Genomic Medicine – The Hope and the Hype

Ten years ago this month, President Clinton, along with Drs. Craig Venter and Francis Collins, announced the completion of the Human Genome Project – the complete DNA sequence of the human genome. As is typical of such announcements, there was much pomp and circumstance, as the President declared it a “day for the ages.”

Why the excitement? It was fully expected by participants in the struggle to sequence our genome that achieving this goal would rapidly lead to a new understanding of the genetics of common disease, and would yield new genomic treatments that would revolutionize the practice of medicine. In fact, Dr. Collins predicted that the genetic diagnosis of disease would be accomplished within 10 years, and treatments would begin to appear 5 years later.

This, sadly, has not happened.

So does that mean the Human Genome Project was a bust? Hardly. While medicine has not been revolutionized, basic biology has been. The complete sequence of the human genome has shed tremendous new light on a variety of ways that genes are regulated, especially by RNA, which would never have been understood without sequence information.

So why has the sequence of the human genome not revolutionized medicine? As discussed in an article from The New York Times, there are several reasons. One reason cited by The Times is that many of the sequence variations associated with common diseases are not found within genes. This raises the possibility that these sequence variations are a statistical fluke, not really associated with the disease at all… or by anything other than chance. More disconcerting, if your goal is to develop a new treatment, is that common diseases may be caused by a large number of very rare sequence variations, so that individuals with a particular disease may have very little in common with each other, and nothing amenable to a drug.

Is this result entirely a surprise? To any serious student of human genetics, the answer has to be, “Not really.”

The First Genetic Disease

After reading any article in the popular press about genomic medicine, one would get the impression that the genetics of human disease is a new field, and that before the human genome was sequenced, there was nothing known about how gene mutations cause disease. This, however, is not true. In a paper published in Science in 1949, Linus Pauling and his colleagues demonstrated that sickle cell anemia is caused by a mutant form of hemoglobin, the protein that carries oxygen in red blood cells. In 1956, Vernon Ingram and his colleagues proved that this mutation was at the 6th amino acid of the protein. This change was soon shown to be the result of a single DNA base pair change.

For more than 50 years now, physicians and scientists have understood Sickle Cell Disease in molecular detail. Nevertheless, we are still unable to explain how this molecular defect causes any of the symptoms of the disease, and we are unable to do anything about it. To this day, despite how long we have understood the molecular biology of the disease, treatment remains supportive (meaning prophylactic antibiotics, pain medicine, and transfusions) or aimed at changing the way the hemoglobin genes are controlled (using a medicine called hydroxyurea). There is no treatment available that is directly related to the genetic cause of the disease, the mutation at amino acid 6.

I think this should be a warning to those who think that the path from the molecular understanding of a disease to a treatment will be straightforward. The era of genomic medicine may be upon us, but it is probably going to be a very slow change, not an overnight revolution.

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What do these disorders have in common? They are all mitochondrial diseases.



What is a mitochondrial disease? Mitochondria are the parts of a cell that are responsible for generating energy. Mitochondria contain DNA, just like the nucleus does. Mutations in mitochondrial DNA can cause them not to function correctly, and some of these mutations cause the diseases listed above (and others).

When a baby is conceived, we think of the baby’s DNA as coming half from the mother and half from the father. That is true for the DNA in the nucleus, but not true for mitochondrial DNA. All mitochondrial DNA is inherited from your mother.

As a side note, the fact that all mitochondrial DNA is inherited from the mother is the basis for anthropological studies that allow scientists to trace the origins of humanity back to “Mitochondrial Eve” in Africa.


Since all mitochondrial DNA is inherited from the mother, replacing mitochondrial DNA that carries a disease-causing mutation with mitochondrial DNA from another source would prevent a woman from passing on such a disease to her children.

That is the basis for the work by Shoukhrat Mitalipov’s group at the Oregon Health and Science University published online in Nature on August 26. This group took an egg from a female monkey and removed the nucleus, replacing it with the nucleus from a different female. This hybrid egg, with nuclear DNA from one female and mitochondrial DNA from another female, was fertilized, and the resulting embryo was allowed to develop. Not every embryo developed normally, but some developed into seemingly normal monkeys like the ones shown above.

This approach would allow a couple with a family history of mitochondrial disease on the mother’s side to have children with mitochondria donated by an unrelated woman, and they could have children with no risk of developing the disease.

The monkeys described in the paper have genetic contributions from 3 adults. Does that mean there are three parents? I guess that depends on how you define “parent.” If you are a parent simply by virtue of having contributed DNA to a child, then yes, these monkeys have 3 parents. Of course, if a parent is defined as the adults who raise you, then a child conceived in this way would have 2 parents. The ones who raise the child.

Experiments like these raise huge ethical issues. Therapeutic cloning like this introduces changes directly into the germline (the DNA that is passed from parent to offspring), something that has long been taboo in the mainstream scientific community. It also raises interesting custody issues (does the donor of the mitochondrial DNA have any parental rights?). I’d be interested to hear what people think about this.

Like it or not, we are on the verge of a new era of genetic medicine. Some aspects of genetic medicine will not be controversial (tailoring medical treatments based on the presence of specific mutations), but other aspects are sure to raise questions (like the experiments described in this paper). It is critical that we begin to have serious, society-wide discussions about these issues, before it is too late and the discussions become arguments.

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Vitamin D in the Spotlight -- Again

Last year, I blogged about vitamin D as an agent to prevent breast cancer. My interest in vitamin D began when I found an ad promoting the health benefits of tanning salons because the exposure to ultraviolet light increases production of vitamin D, something most adults get too little of. Mostly, vitamin D is thought of as important for bone strength, and as something helpful in preventing osteoporosis.

Research presented at the 2008 meeting of the American Society of Clinical Oncology demonstrating that vitamin D may play a role in preventing breast cancer caused a huge sensation. There is also evidence that vitamin D may prevent colon cancer. Of course, everything about nutrition is complicated, including vitamin D needs – too much vitamin D can be a bad thing. Proper balance is everything. Moderation in all things.

As complicated as understanding the role of a vitamin in the health of an adult can be, it is even harder in children, who are growing and therefore can have changing needs. An important study investigating the prevalence of vitamin D deficiency in children and the implications for heart disease was just published in the journal Pediatrics, the official journal of the American Academy of Pediatrics.

A team led by Michal Melamed, from Albert Einstein College of Medicine in New York, surveyed the vitamin D levels of over 6,000 children registered in the National Health and Nutrition Examination Survey and correlated these levels with various cardiovascular risk factors. Their surprising results? Almost 10% of children in the US are vitamin D deficient, and fully 61% were vitamin D insufficient (meaning their levels were too low, but not low enough to be called deficient).

Why is this a problem? Low vitamin D levels were correlated with higher blood pressures and lower levels of high-density lipoprotein (HDL, or “good” cholesterol). Both of these are significant risk factors for heart disease in adults. This finding provides a key link between childhood nutrition and the development of heart disease in adulthood.



This is potentially a very important study. The question of why some adults develop heart disease while others do not is a complicated one, and many of us have long believed that adult disorders can have their roots in childhood. This study supports that belief, and also strongly supports the idea that intervention in the health of a child can have profound implications throughout her life.

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Why Does My Child Need a Flu Shot?

It’s official – we are in the middle of flu season. According to the Centers for Disease Control (CDC), the percentage of flu tests that came back positive during the week ending February 21 (the most recent time period for which we have data) continues to rise steadily and has not yet peaked.

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For most people, influenza is just a nuisance infection. If you get the flu, you have a fever, stuffy nose, and body aches. You rest in bed for a few days, and when it’s over, you’re back to normal. For children, the elderly, and people with underlying medical problems, however, influenza can be a life threatening infection. So far this year, influenza has caused 17 deaths among children in the US. Eight of these deaths occurred just last week! As reported by CNN this week, even perfectly healthy children die of influenza. It is because influenza can kill children even if they have no other medical problems that this year New Jersey began requiring flu shots for children to be allowed to attend preschools and day care centers.

Perhaps even bigger flu-related news, though, came in a pair of articles published this week in the Journal of the American Medical Association (JAMA). Unlike most viral illnesses, there are actually effective drugs to treat influenza. One of these, oseltamivir (Tamiflu®) is FDA-approved to reduce the duration of symptoms if taken within 48 hours of feeling sick. An older drug, Amantadine, is no longer useful for the treatment of influenza because more than 90% of the circulating influenza A viruses are resistant. Because of the way Tamiflu was designed, many physicians and pharmacologists believed widespread resistance to this drug was not possible. Unfortunately, this is not the case. Although in the 2007-2008 flu season only 12.3% of influenza isolates were resistant to oseltamivir, preliminary results from this year (reported in this week’s issue of JAMA) indicate that 98.5% of isolates are resistant! Once again, nature is outsmarting us and drugs that used to be effective for treating infections are becoming useless.

So if we can’t treat the flu, the best thing we can do is prevent the flu. And the only way to prevent the flu is with a flu shot. Who needs a flu shot? According to the Advisory Committee on Immunization Practices (ACIP), all children between the ages of 6 months and 18 years should be vaccinated, as should adults 50 years of age and older and any adult at risk for medical complications from influenza. The recommendation to vaccinate all children arises from concerns that even otherwise healthy children can die of influenza, a concern that sadly is born out year after year in children whose parents asked, “Why does my child need a flu shot?”

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Bravo New Jersey!

Bravo New Jersey!

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It’s that time of year again. The days are getting shorter, Halloween decorations are appearing, and that can only mean one thing. It’s time to get your flu shot.

Every year, the flu shot changes, because every year the strain of influenza virus that circulates changes. Last year’s flu shot does not protect you this year. So every year, people need a new shot.

It also seems that every year, the official recommendation for who needs a flu shot changes as well. This year is no exception. This year, the Centers for Disease Control, the agency that makes the official recommendations, has said that all children over the age of 6 months should be vaccinated against influenza.

The State of New Jersey has taken this recommendation to heart, and this year is requiring influenza vaccination for children to be allowed to attend preschools and day care centers. This law sparked a protest outside of the New Jersey Statehouse on October 16 by parents who oppose this requirement.

Personally, I think this was a good decision, based on sound science. States already require immunization against a large and growing number of infections for all children who attend school. So the idea of requiring a flu shot to attend school (even if it’s preschool) is not out of line with current policies.

In fact, influenza vaccine is probably more important than some of the others that are routinely given. For example, children are required to receive a diphtheria immunization (that’s the D in DTP and DTaP). Prior to universal immunization, diphtheria was a feared disease, and there were 13,000-15,000 deaths in the US every year from diphtheria. Between 1998 and 2004 there were 7 cases in total reported to the CDC. In contrast, every year on average 200,000 Americans are hospitalized because of influenza, and 36,000 of them die. Children are at risk as well. Every year an average of 20,000 children under the age of 5 are hospitalized for complications of influenza. Getting influenza is also a risk factor for potentially serious bacterial infections in children.

Another important factor is that children easily spread influenza to their parents and other household contacts. My colleagues at the University of Maryland demonstrated that a school-based influenza immunization program was able to decrease transmission of influenza to adults who come into close contact with vaccinated children. So by requiring that more children receive this important immunization, New Jersey is likely to see a decrease in influenza-related illness not only in children, but in adults as well. And since so many people die from influenza every year, this is probably a good thing.

Cough Medicine for Kids: Update 2008

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A year ago, I wrote about an effort by the Baltimore Commissioner of Health, Dr. Joshua Sharfstein, to convince the US Food and Drug Administration (FDA) to ban the use of over the counter (OTC) cough medicines for young children. Last October, an FDA advisory panel voted 13 to 9 to recommend that these medicines not be used for children under 6. Unfortunately, it has taken a year for anything substantive to happen.
Better late than never, the Consumer Healthcare Products Association, a trade organization representing OTC drug manufacturers, announced that “the leading manufacturers of these medicines are voluntarily transitioning the labeling on oral OTC pediatric cough and cold medicines to state ‘do not use’ in children under four years of age.” This is a big step forward, because most bottles still say to “consult your pediatrician” before treating kids that age – implying that it is safe, as long as a pediatrician is guiding the dosing.

The American Academy of Pediatrics has been saying for years that these drugs do not work and are unsafe for young children. In fact, the AAP advocates a label saying they should not be given to anyone under the age of 6 as well as a ban on marketing them for that age range. Over 7,000 children a year are seen in emergency rooms for problems related to taking OTC cough and cold medications. The vast majority of them are under the age of 3, so even if pharmaceutical companies do not change their labels to match what pediatricians want, a label suggesting these drugs not be used for children under 4 will help a lot.

Why is this topic so important? Because it shows that just because a medicine works for adults doesn’t mean it works for kids. Too many drugs are marketed to kids without being tested on children, based on the assumption that kids are just small adults. Thankfully, Andrew von Eschenbach, the Commissioner of the FDA, in his own blog, recognizes that this just isn’t so. Hopefully, the future will be full of drugs that are safe to give to children because they are appropriately tested on children, with the same rigor that they are tested on adults. We owe this to our children.

Could Your Heart Medicine Cause Cancer?

There was a series of interesting articles in the last issue of the New England Journal of Medicine concerning a heart medicine called Vytorin. Perhaps you’ve seen the ads on TV. You know the ones… they show high cholesterol foods and a silly looking person dressed to look like the food to reinforce the idea that Vytorin has 2 medicines to address 2 ways your cholesterol could become elevated. In fact, Vytorin is a combination of Simvastatin, a drug that works by blocking your body’s ability to make cholesterol, and Ezetimibe, a drug that works by blocking your body’s ability to absorb cholesterol from the foods you eat.

In theory, this is a great idea. After all, cholesterol comes from 2 sources, why not create a drug that affects them both? This is exactly what Merck and Schering-Plough did in a joint venture using drugs that each company still had under patent.

Having created this drug, the pharmaceutical companies had to get the approval of the FDA to market it. Otherwise, they could not have aired those memorable ads. To earn FDA approval, a drug company has to provide data from a clinical trial showing the drug’s effectiveness. Vytorin was approved based on its ability to lower blood levels of LDL, the "bad cholesterol" that is associated with heart attacks and strokes. After FDA approval, the company launched another study called the ENHANCE study. This study was designed to show an effect on atherosclerosis ("hardening of the arteries"). It lasted just 2 years and enrolled 720 patients with a genetic disorder (familial hypercholesterolemia) that causes high cholesterol levels and heart attacks and strokes at a very young age. The study showed that Vytorin lowers cholesterol levels in these patients, but it did not detect a decrease in heart attacks or strokes.

Importantly, the study did not show that Vytorin was any better than Simvastatin alone.

There have been 2 drug company-sponsored trials since then: the SEAS trial (SEAS stands for Simvastatin and Ezetimibe in Aortic Stenosis) and the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial. Both studies were designed to test whether Vytorin reduces the risk of heart attacks and strokes better than Simvastatin alone. The results of the SEAS trial were released this week (The IMPROVE-IT trial is still ongoing). In a disappointment for the drug companies, Vytorin did not decrease the risk of progression of aortic stenosis (a narrowing of the valve leading from the heart into the aorta, the major artery that drains the heart) or on cardiovascular events in general.

Surprisingly, the patients taking Vytorin had an increased risk of cancer compared with patients taking a placebo.

What’s going on here? Does this new heart medicine not only not work, but also cause cancer?

The answer is probably not that simple.

When the data from all 3 trials are combined, there is no increase in the incidence of cancer in patients who take Vytorin. However, there was an increased risk of dying from cancer.

How could this happen?

Well, one possibility is that this is just a coincidence. The studies were not designed to detect a risk of getting or dying from cancer. So maybe it was a statistical fluke.

But it could be real. An editorial in the New England Journal accompanying the articles warns about this possibility. Ezetimibe inhibits the absorption of plant sterols from the diet, not just cholesterol. Epidemiologic studies have linked diets high in plant sterols to a lower incidence of cancer. Laboratory animals (mice and rats) fed a diet high in plant sterols show modest resistance to chemical carcinogens and to tumors grown from injected human cancer cells. Plant sterols have a number of inhibitory effects on human cancer cells grown in the lab. These findings could provide the basis for a plausible biological explanation for the results in the SEAS study.

I wrote this piece for two main reasons: one reason is that I think this case (and the fiasco surrounding Vioxx) is an important reminder not to be so eager to take a new drug just because it’s new and has a cute ad. FDA approval is no guarantee that a drug is safe, and some relatively rare but certainly very significant side effects only become noticed during what is called post-marketing surveillance. The other reason is as a teaser for my upcoming, first ever book review: Reasonable Rx: Solving the Drug Price Crisis, by Finkelstein and Temin.

Stay tuned.

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This topic was also covered extensively by one of my friends in another blog. Read her posts here and here.

Does your diet determine what sex your baby will be?

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What a fascinating thought! Back when I was in medical school, we learned that a baby’s gender really depends only on whether a sperm with an X chromosome or a sperm with a Y chromosome fertilizes the egg. But low and behold, a study from Oxford suggests it may be more complicated than that. These scientists reviewed the records of 740 women who delivered their first baby, and found a correlation between higher energy intake (calories) around the time of conception, and the birth of boy babies.

The article in the New York Times points out that in vitro fertilization experience shows that high glucose (sugar) levels encourage the growth of male embryos and discourage the growth of female embryos. Interestingly, I remember being taught in medical school that sperm with an X chromosome swam better than sperm with a Y chromosome (I wish I could find the documentation for that…). This article, from a scientist in Germany shows that the hormonal environment can influence sex ratios in the offspring of mammals and of birds. It’s interesting to consider how these findings might all be related, and how it may or may not be adaptive for the species to alter sex ratio of newborns based on environmental conditions. Food for thought…

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HPV Vaccination: It may not be just for girls

On January 29, I thought I was culminating a discussion of the virus/cancer connection by talking about the link between HPV and cervical cancer, and how the development of a vaccine for HPV could prevent cervical cancer in women.

Shortly after that entry posted, Maura Gillison (a colleague of mine), published an article in the Journal of Clinical Oncology on the growing importance of HPV as a cause of oral cancer. Why is that relevant? One reason is that this represents a shift in the importance of various causes of oral cancer, away from tobacco and towards a virus. This reflects the huge success we’ve had in diminishing tobacco use. As tobacco fades as the leading cause of oral cancer, virus-induced cancer is becoming more common. Interestingly, there is some speculation that this finding might also reflect changes in sexual behavior patterns, especially related to oral sex.

The finding that HPV is now a leading cause of oral cancer means that vaccination of men could significantly impact on the incidence of this disease. So a vaccine (that until now has been given almost exclusively to girls to prevent cervical cancer) could also be given to boys to prevent oral cancer in people of both genders.

The idea of giving the vaccine to boys is not new. This article, from last May, discusses heterosexual sex as the main mode of transmission of HPV to girls, and suggests that vaccinating boys could help break the cycle of sexually transmitted cervical cancer. At the time the article was written, it had recently been discovered that HPV can cause throat cancer, but at that point throat cancer was still more commonly caused by smoking and drinking, so the impact of HPV vaccination on throat cancer was expected to be small.

So what makes Maura’s article a more compelling argument to vaccinate boys is the fact that oral cancer is now more commonly caused by HPV than by tobacco, making the impact of the vaccine greater.

Merck, the manufacturer of Gardisil, the only HPV vaccine available in the US, has been conducting trials of vaccine in boys to determine how tolerable it is. As expected, the vaccine is well tolerated and effective. Effectiveness was measured by determining how many boys who received the vaccination developed antibodies against the virus (almost 100%). There was no difference in effectiveness, measured in this way, between boys and girls.

So… will vaccinating boys have any effect on cervical cancer, oral cancer, or anything else? No one really knows yet. It will be fascinating to watch as these trials are conducted.

New Diagnosis: Excessive… Sleepiness?

Think you’ve heard it all?

Well, I thought I had. Until today, when I opened up the Baltimore Sun and learned something new. There is a new medical disorder… and I may have it! Thank goodness, there’s also a drug to treat it.

What’s my diagnosis? ES.



No… not Ewing’s sarcoma (which is what ES used to mean to me). ES is the new acronym for Excessive Sleepiness. I kid you not. But our friends in the pharmaceutical industry have a solution: Provigil.

Now… I’m not anti-medication at all. Heck, I use harsh medicines on my patients every day, and then have to give them more medicines to treat the side effects of the first medications. I’ve even put some of my own patients on Provigil. Kids who required so much narcotic to control their pain that they have a hard time staying awake to be able to interact with family members in a meaningful way… these patients benefit tremendously from Provigil.

But if you think about it, that’s not much of a market. Even if you add in patients with obstructive sleep apnea, who have badly disrupted sleep patterns and often have a hard time functioning during the day, there still isn’t a big market for this drug. Not even the addition of patients with narcolepsy (which is excessive daytime sleepiness even after a good night’s sleep, and is characterized by sudden uncontrollable bouts of sleep, with sleep paralysis and hallucinations) makes the market for this drug very large. BUT… if we make a new medical diagnosis, give it a clever name and acronym… and if that condition is tremendously common… well NOW there’s a market for your drug.

Please don’t misunderstand. Obstructive sleep apnea and narcolepsy are a big deal, and the excessive daytime sleepiness associated with these diagnoses can have a significant impact on patients’ lives. The sleep disturbances associated with shift work is also a significant problem for many people. Provigil plays an important role in the care of people with these problems. My concern is that the creation of a specific “disorder,” especially if it is given a name with such common use, combined with direct-to-the-patient marketing, feels like another example of the overmedicalization of our society. Do people who don’t sleep at night because of OSA benefit from a medication to help them stay awake? Certainly. Do people like me, who don’t sleep at night because they work too hard, need to “ask their doctor if Provigil is right for them”? No. We need to get more sleep.

OK. I’m going to bed.

Today is World Cancer Day

Today, February 4, 2008, has been designated World Cancer Day by the World Health Organization and the International Union Against Cancer. This year’s theme is I Love My Smoke-Free Childhood. As a pediatric oncologist, I have to say, I’m 100% behind this idea. Second hand smoke is a major pediatric health problem. 700 million children - almost half of the world's youth - regularly breathe air polluted by tobacco smoke. Second hand smoke exposure leads to chronic health risks:

· Increases a baby's risk of dying suddenly from unexplained causes (SIDS)
· Contributes to low birth weight in newborns and harms lung development
· Causes bronchitis and pneumonia in young adults
· Increases risk of ear infections, asthma, coughing and wheezing among school-aged children

Facts like these underlie smoking cessation laws sweeping the country. I’m proud that my home state of Maryland just recently enacted one.

Gregory Reaman, MD, the chairman of the Children’s Oncology Group, of which I am a member, said this: "As the world’s largest pediatric cancer research collaborative, the Children’s Oncology Group stands firmly with the world’s leading cancer organizations, demanding that all children have the opportunity to be raised in an environment where they are not exposed to the effects of smoking and second-hand smoke."

The fight against second hand smoke has a fascinating history. The first successful class action suit brought against the tobacco industry was brought by attorneys Stanley and Susan Rosenblatt in October 1991 in Dade County Circuit Court (Miami). The suit sought damages for diseases and deaths caused to flight attendants by exposure to second hand tobacco smoke in airline cabins. One element of the settlement of this case was the establishment of a not-for-profit medical research foundation with funding by the tobacco industry of $300 million. The Flight Attendant Medical Research Institute has already made dozens of awards, including one that was critical to the early success of my laboratory.

If you want to add your voice to those supporting the effort to eradicate tobacco smoke, click here.

Breaking News: the FDA (re)issues warning about fentanyl

In September, I wrote about the double-edged sword of narcotics and pain control for cancer patients. Around that same time, there were news reports of patients dying from improperly prescribed Fentora, which is a preparation of the powerful narcotic, fentanyl, that is absorbed through the lining of the mouth.

Fentanyl is in the news again this week. This time, the issue is with fentanyl patches. These are a favorite tool for oncologists, because the drug is absorbed through the skin. This means the patient need not swallow a pill, a big deal for patients receiving chemotherapy (notorious for causing nausea and vomiting). Fentanyl patches are also great for managing chronic pain in patients who have significant prior narcotic exposure, and it’s hard to imagine practicing oncology in the US without this tool.

However, like all tools, improper use can result in great harm.

At a news conference last week, the FDA reissued a 2-year-old warning about fentanyl patches, which have been linked to at least 120 deaths. They repeated their advice that these patches be reserved for patients with chronic pain and a tolerance to opioids. The patients who have died have all been prescribed for acute pain (in one case, a headache) and had never taken narcotics before.

Fortunately, the FDA does not seem likely to heed the call from some people to limit the ability to prescribe fentanyl patches to pain specialists. This would be a big mistake, because there are only 4,000 pain medicine specialists in the US, and many, many patients with chronic pain are treated safely and effectively by experienced physicians without specific pain training.

Bottom line? Pain medicines are powerful medicines. Used incorrectly, these medications can be deadly. But, used correctly, they can make life tolerable for people who would otherwise suffer terribly. That fact alone is sufficient to keep them on the market, and in the hands of doctors who know how to use them and patients who need them.

I Can Buy it Over the Counter: FDA Followup

In my last entry, I told you that cough and cold remedies marketed for infants had been removed from the shelves of drug stores across the country. This move was made in response to concerns raised by a group of pediatricians who charged that these medications are dangerous and ineffective. An FDA advisory panel met this past week to review these charges and to make recommendations about ongoing sales of these medications and what, if any, warning labels should be attached.

As reported yesterday in The Washington Post, “The Food and Drug Administration panel voted 13 to 9 to recommend against the use of the products for children in that age group [children under the age of 6] after concluding overwhelmingly that there was insufficient evidence the long-used remedies worked in youngsters.”

The group’s chair, Dr. Mary Tinetti, stated, “The sentiment here is that they should not be used.”

The problem is that these drugs have never been adequately tested in children, so there is no evidence that they work. There is evidence, though, that they are dangerous, and the same Washington Post article quotes a report from the Centers for Disease Control that at least 1500 children under the age of 2 suffered complications from the use of these products between 2004 and 2005. These were not minor complications, either, as these drugs have been linked to convulsions, heart problems, neurologic complications, and at least 123 deaths.

I’m very proud that this action resulted from my colleagues in the Baltimore City Health Department speaking up, raising awareness, and pushing the issue, ultimately resulting in safer medication use for our children.

One final note: This issue has larger implications than just cough and cold medicine. These actions by the FDA are a result of inadequate testing of drugs on children, and on the false assumption that dosing of drugs in kids can be estimated by simply giving proportionally less medicine. But, as I was taught in residency – children are not just small adults. New drugs need to be tested not just on adults, but also on children, with particular attention to proper dosing and a real estimate of how well they work. If the financial hit to the pharmaceutical company from this action by the FDA is sufficient, maybe the net result will be more appropriate testing of new drugs in kids, something we sorely need.

I can buy it over the counter, doesn’t that mean it’s safe?

That’s what most of us believe. After all, the FDA watches over the pharmaceutical industry to ensure the safety of whatever we find on the drug store shelves, doesn’t it? No pharmaceutical company is allowed to market a drug they don’t know to be effective, right?

Well, a group of pediatricians in my home town (Baltimore, MD), didn’t believe that. Led by Baltimore's health commissioner, Dr. Joshua M. Sharfstein, these pediatricians petitioned the FDA to stop the sale of cough and cold medications for children younger than 6, saying that there are no data showing that the drugs actually work and there is growing evidence that they pose a risk of serious harm.

As reported in The Washington Post, The Baltimore Sun, and countless other news outlets, cough and cold medications marketed for infants were pulled from store shelves this past week. Is that because these drugs aren’t safe? Or might there be some other reason for this action?

Well… let’s talk about safety before we address the motive behind this “voluntary” withdrawal of product from the market.

In the past 6 years, 4 infants in Baltimore have died because of these medications. Two weeks ago, the FDA released a report that there were 54 deaths in the United States from 1969-2006 involving decongestants and 69 involving antihistamines. Most were in children younger than 2. In 2005, the U.S. Toxic Exposure Surveillance System, a national database of poisoning cases, recorded up to 88,000 calls about juvenile overdoses or adverse reactions to cough and cold medicines and antihistamines. That’s a lot of overdoses and adverse reactions to medications that treat the symptoms of otherwise minor infections. And 123 deaths over 7 years is unacceptable for cold medicine. If these drugs were treating life-threatening conditions like cancer, this would be OK, but who wants their child to die over a runny nose?

So… the big question is this: has the pharmaceutical industry spontaneously decided to stop selling a potentially dangerous product that doesn’t work? I’m not sure this is the case.

Cough and cold medicines are a huge market. Everyone gets colds. No one likes the feeling of a stuffy nose, a runny nose, or a nagging cough. When these symptoms strike children, parents want to do something about it. That’s only natural. According to AC Nielson, about 15% of American households bought cold medicine marketed toward children last year. Total sales reached $311.3 million last year. That’s beyond pocket change, and more importantly represents a 20% increase over the previous year. So it’s a large market, and it’s growing.

Statistics like this have caused leading consumer advocates to question the motives of the pharmaceutical industry. Peter Lurie, of the health research group at Public Citizen, said he believes the voluntary withdrawal was designed to head off a wider ban on marketing the drugs to children under 6 (see video here), which is one of the possible outcomes of FDA hearings scheduled for this week.

"One can only assume that it is fear of additional action that's causing them to take these steps," he said. "It's only the most obvious infant products they are recalling. They probably see the writing on the wall for the younger children and are trying to save the rest of the pediatric market. They are trying to rescue the market for a series of products that do no good, and sometimes cause harm."

This sentiment is echoed by Arthur Levin, director of the nonprofit Center for Medical Consumers and a past member of FDA advisory panels on prescription drug safety.

"At this point, they're worried about their exposure to liability," he said. "There's a level of concern that can't be ignored anymore." The industry, he said, might have calculated that this action would blunt some of the criticism and deflect the FDA from a ban that would extend to children as old as 6.

As a parent, what should you do? Keep in mind that these drugs have never been shown to be any more effective at treating symptoms than drug-free interventions, like drinking plenty of liquids, using a humidifier, and using salt water solutions to treat nasal congestion and sore throats. These methods are safe, and they cost a whole lot less, too!