Reports of drug side effects soar fivefold

FDA database could warn of dangerous products already on market

More than 1 million reports of drug side effects were filed with the U.S. Food and Drug Administration in 2015, a fivefold increase since 2004, according to an analysis by the Milwaukee Jour

nal Sentinel and MedPage Today. Numbers aren’t final for 2016, but they are expected to match that all-time high.

Drugs to treat diseases such as rheumatoid arthritis, psoriasis, multiple sclerosis, a type of cancer and diabetes are among those with the greatest number of reports. Many of the drugs are for conditions that occur in 1% or less of the population, but several have seen increasing use.

For years, the FDA’s adverseevents system has been derided because of its largely voluntary nature — only drug companies, not doctors or patients, are required to report problems. As a result, the system probably was capturing only a small percentage of cases.

In recent years, the number of reports has been multiplying, prompting more independent researchers and drug companies to use the data as a way to detect safety problems, the Journal Sentinel and MedPage Today found. But experts say the information still is largely untapped and — if used more — could become an important alarm that warns of dangerous drugs after they hit the market.

The surge in reports could indicate a growing number of harmed patients or more vigilant reporting of adverse events, a goal of the FDA. Experts say both probably play a role.

Twelve years ago, 206,000 reports of side effects from medications were filed with the FDA — complaints as frivolous as flatulence and as serious as death.

By 2015, the most recent full year of data, the number had grown to 1.2 million.

The FDA has long discouraged use of the system for research

purposes. When it distributes the database, it attaches warnings that say the reports aren’t evidence drugs caused the problems listed, that the data can’t be used to estimate risk and that the information should not be used to compare drugs.

In 2005, the Government Accountability Office estimated the system captured only 1% to 10% of all adverse reactions. Despite the explosion in reports, that remains the most recent estimate of how many cases are caught by the system.

The increased volume of reports has researchers, insurance companies and even some pharmaceutical groups reimagining how the data can be used.

“Sheer numbers have some scientific weight,” says Thomas Moore, senior scientist at the Institute for Safe Medication Practices, a non-profit watchdog group focused on drug safety. “If 500 people report a problem, it is unlikely that they are all wrong.”

For all its warnings about the limitations of the system, the FDA itself has relied on the reports to guide its actions. Case in point: a patch used to treat migraine headaches.

In September 2015, the Zecuity patch was allowed on the market after years of give-and-take with FDA officials. The patch, which looks like a large armband, released a drug through the skin to fight migraines. An early version failed to get approval after the FDA raised concerns that it could “cause severe burns and permanent skin lesions.”

The patch was redesigned and tested on 58 people, none of whom reported problems. The FDA could have required more clinical testing but instead chose to approve the redesigned patch and rely on “postmarket surveillance.” In other words, the safety of the product would be linked to reports of side effects.

The FDA ordered Teva, the manufacturer, to report adverse events within 15 days of receiving any complaint.

Nine months later there were hundreds of reports of blisters, burns, scars and pain. On June 2 of last year, the agency said it was “investigating the risk of serious burns and permanent scarring.” A week later, Teva voluntarily pulled the product.

The company said it worked with the FDA to pinpoint a problem but noted that because the root cause was not identified, the product remains off the market.

Others say, however, that the voluntary and cumbersome nature of the system makes the value of the information limited.

“As a physician, I have tried to use it, and it is very, very clumsy,” says Joseph Ross, an associate professor of medicine at Yale University School of Medicine.

In its own analysis, the Journal

Sentinel and MedPage Today found that among the 10 drugs that accounted for the most reports, seven carry “black box” warnings, the FDA’s most stringent alert for serious or potentially life-threatening side effects.

The 10 drugs account for one of every five reports filed since 2013. Yet, none is on the top-10 list of most-prescribed drugs as determined by IMS Health, a drug market research firm.

“We are concerned,” says Michael Carome, deputy director of Public Citizen’s Health Research Group. “It reflects that the FDA has allowed drugs to come to market without adequately en- suring safety.”

The FDA doesn’t share that opinion. “It’s not always necessary to wait and go through a traditional development program before making a drug available to patients,” says Lyndsay Meyer, an FDA spokeswoman.

She says speeding up drug approval and development goes hand-in-hand with strengthening the adverse-event reporting system. The agency has taken many steps to increase the quality and number of reports, she says.

Couple those actions with increasing consumer participation in the system, she says, and it’s hardly a surprise reports would rise so dramatically.

“In fact, we encourage health care providers and the public to report suspected adverse drug events,” she wrote in a statement.

In 2015, the FDA started requiring companies to report events electronically instead of on paper. That led to an increase in less-serious events in the database and 300,000 additional reports — the largest single-year jump in the program’s nearly 20year history.

Patients, too, have increasingly reported problems. In 2004, just 45,000 reports — about 20% of all those filed — originated with consumers. In 2013, for the first time, more reports originated with consumers than health professionals. By 2015, consumers accounted for 55% of all reports.

Brian Overstreet runs Advera Health, which analyzes the database for insurance companies, pharmaceutical companies and other groups.

He says consumers are increasingly likely to report cases as part of a “virtuous circle.” Because the system has more reports, it gets more attention from the media and the public. Because it gets more attention, consumers are more likely to make reports, which in turn makes the system more complete.

In some cases, companies have started embracing the oncederided FDA database.

Denmark-based Lundbeck, which specializes in neurological drugs, used the data to find out what kind of side effects were most commonly reported within a certain class of drugs, says Ashleigh Duchene, a spokeswoman for the company. If a certain kind of side effect keeps cropping up, she says, the company’s researchers pay special attention to preventing that problem.

“It’s that R&D focus for us, seeing what’s out there,” she says.

“Sheer numbers have some scientific weight. If 500 people report a problem, it is unlikely that they are all wrong.” Thomas Moore, Institute for Safe Medication Practices