Author Affiliations: Stanford Prevention Research Center, Department of Medicine, and Department of Health Research and Policy, Stanford University School of Medicine, and Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, California.
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.
Ioannidis JPA. Mega-Trials for Blockbusters. JAMA. 2013;309(3):239-240. doi:10.1001/jama.2012.168095