RT Journal
A1 Ioannidis JA
T1 MEga-trials for blockbusters
JF JAMA
JO JAMA
YR 2013
FD January 16
VO 309
IS 3
SP 239
OP 240
DO 10.1001/jama.2012.168095
UL http://dx.doi.org/10.1001/jama.2012.168095
AB 
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.