http://pubs.jamanetwork.com/ en-us Wed, 16 Jan 2013 00:00:00 GMT Tue, 15 Jan 2013 19:44:52 GMT Silverchair editor@pubs.jamanetwork.com webmaster@pubs.jamanetwork.com http://pubs.jamanetwork.com/article.aspx?articleID=1557740 Wed, 16 Jan 2013 00:00:00 GMT Ioannidis JA. <span class="paragraphSection">The conduct of very large, simple trials (mega-trials) is uncommon and faces several challenges, in particular cost and difficulty in patient recruitment. However, these challenges can be overcome when interventions are widely used by hundreds of thousands of individuals and when there is a potential profit to accommodate the trial cost. Accordingly, every licensed intervention with annual sales that exceed $1 billion, ie, a blockbuster, should have at least 1 trial performed with at least 10 000 patients randomized to the intervention of interest and as many randomized either to placebo (if deemed to be a reasonable choice) or to another active intervention that is the least expensive effective intervention available. The comparison drug can be a generic drug with a well-established effectiveness and safety profile.</span> 309 3 239 240 10.1001/jama.2012.168095 http://pubs.jamanetwork.com/article.aspx?articleID=1557740