Concerns about the FDA's ability to monitor drug dangers that come to light after drugs have been approved for the market have spurred calls for different approaches to post-marketing surveillance in the United States.
In fact, a recent survey of FDA scientists by the Department of Health and Human Services showed far more concern about the government's drug-safety monitoring after medicines hit the marketplace than about the quality of safety assessments conducted before FDA approval. Two-thirds of the respondents had doubts about the FDA's post-market surveillance capabilities, but the same percentage was mostly or completely confident in pre-approval safety assessments.
The government's existing post-market surveillance system, called MedWatch, was instituted in 1993. It relies on doctors and drug companies to voluntarily report suspected cases of drug reactions. But reports trickle in — with only about 10 percent of adverse reactions being reported — and tracking lacks rigor.
“MedWatch is a bust,” says Kenneth Kaitin, director of Tufts University's Center for the Study of Drug Development.
The FDA announced in February 2005 that it would institute systemic drug-safety reforms, including creation of an independent Drug Safety Oversight Board, which would disseminate information — via an Internet Web site and fliers — about drug-safety concerns that arise after drugs have been on the market. However, critics complain the board will not have the authority to quickly recall a drug that is found to be dangerous or require additional clinical trials.
Meanwhile, many medical facilities and HMOs have instituted their own innovative initiatives to improve data collection on potential drug interactions and side effects. In addition, several hospitals have beefed up their in-house pharmacology departments to add drug investigators and devise comparisons of drugs based on efficacy and cost.
For instance, Brigham & Women's Hospital in Boston, the teaching facility of Harvard Medical School, added its Department of Pharmacoepidemiology and Pharmacoeconomics in 1998 to research the benefits, risks and costs of prescription drugs and disseminate its findings in user-friendly formats.
At Wishard Memorial Hospital in Indianapolis, prescriptions are made over a computerized Entry Order System, which provides interactive information regarding the patient's medical history and other medications he or she is taking. After a drug is administered, doctors and pharmacists look for signals, such as a liver abnormality, that may indicate a drug reaction, says Clement McDonald, director of the hospital's Regenstreif Institute. The system, developed internally in 1986, sends doctors rules and reminders that pop up when they type their prescriptions, though the hospital had to tinker with the alerts.
“Too many, and it gets to be like spam, so we had to work on the balance,” McDonald says. The key to the system's success is to have doctors and pharmacists looking at prescription patterns together, McDonald says.
The hospital also participates in a data-sharing arrangement with five other Indianapolis hospitals and exercises extreme caution over new drugs. “We don't use new drugs unless there's nothing else like them on Earth,” says McDonald. “Otherwise, we wait four or five years.”
At Intermountain Health Care Hospital in Salt Lake City, pharmacists receive alerts about possible symptoms of drug reactions, then visit patients' bedsides looking for signs of adverse events.
Independent programs, some initiated by the federal government, are synthesizing and translating scientific data into digestible, comparative studies of various classes of drugs. Beginning in 1997, the federal Agency for Healthcare Research and Quality has awarded a series of five-year contracts to 12 public and private institutions in the United States and Canada to establish evidence-based practice centers. One of the most active, the Oregon Health & Science University in Portland, established a Drug Effectiveness Review Project and has issued several reports and updates.
Institutions of all sizes — from the 200-doctor Everett Clinic in Washington state to the giant Kaiser Permanente HMO in California — have adopted in-house initiatives to improve drug safety. Both Kaiser and Everett, for example, bar drug-company representatives from visiting doctors unless specifically invited and ban free samples. They also provide doctors with expert pharmacological “counter-detailing,” or price and efficacy comparisons designed to counter the promotional claims made by drug companies and their sales representatives.
“We've been counter-detailing the Cox-2s for years,” said Jennifer Wilson Norton, director of pharmacy services at the Everett Clinic. “The [cardiovascular] problems weren't news to us or to our providers.”
In January, Kaiser Permanente pharmacies stopped stocking Bextra, the first time the HMO has ever banned an FDA-approved drug.
Other countries have developed effective post-market surveillance techniques. For example, more than 20 “pharmaco-vigilance centers” in France have evolved into vast repositories of information about medications. In case of an adverse event, the centers work with doctors to determine if it is tied to a drug or another factor. All information is passed to the country's central drug regulators. The system unearthed a problem with the anti-psychotic drug olanzapine (marketed as Zyprexa in the United States) that was significant enough to warrant a label change.
In England, black triangles are required on the labels of newly approved drugs to signal the need for vigilance by doctors. In addition, the Drug Safety Research unit of Britain's Medicines and Health Care Products Regulatory Agency sends so-called “Green Cards” to doctors seeking information about certain drugs. The compliance rate is better than half.
Pharmacists in England also report adverse reactions to drugs, and computers record long-term side effects. In January 2005, England's health minister announced that regulators would begin collecting and publishing online patient reports of adverse drug side effects.