For millions of Americans, the nation's biggest drug problem is not with illegal street drugs. It's in not knowing whether everyday prescription medicines are safe.
Confusion abounds, and with good reason. In the past six months, the safety of several of the nation's most popular drugs has been questioned. Emotional hearings at the FDA have resulted in mixed actions and reactions.
First came the news that the arthritis drug darling Vioxx doubles the risk of heart attack, the nation's leading killer. As a result, manufacturer Merck & Co. pulled Vioxx from the market Sept. 30. The safety of two other drugs in the same class, Celebrex and Bextra, was also called into question within days.
Then, an FDA advisory panel last month voted 17-15 to allow Vioxx to stay on the market. Discussion was heated, and many who voted in favor did so with reservations.
Dr. Alastair J.J. Wood, associate dean of the Vanderbilt University Medical Center and chair of the panel, voted against Vioxx. He thinks the close vote is far from a blessing for the drug.
"It's more like saying a little more than half the pilots at Hartsfield think a plane is safe to take off, and a little less than half say it's not. Is that a vote of safety?"
The FDA will decide within the next few weeks whether to accept the panel's recommendation. Merck & Co., however, has made no indication that it would return Vioxx, which accounted for more than $2.5 billion in sales last year, to the market.
"Merck has not altered its position on the voluntary withdrawal of Vioxx. Anything further would be speculation," the company said in a statement.
Two weeks ago, the FDA decided not to follow in the steps of Canadian health officials who pulled AdderallXR off the market. Health Canada, the FDA's Canadian counterpart, said research had shown the attention deficit hyperactivity disorder drug had caused 20 sudden deaths among millions of patient over several years. Manufacturer Shire Pharmaceuticals insisted the drug is safe. Thirty-seven million prespcriptions have been written for the drug over 10 years. It generated more than $700 million in sales last year.
Last fall, an FDA panel was moved by wrenching testimony from parents of teenagers who had killed themselves while taking antidepressants. The FDA later agreed that the drugs must now carry a black box warning.
In all three cases, the drugs are considered godsends by millions of patients and doctors.
In such a confusing environment, how can a consumer feel confident that a drug is safe?
"For patients, it is very hard to do," said Abraham Hartzema, professor of pharmaco-economics at the University of Florida. "They must talk carefully with their doctors and discuss risks and medical history. And they need to weigh risks and benefits."
That can be hard. Patients often do not understand what the numbers in a study mean or the differences between various kinds of studies.
Physicians themselves, whose drug training in medical school often consists of two pharmacology courses, sometimes lack thorough knowledge of drugs and their interactions.
Doctors may not know their patients as they move from specialist to specialist, or city to city, often bringing incomplete medical records with them.
Dr. Sidney Wolfe, one of the FDA's most ardent critics and director of the FDA watchdog group Public Citizen, said the consumers should be careful when looking at drug advertising.
Drug companies spend about $3.8 billion each year in direct-to-consumer advertising, according to Ad Age magaine. Amidst all the hype for a new drug, it's hard for consumers to assess the risks, Wolfe said.
FDA spokeswoman Kathleen Quinn said the process works and that drugs approved by the FDA are safe and effective.
"But safe doesn't mean there's no risk," Quinn said. "Products do have some risks."
Quinn noted that risks of all drugs are included in package labeling. No one knows exactly how many U.S. patients actually read package inserts, but some officials estimate the number to be small.
"The studies, the risks are all in the labeling," Quinn said.
Patients should read those labels and become more involved in their decisions to take prescriptions, Quinn and others said.
Atlanta rheumatologist Dr. Hayes Wilson, who testified before the FDA panel, is pleasead that Vioxx could go back on the market.
"Death is a very important event, but everyone has to weigh what does that risk really mean to me," Wilson said of the cardiac deaths of patients on Vioxx. For patients in acute pain with no history of heart disease, taking Vioxx might make sense, Wilson said.
Brenda Slater, 60, of Atlanta, wants Vioxx back on the market - and in her medicine chest.
The former Vioxx user has heard that the drug might be dangerous for those with even a family history of heart disease, which she has.
"And then I read that you're not supposed to take it for long periods of time," Slater said. "And I think, well what's the point. So it's really confusing."
WHAT YOU CAN DO
Ask Your Doctor:
Other Things for You to Do:
ABOUT DRUG SAFETY REPORTS
Clinical Trials: For a drug to win FDA approval, it has to be tested for years in at least three phases of clinical trials. Phase one trials may have fewer than 100 study participants, while Phase III trials can include a few thousand. The gold standard for drug research is a double-blind, placebo trial. This means that one group of study participants is randomly assigned to take a study drug, while another group randomly is assigned to take a placebo, or dummy pill. "Double blind" means that patients nor doctors know whether the patient is taking a drug or placebo. Researchers assess both groups to look for side effects and to see whether the drug works.
Incident Reports: These are required reports of bad side effects in people taking a drug after a drug is already is on the market, as in the AdderallXR incident reports. In assessing the risk of a drug from incident reports, it is important to compare the number of adverse reports to the number of people who have taken the drug. In the case of AdderallXR, the FDA concluded that fewer than 20 sudden deaths in 37 million prescriptions did not warrant taking the drug off the market.
QUESTIONS TO ASK
It's easy to be confused by the numbers in drug studies. Here's what you should ask to help make it more understandable:
For example, were the numbers come from a clinical trial, or from incident reports of serious adverse effects? In the case of AdderallXR, the 20 reported deaths occurred over several years, among millions of patients who took AdderallXR. That's far different from the double-blind placebo trial for Vioxx, in which 31 of about 1,300 patients had cardiac events.
Ask you doctor:
Other things for you to do:
Going through a phase:
Consumers often hear about clinical trials and their various phases, but what do they mean to you as a consumer?
When you hear of a drug in a double-blind, placebo trial, it means that one group of patients not taking the drug is being compared to a group of about the same size who are taking the drug. This is the most reliable way for researchers to see differences in safety and effectiveness.
By the time a drug is on the market, it has been through at least three phases of clinical trials. When the public hears of a problem with a drug already on the market, that drug is sometimes in a Phase IV trial, as was Vioxx.
Phase I trials test a new drug or treatment for the first time in humans in 20-100 healthy volunteers, usually in a closely supervised environment.
Phase II trials study the treatment in larger groups (100-300) evaluating safety and effectiveness in individuals with the disorder of interest. Phase II studies are usually randomized and controlled.
Phase III trials study the treatment in even larger groups (1000-3000) to define effectiveness, side effects, safety, and comparison to other treatments. During this phase, the treatment may be compared to a placebo or standard treatment. Phase III studies can last for many years and enroll thousands of patients.
WHAT THE STUDIES FOUND
Celebrex
Purpose: Anti-inflammatory
Recent actions: The National Cancer Institute said patients in a clinical trial taking the highest doses of Celebrex, 800 milligrams, had a 3.4 times greater risk of cardiovascular problems compared with a placebo. For patients in the trial taking 400 milligrams of Celebrex, the risk was 2.5 times greater.
What it means: FDA advisory panel voted 31-1 to recommend keeping Celebrex on the market.
Bottom line: Read package insert, weigh risks, carefully consult your doctor, especially if you have heart problems.
Adderall XR
Purpose: Extended release version of Adderall, a drug to treat attention deficit hyperactivity disorder
Recent actions: Health Canada suspended authorization after incident reports of 20 sudden deaths among millions of patients. FDA issued a consumer alert but did not pull drug.
What it means: According to FDA officials, some of the patients who died had underlying medical conditions. Because the number of deaths is statistically low, it is hard to say whether those deaths were caused by the drug.
Bottom line: Talk to your doctor. Going down to regular, and not extended release, Adderall could be an option.
Vioxx
Purpose: Anti-inflammatory, pain reliever
Recent actions: A double-blind placebo study trying to see if Vioxx could prevent colon cancer found nearly double the risk of a cardiac event, such as heart attack, stroke or angina, among the 2,600 participants. Merck voluntarily took Vioxx off the market. Food and Drug Administration advisory panel voted Feb. 18 by narrow margin to recommend keeping Vioxx on the market. The FDA has not issued a final ruling.
Bottom line: If Vioxx does return, patients, particularly those with cardiac problems, should weigh the risks and benefits with their doctor, experts said.
Antidepressants
Class of antidepressants used for children and teens, called selective serotonin reuptake inhibitors
Purpose: To treat depression and sometimes obsessive-compulsive disorder
Recent actions: Clinical trials in Great Britain showed increased incidence of suicidal thoughts among youth taking paroxetine, marketed in the United States as Paxil. No deaths were ever reported in any of the clinical trials. Grieving parents of children who had killed themselves while taking the drugs, however, helped convince the FDA that the drugs should carry the FDA's strongest warning, a black box label.
Bottom line: Monitor with the utmost caution any child who takes an antidepressant. Talk to psychiatrist about the risks and make sure the doctor will closely monitor child, especially in the first two weeks.