Interventions to treat premature ejaculation: methods for a rapid systematic review and meta-analysisMarrissa Martyn-St James, Katy Cooper, Eva Kaltenthaler, Kath Dickinson, Anna Cantrell

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Funding / Disclaimer

• This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 13/12/01)

• The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Health Technology Assessment Programme, NIHR, NHS or the Department of Health.

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Objective

• To systematically review evidence for the clinical effectiveness of behavioural, topical and systemic treatments for premature ejaculation (PE)

• To do so within the timescale of a short report

• To employ a rapid review approach

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Treatments to be evaluated• Behavioural interventions

• Topical treatments (local anaesthetics)

• Systemic treatments - antidepressants (SSRIs, SNRIs,TCAs), PDE5s (sildenafil), alpha blockers, opioid analgesics (tramadol)

• Other therapies (acupuncture, Chinese medicine, yoga, delay devices)

• Combinations of any of the above

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Scoping searches• A number of existing systematic reviews

across all treatment areas

• More than one systematic review per treatment

• A number of systematic reviews presenting data some with a meta-analysis of primary outcome – Intravaginal Ejaculatory Latency Time (IELT)

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Searches to August 2013

• 2,283 citations following deduplication

• One hundred two (102) RCTs:

• Based on data extraction rate of two papers per day would take 51 days just to do a single data extraction!

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Breakdown of trials• Behavioural – 12 RCTs, 9 in two previous reviews, none with

a meta-analysis

• Topical – 9 RCTs, 7 in three reviews: 2 with MA

• SSRIs – 50 RCTs, 33 in 13 reviews: 4 with MA

• SNRIs – 3 RCTs, one in a review, no MA

• TCAs – 13 RCTs in 10 reviews, no MA

• PDE5s – 12 RCTs, 10 in five reviews: 1 with MA

• Alpha blockers – 2 RCTs, one in a review, no MA

• Opioid analgesics – 7 RCT, five in reviews: 2 with MA

• Other therapies – 8 RCTs, none in reviews

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Rapid review options• Summarise results from existing

systematic reviews and extract and present results from subsequent RCTsOR

• Extract RCT data directly from existing reviews and pool with RCT data extracted from subsequent RCTs to bring the evidence base up to date

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Advantages• Identify RCTs missed by existing review searches and any

subsequently published RCTs

• More than one review for each treatment to cross-check RCT data for consistency

• Reduced number of papers to extract, therefore double DE possible in short report time scale

• Errors evident in existing reviews (combining RCTs with observational studies, double-counting participants, pooling data from crossover and pairwise RCTs) were addressed

• Facilitate pooling of data across all RCTs to produce effect estimates and to summarise evidence base to date

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Disadvantages

• Unable to check methodological quality of RCTs reported in existing reviews (limited and disparate quality assessment reporting in existing reviews)

• Reliant on accurate data extraction of RCTs in existing reviews – only four reviews reported double data extraction

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Subsequent to HTA short report:• RCT publications for treatment areas are being

obtained and checked against reviews - SSRIs, PDE5s and behavioural papers so far

• IELT data from reviews confirmed as accurate in original RCT publication

• Methodological quality assessment indicates limited reporting of randomisation and allocation methods along with blinding

• Additional data not reported by reviews, mainly numbers of patients experiencing adverse events

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Conclusions• Where only one review of RCT data is available, reliability of

those data cannot be checked across other reviews. In this scenario, revisiting original RCT publications might be more accurate.

• Where methodological quality is disparate across one or more existing review, this may also necessitate obtaining the original RCT publication for a comprehensive quality assessment, especially where further RCTs not included in existing reviews are identified for inclusion.

• Nonetheless, the method has facilitated a narrative and numerical data synthesis of the evidence base across a large number of RCTs within the time constraints of a HTA short report

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Acknowledgements

• Clinical advisors: Professor Kevan Wylie, Dr Leila Frodsham, Dr Catherine Hood

• Clerical and administrative support: Gillian Rooney

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