Sildenafil (Viagra) for male erectile dysfunction: a meta-analysis of clinical trial reports

Meta-analyses that include otherwise unpublished randomised trials are uncommon, but are welcome, and can inform in circumstances where information is contradictory. The example of generic tramadol in acute pain, where information on 3,500 patients was made available, explained the results of two studies, one showing that tramadol was a highly efficacious analgesic, the other showing it to be no different from placebo. The truth was somewhere between. Despite the fact that canadian tramadol had been in common use in some European countries for many years, fulfilling regulatory requirements for the United States required studies to be conducted to contemporary requirements, and meta-analysis brought useful results to light.

Meta-analysis of randomised studies before a new technology has become commercially available is even more rare, though there is at least two examples. Meta-analyses are usually performed some years after first commercial availability because the publication of randomised trials performed for efficacy and/or safety reasons takes time. The importance of meta-analysis in drug development and regulatory procedures is increasingly recognised.

The results of meta-analysis are undoubtedly important, both in the regulatory process and for evaluation of rare but serious adverse events. For COX-2 inhibitors meta-analysis was being planned before the randomised trials in order to examine the relationship between treatments and rare events.

The point of greatest change, though, is in the period immediately after commercial introduction. Media interest can raise patient expectations at a time where healthcare professionals and organisations have least knowledge and experience, and when few have had the opportunity to consider the full implications of the new technology on budgets and services. For sildenafil, for instance, 85% of first time prescriptions occurred in the first 12 weeks of availability in one New England healthcare provider. It is at this point, the point of marketing approval, when there is the greatest need for the best information. At best only a small number of trials may have been published, and though they can be large, and usually are powered to detect a difference from placebo or common current practice, they are unlikely to be able to measure accurately the size of the benefit.

We sought to assess whether clinical trial reports presented for marketing approval would provide the basis for a systematic review at the time of launch if they were publicly available. We did this with reference to the erectile dysfunction treatment sildenafil (Viagra), using clinical trial reports made available by Pfizer Ltd.