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- Original Article -
Treatment preferences in men with erectile dysfunction: an
open label study in Korean men switching from sildenafil
citrate to tadalafil
Tai Young Ahn1, Sung Won
Lee2, Sae-Woong Kim3, Dae Yul
Yang4, Nam Cheol Park5, Kweon-Sik
Min6,
Kwangsung Park7, Jae-Seung
Paick8, Yulia Dyachkova9, Trisha
Dwight10, Myung-Sea Luke Lee11
1Asan Medical Centre, Seoul 138-736, Korea;
2Samsung Medical Centre, Seoul 135-710, Korea;
3Youido St Marys Hospital, Seoul 150-713, Korea;
4Kang Dong Sacred Heart Hospital, Seoul 134-701, Korea;
5Pusan National University Hospital, Pusan 602-739, Korea;
6Pusan Inje University Paik Hospital, Pusan 614-735 , Korea;
7Chonnam National University Hospital, Gwangju 501-757, Korea;
8Seoul National University Hospital, Seoul 110-744, Korea;
9Area Medical Centre Vienna, Eli Lilly Austria, Sydney A-1030, Australia;
10Intercontinental Information Sciences, Eli Lilly Australia, Sydney
2113, Australia; 11Eli Lilly Korea, Seoul 135-280, Korea.
Abstract
Aim: To evaluate patient preferences for sildenafil citrate or tadalafil (PDE-5 inhibitors available for the treatment of
erectile dysfunction [ED]) and assess potential reasons for these
preferences. Methods: This open-label study was
conducted on Korean men taking sildenafil, at least 6 weeks prior to study entry, for ED. Following screening,
patients continued sildenafil treatment for 4 weeks, then after a 1-week washout period, switched to tadalafil for
8 weeks. Patients then continued with their treatment of choice during an extension phase. Psychosocial factors
(time concern, spontaneity, sexual self-confidence) were evaluated using Psychological and Interpersonal
Relationship Scales (PAIRS), while timing of dose to sexual attempt patterns were assessed from patient diaries.
Results: The present study enrolled 160 Korean men (mean age 55 years) with prior median sildenafil use of 585 days. During
the extension phase, 73.7% of patients elected to take tadalafil, whereas 26.3% chose sildenafil
(P < 0.001). After switching from sildenafil to tadalafil, mean PAIRS time concern scores decreased from 2.54 to 2.42
(P = 0.002), with no statistically significant differences observed between the sildenafil and tadalafil assessment phases in sexual
spontaneity and self-confidence scores. Sexual attempts made > 4 h to
¡Ü 36 h post-dose occurred in 4.5% of patients
during the sildenafil assessment phase compared with 17.5% during the tadalafil assessment
phase. Conclusion: After experiencing both sildenafil and tadalafil, the majority of patients exhibited a preference for tadalafil. This
preference might be influenced by psychosocial factors, such as decreased time concerns, and a broader window of
opportunity available for sexual activity. (Asian J Androl 2007 Nov; 9: 760_770)
Keywords: erectile dysfunction; tadalafil; sildenafil citrate; Psychological and Interpersonal Relationship Scales; preference
Correspondence to: Dr Trish Dwight, Intercontinental Information Sciences (ICIS), Eli Lilly Australia Pty Limited, Level 1, 16 Giffnock
Avenue, Macquarie Park NSW 2113, Australia.
Tel: +61-2-8874-5832 Fax: +61-2-8874-5733 E-mail: tdwight@lilly.com
Received 2006-06-22 Accepted 2007-06-11
DOI: 10.1111/j.1745-7262.2007.00319.x
1 Introduction
Over 150 million men worldwide were estimated to
have been affected by erectile dysfunction (ED) in 1995,
with projected estimates of over 320 million by 2025
[1]. E
D has been shown to have a negative impact on a
patients' self-esteem, quality of life and interpersonal
relationships, and has also been associated with increased
age, diabetes, kidney disease, atherosclerosis, vascular
disease and depression [2], although it is unclear as to
whether ED is the initiating disorder or whether it arises
as a result of these other underlying disorders.
Under normal conditions, cyclic guanosine monophosphate (cGMP) mediates relaxation of vascular
smooth muscle to achieve erectile rigidity.
Phosphodiesterase type 5 (PDE-5) is an enzyme that breaks down
cGMP and thereby assists in promoting penile flaccidity
[3]. Oral phosphodiesterase type 5 (PDE-5) inhibitors,
such as sildenafil citrate (sildenafil), tadalafil, and
vardenafil hydrochloride (vardenafil), prevent the
breakdown of cGMP and thereby promote erectile responses
to sexual stimulation. These oral pharmacotherapies are
easier to administer and less invasive than other ED
approaches, such as intracavernosal injections and
penile implants [4]. All three PDE-5 inhibitors, approved
for the treatment of ED, have been shown to be of similar efficacy and tolerability. However, compared
to others in its class, tadalafil has an extended half-life
(17.5 h compared with 4_5 h) [3], has been shown to
be effective for up to 36 h post-dose [5], and food
consumption does not affect its absorption [6].
The present study was conducted primarily to
evaluate patient preferences for sildenafil or tadalafil for the
treatment of ED in a cohort of current sildenafil users in
Korea. Additionally, psychological outcomes, such as
time concerns, spontaneity and sexual self-confidence,
were assessed to determine whether these factors play a
role in patient attitudes towards treatment types.
Furthermore, timing of dose to sexual attempt patterns
was assessed, in each treatment group, to determine
whether experienced sildenafil patients change their
behavior with new dosing instructions that suggest a broader
window of opportunity from dose to sexual intercourse
(while on tadalafil).
2 Materials and methods
2.1 Selection criteria
Men were eligible for the study if they were at least
18 years of age and had at least a 3-month history of
ED (defined as a consistent change in the quality of
erection that adversely affects the patient's satisfaction
with sexual intercourse). Patients presenting with ED
of any functional severity (mild, moderate or severe)
and of any etiological classification (psychogenic,
organic or mixed) were eligible for enrolment, with
disease etiology and severity being defined subjectively
according to each investigator's clinical opinion.
Patients anticipating to have the same female sexual
partner throughout the study and having had at least 6 weeks
prior use of sildenafil (Pfizer, New York, USA), at a
stable dose, were eligible for enrolment. The dose of
sildenafil was determined by the patient and treating
investigator. Patients were excluded from the study
for the following reasons: presentation of ED
associated with premature ejaculation or untreated endocrine
disease; failure to achieve erection after pelvic surgery,
including radical prostatectomy (except bilateral
nerve-sparing); significant penile deformity or penile implant;
clinically significant renal or hepatic insufficiency;
poorly controlled diabetes (hemoglobin
A1c > 13%); unstable cardiovascular diseases (such as unstable angina,
recent myocardial infarction, or coronary intervention,
evidence of congestive heart failure, new significant
conduction defect, or uncontrolled hypertension);
recent history of significant central nervous system
injuries; retinitis pigmentosa; a history of HIV infection;
or previous participation in a tadalafil study.
Concomitant use of other therapies for ED was not allowed.
2.2 Study design
This open-label, single arm study encompassed eight
study sites within Korea. The first patient visit occurred
in June 2004, with the last patient visit occurring in June
2005. The institutional or ethical review board of each
site approved the protocol and all patients provided
written consent prior to enrolment. The study included six
patient visits (Figure 1). At Visit 1, patients signed an
informed consent document, were evaluated for study
inclusion, medical history and demographics, and
subjected to physical examination and clinical laboratory
measurements. For a subsequent week of screening,
they continued taking their own supply of sildenafil at
their pre-study dose. This dose was fixed for all
subsequent exposures (including the extension phase). If it
was considered necessary to titrate the dose of study
medication after enrolment for any patient, they were
discontinued from the study. This ensured optimal
efficacy and tolerability of sildenafil was established prior
to the assessment phase. At Visit 2, patients were
provided with a supply of sildenafil for 4 weeks and a set
of dosing instructions (sildenafil assessment phase). At
Visit 3, patients were provided with a supply of 20 mg
tadalafil (Eli Lilly and Company, Indianapolis, USA) for
4 weeks and a set of dosing instructions; they were
told not to take any tablets for a 1-week period
(wash-out period) and then to commence taking tadalafil for
4 weeks (tadalafil initiation phase). At Visit 4, patients
were provided with another supply of 20 mg tadalafil
and a set of dosing instructions (tadalafil assessment
phase). At Visit 5, patients were given the opportunity
to choose either sildenafil or tadalafil for treatment
during an extension phase of 12 weeks; either treatment
was dispensed accordingly. The study was completed
at Visit 6.
2.2.1 Dosing instructions
For sildenafil, patients were given 12 doses in
commercially available packaging, including the package
insert (patient leaflet). In a set of additional dosing
instructions derived from the current sildenafil label, they
were instructed to take their pre-study dose of sildenafil
with water approximately 1 h before sexual activity, and
informed that the dose could be taken as early as 4 h
before sexual activity and as late as 30 min before sexual
activity. Patients were also instructed that a high fat
meal might delay its onset of action.
For tadalafil, patients were provided with 12 doses
(per treatment phase) of 20 mg tadalafil in a clinical
trial packaging and a set of dosing instructions.
Patients were instructed to take no more than one dose
per day with water before the potential for sexual
activity. They were told tadalafil was shown to be
effective up to 24 h after dosing and, in many patients, as
early as 30 min after dosing. Patients were advised to
initiate sexual activity at various times after dosing to
determine their own optimal window of responsiveness.
At the time of study initiation, a decision was taken to
instruct patients on a 24-h duration of action for tadalafil,
even though it has previously been shown to be
effective for up to 36 h. This was because, at that time,
some country-specific product labels were approved
for only 24-h duration.
For the extension phase, patients were dispensed 36
doses of their chosen treatment, either sildenafil in
commercially available packaging or bottles of tadalafil,
and a set of treatment specific dosing instructions.
Both medications were given as needed before sexual
activity.
2.2.2 Outcomes and measures
The primary outcome was patient preference for ED treatment, which was measured by the proportion
of patients electing (at Visit 5) to take sildenafil or
tadalafil during the extension phase. Secondary
outcomes included sexual encounter attributes (as
measured by the Psychological and Interpersonal
Relationship Scales [PAIRS]) and tolerability, and
post-hoc analyses were performed to assess the time between dosing
and sexual attempt.
PAIRS is a validated, self reported measure used to
assess three conceptual domains: time concern,
spontaneity and sexual self-confidence during sexual
encounters (Table 1) [7]. PAIRS was given to patients at Visit
2 (prior to the sildenafil assessment phase), Visit 3 (after
the sildenafil assessment phase), Visit 5 (after the tadalafil
assessment phase) and Visit 6 (on completion of the
study, after the extension phase) for the assessment of
patient sexual encounter attributes. Dosing diaries and
sexual attempt timing diaries were given to patients at
Visit 2 (prior to the sildenafil assessment phase), Visit 3
(after the sildenafil assessment phase) and Visit 4 (prior
to the tadalafil assessment phase). At Visit 5 (the
beginning of the extension phase), only dosing diaries
were dispensed. Diaries were collected and reviewed
at Visits 3, 4, 5 and 6. Adverse event data and vital
signs were assessed at all visits.
2.3 Statistical methods
2.3.1 General
All analyses included patients with baseline and at
least one postbaseline measure. Safety summaries
included all patients. All hypothesis testing was two-sided
using a 0.05 level of significance and 95% confidence
intervals. Analyses were conducted using the SAS
statistical package version 8.02 for Windows (SAS Institute,
Cary, NC, USA).
The proportion of patients electing to take sildenafil or
tadalafil during the extension phase was analyzed using a
binomial proportion test; an exact 95% confidence
interval for the percentage of patients selecting tadalafil was
calculated.
2.3.2 PAIRS
The following domains from PAIRS (Table 1) were
assessed prior to and during the extension phase: time
concerns, spontaneity and sexual self-confidence. The
mean of individual questions for a single patient was taken
as the domain score for that visit (range 1_4). Unless
stated otherwise, all scores are summarized by mean
± SD. Standard error of the mean is denoted as SEM.
For each PAIRS domain, the change from the sildenafil assessment phase (Visit 3) to the tadalafil
assessment phase (Visit 5) was analyzed using linear mixed
effects models adjusting for baseline score (Visit 2).
The null hypothesis for this analysis was that there was
no difference between PAIRS domain scores at Visit 3
compared to those at Visit 5. The change from the tadalafil
assessment phase to the extension phase in PAIRS
domain scores was analyzed using an analysis of
covariance model with terms for treatment choice and baseline
PAIRS score. The null hypothesis was that there was
no difference between changes in PAIRS domain scores
recorded by patients who preferred tadalafil compared
with those who preferred sildenafil.
Post-hoc analyses were also performed to investigate the null hypothesis
that there was no difference in domain scores between
preference groups at Visits 2 (baseline), 3 and 5.
2.3.3 Analyses of timing
Patients recorded the time of each dose taken and
each sexual intercourse attempt between all visits except
Visit 6. The duration of time between a dose and each
subsequent intercourse attempt (prior to the next dose)
was calculated in hours. As patients might have made
several attempts between each visit, for each patient, the
duration between dose and sexual intercourse attempt
was summarized by median at each visit. The median
was calculated because of the skewed distribution of data
as it provides a more robust estimate of the centre of the
measured values. Paired t-tests were used to compare
the median time from dose to intercourse attempt, as
well as the number of doses taken per week and the
number of sexual intercourse attempts between visits.
The proportion of sexual intercourse attempts occurring
¡Ü 4 h, > 4 h to < 8 h,
¡Ý 8 h to < 12 h, and
¡Ý 12 h post-dose were summarized for each study phase.
A cut-off point of 36 h was used for all summaries
and analyses in the study to eliminate the potential effect
of any outliers skewing the distribution for either study
drug. This cut-off point was chosen because 36 h is the
longest published duration of efficacy of a PDE-5
inhibitor for ED.
3 Results
3.1 Patient characteristics
Baseline clinical and demographic patient
characteristics are outlined in Table 2. A total of 160 patients
with ED from Korea were enrolled. All enrolled patients were of East/Southeast Asian origin, with the
majority having a moderate severity of ED (68.8%), as
assessed by the investigator. Patient age ranged from
32 to 75 years, with a mean of 55 years. The median
duration of sildenafil use prior to enrolment was 585 days
(range: 43_2 016 days), with the only doses of sildenafil
used being 50 mg (45.6%) and 100 mg (54.4%).
Of the 160 patients enrolled, four (2.5%) did not
complete the study. Of these, two patients made the
decision to discontinue the study (one after the sildenafil
assessment phase, the other after the tadalafil initiation
phase), one patient discontinued because of a lack of
efficacy, as perceived by the patient (after the tadalafil
initiation phase), and another patient discontinued as a
result of adverse events (headache, facial flushing and
gastric discomfort; after the tadalafil initiation phase).
3.2 Patient treatment preference
Of the 156 patients expressing a treatment
preference (as noted at Visit 5), 115 (73.7%) elected to take
tadalafil during the 12-week extension phase, compared
to 41 (26.3%) patients who elected to take sildenafil
(P < 0.001). Baseline clinical and demographic patient
characteristics by treatment preference group are
outlined in Table 2.
3.3 PAIRS domain scores
PAIRS domain scores, analyzed using linear mixed
effects models adjusting for baseline score (Visit 2),
are summarized in Figure 2 (time concern), Figure 3
(sexual spontaneity) and Figure 4 (sexual
self-confidence). After switching from sildenafil to tadalafil,
a statistically significant (P = 0.002) decrease in the
mean PAIRS time concern domain scores was observed,
with a mean (± SD) PAIRS time concern domain score
of 2.54 (± 0.34) at Visit 3 (after the sildenafil
assessment phase) and 2.42 (± 0.38) at Visit 5 (after the
tadalafil assessment phase; Figure 2). No statistically
significant differences were observed, after
switching from sildenafil to tadalafil, in the mean PAIRS
spontaneity and self-confidence domain scores (Figures 3
and 4).
3.4 Change in PAIRS domain scores based on preference
The change in PAIRS domain scores, based on patient treatment preference groups, between the sildenafil
(Visit 3) and tadalafil (Visit 5) assessment phases, was
determined using an analysis of covariance model with
terms for patient's treatment preference and baseline
PAIRS score. A reduction in time concerns was observed regardless of the patient's treatment preference;
however, these reductions were not significantly
different between preference groups (P = 0.70; mean
change [± SD]: _0.12 [± 0.37] in patients preferring
sildenafil, _0.11 [± 0.39] in patients preferring tadalafil).
Likewise, no statistically significant changes in
spontaneity were observed, in either preference group, between
the sildenafil and tadalafil assessment phases
(P = 0.33; mean change [± SD]:
_0.02 [± 0.48] in patients preferring sildenafil, 0.03 [± 0.30] in patients preferring
tadalafil). Significantly different changes in sexual
self-confidence were, however, observed between
preference groups (P = 0.011), with improvements in sexual
self-confidence observed in patients preferring tadalafil
(mean change [± SD]: 0.12 [± 0.42]), while a decrease
in sexual self-confidence was observed in patients
preferring sildenafil (mean change [± SD]:
_0.08 [± 0.49]).
3.5 Dosing and sexual attempt timing
A statistically significant (P < 0.001) difference in
median time from dose to sexual attempt was observed
between the sildenafil and tadalafil assessment phases,
with a median time between dosing and sexual attempt
of 1 h (ranging from 0 h to 6 h) during the sildenafil
assessment phase and 1.5 h (ranging from 0 h to 15 h)
during the tadalafil assessment phase.
Differences in the proportion of sexual attempts,
occurring over a 36-h timeframe, were observed between
the sildenafil and tadalafil assessment phases. During
the sildenafil assessment phase patients reported 4.5%
of sexual attempts occurred > 4 to ¡Ü 36 h post-dose,
whereas this proportion increased to 17.5% during the
tadalafil assessment phase.
3.6 Tolerability
There were no deaths or serious adverse events
reported during the present study; however, one patient
discontinued, after the tadalafil initiation phase, because
of several adverse events (headache, facial flushing and
gastric discomfort). Treatment-emergent adverse events
were reported in 13.1% (sildenafil assessment phase),
13.8% (tadalafil initiation phase), and 12.2% (tadalafil
assessment phase) of patients. The most frequently
occurring (¡Ý 1%) treatment-emergent adverse events
reported during the sildenafil assessment phase were
flushing (n = 10, 6.3%), nasal congestion
(n = 3, 1.9%) and headache
(n = 2, 1.3%); during the tadalafil initiation phase
were flushing (n = 3, 1.9%), epigastric discomfort
(n = 3, 1.9%), headache
(n = 3, 1.9%), hypertension
(n = 3, 1.9%) and nasopharyngitis
(n = 2, 1.3%); and during the tadalafil assessment phase were headache
(n = 2, 1.3%) and hypertension
(n = 2, 1.3%).
4 Discussion
Because there are several effective and safe oral
PDE-5 inhibitors (sildenafil citrate, vardenafil hydrochloride and
tadalafil) for the treatment of ED, various factors (such
as biological, social, psychological and/or cultural)
important to both the patient and their partner will influence
the treatment choices made. Although several previous
studies have focused on determining patient treatment
choices [8_10], the reasons surrounding these treatment
choices have not been fully explored. The present study
was conducted primarily to evaluate patient preferences
for sildenafil or tadalafil in the treatment of ED, and the
potential reasons for these preferences, within a cohort
of current sildenafil users in Korea. The majority of
patients expressing a treatment preference elected to
take tadalafil (73.7%) during the 12-week extension
phase, whereas the remainder (26.3%) chose to take
sildenafil. This finding is in alignment with several
previous studies, where the majority of patients expressed
a treatment preference for tadalafil, as opposed to
sildenafil [8_10].
PAIRS were developed to incorporate outcomes, such
as time concerns, spontaneity and sexual self-confidence,
which are not assessed in existing measures of sexual
function. This is another approach that can be used to
identify some of the possible reasons as to why patients
have preferences for one form of treatment over another.
A statistically significant decrease in the mean PAIRS
time concern domain scores was observed when patients
switched from sildenafil (Visit 3) to tadalafil (Visit 5),
indicating that patients were less concerned about time
in relation to sexual activity whilst taking tadalafil, as
compared with when they were taking sildenafil. A study
by Rosen et al. [11] showed similar results to those in
the present study, whereby mean PAIRS time concern
domain scores were statistically significantly lower after
treatment with tadalafil when compared to post sildenafil
treatment. In the present study, mean PAIRS time
concern domain scores in those choosing sildenafil in the
extension phase were also numerically higher (i.e. worse)
than those who chose tadalafil. Furthermore, regardless
of treatment preference, similar reductions in time
concern domain scores, from the sildenafil to tadalafil
assessment phase, were observed. Together, these results
suggest that time concerns appear to play a role in
patient decisions regarding ED treatment type.
No statistically significant difference in the mean
PAIRS spontaneity domain scores was observed in the
present study when patients switched from sildenafil (Visit
3) to tadalafil (Visit 5). Furthermore, there was no
difference in mean PAIRS spontaneity domain scores in
patients choosing to take sildenafil or tadalafil in the
extension phase. It is of interest to note that previous studies,
encompassing patients in Australia, Canada, Italy,
Sweden, the UK and the USA, report statistically
significantly higher sexual spontaneity in patients on tadalafil
treatment when compared with sildenafil treatment [11,
12]. Also, studies in Asian populations, such as Hong
Kong (China), Malaysia, Singapore, Taiwan (China) and the Philippines, have shown statistically
significant differences between the two treatment groups in
all three PAIRS domains [13, 14]. We are not sure
why we did not observe this finding in the current study,
but it is possible that this Korean population or the
Korean culture does not place great importance on sexual
spontaneity.
Although Rosen et al. [11] observed higher sexual
self-confidence in patients taking tadalafil than that in
patients taking sildenafil, in the present study no
statistically significant difference in the mean PAIRS
self-confidence domain scores was observed when patients
switched from sildenafil (Visit 3) to tadalafil (Visit 5).
Again, our finding could be attributed to cultural
differences. However, statistically significant
differences between the two treatment groups in PAIRS
self-confidence domain scores have been observed in
similar geographical locations (Hong Kong [China],
Malaysia, Singapore, Taiwan [China] and the Philippines)
[13, 14]. Additionally, there was no difference in mean
PAIRS self-confidence domain scores in patients
choosing to take sildenafil or tadalafil in the extension phase.
However, statistically significant differences between
the two preference groups were observed in terms of
change in sexual self-confidence (from Visit 3 to Visit
5), with improvements in self-confidence observed in
patients preferring tadalafil, wheras those preferring
sildenafil showed decreased sexual self-confidence.
These findings suggest that sexual self-confidence might
be a consideration when patients make a choice
regarding treatment for ED.
Another factor that might play a role in the decision a
patient makes regarding the choice of PDE-5 inhibitor is
the window of opportunity available to them for sexual
activity post-dose. Timing of dose to sexual attempt
patterns were assessed in each treatment group to
determine whether experienced sildenafil patients changed their
behavior with new dosing instructions, for tadalafil, to
suggest a broader window of opportunity from dose to
sexual intercourse. Although a statistically significant
increase in median time from dose to sexual attempt was
observed during the tadalafil assessment phase, when
compared with the sildenafil assessment phase, this
increase was not of clinical relevance and could be a result
of the treatment specific dosing instructions. This
indicates that, on average, previous sildenafil users in the
present study did not modify their sexual attempt timing
greatly even when provided with a treatment option that
allowed for increased time from dose to sexual attempt.
Interestingly, in previous studies, a statistically and
clinically significant difference has been observed between
the two treatment groups in terms of time from dose to
sexual attempt, with greater time from dose to sexual
attempt being observed in tadalafil treated patients [9,
10, 15]. It is possible that cultural differences play a role
in the extent to which patients experiment beyond their
normal dose-timing patterns. Previous studies have shown
that the magnitude of change observed in dose-timing
patterns, when patients change from sildenafil to tadalafil,
varies between different geographical locations, with
smaller changes in dose-timing patterns observed in Asian
countries [13, 16] when compared to central/eastern
Europe and eastern Mediterranean regions [17], and
Australia and New Zealand [18]. Although the median time
from dose to sexual attempt did not differ clinically
between the two treatment groups, the window of time in
which sexual attempts were being made was broader during the tadalafil assessment phase when compared to
the sildenafil assessment phase. Previous studies [10,
15] also show that sexual attempts are made over a broader
time period when patients are taking tadalafil, when
compared to sildenafil. It is possible that the larger window
of opportunity observed in the present study during the
tadalafil assessment phase might be a result of the
different dosing instructions, as for the two treatment
types, as patients were informed that tadalafil had been
shown to be effective up to 24 h post-dose, whereas
sildenafil could be taken up to 4 h before sexual activity.
Additionally, with tadalafil, patients were advised to
initiate sexual activity at various times after dosing to
determine their own optimal window of responsiveness.
Although over 70% of patients in the present study
expressed a preference for tadalafil during the
extension phase, it is somewhat surprising that PAIRS time
concern domain scores were the only measure in which
statistically significant differences between the two
groups support this preference pattern. One possible
explanation for this disparity might be that there are
other factors, not analyzed in the current study, that
might be responsible for the patient preference patterns
observed [19]. Furthermore, although the present study
measured the number of sexual attempts made by patients during each treatment phase, the number of
successful sexual attempts was not measured and it is
possible that the incorporation of other measures, such as
efficacy measures (International Index of Erectile
Function [IIEF] or Sexual Encounter Profile [SEP]), or a
drug attribute questionnaire, might have furthered our
understanding of why patients exhibit particular
preferences for treatments. Additionally, it is possible that
differences in spontaneity and sexual self-confidence
might not have been experienced by the patients as they
did not appear to utilize the extended period of efficacy
offered by tadalafil.
The present study indicates that both sildenafil and
tadalafil are well-tolerated, as reflected by other studies
[9, 10, 15]. The frequency and type of
treatment-emergent adverse events (TEAE) reported in the present study
were similar between the two treatment groups, and it
therefore seems unlikely that TEAE were a factor in
patient preference choices.
There are several limitations of the present study
that should be taken into account when interpreting its
results. First, sildenafil-specific and tadalafil-specific
dosing instructions were given consistent with product
labeling. Although bias is incurred as a result, the
open-label nature of the design was chosen to ensure that
instructions would be therapy-specific. Additionally,
as patients had previous experience with sildenafil it
would be likely, even if blinding occurred, that patients
would be able to determine the treatments due to the
differences in dosing instructions. Second, patients
received treatment in a fixed order (sildenafil followed
by tadalafil) and it is possible that patients might have
preferred whichever treatment they received last. As
patients had been previous long-term sildenafil users,
we believe that because of the short amount of time in
which patients were taking tadalafil during the
assessment phase, the likelihood of patients continuing with
tadalafil if they did not actually prefer the new
treatment would have been relatively low. Further to this,
other studies have shown that the sequence in which
treatments are given (i.e. sildenafil followed by tadalafil
or vice versa) does not appear to affect patient
treatment preference [10, 20]. Third, although the issue of
imbalance between groups was attempted to be addressed by adjusting for baseline confounders, it is
possible that these baseline corrections might not fully
address the potential biases of this open-label study.
Finally, interest in a novel therapy might have increased
the proportion of patients electing to take tadalafil
during the extension phase, when compared with sildenafil.
Although the current study focuses purely on patients within Korea, this may be viewed as a strength as
it provides ED information on a distinct cultural group,
especially in light of the fact that the PAIRS findings for
this study seem to be contradictory to what has been
observed for other populations. The median duration of
previous sildenafil use might be considered a strength of
the present study, as optimal efficacy and tolerability of
sildenafil should have been established prior to the
assessment phase.
This study not only focuses on patient treatment
preferences, but also attempts to identify the reasons
surrounding a patients' choice of treatment for ED, as
increased knowledge of the factors contributing to
patient treatment choices will enable physicians to
determine the most appropriate treatment for their patients.
The present study shows that after patients had
experienced both sildenafil and tadalafil, the majority of
patients exhibited a preference for tadalafil. The results
also suggest that this preference for tadalafil might be
influenced in part by psychosocial factors and the
window of opportunity available for sexual activity, as a
decrease in time concerns was observed during the tadalafil
assessment phase and the window of time in which sexual
attempts were being made was broader during the tadalafil
assessment phase. Furthermore, the results also
suggest that the importance of different factors might vary
as a result of different cultural groups.
Acknowledgment
The authors would like to thank the H6D-KL-S002
study group for their participation and contribution to
the study.
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