Strengths
Methodological considerations
This report has systematically reviewed the evidence for a range of treatments for PE. RCT evidence reported in existing reviews along with further identified RCTs was included. Our literature search covered all dates (from database inception to August 2013) in order to capture any studies missed by existing reviews in addition to those published more recently. The current evidence base includes several systematic reviews of PE treatments, many of which do not report a meta-analysis. Where meta-analyses are undertaken, methodological errors are evident. These include combining RCTs with observational studies (and not reporting which are which), double-counting participants within the meta-analyses (including the control
group from a RCT twice when different treatments are assessed), pooling data from crossover and pairwise RCTs (double counting for crossover trials), pooling between-group comparisons on questionnaire domains (subgroups) as an overall effect for the same trial (double counting), and applying a standardised MD to pool IELT effects where a MD is statistically more appropriate. This assessment report has pooled data across RCTs, when appropriate, in a meta-analysis using a MD to summarise IELT outcomes, has avoided double-counting of participants in the analysis and has considered pairwise and crossover RCT data separately. Furthermore, a formal assessment of methodological quality was undertaken. This was undertaken for both reviews from which RCT data were extrapolated and for any further RCTs identified by the searches not included in reviews.
Range of interventions assessed
The treatments evaluated in this assessment report were those relevant to the UK setting. In addition to treatments currently recommended in clinical practice, other treatments, including Chinese medicine, acupuncture, yoga and delay devices, were also evaluated, as patients might access these outside clinical practice. These treatments have not previously been reviewed in the management of PE.
Limitations
Methodological considerations
This assessment report summarises a wide range of interventions from a large volume of trial evidence and was undertaken within a limited timeframe. While RCT publications not already included in a review were obtained in full and data extracted (and checked by a second reviewer), data for RCTs reported in reviews were extracted (and checked) from the review article and not the original RCT publication. While data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within the reviews cannot be guaranteed by this assessment report. The methodological quality of the majority of existing reviews was low. Only four reviews reported independent double data extraction36,53,135,149(seeAppendix 4). Reported search strategies varied in terms of the search dates and resources searched. The search strategy for this assessment report covered all dates (from database inception to August 2013) in order to capture any studies missed by existing reviews. Within this assessment report, although quality assessment was undertaken for RCTs not included in reviews, the methodological quality of individual RCTs reported in existing reviews was not assessed. Of the nine existing reviews that reported undertaking quality assessment,35,36,38,51,53,64,65,108,110quality scores were reported by only four,35,51,53,64across which the assessment method was diverse, including use of an assessment instrument not appropriate for RCTs53(the Newcastle–Ottawa Scale for assessing the quality of non-randomised studies in meta-analyses).
Although the search strategy for this assessment report was comprehensive, the possibility of a publication bias cannot be discounted. Nonetheless, given the unclear methodological quality of the majority of included RCTs, coupled with the variability of treatment effects on IELT, it could be considered unlikely that any additional unpublished data would contribute significantly to the overall findings.
Nature of the available evidence
Most trials comprised men with primary PE without a concomitant condition and excluded those with erectile dysfunction. When reported, men were mainly recruited from specialist sexual health settings. For this reason, effectiveness of in men with secondary PE, PE concomitant to another condition, or not attending specialised clinics, is less certain. Trials were undertaken in a variety of European Union (EU) and non-EU countries. Variability in cultural attitudes towards PE and acceptability of the various treatments in trial populations, coupled with variability in PE definitions and IELT entry criteria, also limits the generalisability of the findings.
Within the current evidence base, there are very few RCTs of robust methodological quality that compare one treatment with another in pairwise comparisons. A network meta-analysis has not been undertaken to date. It is therefore difficult to make comparisons of efficacy between treatments. The only treatment licensed for PE in the UK is dapoxetine, which has demonstrated modest but statistically significant improvements in IELT and other outcomes, but is associated with AEs similar to those of other SSRIs. Although some other treatments (e.g. topical) have shown greater IELT improvements than dapoxetine, other treatments have not been so extensively investigated.
Treatment duration within RCTs ranged from 2 to 24 weeks. No studies reported long-term follow-up (>6 months) of patients either continuing on or withdrawing from treatment; thus, there was no assessment of long-term safety and efficacy, or effects of treatment withdrawal.
The majority of RCTs assessed IELT and, when reported, the assessment method was mainly by stopwatch. The duration of treatment effects on IELT ranged from<0.50 minutes to>6.00 minutes. Many
interventions also demonstrated improvements in ejaculation control, sexual satisfaction and other outcomes. However, these outcomes were often measured using different assessment scales and the reporting of outcome data was often limited. IELT is reported to have a significant direct effect on
perceived control over ejaculation, but not a significant direct effect on ejaculation-related personal distress or satisfaction with sexual intercourse.172There is currently no published literature which identifies a clinically significant threshold response to intervention.23Although the observed increases in IELT were statistically significant in favour of active treatments, it is difficult to quantify how acceptable and meaningful these changes are for men with PE, without being able to evaluate the relationship between IELT, ejaculation control and sexual satisfaction within the current RCT evidence base.
Adverse event reporting, both in reviews and in further RCTs, was limited. Although the nature of AEs associated with specific treatments could be identified, evidence surrounding proportions of patients withdrawing from treatment owing to AEs was either unclear or not reported. Furthermore, patient adherence to and acceptability of PE treatments has not yet been fully evaluated in the current evidence base.