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european urology 52 (2007) 321–323
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Editorial –
referring to the article published on pp. 565–573 of this issue
Ejaculatory Latency vs. Patient-Reported Outcomes (PROs) as
Study End Points in Premature Ejaculation Clinical Trials
Chris G. McMahon *
Australian Centre for Sexual Health, Suite 2-4, Berry Road Medical Centre, 1a Berry Road, St Leonards, NSW, Australia 2071
Premature ejaculation (PE) is often reported, perhaps erroneously, as one of the most common male
sexual disorders but remains poorly defined and
inadequately characterised. As a result, a substantial disparity exists between the reported incidence
of PE in many epidemiologic studies [1], which rely
heavily on self-reported PE, and that suggested by
community-based normative stopwatch intravaginal ejaculation latency time (IELT) studies [2].
Quantitative measures of intercourse, such as the
IELT, and subjective patient-reported outcome (PRO)
measures of voluntary control over ejaculation or
self-efficacy, the extent of patient sexual satisfaction, and the level of bother or distress have been
described and used as patient-related outcomes in
clinical trials of PE. Each of the three criteria above
has been operationalised, although not always with
consistency. However, these dimensions may not be
equally weighted, may vary in importance among
patients, and may have differing meanings in
different cultures where the attitude of the partner
and culturally determined extent of emancipation
may have an impact on the patient’s subjective
diagnosis of PE.
The medical literature contains several univariate
and multivariate operational definitions of PE. The
multivariate DSM-IV-TR definition of PE encompasses the main dimensions of PE, ejaculatory
latency, control, and sexual satisfaction; however,
it is vague, imprecise, subject to multiple interpretations, and a construct of authority-based
opinions and not well-controlled clinical and epidemiologic studies [3]. Because the DSM-IV-TR
definition of PE fails to nominate a quantified
diagnostic IELT cut-off point, strict adherence may
result in men with long IELT values of, for example,
10–20 min, being diagnosed with PE if they perceive
themselves as suffering from PE [4].
The lack of consensus as to what constitutes PE
continues to hamper clinical practice and basic and
clinical research into the aetiology and management
of this condition. The results of PE epidemiologic
and drug treatment clinical trials are only reliable,
interpretable, and capable of being generalised to
patients with the disorder studied when consistent
objective physiologic measures or sensitive, validated outcome assessment instruments are used as
study end points [5] in well-defined and consistent
populations where lifelong, acquired PE or PE with
comorbid erectile dysfunction (ED) are treated as
separate PE subgroups. Several validated PRO
instruments using PROs of ejaculatory control,
sexual satisfaction, and bother/distress have been
reported and suggested as diagnostic tools and
investigational end points in both epidemiologic and
drug treatment clinical trials [6,7].
Treating physicians must interpret patient selfreports of PE and self-estimations of IELT with some
caution because the estimation of ejaculatory
latency by men and women may correlate poorly
with stopwatch-recorded IELT. However, several
authors have reported that patient self-estimation
DOI of original article: 10.1016/j.eururo.2007.01.028
* Tel. + 61 2 94373906; Fax: + 61 2 99065900.
E-mail address: [email protected].
0302-2838/$ – see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eururo.2007.03.081
322
european urology 52 (2007) 321–323
of IELT correlates reasonably well with subsequent
stopwatch IELT [8].
In the physician’s office, the diagnosis of PE is
simple and can be achieved with a detailed medical
and sexual history and a targeted physical examination. Stopwatch measurement of IELT and PRO
inventories are not required. Investigations to
determine the aetiology of PE are not indicated
except in patients with ED, lower urinary tract
symptoms (LUTS), or signs/symptoms of hyperthyroidism. However, patient self-estimation of IELT
may be useful, especially when combined with a
patient’s impression of change, in the assessment of
response to treatment.
Ejaculatory control is a subjective measure that
is difficult to translate into quantifiable terms and
is the most inconsistent dimension of PE. It has not
been adequately operationalised to allow comparison across studies. Patrick et al reported that
voluntary control differentiated men with PE from
men without PE with 72% of men with PE describing ‘‘very poor’’ to ‘‘poor’’ compared to 5% in a
group of normal controls [4]. However, diminished
control is not exclusive to men with PE and some
men with a brief IELT report adequate ejaculatory
control [4]. Furthermore, there is a higher variability in changes in control compared to IELT in
men treated with selective serotonin reuptake
inhibitors (SSRIs) [9].
Men with PE report lower levels of sexual
satisfaction than do men with normal ejaculatory
latency. Patrick et al reported sexual satisfaction
ratings of ‘‘very poor’’ or ‘‘poor’’ in 31% of men with
PE, compared with 1% in a group of normal controls
[4]. However, caution should be exercised in attributing improved satisfaction solely to the effect of
drug treatment and contributions from other difficult-to-quantify issues such intimacy, friendship,
sexual attraction, and communication should not be
ignored.
PE usually causes considerable distress among
those men who seek treatment. Patrick et al
reported that 64% of men with PE rated their extent
of personal distress as ‘‘quite a bit’’ or ‘‘extremely’’
compared to 4% of the normal controls [4]. Men with
PE may develop a pattern of sexual or relationship
avoidance due to their fear, either assumed or
actually based on previous criticism or actual
ridicule from previous partners, that they will be
unable to satisfy their partner. However, the word
‘‘distress’’ has negative social implications and its
existence is denied by many men with PE. This
dimension of PE is better captured by the word
‘‘bother.’’ The extent of psychological impact on
patients, partners, and the overall relationship are
perhaps the most important aspect of treatmentseeking behaviour and best define the severity of PE.
Symonds et al [10] report the development and
validation of brief self-administered five-item questionnaire to diagnose PE in clinical trials. A pilot
development tool of nine questions was derived from
qualitative research involving focus group and
individual interviews of men with either physiciandiagnosed or self-reported PE and consultation with a
panel of experts. Psychometric validation of this pilot
development tool and development of a scoring
system was achieved using men with either a
stopwatch IELT < 2 min or a self-reported population
of men with and without PE, and distilled this tool
into a five-item, 0–25 score, one-dimensional measure that captures the essence of DSM-IV-TR and the
dimensions of control, satisfaction, personal distress,
and interpersonal distress. Sensitivity/specificity
analysis suggests that a score 11 indicates PE.
Although the methodology of the study is sound, it
is complex and limited in several respects. The study
population for the focus groups is relatively small
(n = 40), has a higher mean age that that of a typical
PE patient, and is derived from only the United
States, Germany, and Spain. The self-reported
population of men with and without PE was recruited
from participants in a US Web-based survey system
and, as such, represents a highly selected population
of Internet users with an educational and socioeconomic profile that may substantially differ from
the general population. Of particular interest is the
report that the study group tended to complain more
of lack of control and an inability to defer ejaculation
as opposed to the typical PE patient’s primary
complaint of brief latency. The authors fail to report
whether younger men shared the same focus on
control as the overall study group. These study
design limitations suggest that the study population
may not be truly representative of an international
and multicultural population of men. The authors, in
part, acknowledge these limitations and state that
cross-cultural validity of this measure is required.
Notwithstanding these comments, the tool represents a significant development towards simplifying
the methodology of PE drug studies. Future development of this diagnostic tool would be incomplete
without further validation to determine the potential relationships among scores, severity of PE, and
response to treatment. Regulatory approval of new
drug treatments for PE demands evaluation in large
efficacy and safety trials, where clinical trial design
and, in particular, the use of reliable, reproducible,
and cost-effective study end points is paramount.
The reliability of stopwatch IELT alone in assigning
PE status, the use of PROs to replace stopwatch IELT,
european urology 52 (2007) 321–323
or the predictive value of single-item PRO measures
compared to multiple-item measures are incompletely understood issues. PRO measures, though
providing important information, are at best subjective and relate to highly interpretable and
imprecise dimensions of ejaculation, and their
significance is weighted differently for different
patients. On the other hand, IELT may not adequately categorise patients because some patients
with a brief IELT report little or no bother and are
therefore asymptomatic and not ‘‘suffering’’ from
PE. Clearly, none of the dimensions of PE can
universally distinguish men with PE from men
without PE. The current consensus is that a
combination of stopwatch IELT and a validated,
patient-administered tool of PROs of control, satisfaction, personal distress, and interpersonal distress
can adequately identify PE status in prevalence
studies, in the screening phase of drug trials, and in
measuring response to treatment.
Conflicts of interest
Associate Professor Chris G. McMahon is a paid
consultant, member of a speaker’s panel and
investigator for Pfizer, Bayer, Johnson & Johnson,
and Solvay.
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