Not all FDA-approved drugs get same level of testing

http://www.usatoday.com/story/news/nation/2014/01/21/fda-drug-testing/4713621/
Not all FDA-approved drugs get same level of testing
Liz Szabo, USA TODAY, January 22, 2014
Evidence behind FDA-approved drugs and devices often has major limitations.



Patients might assume that all approved drugs are created equal.

Yet new research finds that there can be big differences in the amount of testing that drugs and medical devices go through before being approved or given to patients, according to a series of articles in the Journal of the American Medical Association.

Many heart devices, for example, have been approved through a Food and Drug Administration process that assumes newer models are safe and effective based on the approval of earlier versions, a study shows.

These devices, which include implanted defibrillators that shock a faltering heart back into normal rhythm, go through rigorous review when they're first approved, says Aaron Kesselheim, author of one of the studies and an assistant professor at Harvard Medicine School. Subsequent changes, however, are often made through a "supplemental" review process that doesn't necessarily require them to be tested in clinical trials in humans, Kesselheim says.

He found that these devices receive an average of 50 approved changes in the years after their initial approval.

"If you took a device approved 15 years ago and you put it side by side with the one from today, they might look nothing like each other," Kesselheim says.

Malfunctioning wires in two recalled defibrillators – the Medtronic Sprint Fidelis and St. Jude Medical's Riata – have been linked to a number of patient deaths. Neither of those wires had been tested in people as part of their FDA review process, Kesselheim says.

Another study found that many drugs receive less extensive testing than others.
Although the FDA usually requires two trials before approving a drug, a study led by the Yale University School of Medicine found that 37% of approved drugs were backed by a single study. Many studies were quite short, with only 34% of new drug approvals backed by a study that lasted more than six months.

Research shows that patients don't always understand these limitations, says Yale's Joseph Ross, who analyzed the FDA's handling of 188 new medications approved from 2005 to 2012.

A 2011 survey, for example, found that 39% of people believe that the FDA approves only "very effective" drugs, while 25% believe the agency approves only drugs without serious side effects.

Neither assumption is true, says Ross, an assistant professor at the Yale School of Medicine. " 'New and approved' doesn't necessarily mean 'new and improved,' " he says.

Many approved drugs had less-than-ideal testing, he found.

In 45% of drug approvals, researchers measured a drug's effect on "surrogate endpoints" – such as blood test results or cholesterol scores – instead of its effect on real health conditions, such as heart attacks. While lowering cholesterol sounds impressive, what patients really need are ways to reduce their risk of having a heart attack or dying, Ross says.

Ross found other limitations in drug-approval studies.

Only 32% of drug studies compared a new product with an existing one. Most studies simply compared new therapies to a placebo. In the real world, however, patients don't want to know whether taking a drug is better than taking nothing, Ross says. Instead, patients need to know which drugs are better than others.These sorts of studies are risky for drug companies, however, because they might show that a new drug doesn't work as well as an older, cheaper one. Through the Affordable Care Act, the federal government is now funding more of these studies, Ross says.

Still, Ross notes that FDA drug trials are generally well done and meet basic standards. Nearly 90% of approved drugs were studied in randomized trials, with patients randomly assigned to receive one intervention or another, a design that's considered the gold standard of medical research. About 80% of studies were double-blinded, another strong study design in which neither researchers nor patients knew whether they were getting an active drug or a placebo. On average, approved drugs were studied in a total of about 760 patients.

And Ross says the FDA needs to have some flexibility when approving drugs, so that cancer patients and others with life-threatening illnesses can try promising therapies. But given the side effects and huge expense of new cancer medications – which may cost thousands of dollars a month – Ross says doctors should be frank.

Doctors "could say, 'Listen, this new drug is approved, but it was only studied in 150 patients. The FDA says it works, but we don't know if it improves mortality. But it shrinks the tumor, and I think we should try it.' That sort of nuance is mandatory when a patient is considering a drug," Ross says.

"We're talking about families going into debt so their loved one can get access to a medication," he says. "Maybe if they know that a drug doesn't prolong life, they will be less likely to mortgage their home. People should have access to the full spectrum of information."

In an accompanying editorial, doctors Steven Goodman and Rita Redberg note that the side effects of new drugs often aren't known until years after approval.

In 2009, for example, the FDA took 181 major safety-related actions on drugs, including 25 "black box" warnings. On average, the time between approval and these safety actions is about 11 years, Goodman and Redberg write.

And while the FDA may require drugmakers to conduct follow-up studies – to make sure that drugs are safe when used in the real world – many of these studies are never done. Only 31% of the follow-up studies requested in 2008 had been completed by January 2013, Goodman and Redberg note.