“The concept of safety is much more complex than most people think about until they look into it deeply,” Califf said. “All drugs have risk. None of them are absolutely safe. And the actual safety risks are only revealed through clinical trials with the same quality and number of patients involved as it takes to look at efficacy.”
About 92% of drugs that get into human clinical trials don't make it to market because they fail to show any benefit or, worse, they have unexpected toxicity, he said.
“Declaring a drug is safe after very little information is treacherous,” Califf said.
Califf recently wrote for JAMA on the FDA's balancing act of protecting the public and encouraging innovation. And the FDA released a paper last month documenting examples of a promising drug, vaccine or device that each did well in a Phase 2 clinical trial but “bombed out” in Phase 3, Califf said. Drugs typically go through three “phases” of studies called clinical trials before gaining FDA approval. With each new phase, researchers test drugs or other products on more people and on more measures of safety and effectiveness.
“It's 22 examples of why it's a big mistake to think that you can judge the balance of risk and benefit from a small amount of data,” Califf said.