There is a looming drug crisis approaching and the results of a new paper about the FDA understanding of clinical trials is only going to make it worse.

Right now, the private sector conducts drug development and they are vilified by the media, the public and their competitors in government-funded academia. But drug development fails 95% of the time before getting to market, it costs billions, has to undergo rigorous testing and then has a short window for sales, during which time everyone complains that greedy companies charge too much. As a result of a hostile business climate and increased regulation, drug development is disappearing rapidly, to be replaced by...nothing. Government-controlled science can't do applied research.

In popular culture, media reports commonly complain that drug X available in Asia as some miracle cure but is held up by the federal Food and Drug Administration (FDA) in the U.S., while they report about the side-effects and lawsuits of drug Y that has passed scrutiny. 

A new paper, what the authors call the first systematic analysis of the standard used by the FDA in making drug approval decisions, shows that the clinical trials used by the FDA to approve new drugs between 2005 and 2012 varied widely in their thoroughness. The safety and effectiveness of newly approved drugs isn't all that understood.  

"We found that during the study period, more than one-third of the drugs were approved on the basis of a single trial, without replication, and many other trials were small, short, and focused on lab values, or some other surrogate metric of effect, rather than clinical endpoints like death," said first author and Yale School of Medicine student Nicholas S. Downing, who conducted the study with senior author Joseph Ross, M.D., and colleagues at the Yale Center for Outcomes Research&Evaluation (CORE).

The team evaluated the strength of clinical trial evidence supporting FDA approval decisions for new drugs by characterizing key features of efficacy trials, such as trial size, design duration, and end points. They used publicly available FDA documents to identify 188 novel therapeutic agents for seven years. These medical review documents summarized in great detail the rationale behind FDA approvals. 

"Based on our analysis, some drugs are approved on the basis of large, high-quality clinical trials, while others are approved based on results of smaller trials," said Ross, assistant professor of internal medicine at Yale School of Medicine. "There was a lack of uniformity in the level of evidence the FDA used. 

"We also found that only 40% of drug approvals involved a clinical trial that compared a new drug to existing treatment offerings. This is an important step for determining whether the new drug is a better option than existing, older drugs." 

In surveys, patients expect drugs approved by the FDA to be both safe and effective. "Based on our study of the data, we can't be certain that this expectation is necessarily justified, given the quantity and quality of the variability we saw in the drug approval process," Downing noted.  



 Published in JAMA.