Although the gold standard, many drugs approved without randomized trials

Despite the perception that most drugs require a randomized controlled trial with a survival endpoint to gain FDA approval, a recent study found that almost half of the oncology drugs approved since 1973 were approved without a randomized trial and most have a long-term safety and efficacy record. In fact, endpoints other than survival have been the basis for approval for 68% of oncology drugs granted approval from 1990 to 2002.

Researchers from The University of Texas M.D. Anderson Cancer Center evaluated initial applications for investigational cancer drugs from 1973 to 2006. They reviewed initially approved indications and compared them to current indications.

Thirty-one new drugs without randomized trials with a comparator arm, supportive care or placebo arm had been approved since 1973. Twenty-three of these drugs did not have accelerated approval. Forty-two percent of the drugs approved without randomized trials were initially approved for a form of leukemia.

Researchers observed a drastic increase in the number of these drugs approved after 1995. They posited that the increase is likely due in part to the FDA’s introduction of its accelerated drug approval program.

Despite being approved without a randomized trial, all but one of the 31 drugs are still fully approved, with many gaining new indications since their approval. Three drugs are no longer recommended for their initially approved indication due to the discovery of more effective drugs, but no drug’s approval was revoked due to a safety concern.

Tsimberidou AM. J Clin Oncol. 2009;doi:10.1200/JCO.2009.23.6018.