New medicines that win U.S. marketing approval without conclusive evidence of their effectiveness aren’t always proven to work after they go on sale, a recent research review suggests.

Researchers focused on medicines approved for sale based on single pivotal trials or based on what’s known as “surrogate markers,” such as lab tests and signs of risk for disease such as cholesterol levels instead of true clinical outcomes like heart attacks or deaths. Many times no follow-up studies were published after these medicines went on sale, and when studies were published they often continued to rely on surrogate markers to suggest potential effectiveness.

“Everyone wants new drugs to be approved for use as quickly as possible – patients want access to innovative therapies and physicians want alternatives for their patients, particularly if they work better or are safer,” said senior study author Dr. Joseph Ross of Yale University in New Haven, Connecticut.

“However, speeding up the approval process increases our collective uncertainty about drugs’ benefits and safety,” Ross said by email. “This exposes patients to risks – the risk that they are spending their resources on therapies that do not work as well as expected as well as the possibility that they are taking drugs that have underlying safety risks that have not yet been figured out.”

For the study, researchers examined published studies of 117 medicines approved for treating 123 medical conditions by the U.S. Food and Drug Administration between 2005 and 2012, based on either a single pivotal trial or on trials that relied on surrogate endpoints.

Overall, no follow-up studies were published for 43 of the 123 approved indications, or 35 percent, researchers report in the BMJ. They examined research published up to about five years after the drugs won FDA approval.

For half of the conditions, no more than one post-approval study was published, the researchers found.

For the medicines cleared for sale based on surrogate markers, 90 percent of the studies published after they went on sale also used surrogate markers of disease.

Only six of the 33 uses for the drugs that had been approved by the FDA based on a single pivotal trial had a study published after approval that was a random experiment and proved the medicine worked better for specific clinical outcomes than a placebo or an alternative therapy.

Just one of the 49 uses approved based only on studies of surrogate markers had a gold-standard randomized study of clinical outcomes published after it went on sale that proved it worked better than no treatment or alternatives.

And only two of the 41 uses approved with a single pivotal trial and surrogate markers had a randomized study proving superior clinical effectiveness published after it was cleared for sale.

It’s possible that studies published after the analysis was done might have proven some of the medicines worked better than alternatives for specific clinical outcomes, the authors note. The results might also look different for other medicines that were approved with multiple pivotal trials instead of with only one, they say.

Even so, The study should make patients cautious about whether they are benefiting from new medicines before the health effects of the drugs are fully understood, said Dr. Barbara Mintzes, a researcher at the University of Sydney who wasn’t involved in the study.

“This study raised a strong note of caution because the follow-up studies needed to show if these medicines are truly beneficial are either not being done or do not use the type of rigorous scientific methods needed to adequately test these medicines,” Mintzes said by email. “In many cases, when a new medicine is approved, there are already better tested treatments available.”

Author: Lisa Rapaport

Source: BMJ, online May 3, 2017.