The number of serious adverse events and deaths attributed to prescription medications has nearly tripled since the Food and Drug Administration initiated a system in 1998 to make it easier to report significant side effects, researchers said Monday.
Twenty percent of drugs accounted for 87% of adverse effects, and the biggest offenders were painkillers and drugs that modify the immune system to treat arthritis, according to the report in the Archives of Internal Medicine.
A quarter of the increase could be attributed to a boost in prescriptions and an additional 15% to the introduction of new biotechnology drugs since 1998, but the rest could not be explained, said drug safety expert Thomas J. Moore of the Institute for Safe Medication Practices in Huntingdon Valley, Pa.
"The clear finding is that we are losing ground in terms of drug safety, and that ought to be of great concern," said Moore, who led the study.
Both the FDA and a trade group representing drug makers agreed that the number of reported adverse events had been increasing, but they attributed much of the rise to an increase in voluntary reporting of the events. Studies have estimated that from as little as 3% of adverse events to a maximum of about 33% have been reported to the FDA.
"There are clearly other factors responsible for this increase, such as the increase in public attention to drug safety and use of the Internet to make it easier for the public to . . . report adverse events to the FDA," said Dr. Gerald Dal Pan, director of the FDA's office of surveillance and epidemiology.
Researchers analyzed all of the serious adverse-event drug reports submitted to the FDA through its Adverse Event Reporting System, commonly known as MedWatch reports. Physicians and the public submit reports to the FDA or to drug makers, which are required to forward them to the FDA.
The new system upgraded the FDA's Spontaneous Reporting System to increase the efficiency with which the agency received, filed and analyzed the reports.
Adverse events are those defined as resulting in death, a birth defect, disability, hospitalization or requiring intervention to prevent harm. The number of such events grew from 34,966 in 1998 to 89,842 in 2005. During the same period, the number of deaths rose from 5,519 to 15,105.
From 1998 to 2005, the number of prescriptions written each year grew by 25%.
Women were involved in 55.5% of the events. A disproportionate share occurred among the elderly -- a full third of events in a group that accounts for 12.6% of the population. Fewer events than expected occurred among children younger than 18 -- 7.4% in a group that represents 25% of the population.
Five of the top six drugs causing deaths were painkillers: Oxycontin, Fentanyl, morphine, acetaminophen and methadone. The sixth was the antipsychotic drug Clozapine.
Among the drugs causing the most nonfatal adverse events were estrogens, insulin, interferon beta, Paroxetine, Clozapine, Oxycontin, warfarin and Fentanyl. Paroxetine is an antidepressant, interferon beta is used to treat multiple sclerosis and cancer, and warfarin is an anti-clotting agent.
Moore said he was particularly disturbed by the appearance of drugs such as insulin and warfarin on the list.
"We have drugs out there we know how to manage, whose risks are well-known, and for which we don't have adequate programs in place to manage those risks," he said.
Both Moore and the Pharmaceutical Research and Manufacturers of America, or PhRMA, agreed that the FDA needed more funding to monitor drugs after they were introduced to the market. Such funds would allow the FDA to tap into electronic databases and other information technology systems and to develop novel approaches for monitoring drugs, said Ken Johnson, PhRMA's senior vice president.
The FDA's office of surveillance and epidemiology also needs greater independence to upgrade drug warnings and mandate restrictions, Moore said. Currently, the office can only provide advice that may be acted on by other parts of the agency.