My Health

FDA pledges better communication on drug safety: AMNews interviews Andrew von Eschenbach, MD

March 31, 2008 on 11:44 pm | In Uncategorized | Comments Off Washington -- Muscle provided by Congress last fall was intended to allow the Food and Drug Administration to police drugs already on the market. Findings from this effort could enhance physicians' understanding of a medication's potential for harm or their ability to identify patients at risk for adverse events.

Now the issue is how to get word of these findings to physicians quickly. Current methods, such as the FDA's "Dear Doctor" letters, don't always reach physicians. Figuring out which new communication approaches and technologies will work is one of the challenges the agency faces.

The FDA Amendments Act of 2007 provided more funds to monitor drugs through their life cycles as well as authority to require warnings or studies when risks are first suspected.

In the lead-up to this change, the agency's reputation as drug safety watchdog took major hits when drugs such as the pain reliever Vioxx and the diabetes drug Avandia were pulled from the market.

FDA Commissioner Andrew von Eschenbach, MD, has vowed to improve the agency's record.

AMNews: Should doctors be looking for more messages from the FDA?

Dr. von Eschenbach: We feel strongly communications need to be timely. It is something we have to look at from both sides of the equation.

We have to be careful about saturation and overload. We don't want to be Chicken Little, but we want doctors and care providers to know what we know as early as we know it and then participate in it. But we want to put it in context. We'll tell you when it is something that demands your attention and immediate action, and we'll tell you when it is something we are concerned about but are still gathering information on. And we hope you will help us with that. It will take a little time to get there.

AMNews: How will you do this?

Dr. von Eschenbach: What the FDA wants to do is collaborate and cooperate with the AMA, with nurses, with pharmacists, with the media disseminating information and with the pharmaceutical and biotech industry that also disseminates information. What we want to do is to try to get it right.

We all grew up with the Physicians' Desk Reference, which is a great tool, but in the 21st century it is not the appropriate tool. We are going to move to communications that are not paper-based but electronic-based. It won't depend on one thing, but it will depend on our ability to put in place a variety of strategies, and we will have to do it in collaboration with those who are partnering with us so they know what we know when we know it, in real time.

AMNews: Are physicians reporting their observations on drug effects to the FDA?

Dr. von Eschenbach: No. We don't have all the tools in place yet for them to do this. One of the most effective communication tools today is the Web, and the FDA is doing a complete revision of its Web site. We started a year ago revising it for consumers. It is now far more user-friendly than it was before. It is written in styles appropriate to patients and to physicians, who will have a separate entry portal.

AMNews:MedWatch is already in place. Isn't that effective?

Dr. von Eschenbach: MedWatch isn't going away. We are trying to enhance it.

AMNews:What kind of feedback will you want from physicians?

Dr. von Eschenbach: It's a spectrum. First of all, I think it's important for them to feed back to us whether the information we are providing to them -- whether it's a patient label, medication guide or a public health advisory -- is effective, useful and whether it is accessible in a way that is helping them in their practices.

We have to engage in a dialogue that respects the fact we have to make regulatory decisions about these products. We have to determine whether products should or should not be on the market and whether the way they are being utilized is being framed properly by the label. And we can't do that without physicians telling us what is happening, because they are on the front lines.

We need to ask them to share medical information and data. I know as a physician it is a burden in a very busy practice, in time, energy and effort. And I know, for many, it is a burden financially to put their practice information on an electronic medical record database. But that's what has to be done. It's not just so it's more efficient for them in office management, but so they can use and process that information in a way they can learn from the experience. And if they can share that information with us and contribute to a larger pool, we will know so much more.

AMNews: What about the solo physician in a rural practice?

Dr. von Eschenbach: They may not have the scale and scope, but they do have the experience. On a case-by-case basis, their experience may be more insightful than others' experiences. Sometimes, even in a small practice, encountering a very unusual outcome may lead to discoveries you can't even imagine.

AMNews:When you were in practice six years ago, did you find it difficult to keep up with FDA information?

Dr. von Eschenbach: It's a problem across the board for physicians trying to keep up. You go from reading every journal article, to reading every abstract, to the abstracts in your area of interest. You have to hone down.

Also a challenge was how other people are using information. Patients would come in with information they had gotten off the Web. It's not an absence of information but an abundance of information, and you need to define good information. For patients, that's confusing.

A challenge for both the AMA and the FDA is to be seen as the source of accurate and reliable information. We want the physicians and the consumer to see us as the source of the most accurate, most insightful and most complete information about medical products, drugs, biologics and devices. Because we are at the epicenter, we know more about those products than anyone else, including the person who discovered it or is making it, because we are gathering information across the spectrum.

AMNews:Does the FDA have enough money to do its job?

Dr. von Eschenbach: We've seen increases in 2007 and 2008, and we hope to see increases in 2009. But to do more, we need more. I hope the American people, through their representatives, will see this as a crucial and absolutely worthwhile investment.

Ibuprofen may lessen benefit of daily aspirin

March 31, 2008 on 11:44 pm | In Uncategorized | Comments Off Patients taking ibuprofen for pain and aspirin to reduce their chances of a second stroke may not be receiving the full benefit of their prevention efforts, according to a study in The Journal of Clinical Pharmacology in January.

Researchers assessed the combined effect of these two drugs on 10 healthy volunteers and 18 others who were using the medications for pain relief and stroke risk reduction. The blood-thinning effect of the aspirin was blunted in the healthy participants, while those who were attempting to prevent a stroke appeared to be resistant to the effects of aspirin until ibuprofen was discontinued. Also, 13 people in the latter group experienced a stroke while taking these two drugs together over a 27-month period.

"Those strokes were preventable," said Francis M. Gengo, PharmD, lead author and associate professor of pharmacy practice and neurology at University at Buffalo in New York.

Several studies have suggested that ibuprofen may interfere with the vascular benefits of aspirin. It's unclear how clinically relevant this phenomenon may be, but the Food and Drug Administration issued a statement in September 2006 calling for physicians to be aware of this interaction. The authors of this latest piece are calling for greater awareness of the possibility regarding stroke prevention.

"This interaction between aspirin and ibuprofen or prescription NSAIDs is one of the best-known but well-kept secrets in stroke medicine," said Dr. Gengo.

Physicians treating patients at high risk for a stroke or myocardial infarction responded that those taking daily aspirin should be cautioned against also taking ibuprofen regularly. This study, however, was too small to be conclusive, although it did make sense in light of findings by others who have investigated the issue.

"The only limitation is the very limited sample size, but this fits very well with previously published studies," said Tobias Kurth, MD, ScD, an epidemiologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School in Boston.

Cardiologists also expressed reservations about this paper's conclusions because, although aspirin reduces the risk of stroke, it does not cut it to zero. The strokes seen during the study may have occurred with or without the use of ibuprofen.

Sweetener scrutiny: Are sugar substitutes a helpful tool or an ineffective crutch?

March 31, 2008 on 11:44 pm | In Uncategorized | Comments Off The rats in the West Lafayette, Ind., laboratory of Susan Swithers, PhD, don't lose weight when they eat artificially sweetened food. They eat more, and gain more. "Rather than these kind of products making it automatically easier to lose weight, they might make it automatically harder," said Dr. Swithers, a Purdue University associate professor of psychological sciences.

Her study documenting this phenomenon, in the February Behavioral Neuroscience, is the latest flare-up in the decades-long debate regarding the safety of artificial sweeteners and whether they aid weight loss. Cancer fears related to these products may have faded, but the theory they might trigger overeating lives on.

New evidence from some epidemiological studies supports that view. A paper in the Feb. 12 Circulation, for instance, associated drinking one can of diet soda per day with a 34% increased risk of developing metabolic syndrome compared with those who did not drink any carbonated beverages. People who drank the sugar-sweetened versions had a 10% increase in risk.

"I'm wondering if maybe the artificial sweetener makes you feel hungrier somehow," said Lyn Steffen, MPH, PhD, one of the authors and associate professor at the University of Minnesota in Minneapolis. "You drink this artificially sweetened drink, and you might feel satisfied for a short time. At the end of the day, it actually makes you eat more."

It's not clear why artificial sweeteners somehow might make weight gain more likely, but preliminary data suggest that it could be how the brain reacts. A study in the Feb. 15 Neuroimage compared the brain activity of 12 healthy women fed sugar or the artificial sweetener sucralose. Both substances activated areas of the brain associated with pleasant taste, but sugar had a stronger effect in those areas that played a role in expectation and satisfaction. The authors suggest that this finding indicates sugar may turn off the desire for more sweetness, but artificial sweeteners do not. Additional calories are needed to get it to stop.

"If you eat a pound of chocolate, you're done with it. At least for most people, your brain says, 'That's enough.' This is hypothetical and needs to be tested, but maybe the sucralose sets the sweet taste response in motion but it might not turn the brain response off," said Dr. Guido Frank, lead author on that paper and assistant professor of child and adolescent psychiatry at the University of Colorado, Denver.

Artificial sweeteners really to blame?

Despite two decades of suggestive studies like these, the theory that artificial sweeteners may lead to weight gain rather than loss has never been proven. Manufacturers and the Food and Drug Administration, which regulates the sugar substitutes as food additives, say they are safe.

"The causes of obesity are multifactorial. Although surveys have shown that there has been an increase in the use of 'sugar-free' foods over the years, portion sizes of foods have also increased, physical activity has decreased and overall calorie intake has increased," said Beth Hubrich, a registered dietician with the Calorie Control Council, a nonprofit that represents the industry.

194 million Americans consumed low-calorie or sugar-free products in 2007, up from 78 million in 1986.

And these more recent studies are hardly definitive. Critics of the rat study point out that it may not translate to humans. The number of rats, 27, was small, and the sweetener used was saccharin, which is not the most common human-consumed, noncaloric sweetener.

"They were relatively short-term studies, and there were not a lot of rats," said Keith Ayoob, EdD, director of the nutrition clinic at the children's evaluation and rehabilitation center at Albert Einstein College of Medicine, New York.

Others say the brain studies are too preliminary. The epidemiological studies, for example, don't necessarily prove that diet soda causes obesity instead of being something those who carry excess weight are more likely to choose to consume.

"It's not that drinks with zero calories cause obesity but that people who are overweight or obese are trying to do things to lower their calorie intake, including consuming low-calorie alternatives to sodas," said J. Michael Gonzalez-Campoy, MD, PhD, chief executive officer of the Minnesota Center for Obesity, Metabolism and Endocrinology in Eagan. He also is a Minority Affairs Consortium delegate to the American Medical Association and frequently speaks on obesity-related issues.

Several other studies suggest that artificial sweeteners can play a role in weight loss. Reviews such as one in the June 2007 European Journal of Clinical Nutrition concluded that humans were not that good at regulating food intake when dealing with artificial or real sweeteners.

The policy of the American Dietetic Assn. is that full and reduced-calorie products can be consumed safely. "Using [artificial sweeteners] judiciously can fit into a healthy diet," said Christine Gerbstadt, MD, a registered dietician and ADA spokeswoman.

Still, the doubt continues. Every so often, a paper seems to support this theory, and some experts suggest that persistence may have less to do with science than human nature.

"Whenever people talk about artificial, people have this strange feeling about it. Also, we're all trying to attribute blame on something. This is an easy target," said Michael Tordoff, PhD, a researcher at the Monell Chemical Senses Center in Philadelphia. He investigated this question in the late 1980s and early 1990s, and concluded that artificial sweeteners did not play a role in weight gain.

And their role in weight loss remains an open question for some physicians who advocate reducing the use of all sweeteners in favor of a more natural diet.

"I don't know if I have any science behind my recommendations, but if you asked me to recommend diet soda or water, I think every physician in the world is going to recommend water," said James Cunnar, MD, a family physician and medical director of DuPage Family Medicine in Naperville, Ill. "Personally, I have two cups of coffee every morning, and I use one teaspoon of sugar. It's a total of 30 calories, and in the grand scheme of the day, I would much rather use something more natural than a chemical to give that sweet taste."

More guidance needed

What is clear is that artificial sweeteners are very popular and that patients are unlikely to give them up. When the FDA threatened to pull saccharin from the market in the 1970s and 1980s, the backlash was significant. Gilda Radner sang songs about it on "Saturday Night Live." And according to the Calorie Control Council, that popularity of these products has not ebbed.

In 2007, 194 million Americans consumed low-calorie or sugar-free products -- a significant increase from the 78 million who did so in 1986.

Because the science is so mixed, some physicians faced with an increasingly obese population feel the need for more guidance.

For instance, Abraham Jelin, MD, a pediatric gastroenterologist in Brooklyn, N.Y., proposed at the American Academy of Pediatrics's Annual Leadership Forum last month that the organization issue a report on the appropriate use of artificial sweeteners by children. This issue now has been added to the AAP's agenda as the possible subject of a policy statement or clinical guideline.

"Kids like to have soda and sweet things, and if it's safe to give them food that's artificially sweetened, then I think we shouldn't restrict them," said Dr. Jelin, who is also vice president of his local AAP chapter as well as the head of its youth advocacy committee. "It's important that we have good studies that clearly show they're safe or show that they're not safe or they're safe in moderation."

Current AAP policy advocates limiting the intake of sweetened drinks and increasing consumption of fruits and vegetables.

"There's no official recommendation about using [artificial sweeteners] or not using them," said Ronald Kleinman, MD, chair of the pediatrics department at Massachusetts General Hospital in Boston and editor of the AAP's Pediatric Nutrition Handbook. "I tell parents I don't have any concerns about bad effects of artificial sweeteners, but at the same time, the carbonated beverages that are usually the source of artificial sweeteners are not the best things for kids to be drinking in the first place."

Many physicians also say consuming artificial sweeteners is not the only thing needed to lose weight. The real problem may be that too many patients rely on this to achieve the overarching goal. Weight-loss experts say consuming a diet soda rather than one with sugar or high fructose corn syrup is one of numerous possible choices patients can make.

"Many, many people lose weight by eating artificially sweetened foods as part of their weight-loss plan. There's years of clinical experience demonstrating that," said Mary Vernon, MD, board chair of the American Society of Bariatric Physicians and one of the authors of the Atkins Diabetes Revolution. "But we don't usually counsel people to eat unlimited quantities of artificially sweetened things."

Also, unlike rats, which subconsciously may be eating more, humans may be doing so with awareness.

"Diet soda is one of those interesting quandaries that people use to almost feel better about their other bad behaviors. People order a Double Quarter Pounder and a diet soda. How often do we all observe that happening?" Dr. Cunnar asked.

To answer the question of what role artificial sweeteners may play in weight, researchers plan to continue several lines of study. Dr. Swithers is looking for the physiological mechanisms that may link artificial sweeteners with increased food intake. Dr. Frank will investigate how artificial sweeteners affect the brain development of children and adolescents, and Dr. Steffen will dig into observational studies to determine if an association between diet soda and the development of insulin resistance and other metabolic issues emerges.

Sleep times drop during workweek

March 17, 2008 on 11:30 pm | In Uncategorized | Comments Off Washington -- Long workdays are taking a toll on Americans' ability to get enough sleep, according to a new poll released on March 3 by the National Sleep Foundation. Sleep experts worry that the trend could hurt people's health.

A phone survey of 1,000 adults found that about 90% of respondents worked outside the home and arose, on the average weekday, at 5:35 a.m. after sleeping for about 6 hours and 40 minutes. This average worker reported spending 9½ hours at the workplace each day topped off by another 4½ hours per week working from home.

This combination of too much work and too little sleep has serious repercussions. Thirty-six percent of those surveyed reported they had nodded off or dozed while driving, and 32% said they drive while drowsy at least one to two times per month.

Many people, even when they try to sleep, have trouble dozing off, wake during the night and often feel unrefreshed when they get up. Forty-four percent of survey respondents reported that they experience such problems almost every night.

Many health problems also are associated with sleep loss. It is linked to the obesity epidemic and its accompanying chronic illnesses, including diabetes and hypertension.

Chronic sleep loss appears to interfere with the immune and endocrine systems. Evidence also is building that it is associated with a rise in blood pressure during the night that lasts through the following day. An association exists between too much or too little sleep and an increased risk of coronary heart disease in women, according to information from the sleep foundation.

A 2006 Institute of Medicine report on sleep disorders added cardiovascular disease, anxiety symptoms, moodiness, depression and alcohol use to the list of ills caused by sleep deficiency, which was defined as less than seven hours per night.

The new poll was released during the sleep foundation's conference, "The Role of Sleep in Memory and Learning," held March 3 and 4 in Washington, D.C. The foundation is an independent, nonprofit research group based in Washington.

Effects of the life cycle

Researchers presented findings that covered sleep quality from birth to old age. Age is the strongest factor influencing normal sleep and its distribution between REM, or active phases, and non-REM phases, said Phyllis Zee, MD, PhD, professor of neurology and physiology and associate director of the Center for Sleep and Circadian Biology at Northwestern University Medical School in Chicago.

A newborn will sleep for an average of 14½ hours per day, with about 50% being in the REM phase. Hours begin to drop during the toddler and preschool years, and the REM phase dips to about 35% of total sleep time.

36% of workers report dozing or nodding off while driving.

A marked change in the timing of sleep and wakefulness occurs during adolescence. Nine hours of rest is recommended for this age group. Teens' biological clocks run longer and collide with the generally early start of the school day -- a phenomenon that has been noted in recent studies. Early school start times result in chronic sleep loss for many teens who often will recover this loss on weekends with marathon sleep-ins, Dr. Zee noted.

Needs during young adulthood and middle age remain fairly constant, with most people requiring seven to eight hours of sleep each night, she said. During this time, the REM phase remains relatively stable at 20% to 25% of total sleep time.

A change occurs at about age 60, she said, when the percentage of REM sleep begins to decline. The combination of normal age-related changes in circadian rhythms and the poorer health and disorders that can accompany aging can lead to chronic sleep loss in this age group, she said. This in turn, may contribute to cognitive decline.

As sleep deteriorates with advancing age, individuals may be less able to deal with more challenging tasks and may need more time or effort to perform such tasks, said Michael Vitiello, PhD, professor of psychiatry and behavioral sciences at the University of Washington in Seattle. But, Dr. Vitiello asked, "Are older adults chronically sleep deprived?" Additional research will be necessary to answer this question, he concluded.

States battle obesity epidemic with new laws

March 17, 2008 on 11:30 pm | In Uncategorized | Comments Off Using tactics that have helped to reduce the number of smokers, states increasingly are considering bills that are designed to influence people's weight and to curb the obesity epidemic.

"States are where the action is," said Kelly Brownell, PhD, director of the Rudd Center for Food Policy and Obesity at Yale University in New Haven, Conn.

The legal remedies range from silly to serious. One of the more impractical possibilities, which was proposed in Mississippi in January, called for restaurants to be banned from serving obese diners. Even its sponsor, Republican Rep. John Read, said this measure was written to bring attention to the problem rather than to become law. It quickly died in committee after generating opposition from many quarters across the country.

"There's sense in legislating some things, but refusing to serve people is taking it a little bit too far," said Steven C. Brandon, MD, president of the Mississippi Academy of Family Physicians.

But other types of proposals, particularly those targeting children in the school setting, have had the most success and garnered the most support. American Medical Association policy calls for schools to incorporate evidence-based nutrition standards and address the benefits of exercise in the curriculum.

27 states have passed laws on school nutrition since 2003.

"We will do best if we target the young, and school is a place where we can get a great amount of benefit [by] increasing physical activity and access to healthy food," said Mary Armstrong, MD, an AMA delegate and a health officer for the Mississippi Dept. of Health, although she was speaking personally. "We develop habits early in life, and lots of times students teach their parents and all the adults around them what they learned in school."

This approach is favored by many states. According to the American Academy of Pediatrics' "2007 State Legislation Report," 27 states have passed laws on school nutrition since 2003. Laws on physical activity have been added by 24 states. Seven now mandate body mass index screening, and many more are considering doing so.

"[Measuring BMI] is a long overdue thing to do for students. It's important that this be educational and lead to parents taking more of an active role in trying to get students more active," said John Antalis, MD, a family physician and past president of the Medical Assn. of Georgia. That state is considering a bill, supported by MAG, that would include this information on report cards.

Legislation that would affect the world outside the school setting has faced far more difficulty. Last year, California considered a measure that would require restaurant menus to provide nutritional information. This action was supported by numerous medical societies, including the American Cancer Society and the AMA, although it generated backlash from the food industry. The Legislature ultimately passed it, but Republican Gov. Arnold Schwarzenegger vetoed it, arguing that it did not give restaurants enough flexibility in how this information would be presented. It has since been reintroduced, and efforts to enact it continue.

"We need to give consumers the information they need to make healthy choices. Restaurants should provide information on calories and the nutritional contents of the foods they sell," said AMA President Ron Davis, MD.

A taxing angle

A less popular approach, even among public health advocates, is taxing activities or foods that may be playing a role in the obesity epidemic.

"The key is the removal of barriers to engaging in sound nutrition and physical activity, and we're more on the incentive side than for taxes," said Richard Hamburg, MPA, director of government relations at Trust for America's Health, a national public health advocacy organization based in Washington, D.C.

At least 17 states have added taxes to soda and junk food.

Such taxes tend to be low. And, unlike those levied on tobacco products, which are high in order to deter consumption, food and activity taxes are primarily used to raise funds, some of which are used to battle obesity. For instance, New Mexico's Legislature is debating whether to add a 1% tax to the sales of television sets and video game consoles to finance a "No Child Left Inside" fund that would pay for outdoor educational programs. Also, at least 17 states and the District of Columbia have added taxes to soda and junk food.

Legislating against obesity is the "new frontier" of public health law, stated an editorial in the June 15, 2006, New England Journal of Medicine. Still, the biggest challenge facing backers of these efforts is the lack of evidence as to what, if anything, will work. Opponents have seized on that fact.

Obesity is also a far more complicated problem than smoking. "With tobacco, there's just one product, and a small number of companies involved," said Dr. Brownell. "With food, there's thousands of products and thousands of companies. It's hard to know exactly how to change."

Those who support such endeavors maintain, however, that many of them make sense, and the evidence will likely come in time.

"I don't think there's a lot of convincing evidence out there, but ... that's more a function of not having enough research being done and not testing programs that are likely to be effective," said Dr. Davis.