The following is a list of excerpts from articles published in recent issues of HealthFacts.

> Preoperative Fasting (June 2002)
> Clarinex (May 2002)
> Mental Deficits After Major Surgery (April 2002)
> Postmenopausal Hormones: An Update (March 2002)
> Light Cigarettes No Safer (January 2002)
> Lung Cancer Screening (January 2002)
> Hospital Drug Errors (December 2001)
> Drug Advertising (December 2001)

 

Preoperative Fasting: Rules Changed
by Maryann Napoli
(June 2002)

Telling people to fast before they undergo surgery is a hospital custom that will not die. In 1999, the American Society of Anesthesiology revised its practice guidelines for healthy people about to undergo elective surgery. Well before these guidelines changed studies had demonstrated that, thanks to modern anesthesia techniques, the major concern-pulmonary aspiration*-rarely occurs. Yet the fasting itself causes hardship that only adds to the normal anxiety anyone would experience before surgery.

Headaches, dehydration, irritability, and hypoglycemia are but a few of the consequences for people given the old advice of no food or liquids after midnight, the night before surgery. The advice was standard whether the operation was scheduled for dawn, or for 1:00 p.m. the next afternoon.

The new practice guidelines that should have changed everything now recommend telling people the following: "Clear liquids up to two hours before elective surgery, a light breakfast (tea and toast, for example) six hours before the procedure, and a heavier meal eight hours beforehand."

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Clarinex

by Maryann Napoli
(May 2002)

The giant Clarinex pill comes spinning out at you in the new ads, promising "all day, all night, all year allergy relief." The ads, which seem to be everywhere, are part of a massive campaign by the Schering Corporation to sell the idea that Clarinex is an improvement over Claritin. It isn't-but more on that later.

Both drugs are produced by the Schering Corporation, whose ads signify a desperate attempt to maintain market share. The patent is about to run out on Claritin, the most profitable antihistamine of all time with annual sales of more than $2 billion. Schering is not the first company to introduce a "new" drug to compete with its own blockbuster in the months before patent protection expires and the cost drops considerably. Last year, AstraZeneca introduced Nexium, purported to be an improvement over its enormously successful heartburn drug, Prilosec (see HealthFacts, 9/01). There is one difference, however, Prilosec will remain a prescription drug, albeit sold by generic companies at two-thirds the current cost. By the end of the year, Claritin is expected to be available over the counter at a more precipitous reduction in its current cost of $85 for a month's supply.

In both cases, the "new" drug is merely a knock-off of the blockbuster drug. And Claritin's efficacy was marginal to begin with. The drug is no more effective than older, cheaper antihistamines. Lack of drowsiness was supposed to be its advantage over older antihistamines.

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Mental Deficits After Major Surgery

by Maryann Napoli
(April 2002)

It took about ten years for the rumors to surface after coronary-artery bypass surgery was first introduced in the late 1960s. Some people had mental deficits that persisted long after they had been discharged from the hospital. The initial recipients were primarily men in early middle age, so it should have been difficult for surgeons to dismiss the reports as unrelated to the operation. But dismiss they did, and the researchers would not take on the subject for another 10 years. Now there is mounting evidence that cognitive decline can occur at any age, not only as a result of coronary-artery bypass surgery but other major operations as well. Those most likely to be afflicted, however, seem to be elderly people who undergo an operation of long duration.

Had coronary-artery bypass surgery not rapidly become one of the most common major operations in the country, we might never have learned about its adverse cognitive effects that include memory problems and difficulties processing information. But, in time, the research could not be ignored. By the 1990s, several studies with long-term follow-ups found the incidence of cognitive decline to be highest right after the operation, but decreasing over time. At discharge, 50-80% of the people showed cognitive dysfunction, 20-50% at six weeks, and 10-30% at six months. These studies were conducted at a time when the age of a person undergoing coronary-artery bypass surgery had been slowly rising to the current average of 66 years.
Last year, a study conducted at Duke University Medical Center provided even longer follow-up information on 172 people (mostly male with an average age of 61 years) with much more sobering results. Five years after surgery, 42% still showed cognitive dysfunction (New England Journal of Medicine, 2/8/01).

These adverse effects had long been attributed to the use of the machine that takes over the function of the heart during all major chest operations. The heart-lung machine not only cools the heart, but also temporarily paralyzes it so that the surgeons can operate. The patient's blood is diverted to the heart-lung machine, where oxygen is introduced and carbon dioxide removed, before the blood is returned to the body. Tiny air bubbles obstructing the blood flow to the brain were identified as a suspected main cause of cognitive deficits. Consequently, some surgeons have been experimenting with what they call the off-pump version of coronary-artery bypass surgery, now used in 20% of all such operations performed in the U.S.

Last month, the largest randomized clinical trial to compare both techniques published discouraging results in the Journal of the American Medical Association. The 420 participants (mean age 61 years) were facing their first coronary-artery bypass surgery. All had been randomly assigned to either on-pump (the standard procedure) or off-pump surgery. Psychologists had tested the participants before and after the operation.

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Postmenopausal Hormones: An Update

by Maryann Napoli
(March 2002)

Postmenopausal hormones have been promoted to women (and doctors) for nearly four decades with promises of everything from youthful skin to increased longevity. The currently popular indications-prevention of heart attack and hip fracture-are not supported by good research. Two large trials, which randomly assigned women to take hormones or not, have failed to confirm estrogen's heart protective effects. And while many randomized controlled trials (RCTs) have proven estrogen's ability to stop the loss of bone density, none lasted long enough to show that this hormone actually prevents fractures.

Estrogen is still prescribed to women as a treatment for osteoporosis (bone loss), though the Food and Drug Administration removed this indication in 1999 because of lack of evidence. Only one indication for taking hormones is backed up with good research support-the relief of menopausal symptoms, such as hot flashes.

The two large RCTs, which provided the heart-related results, are the Women's Health Initiative (WHI) and the Heart and Estrogen/Progestin Study (HERS). Together they included about 30,000 participants. The HERS was designed to determine whether hormones can prevent heart attacks in women, aged 44 to 79 years, who have heart disease. And the WHI, which includes healthy women, aged 50-79 years, is exploring the effects of hormone therapy on the prevention of heart disease and osteoporosis-related fractures, and on the risk of breast and uterine cancers. All participants had been randomly assigned to take a placebo (inactive pill) or hormones (estrogen alone for women who had a hysterectomy or estrogen plus progestin for women with an intact uterus).

The data from these and other RCTs are being searched for information about a range of health effects associated with hormone therapy:

Cardiovascular Events: Both the HERS and the WHI found a small increase in the number of heart attacks, strokes, and blood clots in the lungs in the first one to two years of hormone use. Researchers initially thought that this small risk (fewer than 1% altogether) would disappear after two years, but longer follow-up showed otherwise. Last year, the WHI reported a continued increase in heart attacks, strokes, and blood clots in women taking hormones.

Prevention of Another Stroke: Among 652 women (mean age 71 years) who had suffered a non-disabling stroke or a transient ischemic attack, those who had been randomly assigned to take oral estradiol did not show a lower incidence of death or stroke. Worse, the rate of fatal stroke was significantly higher among those taking estradiol (a form of estrogen).

Fractures: The WHI is designed to answer the question of whether hormones prevent fractures, following its participants for eight to 12 years.

Urinary Incontinence: 1,525 women with urinary incontinence participated in the HERS. All were younger than 80 years and had experienced at least one episode of urinary incontinence per week. Incontinence improved in 26% who had been assigned to take a placebo for four years, as compared with 21% assigned to take hormones. Urinary incontinence worsened in 27% of the placebo group, as compared with 39% of the hormone group.

Dry Eye Syndrome: 665 participants of Women's Health Study, a RCT that began in 1992, found a slight increased incidence of dry eye syndrome in hormone users (past and current), especially among the women on estrogen alone. According to questionnaires completed by the participants: 9% of those taking estrogen alone reported severe symptoms diagnosed by physician, as compared with 7% among the estrogen plus progesterone or progestin, and 6% among those who never used hormones. Dry eye syndrome, a condition with no effective treatment, can damage the surface of the eye.

Urinary Tract Infection: Women in the HERS who had been randomly assigned to take hormones for four years did not have a lower incidence of urinary tract infections.

Gallbladder Disease: The HERS showed gallbladder disease to be 38% higher among those who had been assigned to take estrogen/progestin therapy.

Annoying "Minor" Side Effects: Breast tenderness with uterine bleeding caused 30% to stop taking hormones by the end of one year.

What's Wrong With Observational Studies?

Many benefits attributed to hormones, such as prevention of Alzheimer's disease, have yet to be validated in an RCT. Such information comes from less reliable research, known as observational studies. Such research takes a backward look at women who chose to take hormones to determine whether their health status differs from that of women who did not take hormones.

The problem with observational studies is this: Women who take hormones tend to be upper income and well educated. Both characteristics are associated with better heart health and longevity. Susan Love, MD, author of Dr. Susan Love's Hormone Book, identified the problem: "We don't know whether hormones made the women healthy, or whether healthy women take hormones." It is the observational studies that misled so many gynecologists to believe that estrogen prevents heart disease.

An RCT provides more trustworthy results because participants of similar age, health status, etc, are randomly assigned to take the drug or not. Then they are followed for years. Most RCTs are double-blind, which means that neither the participants nor the health professionals monitoring them know who is on the placebo and who is taking the active drug.

Benefits and Risks Yet to Be Confirmed:

Colorectal Cancer: Observational studies have produced inconsistent findings regarding the possibility that hormones lower the risk of colorectal cancer. The results range from no reduction to a 33% reduction in colorectal cancer.

Cognition: Observational studies suggest that hormone therapy may reduce the risk of cognitive decline. A systematic review of all studies, including some RCTs, that explored this topic was published last year in the Journal of the American Medical Association. The participants, who had been taking hormones for the symptoms of menopause, showed improvements in "verbal memory, vigilance, reasoning, and motor speed, but no enhancement in other cognitive functions." The authors went on to explain that most of these studies had significant limitations.

Alzheimer's Disease: No RCT has been conducted regarding the risk of dementia. Earlier observational studies suggest that women taking hormones were less likely to develop Alzheimer's disease, but more recent observational studies did not find this benefit.

Breast Cancer: Does estrogen use increase the risk of developing breast cancer? More than 30 observational studies have been conducted to answer this question. But, here too, the results have been inconsistent. Some found estrogen use to be associated with a reduced risk of developing breast cancer; others found an increased risk of breast cancer beginning after five years of use. And some studies found no risk. The WHI has been designed to provide a reliable answer to the question of whether there is an association between estrogen and breast cancer.

Endometrial (uterine) Cancer: Ever since it became known that estrogen increases a woman's odds of developing uterine cancer, the drug is now prescribed with another hormone, progestin, to women with an intact uterus. Not all doses of progestin protect the uterus, however. For the results of a review of all trials that determined appropriate doses, see "Protecting the endometrium" by Gibbons and Thorneycroft in the Journal of Reproductive Medicine (2/99).

For More Information About the WHI:

The Women's Health Initiative is sponsored by the U.S. National Heart, Lung and Blood Institute. Visit its Web site at www.nhlbi.nih.gov/whi/hrt/htm for more information about the progress of this trial.

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LIGHT CIGARETTES NO SAFER

by Maryann Napoli
(January 2002)

The National Cancer Institute just released a report showing that the tobacco industry's capacity for duping the public can never be overestimated. The latest example involves the marketing and promotion of low-tar or "light" cigarettes. Many smokers have turned to these cigarettes on the mistaken belief that they are safer. All the while, the tobacco industry was putting its considerable engineering skills into the design of cigarettes that only appeared to be safer.

In the 50 years since the link between smoking and lung cancer was first identified, cigarettes have changed dramatically. Filters were added to reduce the amount of tar, for example, and cigarettes that provided less nicotine became available. Use of these so-called light cigarettes grew steadily in the 1980s and 1990s to the point where they now represent 97% of the cigarettes sold in the U.S. But this hasn't led to the expected drop in lung cancer deaths. On the contrary, lung cancer rates continued to rise until the early 1990s. Rates have dropped since then because so many smokers have quit, not because cigarettes became safer. The new report from the National Cancer Institute provides some explanations.

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LUNG CANCER SCREENING

by Maryann Napoli
(January 2002)

Over the last two years, hospitals have begun to promote lung cancer screening to the public in newspaper ads and mailings. Central to the promotion is computed tomography, or CT scan. A new study from Duke University challenges this technology's biggest selling point (Cancer, 12/15/01). CT scans are promoted as having a major advantage over chest x-rays because they can detect smaller tumors. But the Duke investigator found that catching a tumor at the smallest possible size may not affect a person's odds of dying from lung cancer.

Dr. Edward F. Patz of Duke University in Durham, North Carolina, and colleagues, knew beforehand that chest x-rays can find tumors as small as 1 centimeter in diameter; while CT scans can pick up tumors as tiny as 5-10 millimeters. To determine whether tumor size at diagnosis matters, the investigators studied 620 people who had been diagnosed at different stages of lung cancer. Each person's tumor size was determined, along with how far each person's disease had advanced. Dr. Patz and colleagues found that a tumor's size was less relevant to disease spread than its molecular and genetic characteristics. Contrary to the standard message to the public: Small was not synonymous with less advanced or more treatable.

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HOSPITAL DRUG ERRORS

by Arthur Aaron Levin
(January 2002)

A new study from Norway found that nearly one out of five deaths of hospital patients are likely to be associated with a prescription drug (Archives of Internal Medicine, 10/22/01). The death rate is similar to that found in a 1998 study of U.S. hospitals.

The Norwegian researchers examined the records of all 732 patients who died of any cause while under care at Central Hospital of Akershus, Norway, over a two-year period. They then identified 133 patients whose death was associated with one or more drugs administered in the hospital. The researchers, led by Dr. Just Ebbesen, believe that theirs is the first study to routinely use both autopsy results and pre- and postmortem blood specimens for drug analysis in addition to medical records. Each hospital death was reviewed by the team of six researchers and a case by case consensus conference held to determine whether an adverse drug event was likely to be the cause of death or not. Most previous studies of drug-related hospital deaths have relied solely on medical records.reated by "To Err is Human" almost two years ago appears to have dissipated. The IOM report challenged the U.S. health care system to halve the medical error rate by 2005 and recommended that prescription drugs are the best place to start.

While computerized drug order systems are the gold standard, other interventions can be just as effective as computers in improving patient safety. For example, having doctoral level pharmacists in hospitals working with doctors to select the right drug, dose and route of administration for a patient appears just as effective as computers in eliminating many types of errors. Using bar-coding to match up prescriptions and patients can eliminate wrong drug/wrong patient mistakes. Even simple measures, such as prohibiting the use of easily misunderstood verbal drug orders by doctors or the use of abbreviations in prescriptions can make a meaningful difference.

Unfortunately, only a minority of U.S. hospitals has taken the necessary steps to meet the challenge. With all due respect to the threat of bioterrorism, it’s time for the public to hold both federal and state governments accountable for the lack of progress in improving patient safety.

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Exposure to Light at Night Increases Risk of Breast Cancer

by Maryann Napoli
(November 2001)

Women who work the night shift show an increased rate of breast cancer, according to a study published last month in the Journal of the National Cancer Institute. Prolonged exposure to light suppresses the normal nighttime production of melatonin, which researchers describe as the “hormone of darkness.” Earlier studies have already shown melatonin suppression to be associated with the release of estrogen by the ovaries.
There are many reasons to pursue the suppressed melatonin/breast cancer link. In an editorial that accompanied the new studies, Johnni Hansen, PhD, of the Danish Cancer Society, wrote, “Melatonin is a mammalian hormone involved in circadian rhythms and sleep and potentially in restraining tumor growth.” Four previous studies of blind women showed that they have a 20-50% lower rate of breast cancer, as compared with sighted women. Because blind women are not sensitive to changes in light, their melatonin levels remain constant.

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Baycol and Other "Statin" Drugs

by Maryann Napoli
(October 2001)

Soon after the cholesterol-lowering drug, Baycol (cerivastatin,) was withdrawn due to a rare and serious muscle-damaging side effect, competing drug companies moved in to snare some new customers. Full-page ads began appearing in newspapers urging people who have stopped taking Baycol to ask their doctors about going on another drug in the same class called "statins." These include Pravachol (pravastatin), Zocor (simvastatin), Lipitor (atorvastatin), and Lescol (fluvastatin).

Bayer A.G., the German pharmaceutical and chemical conglomerate, voluntarily withdrew its drug, Baycol, last August after 31 confirmed deaths had occurred in people who had been taking the drug. All died of a rare condition called rhabdomyolysis, which causes a break down of muscle tissue. At the time, news reports acknowledged that other statin drugs have also been linked to rare cases of muscle cell damage, but the FDA found the problem to be much more common with Baycol than with other drugs in the same class.

This FDA contention was explored in a recent issue of The Medical Letter, a physician publication with no drug advertising. It concluded that there is no good evidence that any one of the statin drugs is less likely than any other to cause rhabdomyolysis. The risk, though rare, appears to increase with higher doses of statins, and may be greater in patients with renal failure, according to The Medical Letter. Doctors are advised to tell their patients to promptly report unexplained muscle pain, tenderness or weakness, especially if they are taking a statin and gemfibrozil (another anti-cholesterol drug) together.

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Chronic Fatigue Syndrome

by Maryann Napoli
(October 2001)

It's been called everything from "the yuppie flu" to nonexistent. But Chronic Fatigue Syndrome was given its due last month when the Journal of the American Medical Association published a systematic review of all relevant studies to determine which treatments are effective.Results favored two non-drug interventions.

Chronic Fatigue Syndrome is a constellation of symptoms that include headache, fatigue, sleep disturbances, impaired concentration, and musculoskeletal pain. The cause of CFS is unknown, but experts have considered a range of possibilities, such as viral, hormonal, immunological, or psychological disturbances. Among the many treatments for CFS are exercise, dietary supplements, antidepressants, corticosteroids, cognitive behavioral therapy, immunotherapy, and prolonged bed rest.

Penny Whiting, MSc, of the University of York, England, and colleagues searched 19 databases for both published and unpublished CFS treatment studies. Forty-four trials were found with a combined total of 2,801 participants. Two interventions were deemed useful: exercise and cognitive behavioral therapy. "Neither is remotely curative," observed Simon Wessely, MD, in an editorial that accompanied this review.

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Tobacco Companies Still Advertise to Kids

by Maryann Napoli
(September 2001)

As part of its landmark settlement, the tobacco industry agreed to stop advertising cigarettes to children. Now, three years later, the agreement "appears to have had little effect on cigarette advertising in magazines and on the exposure of young people to these advertisements," according to a new analysis conducted by Charles King, III, JD, and Michael Siegel, MD, of the Harvard Business School and the Boston University School of Public Health, respectively. Their results were published last month in The New England Journal of Medicine (8/16/01).

King and Siegel examined the cigarette advertising expenditures and the exposure of young people to advertising before and after the Master Settlement Agreement with the four largest tobacco companies in the U.S. They estimated that, in 2000, magazine ads for "youth brands" of cigarettes reached more than 80% of young people in the U.S. an average of 17 times each. The researchers looked at the trends in advertising expenditures for 15 different cigarette brands and the cigarette ads aimed at young people in 38 magazines between 1995 and 2000. They found that advertising expenditures for youth brands in youth-oriented magazines had actually increased since the settlement-from $56.4 million in 1995 to $59.6 million in 2000.

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Celebrex and Vioxx

by Maryann Napoli
(September 2001)

Ever since the anti-inflammatory drugs, Celebrex and Vioxx, came on the market two and a half years ago, questions have surrounded them. Do these costly drugs offer a safer alternative to other arthritis drugs? Do they have a lower rate of the gastrointestinal side effects associated with older painkillers, such as aspirin, ibuprofen, and acetaminophen? If so, is this benefit canceled by heart-related risks linked to Celebrex and Vioxx?

A new analysis of all clinical trials that had attempted to answer these questions was conducted by Debabrata Mukherjee, MD, and colleagues at the Cleveland Clinic Foundation. But before their analysis appeared in the Journal of the American Medical Association last month, a controversy erupted over the validity of the results from the largest and most important clinical trial involving Celebrex. Its manufacturer, Pharmacia, withheld long-term data, which made Celebrex appear safer than it really is.

Celebrex and Vioxx belong to a relatively new class of drugs called selective COX-2 inhibitors, which control inflammation by blocking enzymes called prostaglandins. Celebrex was the first COX-2 inhibitor to appear on the market (in 1999); Vioxx followed soon after. Both are prescribed for osteoarthritis, rheumatoid arthritis, and other chronically painful conditions

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Drug Advertising
by Maryann Napoli
(December 2001)

Fear mongering is the subtext of many of the prescription drugs ads you see on TV and in print. These ads might just as well come out and say: OK, you're healthy now, but any time in the near future you can die from a heart attack, cancer, or hip fracture. The surest route to high profits is the expensive drug that must be taken daily for years, preferably for life, out of fear of a disease that might create symptoms 10, 20, 30 years down the road.

Many of the ads play on fears of aging. Middle-aged people (with the necessary drug-coverage) are the natural targets. It helps to read these ads skeptically because many are riddled with half-truths. Here are some representative examples of the different approaches to advertising prescription drugs to the public. All are bound by the rules of the Food and Drug Administration (FDA).

SELL FEAR OF THE DISEASE

"Osteoporosis--Could you be at Risk" This is the headline of the current ad campaign sponsored by Eli Lilly, which does not mention its osteoporosis drug, Evista (generic name: raloxifene). Anytime the drug and its purpose appears in an ad, then the side effects and adverse reactions must also be included. But Eli Lilly's ad illustrates another option in drug advertising. Instead of identifying its drug, a company can choose to sell the dangers of a given disease, in this case, osteoporosis. Ads like this one must list an 800 number that will generate a free packet of information and your name on the company's mailing list for life.

"Up to half of women over age 50 will break a bone due to osteoporosis in their lifetime. And the risk increases when menopause ends," warns the Eli Lilly ad, which features a fiftyish woman. The statement is true, but choosing the age of 50 as the cut-off is guaranteed to instill fear. The following statements are not found in the ad, but they are also true: A woman's odds of having an osteoporosis-related hip fracture between the ages of 50 and 70 are low. Half of all hip fractures in women occur after the age of 80.

Years ago, the diagnosis of osteoporosis was made only after the person experienced a fracture due to thinning bones. Now, the definition of osteoporosis has changed to simply mean low bone mass. In other words, what was once a risk factor for fracture is now a disease. Susan M. Love, MD, author of Dr. Susan Love's Hormone Book, writes that the panel of experts that changed the definition of osteoporosis was funded in part by pharmaceutical companies.

SELL A TEST

"See how beautiful 60 can look? See how invisible osteoporosis can be?" This is the headline for Merck's ad, featuring an older woman. It's a good example of the indirect approach to selling drugs: Encourage people to go for testing and invariably you will create many new customers for your drug. Several years ago, Merck announced that it had entered a financial agreement with a major bone density measurement equipment company, in order to get these expensive machines into as many doctor offices as possible.

Merck does not mention its osteoporosis drug, Fosamax, in this ad which simply advises, "Ask your doctor if a bone density test is right for you." It almost comes across as a public service announcement. To prompt the hesitant women into action, Merck adds, ominously, "The fact is, if you're 60 or older, there's a nearly 1 in 2 chance you have osteoporosis." Yes, this statement is probably true given the above, expanded redefinition of the "disease." However, there is a debate among osteoporosis researchers about the value of measuring bone density because the test can’t predict who will eventually have a fracture. Some evidence indicates that bone turnover may be more relevant, but there is no available test for it.

NAME THE DRUG...AND ITS SIDE EFFECTS

"HIGH CHOLESTEROL ISN'T JUST A NUMBER IT'S A WARNING." The message screams out from Bristol-Myers Squibb's ad for its cholesterol-lowering drug, Pravachol (generic name: pravastatin sodium). This represents the type of ad that identifies the drug and its purpose ("protect your heart"), so it must also list side effects and adverse reactions. In the case of a print ad, the side effects appear in tiny type on the next page. Surveys show that few people read the fine print, and this includes doctors.

The ad emphasizes the Pravachol's safety because a competing cholesterol-lowering drug, Baycol, was withdrawn last summer after it caused 31 deaths. The ad attempts to get the people who just went off Baycol to: "Ask your doctor to tell you more about high cholesterol, the risk of heart attack, and if Pravachol is right for you."

The safety claims in this ad are: "Pravachol is no more likely to cause side effects than a placebo (sugar pill) in landmark clinical studies." Well, yes, that's true, but only the people who turn the page and read the fine print will learn that this refers solely to the FDA-required trials that lasted only four months. Most people who take cholesterol drugs do so indefinitely, and the fine print has 16 lines of side effects experienced by drug-treated people in the longer trials that lasted five to six years.

The long list of side effects was attributed to the entire class of "statin" drugs, which includes Pravachol (pravastatin) and Baycol (cervistatin), Mevacor (lovastatin), and Zocor (simvastatin). The 31 deaths attributed to Baycol were due to a rare condition called rhabdomyolysis, which causes a breakdown of muscle tissue. All statin drugs have this rare risk, according to The Medical Letter (9/10/01), a physician publication with no drug advertising.

NAME THE DRUG, BUT NOT THE CONDITION

This is the strangest approach to drug advertising because it mentions the name of a drug but not what it's for. This type of ad circumvents the FDA-requirement of listing side effects once the drug's purpose is identified. It is best exemplified by Schering-Plough Corporation's ads for Claritin, a drug for seasonal allergies. They usually feature a close-up of a young woman's face against a bright blue sky and often some flowers in the background. The message is simply: "Ask your doctor about Claritin."

Claritin stands as a testament to the power of advertising and as a classic example why a drug doesn't have to be any good to become a big seller. Schering-Plough spent a record $136.8 million advertising Claritin directly to consumers in 1999 alone. It paid off. Claritin is the most profitable antihistamine of all time, with annual sales of more than $2 billion, according to The New York Times. A month's supply costs about $85.

Claritin is no more effective than older, cheaper antihistamines. Its much-touted advantage is the lack of drowsiness that comes with other antihistamines. Two FDA-required trials showed that Claritin is better than a placebo, but not much better. At 10-milligram doses, Claritin was only 11% more effective than a placebo. Taken at higher, more effective doses, the drug causes drowsiness.

END-RUN AROUND THE FDA

TV ads are generally bound by rules similar to those of print ads. In 1997, however, the FDA relaxed the rules for broadcast advertising where it concerns side effects. From that year on, only the major side effects had to be mentioned in radio and TV ads that name the drug and its purpose. This accounts for the massive increase in TV ads for prescription drugs.

But some major side effects can be a major turn-off, and that has led to some creative bending of the FDA rules. And this is best illustrated by Roche's ads for Xenical, a weight-loss drug. How many people would run out and ask their doctors for Xenical after hearing that anal leakage is a common side effect?

Roche has found a way to avoid this information with its two-part TV commercials for Xenical. The first ad does not mention Xenical; it simply shows quick images a baby growing up to be a heavy-set woman while describing excess weight as unhealthy. The second ad names the drug but not the condition, using the same background music and images. By separating the two ads with brief unrelated commercials, Roche has circumvented FDA rules about describing side effects. The ads appeared early this year, and thus far, no warning letter to Roche from the FDA has appeared on the agency’s Web site.

WHAT TO CONSIDER WHEN READ A DRUG AD:

-Many ads leave the impression that everyone who takes the drug will benefit from it. You will want to know how effective the drug has been proven to be in terms of, say, reducing heart attacks, fractures, or cancer recurrences, etc. Rarely, will a drug ad ever provide this crucial information. Consult the Physicians' Desk Reference, which is available at most community libraries. It can also be purchased at most chain bookstores. The book is difficult to read, but it is the only readily available source of data concerning what has been proven in drug trials and how long the trials lasted.

-Avoid taking any newly approved drug when there is an alternative. The pre-approval studies required by the FDA usually last only a few months and do not include enough participants to uncover rare side effects. In the last decade, a number of prescription drugs have been withdrawn within five years of becoming available due to life-threatening side effects. This has led many consumer advocates to advise people to wait at least five years from the date of release before taking any new drug. This also allows time for follow-up studies to determine whether the new drug is truly an improvement over the older versions of the same medication.

-These ads are increasing the cost of health care for everyone. The 50 most-advertised prescription medicines contributed significantly last year to the increase in the country's spending on drugs, according a new report. It also found that these 50 drugs accounted for almost half of the $20.8 billion increase in drug spending last year. The report was prepared by the National Institute for Health Care Management, a nonprofit research foundation. Only the drugs still under patent, and therefore expensive, are advertised directly to the public.

-Drug ads are not checked by the FDA for accuracy beforehand, though drug companies are free to do so voluntarily. This occurs infrequently. Instead, the ads are pulled only after complaints are made and verified. This usually takes about six months, and the drug company is given several additional months grace period. Companies whose ads are judged to be misleading will receive a warning letter that is published on the FDA Web site. Offending drug companies incur no penalty for misleading the public. They are merely told to withdraw the ad. Many drug companies change their ads every six to 12 months anyway. On rare occasions, a company may be required to run a corrective ad.

-Go to the FDA’s Web site (www.fda.gov). You will find a wealth of information about drugs, as well as dietary supplements (herbs and vitamins). On the home page alone, you can go to "Safety Alerts" and see the latest recalls; "Product Approvals" for information about the new drug approvals; "How to Report a Problem to the FDA;" and "Drug Information" for standard labeling facts, such as side effects, purpose, warnings for specific drugs.

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Ambigious Pap Test Results
by Maryann Napoli
(June 2001)

Many women with ambiguous Pap test results go on to have unnecessary diagnostic procedures, biopsies, and treatment. Now a small step has been taken to reduce the excesses associated with this screening test for cervical cancer. A new study has shown that testing for the human papilloma virus (HPV), which is present in 95% all cases of cervical cancer, will identify some women who can safely avoid a followup diagnostic procedure.

The new finding comes from a large National Cancer Institute-sponsored clinical trial whose long-range - and yet to be realized - goal is to determine which of the ambiguous or borderline abnormalities found by the Pap test will eventually become cervical cancer. At present, doctors cannot accurately make this distinction for the cellular abnormalities that fall into the "grey" zone of Pap results between cancer and benign. The medical name given to these abnormalities says it all; they are called atypical squamous cells of undetermined significance, or ASCUS.

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Free Cancer Information: A Helpful But Flawed Service
by Maryann Napoli
(January 2001)

Credible, Current, Comprehensible. These are the words that the National Cancer Institute uses to describe its free information service for physicians and the general public. The NCI’s database called Physician Data Query, or the PDQ, contains peer-reviewed summaries of the evidence to support everything from treatment options to screening tests. It is enormously influential. The PDQ gets 15 million hits a month via the NCI Web site; it is the major source of information for the trained specialists who answer the national hotline (1-800-4-CANCER); and it has extensive licensing agreements with other widely used cancer databases, such as Oncolink and CenterWatch. You can access the database in a variety of ways. Relevant pages from the databases will be mailed to callers to the NCI's hotline. And everyone with access to the Internet or a fax machine can get a printed version of the information directly. Unfortunately, the service which is financed with taxpayer money serves physicians far better than it does the general public.

Prostate Cancer

A person newly diagnosed with cancer, for example, will find that the PDQ is divided into two sections—one for patients and one for health professionals. The patients get a watered down version of the health professional summaries, demonstrating the retro position that all important information must be filtered through your doctor. A case in point is the section called treatment options for early prostate cancer, which contains several instances of "A doctor may choose ..." Or "Your doctor will..." It assumes passivity on the part of the consumer. If ever there were a cancer that cries out for people to be proactive, early prostate cancer is it. Three studies followed untreated men and found their survival rate to be similar to that of men given prostatectomy (88%). Four treatment options, including "watch and wait," are listed, but no head-to-head comparison has ever been done to guide men in their decision-making. This goes unmentioned. Surgery is described as "one of the most common treatments" without explaining that this merely means the prostatectomy is done out of tradition and not because there's definitive evidence that its better than radiation therapy or doing nothing at all.

Patients do not receive a summary of the evidence; instead they merely get a laundry list of treatment options. For information about the supporting research for each, the PDQ user must go to the version intended for health professionals. Only there will the reader find, for example, the evidence to support the decision to forego treatment. "One population-based study with 15 years of follow-up has shown excellent survival without any treatment in patients with well—or moderately well—differentiated tumors clinically confined to the prostate, irrespective of age." The patient's version of PDQ also leaves out information on treatment complications based on the arguable contention that this will be addressed by each man's physician. But studies show a discrepancy between the doctors' idea of the complications risk and what men treated for prostate cancer actually experience. In a recent issue of the Journal of the National Cancer Institute (JNCI News Section, 12/6/00), Dr. Michael J. Barry, who is described as an "advocate for evidence-based medicine," contrasted beliefs of surveyed urologists and radiation oncologists with reports from patients themselves. About 80% of prostate cancer patients surveyed said they became impotent after surgery, but Dr. Barry's study found that surgeons estimated the rate of impotence after the much-heralded nerve-sparing surgical procedures to be in the range of 45% to 60%.

Radiation oncologists also underestimated this complication. They thought that impotence resulted in 23% to 39% of men treated with radiation therapy, though this complication occurred in 62% of men so treated. Why the gap between physician belief and reality? Dr Barry told the JNCI that lower impotence rates associated with nerve-sparing prostatectomies performed at teaching hospitals are not likely to be matched by surgeons in community hospitals. (This risk information gap, by the way, is not confined to the treatment of prostate cancer.) The PDQ won't help the man who wants a realistic complication estimate—unless he goes to the health professional version. Be reminded that the rates do not necessarily reflect the real world of medical practice; they come from clinical trials of treatments done under the best of circumstances at academic medical centers.

Stage 0 Breast Cancer

Treatment options for early breast cancer merit only a much-abbreviated listing in the patient version of the PDQ. The woman with a very early breast cancer called ductal carcinoma in situ (DCIS) wont find out about uncertainties concerning the best way to treat this microscopic lesion within the milk duct; nor will she learn that, left untreated, DCIS will become invasive in only about 20-30% of cases. The patient version of the PDQ assumes that all women want the most aggressive treatment, and neglects to mention that the sole treatment of this tiny lesion can be its surgical removal. The women whose doctor recommends the most common treatment—excision plus radiation—won't learn from the PDQ that the addition of radiation therapy will decrease her odds of a recurrence by only 13%, according to eight-year results of an ongoing clinical trial. Mastectomy is listed as her second treatment option for DCIS, but only the professional version of the PDQ points out that the mortality rate is the same (1% at eight years) whether she chooses this extreme treatment (removal of the entire breast) or the minimal treatment, excision alone. Perhaps some women would decide that the small reduction in odds of recurrence isn't worth the side effects of the more aggressive treatment options. The PDQ doesn't even seem to consider this possibility.

Small Cell Lung Cancer

"The majority of patients with small cell lung cancer die of their tumor despite the best available treatment. Most of the improvements in survival of patients with SCLC are attributable to clinical trials which have attempted to improve on the best available, accepted therapy. Patients entry into such studies is highly desirable." This sobering assessment of the survival chances for people with this common form of lung cancer comes from the PDQ for professionals. One might expect the equally realistic viewpoint expressed in the patient version, if for no other reason than to encourage more clinical trial participation. But once again, the patient merely gets a list of treatment options without a hint of how marginal the chances are of success. Anyone prepared to take on the side effects of chemotherapy plus radiation therapy, for example, deserves to know that this treatment option only improves the three_year survival rate by 5%, compared to chemotherapy alone. Only the health professionals receive this information, along with the fact that this modest benefit was largely confined to people under the age of 65 years.

Clinical trials are crucial to finding more effective treatments, but the PDQ never explains that they exist because doctors know that a certain percentage of cancer patients are not helped by the standard treatments. In a recent National Cancer Institute survey, 38% of cancer patients reported that they did not want to participate in a clinical trial because they believed the "standard treatment to be better." Unless each PDQ treatment section identifies the gaps in knowledge and the percentage of treatment failures, not many cancer patients would be motivated to move on to the section of the database that describes clinical trial participation.


What You Can Do

Whether you access this database by calling the National Cancer Institute's hotline (1-800-4-CANCER), using its Cancerfax service (1-800-624-2511) or going to the Web site (www.cancernet.gov), don’t bother with the information directed to patients. The professional versions of the PDQ not only provide in-depth information but also list the medical journal references and a numerical system for rating the levels of scientific evidence for each treatment option. This type of information is just as, if not more, important to cancer patients as it is to health professionals. Unfortunately, the writing can often be tough going for people without a medical background. Despite its flaws, the PDQ is the best source of evidence-based cancer treatment information. The service has been available for over 17 years, but it continues to ignore the consumer's need for in-depth evidence-based information that is comprehensible.

Maryann Napoli is the associate director of the Center for Medical Consumers in New York.




Recommended Databases For the Medical Consumer

Two medical databases have managed to provide free, evidence-based information that is not "dumbed down" for consumers. Both deal with a wide variety of medical concerns and are accessible via the Internet. One is the consumer network Web site of the Cochrane Collaboration. The Cochrane Collaboration began in the U.K. and has become a worldwide network of volunteer experts who review the medical literature on a broad range of medical interventions to determine what works. The reviews are updated regularly. The consumer network Web site of the Cochrane Collaboration is located in Australia. Click into "Whats New" and it will lead you to over 800 abstracts on everything from "Echinacea for the Prevention and Treatment of the Common Cold" to "Interventions for Preventing Oral Mucositis or Oral Candidiasis for Patients with Cancer Receiving Chemotherapy." The Cochrane Collaboration expects to include a six-line consumer synopsis for most of their reviews by next year; at present, this is available for only 80 subjects. There is a charge for the full text of each review and its list of references.

The other recommended database is sponsored by the American College of Physicians, which publishes Annals of Internal Medicine. Last year, this twice monthly journal began publishing "summaries for patients" for its lead articles. The summaries are available on the Annals of Internal Medicine Web site. Click into each article, and you will have free access to the full text, as well as the "summaries for patients." An archive of past summaries is also available at no charge. For example, a person searching for information about gastroesophageal reflux disease, or GERD, will find eight recent articles on the subject. The format is what makes the summaries unique. For each study that is summarized, the site breaks down the information into seven parts under the following headings: What is the problem and what is known about it so far? Why did the researchers do this particular study? Who was studied? How was the study done? What did the researchers find? What were the limitations of the study? What are the implications of the study?

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