Yale researchers chide the FDA for failing to enforce high R&D standards

Some researchers at Yale want the world to know that there is no firm FDA standard for proving whether a drug is safe and effective--and they see that as a serious problem that needs to be addressed.

In what they call the first systematic analysis of the agency's standard for drug approval, the investigators found that about a third of the 188 new drugs they reviewed were given a green light on the basis of a single, unconfirmed trial which was often short and designed to hit a surrogate marker (like tumor shrinkage) as opposed to a hard and fast target like survival rates. And drug steer clear of head-to-head studies in a majority of cases.

"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 Joseph Ross at the Yale Center for Outcomes Research & Evaluation. "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."

But some of their broad conclusions raise some obvious questions. The entire industry has been moving away from the big new drugs that address large populations and require huge and expensive late-stage studies for an approval. Instead, small populations have become a more desirable target, and rare diseases are more attractive in part because smaller trials produce relevant data on safety and efficacy. The overall goal has been to design better and more efficient small studies that can produce conclusive data on targeted therapies.

Bloomberg also notes that the FDA's outside experts don't apply a uniform standard during their reviews, especially when patients don't have anything available to treat their ailment, a fact that recently helped Chelsea Therapeutics' Northera pass muster at an AdCom meeting--though there's no guarantee the drug will be cleared given the agency's lingering doubts about the data available.

Some flexibility can be a good thing, says Ross, but consumers and physicians need to understand that not every therapy OK'd by the FDA can be considered safe and effective.

"Most people presume that when a drug is approved for us that it's safe and effective," Ross told the New Haven Register. "There's always uncertainty in the drug-approval process."

One way of dealing with the variable standards for approval, the Yale study suggests, is enforcing more of a life-cycle review that can continue to provide insights on safety and efficacy. The problem is, the agency hasn't applied a set standard for post-approval studies. And that's unlikely to change.

- here's the release
- here's the story from Bloomberg
- here's the report from the Register