the
PDE5
inhibitor
included
all
other
prescriptions.
There
was
a
significant
difference
in
relative
frequency
of
prescriptions
(tadalafil
and
sildenafil)
before
versus
after
PDE5
inhibitor
change
in
patients
familiar
with
“both”
drugs.
*
p
<
0.05
(two
tailed)
from
several
pairwise
comparisons
using
Fisher’s
exact
test.
PDE5
=
phosphodiesterase-5;
PDE5i
=
PDE5
inhibitor.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
3
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019

Fig.
2
–
Preference
for
tadalafil
over
sildenafil
driven
by
ED
patients
under
40,
not
overweight,
and
with
sustained
morning
erections.
(A)
In
contrast
to
patients
older
than
40
yr,
there
was
a
significant
difference
in
relative
frequency
of
prescriptions
(tadalafil
and
sildenafil)
before
versus
after
PDE5
inhibitor
change
in
patients
40
yr
old.
(B)
In
contrast
to
patients
with
BMI
>25,
there
was
a
significant
difference
in
relative
frequency
of
prescriptions
(tadalafil
and
sildenafil)
before
versus
after
PDE5
inhibitor
change
in
patients
with
BMI
25.
(C)
In
contrast
to
patients
without
morning
erections,
there
was
a
significant
difference
in
relative
frequency
of
prescriptions
(tadalafil
and
sildenafil)
before
versus
after
PDE5
inhibitor
change
in
patients
with
sustained
morning
erections.
*p
<
0.0125
(two
tailed)
from
several
pairwise
comparisons
using
Fisher’s
exact
test
with
Bonferroni
correction
for
multiple
comparisons.
BMI
=
body
mass
index;
ED
=
erectile
dysfunction;
n.s.
=
not
significant;
PDE5
=
phosphodiesterase-5;
PDE5i
=
PDE5
inhibitor.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
4
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019

comparable
with
the
previous
literature
[20]),
and
show
an
earlier
stage
of
illness,
with
61–62%
of
patients
having
sustained
morning
erections
compared
with
the
popula-
tions
described
in
related
ED
studies.
In
contrast,
the
approval
study
populations
were
clini-
cally
tied
to
university
hospitals,
older,
and
at
a
more
severe
stage
of
ED.
The
sildenafil
approval
study
included
816
patients
with
a
mean
age
of
59
yr,
and
the
percentage
of
psychogenic
ED
was
11%
and
that
of
mixed
cause
was
18%
[6].
Approval
studies
of
tadalafil
included
1112
patients
with
an
average
age
of
59
yr,
and
an
overall
percentage
of
psy-
chogenic
ED
of
9%
and
that
of
a
mixed
cause
of
31%
[7].
Our
Table
1
–
PDE5
inhibitor
prescriptions
Patients
All
Familiar
with
“both”
PDE5i
Prescriptions
P
1
;
n
=
36405
P
2
;
n
=
1388
PDE5
inhibitor
Sildenafil
Tadalafil
Both
Parameter
n
(%)
n
(%)
n
(%)
p
value
Prescriptions
#
Total
30
846
5043
1351
25
mg
1991
(6.5)
16
(2.3)
<0.0001
50
mg
23
428
(76.0)
516
(75.0)
100
mg
5427
(17.6)
156
(22.7)
5
mg
481
(9.5)
42
(6.3)
<0.0001
10
mg
2245
(44.5)
233
(35.1)
20
mg
2317
(45.9)
388
(58.5)
#
Testkits
a
516
37
PDE5
=
phosphodiesterase-5;
PDE5i
=
PDE5
inhibitors.
Chi-square
tests
were
used
for
statistical
analysis
of
categorical
data
(p

0.05).
a
Definition:
“Testkit”
prescription
is
an
order
including
both
sildenafil
50
mg
and
tadalafil
10
mg,
with
a
pack
size
of
four
each.
Table
2
–
Patient
characteristics
derived
from
PDE5
inhibitor
prescriptions
Patients
All
Familiar
with
“both”
PDE5i
Prescriptions
P
1
;
n
=
36
405
P
2
;
n
=
1388
PDE5
inhibitor
Sildenafil
Tadalafil
Both
Parameter
n
(%)
n
(%)
n
(%)
p
value
Age
Mdn
49
49
48
a
0.0038
IQR
38–57
39–56
39–55
BMI
Mdn
26.31
26.12
b
26.30
0.0003
IQR
24.54–29.03
24.49–28.69
23.96–29.05
<18.5
kg/m
2
45
(0.1)
5
(0.1)
0
(0)
<0.0001
18.5–25
kg/m
2
9938
(32.7)
1661
(34.6)
491
(36.7)
25–30
kg/m
2
14
782
(48.7)
2335
(48.7)
579
(43.3)
>30
kg/m
2
5615
(18.5)
795
(16.6)
267
(19.9)
ED
characteristics
>12
mo
26
854
(87.3)
4459
(88.4)
118 8
(88.0)
0.064
w/ME
19
186
(62.4)
3061
(60.7)
859
(63.7)
<0.0001
Smoking
c
#
Total
4854
116 2
321
None
3048
(62.8)
782
(67.3)
221
(68.8)
0.0321
Irregular
693
(14.3)
166
(14.3)
40
(12.5)
Regular
with
<1
pack/d
and
<5
yr
311
(6.4)
58
(5.0)
19
(5.9)
Regular
with
<1
pack/d
and
5–10
yr
334
(6.9)
69
(5.9)
14
(4.4)
Regular
with
>1
pack/d
or
>10
yr
468
(9.6)
87
(7.5)
27
(8.4)
BMI
=
body
mass
index;
ED
=
erectile
dysfunction;
IQR
=
interquartile
range;
Mdn
=
median;
PDE5
=
phosphodiesterase-5;
PDE5i
=
PDE5
inhibitors;
w/ME
=
with
sustained
morning
erection.
Analyzing
all
three
groups
(sildenafil,
tadalafil,
and
both),
Kruskal-Wallis
tests
were
used
to
examine
differences
in
mean
age
and
BMI;
Testkit
prescriptions
are
not
included
in
the
analysis
of
age,
BMI,
and
ED
characteristics.
Chi-square
tests
were
used
for
statistical
analysis
of
categorical
data
(p

0.05).
a
A
significant
difference
in
comparing
prescriptions
by
all
patients
in
respective
treatment
groups
versus
prescriptions
by
the
patient
subgroup
familiar
with
“both”
PDE5
inhibitors
based
on
Dunn’s
multiple
comparison
test
(p

0.05).
b
A
significant
difference
in
comparing
sildenafil
versus
tadalafil
within
P
1
based
on
Dunn’s
multiple
comparison
test
(p

0.05).
c
Answer
options
for
smoking
behavior
in
the
medical
questionnaire
were
formulated:
"I
do
not
smoke,"
"I
smoke
irregularly
(eg,
at
parties),
but
never
more
than
half
a
pack
a
day,"
"I
smoke
regularly,
but
for
<5
yr
and
less
than
one
pack
a
day,"
"I
smoke
regularly,
for
>5
but
<10
yr
and
less
than
one
pack
a
day,"
and
"I
have
been
smoking
regularly
for
>10
yr
or
more
than
one
packet
a
day."
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
5
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019

Fig.
3
–
Pack
sizes
of
prescribed
PDE5
inhibitors,
generic
versus
original
brand
and
price
per
pill.
Analysis
was
based
on
the
P
1
study
cohort
excluding
“Testkit”
prescriptions.
(A)
The
number
of
packs
of
sildenafil
and
tadalafil
prescribed
depending
on
the
pack
sizes
and
the
different
dosages.
(B)
The
percentage
distribution
of
the
pack
sizes
between
sildenafil
and
tadalafil.
(C)
The
proportion
between
the
generic
version
and
the
original
brand
was
similar
for
sildenafil
and
tadalafil.
(D)
The
price
of
tadalafil
was
s5.8
(SD:
6.7),
higher
than
the
price
of
sildenafil
at
s7.6
(SD:
5.7).
The
p
values
(two
tailed)
using
Mann-Whitney
U
test
were
<0.05.
PDE5
=
phosphodiesterase-5;
PDE5i
=
PDE5
inhibitor;
SD
=
standard
deviation.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
6
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019

OPP
study
population
had
a
median
age
of
49
yr
in
the
treatment
groups.
The
number
of
patients
without
prior
therapy
was
higher
than
reported
in
previous
studies
(63.5%),
which
is
likely
due
to
the
younger
age
and
the
lower
contact
exposure
as
a
result
of
the
digital
treatment
and
home
delivery
of
the
drug
[5].
The
proportion
of
tadalafil
prescriptions
increased
sig-
nificantly,
considering
repeat
orders
over
time
in
all
patients.
As
patients
who
had
a
history
with
only
one
type
of
PDE5
inhibitor,
“without
change”
of
medication,
showed
no
significant
difference
in
the
relative
frequency
of
orders
between
prescription
sequences
“one”
and
“eight”,
the
increasing
proportion
of
tadalafil
prescriptions
in
the
over-
all
population
(P
1
)
was
therefore
due
to
patients
who
had
a
history
of
“both”
PDE5
inhibitors
(P
2
).
Preference
was
investigated
by
focusing
on
cohort
P
2
.
We
were
able
to
show
a
switch
of
orders
from
a
55:45
ratio
(sildenafil:tadalafil)
to
a
45:55
ratio
after
the
change
of
PDE5
inhibitor,
indicating
a
significant
preference
for
tada-
lafil
over
sildenafil.
Several
research
groups
showed
that
ED
patients
with
a
history
of
taking
both
substances
preferred
tadalafil
in
randomized
three-phase
studies
[16,21,22],
for
example,
Dean
et
al’s
[16]
study
with
12
wk
of
tadalafil
followed
by
12
wk
of
sildenafil
or
vice
versa,
and
then
concluding
with
8
wk
of
free
choice.
Men
with
ED
who
initiated
treatment
with
tadalafil,
routine
or
PRN,
adhered
to
their
original
treatment
for
a
significantly
longer
time
than
men
starting
with
sildenafil
PRN,
although
efficacy
and
tolera-
bility
were
not
significantly
different
between
treatment
Fig.
4
–
Increasing
proportion
of
tadalafil
in
represcriptions
driven
by
ED
patients
familiar
with
“both”
PDE5
inhibitors.
In
order
to
be
able
to
map
a
minimum
"number
of
prescriptions"
per
"prescription
sequence,”
only
the
prescription
sequence
up
to
prescription
“eight”
in
the
entire
population
(n
=
36
405;
>99.8%
of
data
points
shown),
the
patient
subgroup
"without
change"
(n
=
31
958;
>99.9%
of
data
points
shown),
and
the
patient
subgroup
"both"
(n
=
1388;
>99.7%
of
data
points
shown)
are
displayed
on
the
x
axis.
(A)
There
was
a
significant
difference
in
the
prescription
frequency
of
sildenafil
versus
tadalafil
from
order
sequence
“one”
to
“eight.”
(B)
There
was
no
significant
change
in
the
relative
frequency
of
tadalafil
versus
sildenafil
prescriptions
from
order
sequence
“one”
to
“eight.”
(C)
There
was
a
significant
difference
in
the
prescription
frequency
of
sildenafil
versus
tadalafil
from
order
sequence
“one”
to
“eight.”
Chi-square
tests
were
used
for
the
statistical
analysis
of
categorical
data
of
the
sildenafil
and
tadalafil
prescriptions
(without
"Testkit")
in
respective
groups
(p

0.05).
ED
=
erectile
dysfunction;
n.s.
=
not
significant;
PDE5
=
phosphodiesterase-5;
PDE5i
=
PDE5
inhibitor.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
7
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019

groups.
In
contrast
to
these
earlier
PDE5
inhibitor
prefer-
ence
studies,
this
was
a
setting
with
a
free
choice
of
sub-
stance
for
every
purchase
on
the
patient
side
in
a
real-life
sales
setting
without
medical
aid
reimbursement.
Tadalafil
preference
was
shown
with
an
increase
of
pre-
scriptions
after
change
of
PDE5
inhibitor
from
45%
to
59%
in
the
patient
group
with
residual
morning
erections.
One
probable
reason
for
this
preference
is
the
higher
flexibility
gained
by
the
significantly
longer
half-life
compared
with
that
of
sildenafil
[6,7].
This
is
supported
by
the
studies
of
Rubio-Aurioles
et
al
[13],
Althof
et
al
[23],
and
Tsujimura
et
al
[24],
which
showed
that
routine
and
PRN
tadalafil
demonstrated
great
improvements
in
sexual
self-confi-
dence,
time
concerns,
and
spontaneity
when
compared
with
PRN
sildenafil.
We
must
acknowledge
the
limitations
of
this
retrospective
cross-sectional
study
without
randomization.
The
treatment
group
definition
is
based
on
a
patient's
self-assessment
and
nonstandardized
questionnaire
without
invasive
diagnostic
to
confirm
ED.
The
latter
is
not
recommended
in
the
basic
workup
of
ED
patients
in
the
European
Association
of
Urology
guidelines
on
male
sexual
function
[1].
Some
patients
might
have
answered
inaccurately
sensitive
questions
in
the
ques-
tionnaire.
Further,
we
must
consider
that
the
population
might
differ
from
the
general
ED
population
due
to
marketing
channels
used,
and
patient
selection
bias
caused
by
the
careful
and
systematic
exclusion
of
patients
with
risk
factors
for
potential
substance
side
effects
[5].
OPPs
seem
to
be
an
important
complement
to
the
treat-
ment
options
of
patients.
They
offer
facilitated
access
inde-
pendent
of
regular
medical
office
hours
[5,25]
and
low
contact
burden
in
circumstances
with
high
contact
barriers
[26].
This
example
shows
that
long-term
treatment
in
cer-
tain
indications
seems
to
be
possible
safely.
Using
a
struc-
tured
questionnaire
for
risk
factor
stratification,
there
is
potential
to
transfer
untreated
patients
with
potential
car-
diovascular
risk
factors
to
other
specialties.
This
important
bridge
between
offline
and
online
medicine
could
increase
the
number
of
preventive
medical
examinations
in
risk
groups,
as
almost
63.5%
of
the
OPP
customers
are
lacking
any
medical
attention
[5].
Therefore,
OPPs
might
be
a
useful
addition
in
treatment
options
for
patients,
and
an
increase
of
indications
and
services
are
imaginable
in
the
future.
Additionally,
there
is
potential
opportunity
in
conducting
prospective
studies
using
OPP
data,
rather
than
focusing
solely
on
retrospective
research.
5.
Conclusions
Tadalafil
and
sildenafil
have
shown
comparable
efficacy
for
the
treatment
of
ED.
We
confirmed
preference
for
tadalafil
over
sildenafil,
especially
in
young,
not
overweight
patients
withpersistentmorningerections.We suggestachangeinthe
clinical
substance
sequence
in
the
treatment
of
ED,
especially
if
spontaneous
erections
still
persist.
With
the
preference
for
tadalafil
over other
PDE5
inhibitors
bythis
group
of
OPP
users,
we
were
able
to
show
which
kind
of
data
for
health
services
research
can
be
obtained
by
a
well-managed
OPP
database.
Further,
we
could
use
available
data
provided
by
an
OPP
for
structured
postclinical
research.
Author
contributions:
Moritz
von
Büren
had
full
access
to
all
the
data
in
the
study
and
takes
responsibility
for
the
integrity
of
the
data
and
the
accuracy
of
the
data
analysis.
Study
concept
and
design:
J.
von
Büren,
Wülfing,
Gratzke.
Acquisition
of
data:
Schröder.
Analysis
and
interpretation
of
data:
M.
von
Büren,
Wiesenhütter.
Drafting
of
the
manuscript:
M.
von
Büren.
Critical
revision
of
the
manuscript
for
important
intellectual
content:
Gratzke,
Stief,
Rodler.
Statistical
analysis:
Buchner,
M.
von
Büren.
Obtaining
funding:
None.
Administrative,
technical,
or
material
support:
M.
von
Büren.
Supervision:
J.
von
Büren,
Wülfing.
Other:
None.
Financial
disclosures:
Moritz
von
Büren
certifies
that
all
conflicts
of
interest,
including
specific
financial
interests
and
relationships
and
affiliations
relevant
to
the
subject
matter
or
materials
discussed
in
the
manuscript
(eg,
employment/affiliation,
grants
or
funding,
consultan-
cies,
honoraria,
stock
ownership
or
options,
expert
testimony,
royalties,
or
patents
filed,
received,
or
pending),
are
the
following:
Severin
Rodler
and
Christian
Wülfing:
members
of
the
medical
advisory
board
of
Well-
ster
Healthtech
Group.
Florian
Schröder
and
Johannes
von
Büren:
employees
of
Wellster
Healthtech
Group.
Christian
Wülfing:
stock
own-
ership.
Christian
Wülfing
and
Johannes
von
Büren:
stock
options.
Funding/Support
and
role
of
the
sponsor:
None.
Appendix
A.
Supplementary
data
Supplementary
material
related
to
this
article
can
be
found,
in
the
online
version,
at
doi:https://doi.org/10.
1016/j.euf.2021.04.019.
References
[1]
Hatzimouratidis
K,
Amar
E,
Eardley
I,
et
al.
Guidelines
on
male
sexual
dysfunction:
erectile
dysfunction
and
premature
ejaculation.
Eur
Urol
2010;57:804–14.
[2]
Gratzke
C,
Angulo
J,
Chitaley
K,
et
al.
Anatomy,
physiology,
and
pathophysiology
of
erectile
dysfunction.
J
Sex
Med
2010;7(1
Pt
2):445–75,
[published
correction
appears
in
J
Sex
Med
2010;7:1316].
[3]
Sontag
A,
Ni
X,
Althof
SE,
Rosen
RC.
Relationship
between
erectile
function
and
sexual
self-confidence:
a
path
analytic
model
in
men
being
treated
with
tadalafil.
Int
J
Impot
Res
2014;26:7–12.
[4]
Zou
Z,
Lin
H,
Zhang
Y,
Wang
R.
The
role
of
nocturnal
penile
tumes-
cence
and
rigidity
(NPTR)
monitoring
in
the
diagnosis
of
psycho-
genic
erectile
dysfunction:
a
review.
Sex
Med
Rev
2019;7:442–54.
[5]
Rodler
S,
von
Büren
J,
Buchner
A,
et
al.
Epidemiology
and
treatment
barriers
of
patients
with
erectile
dysfunction
using
an
online
pre-
scription
platform:
a
cross-sectional
study.
Sex
Med
2020;8:370–7.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
8
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019

[6]
Goldstein
I,
Lue
TF,
Padma-Nathan
H,
Rosen
RC,
Steers
WD,
Wicker
PA.
Oral
sildenafil
in
the
treatment
of
erectile
dysfunction.
Sildenafil
Study
Group.
N
Engl
J
Med
1998;338:1397–404,
[published
correc-
tion
appears
in
N
Engl
J
Med
1998;339:59].
[7]
Brock
GB,
McMahon
CG,
Chen
KK,
et
al.
Efficacy
and
safety
of
tadalafil
for
the
treatment
of
erectile
dysfunction:
results
of
inte-
grated
analyses.
J
Urol
2002;168(4
Pt
1):1332–6,
[published
correc-
tion
appears
in
J
Urol
2005;173:664.
Dosage
error
in
published
abstract;
MEDLINE/PubMed
abstract
corrected].
[8]
Gong
B,
Ma
M,
Xie
W,
et
al.
Direct
comparison
of
tadalafil
with
sildenafil
for
the
treatment
of
erectile
dysfunction:
a
systematic
review
and
meta-analysis.
Int
Urol
Nephrol
2017;49:1731–40.
[9]
Walker
DK,
Ackland
MJ,
James
GC,
et
al.
Pharmacokinetics
and
metabolism
of
sildenafil
in
mouse,
rat,
rabbit,
dog
and
man.
Xeno-
biotica
1999;29:297–310.
[10]
Forgue
ST,
Patterson
BE,
Bedding
AW,
et
al.
Tadalafil
pharmacoki-
netics
in
healthy
subjects.
Br
J
Clin
Pharmacol
2006;61:280–8.
[11]
Tsertsvadze
A,
Fink
HA,
Yazdi
F,
et
al.
Oral
phosphodiesterase-5
inhibitors
and
hormonal
treatments
for
erectile
dysfunction:
a
systematic
review
and
meta-analysis.
Ann
Intern
Med
2009;151:650–61.
[12]
Chen
L,
Staubli
SE,
Schneider
MP,
et
al.
Phosphodiesterase
5
inhibi-
tors
for
the
treatment
of
erectile
dysfunction:
a
trade-off
network
meta-analysis.
Eur
Urol
2015;68:674–80.
[13]
Rubio-Aurioles
E,
Porst
H,
Kim
ED,
et
al.
A
randomized
open-label
trial
with
a
crossover
comparison
of
sexual
self-confidence
and
other
treatment
outcomes
following
tadalafil
once
a
day
vs.
tadalafil
or
sildenafil
on-demand
in
men
with
erectile
dysfunction.
J
Sex
Med
2012;9:1418–29.
[14]
Hatzimouratidis
K,
Buvat
J,
Büttner
H,
et
al.
Psychosocial
outcomes
after
initial
treatment
of
erectile
dysfunctionwith
tadalafil
once
daily,
tadalafil
on
demand
or
sildenafil
citrate
on
demand:
results
from
a
randomized,
open-label
study.
Int
J
Impot
Res
2014;26:223–9.
[15]
Rosen
R,
Broderick
G,
Shabsigh
R,
Swindle
R,
Lockhart
D,
Cameron
A.
Sensitivity
of
the
psychological
and
interpersonal
relationship
scales
to
oral
therapies
for
erectile
dysfunction.
J
Sex
Med
2005;2:461–8.
[16]
Dean
J,
Hackett
GI,
Gentile
V,
et
al.
Psychosocial
outcomes
and
drug
attributes
affecting
treatment
choice
in
men
receiving
sildenafil
citrate
and
tadalafil
for
the
treatment
of
erectile
dysfunction:
results
of
a
multicenter,
randomized,
open-label,
crossover
study.
J
Sex
Med
2006;3:650–61.
[17]
Bai
WJ,
Li
HJ,
Jin
JJ,
Xu
WP,
Sebastian
S,
Wang
XF.
A
randomized
clinical
trial
investigating
treatment
choice
in
Chinese
men
receiv-
ing
sildenafil
citrate
and
tadalafil
for
treating
erectile
dysfunction.
Asian
J
Androl
2017;19:500–4.
[18]
Nicholls
SG,
Quach
P,
von
Elm
E,
et
al.
The
REporting
of
Studies
Conducted
Using
Observational
Routinely-Collected
Health
Data
(RECORD)
statement:
methods
for
arriving
at
consensus
and
devel-
oping
reporting
guidelines.
PLoS
One
2015;10:e0125620.
[19]
O’Donnell
AB,
Araujo
AB,
Goldstein
I,
McKinlay
JB.
The
validity
of
a
single-question
self-report
of
erectile
dysfunction.
Results
from
the
Massachusetts
Male
Aging
Study.
J
Gen
Intern
Med
2005;20:515–9.
[20]
Capogrosso
P,
Colicchia
M,
Ventimiglia
E,
et
al.
One
patient
out
of
four
with
newly
diagnosed
erectile
dysfunction
is
a
young
man—
worrisome
picture
from
everyday
clinical
practice.
J
Sex
Med
2013;10:1833–41.
[21]
Ahn
TY,
Lee
SW,
Kim
SW,
et
al.
Treatment
preferences
in
men
with
erectile
dysfunction:
an
open
label
study
in
Korean
men
switching
from
sildenafil
citrate
to
tadalafil.
Asian
J
Androl
2007;9:760–70.
[22]
Ströberg
P,
Murphy
A,
Costigan
T.
Switching
patients
with
erectile
dysfunction
from
sildenafil
citrate
to
tadalafil:
results
of
a
European
multicenter,
open-label
study
of
patient
preference.
Clin
Ther
2003;25:2724–37.
[23]
Althof
SE,
Berner
MM,
Goldstein
I,
et
al.
Interrelationship
of
silden-
afil
treatment
effects
on
the
physiological
and
psychosocial
aspects
of
erectile
dysfunction
of
mixed
or
organic
etiology.
J
Sex
Med
2010;7:3170–8.
[24]
Tsujimura
A,
Kiuchi
H,
Soda
T,
et
al.
Sexual
life
of
Japanese
patients
with
erectile
dysfunction
taking
phosphodiesterase
type
5
inhibi-
tors:
an
Internet
survey
using
the
Psychological
and
Interpersonal
Relationship
Scales-Short
Form
questionnaire.
Int
J
Urol
2014;21:821–5.
[25]
Jain
T,
Schwarz
EB,
Mehrotra
A.
A
study
of
telecontraception.
N
Engl
J
Med
2019;381:1287–8.
[26]
Orizio
G,
Merla
A,
Schulz
PJ,
Gelatti
U.
Quality
of
online
pharmacies
and
websites
selling
prescription
drugs:
a
systematic
review.
J
Med
Internet
Res
2011;13:e74.
E
U
R
O
P
E
A
N
U
R
O
L
O
G
Y
F
O
C
U
S
X
X
X
(
2
0
2
1
)
X
X
X
–
X
X
X
9
EUF-1122;
No.
of
Pages
9
Please
cite
this
article
in
press
as:
von
Büren
M,
et
al.
Digital
Real-world
Data
Suggest
Patient
Preference
for
Tadalafil
over
Sildenafil
in
Patients
with
Erectile
Dysfunction.
Eur
Urol
Focus
(2021),
https://doi.org/10.1016/j.euf.2021.04.019