Indirect comparison of interventions using published randomised trials: systematic review of PDE-5 inhibitors for erectile dysfunction

R Andrew Moore, Sheena Derry, Henry J McQuay, R Andrew Moore, Sheena Derry, Henry J McQuay

Abstract

Background: There are no randomised and properly blinded trials directly comparing one PDE-5 inhibitor with another in a normal home setting. Valid indirect comparisons with a common comparator must examine equivalent doses, similar duration, similar populations, with the same outcomes reported in the same way.

Methods: Published randomised, double-blind trials of oral PDE-5 inhibitors for erectile dysfunction were sought from reference lists in previous reviews and electronic searching. Analyses of efficacy and harm were carried out for each treatment, and results compared where there was a common comparator and consistency of outcome reporting, using equivalent doses.

Results: Analysis was limited by differential reporting of outcomes. Sildenafil trials were clinically and geographically more diverse. Tadalafil and vardenafil trials tended to use enriched enrollment. Using all trials, the three interventions were similar for consistently reported efficacy outcomes. Rates of successful intercourse for sildenafil, tadalafil and vardenafil were 65%, 62%, and 59%, with placebo rates of 23-28%. The rates of improved erections were 76%, 75% and 71%, respectively, with placebo rates of 22-24%, and NNTs of 1.9 or 2.0. Reporting of withdrawals was less consistent, but all-cause withdrawals for sildenafil, tadalafil and vardenafil were 8% 13% and 20%. All three drugs were well tolerated, with headache being the most commonly reported event at 13-17%. There were few serious adverse events.

Conclusion: There were differences between trials in outcomes reported, limiting comparisons, and the most useful outcomes were not reported. For common outcomes there was similar efficacy between PDE-5 inhibitors.

Figures

Figure 1
Figure 1
Results of percentage of men with improved erections in individual trials of sildenafil, tadalafil, and vardenafil.
Figure 2
Figure 2
Summary of percentage of successful attempts at intercourse (Successful), percentage of men with improved erections (Improved), and of all-cause withdrawals (Withdrawals) for top doses of sildenafil, tadalafil and vardenafil.

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