Thousands of Americans are getting sick and many are dying each year from prescription drugs that were pushed onto the U.S. market ahead of the rest of the world.
A Knight Ridder analysis shows that as the number of new drugs given first to Americans has increased, the reports of drug-induced ailments have soared. Yet, even as the deaths and damage have increased, the Food and Drug Administration has never instituted an aggressive system to track the safety of drugs once they’re on the market.
On Friday, the makers of the painkiller Celebrex and the attention disorder remedy Strattera warned consumers that health problems associated with the drugs had surfaced, requiring changes in their use. Both were introduced first in the United States, Celebrex in 1998, Strattera in 2002.
Nearly 60 percent of all the genuinely new drugs sold in the world in 2003 those with active ingredients never before marketed were first dispensed in America. That’s up from about 3 percent 20 years ago when most drugs were first introduced abroad, where the approval process in many countries is much more stringent than in the United States.
“We’re the guinea pigs in the sense of extensive population exposure,” said Dr. Marcus Reidenberg, a professor of pharmacology, medicine and public health at Cornell University Medical School in New York City.
FDA defends safety system
FDA officials strongly deny that their safety monitoring system is broken and say it’s great that most new drugs make their debuts here.
“Lives are saved and suffering is reduced in the U.S.” because drugs for cancer, diabetes and other ailments are released here first, said Dr. Steve Galson, the FDA’s acting director of the Center for Drug Evaluation and Research, which oversees drug safety.
Knight Ridder found that in 1992, just before Congress directed the FDA to speed up drug approvals, there was an average of one adverse drug reaction for every 16,300 prescriptions filled. In 2003, adverse reactions of all drugs, no matter where they debuted hit one in 9,000.
While the FDA has no official estimate on the number of people killed by these drugs, the agency says 106,000 people a year die from all types of drug reactions. One new drug, the painkiller Vioxx, which was pulled from the market this fall, may have caused 55,000 deaths, a top FDA scientist said recently.
Prescription drug safety is under severe pressure because of several factors:
The 12-year-old law that cut drug approval time nearly in half.
Price controls in many other countries that make the U.S. market, the world’s largest with sales of $216 billion in 2003, much more profitable and attractive to drug makers.
Widespread consumer advertising for prescription drugs in the United States that puts public pressure on regulators and physicians.
These problems worry FDA scientists.
A FDA survey of agency scientists, released this month by a public interest group, found that 66 percent of respondents were less than fully confident in the FDA’s ability to monitor the safety of drugs being given to consumers.
“We believe very strongly that, overall, the fact that drugs are (first introduced here) is a very, very strong positive benefit for the public health of America,” the FDA’s Galson said.
But on Friday, one of those drugs, Celebrex, was found in one study to increase the risk of heart attack. FDA officials advised doctors to minimize its use.
Drugs popular for arthritis
Vioxx and Celebrex are in a class of painkillers known as cox-2 inhibitors, which are popular with arthritis patients because they are easier on the stomach than previous pain medications. Consumer advocates have railed for years that the FDA has failed to act aggressively after many studies linked cox-2 drugs to heart problems.
Vioxx and Celebrex were sold in the United States before they were sold in Europe.
In 1998, the United States surpassed Europe and Japan as the world leader in the introduction of unique medicines.
Knight Ridder’s analysis found that 72 percent of unique new drugs approved by the FDA in the last six years were sold in America before they were sold in Europe. In the 1980s, most were launched in Europe.
Europeans adopted more aggressive ways to evaluate the safety of drugs already on the market. Great Britain, for example, keeps track of all drugs and how patients react to them and looks for emerging problems.
“You know their (monitoring) system would have picked up a problem earlier than ours would have, ”said former FDA Commissioner and Stanford University president emeritus Donald Kennedy. “Because (Europeans) are better than us way better.”
That may help explain why the number of Americans reporting adverse drug reactions is soaring. The 357,392 bad reactions reported to the FDA in 2003 is more than double 1995’s figure and more than four times higher than those reported in 1990.
The FDA’s Galson said the increase may reflect the fact that more Americans roughly 44 percent now take prescription drugs.
But the number of adverse drug reactions is growing more than twice as fast as the number of prescriptions being filled in the United States. From 1994 to 2003, the number of bad drug reactions reported jumped 145 percent while the number of prescriptions filled increased 59 percent, Knight Ridder found.
The FDA estimates that about 390,000 adverse reactions will be reported this year. Yet the FDA cautions that the actual number is likely to be between 10 and 100 times higher because of under-reporting.
The issue of drug reaction and monitoring is a simple case of numbers. Before the FDA approves a drug as safe for sale, it’s tested on a few thousand people. It’s enough of a sample to find big and obvious side effects, the kind that hit maybe one out of every 100 users.
But when drugs are sold commercially and used by millions of patients, rare side effects can show up, some with deadly consequences. A rare side effect that would hurt maybe one person in 10,000 wouldn’t show up in the initial study, but it would in the mass marketplace. That’s what happened with Vioxx.
“We launch into overuse of these drugs when we don’t know their effects,” said Dr. Brian Strom, a University of Pennsylvania public health and preventive medicine professor.
That means consumers should be wary.
“If you don’t want to be a guinea pig, don’t take them for the first couple of years after they’ve been approved, ”said Sean Hennessey, a University of Pennsylvania professor of pharmacology and epidemiology. “It’s a common teaching in clinical pharmacology that it’s never good to be the first person to use a new drug.”
Pat Peebles, a 60-year-old retiree in McDavid, Fla., started taking Vioxx in 2001 for arthritis. She figured it was safe because the government approved it.
But on the night of Sept. 23, 2003, Peebles began to sweat profusely. She felt pain in her stomach, then fell to the floor. Her heart stopped, and paramedics spent 45 minutes reviving her.
By then, experts knew something was amiss as studies and international alerts linked the drug to heart problems. By 2001, Vioxx was the No. 1 prescription drug problem in the FDA’s adverse effects reporting system.
“I’m more cautious because of that night that I died,” said Peebles, who’s now on other medications. “When (drug companies) come up with these new drugs and say the government approved it, I wonder if it’s going to be safe down the road.”
Drug law passed in 1992
The United States became drug makers’ choice for new drug debuts after Congress passed the Prescription Drug User Fee Act in 1992. The law allowed drug companies to fund most of the FDA’s costs for approving new drugs. In return, the FDA pledged to cut sharply drug approval times.
Faster approval of HIV drugs the legislation’s goal was the first result. Then came a rash of new U.S. drug applications that shifted from Europe and Japan, where approval was relatively slow.
“There’s more money here, a bigger market, less price regulation than anywhere else in the world,” said Stephen Schondelmeyer, a professor of pharmacy at the University of Minnesota.
Maintaining drug safety while approving more drugs, according to the FDA’s Galson, “means that we have to have a robust post-approval program” to detect problems once drugs are on the market.
That’s not what the FDA has, says Dr. Wayne Ray, a professor of preventive medicine at Vanderbilt University in Nashville, Tenn. The system, he said, “is broken.”
The system is designed to be passive: Doctors, drug companies and patients report adverse reactions to the FDA, which keeps the records in a giant database. What’s needed but not done is active searching of these records and other databases for patterns of problems and any side effects from new drugs, said experts.
In fact, so few doctors or patients submit adverse reaction reports and drug company submissions are so spotty that the database is little more than a collection of anecdotes, said Pennsylvania’s Hennessey.
In addition, most of the 300,000-plus adverse reaction reports that the FDA receives annually are on paper, said Galson, and computerizing them is “a very time-consuming process.”
Complained Strom: “We shouldn’t be relying on this 1950s system as our way of discovering adverse reactions.”
Electronic system offered
The FDA does offer doctors an electronic reporting system for adverse effects, called Medwatch, but the agency does little to promote it, said Dr. Mary Frank, president of the American Academy of Family Physicians. “I can tell you as a physician in practice for 26 years that I have never heard from the FDA about that.”
The FDA’s record-keeping problems even afflict the World Health Organization’s Uppsala Monitoring Centre in Sweden, which collects adverse drug reaction reports from 75 countries to spot early signs of problem drugs.
FDA-provided reports make up nearly half of the agency’s trove of 3.2 million, said Sten Olsson, head of external affairs at the Uppsala Centre. But the reports arrive a year after they’re filed, making it difficult to spot problems with new drugs before they get out of hand.
“We got 30,000 to 50,000 reports from them last month that were a year old. It’s very difficult to tell what problems we might have identified if we’d had their data,” in a timely manner, Olsson said.
The FDA could do a lot more, said Dr. Richard Platt, chairman of preventive medicine at the Harvard School of Medicine in Boston. He recommended that the agency scour private-sector databases of patient records for possible side effects, just as Kaiser Permanente, a big U.S. health care manager, did to find cardiac problems with the painkiller Vioxx.
“Are we doing the obvious?” asked Lisa Herrinton, a research scientist at Kaiser Permanente’s Division of Research in Oakland, Calif. “No, we’re not.”
She and others say the FDA isn’t investing enough in monitoring side effects.
And how much is that? After two weeks of searching their budget records, FDA officials said they still don’t know.
However, the Bush administration has significantly increased the number of FDA personnel involved in post-approval drug safety surveillance. It’s up to 103 this year, from 77 three years ago. That comes to one FDA drug safety monitor for every 31 million prescriptions filed in the United States.
More federal workers do maintenance and landscaping on Capitol Hill than check for adverse drug reactions nationwide.
It’s not a new problem. Twenty-five years ago next month, Congress’ Joint Commission on Prescription Drug Use offered this as its top recommendation: “A systematic and comprehensive system of post-marketing drug surveillance should be developed.”
It still hasn’t happened.