Thank you for the opportunity to testify as president of the National Research Center for Women & Families. Our nonprofit research and education center does not accept contributions from companies that make medical products, so our Center has no conflicts of interest.

However, I personally own stock in one of the companies that makes one of the most popular children's cold medications.

So, I have a personal conflict of interest that could potentially bias me in favor of these medications. It would harm me personally if the value of my stock went down because the company could no longer sell some of its very popular products. However, it is even more distressing to me as a stock holder that this company sells products that do not work and instead harm children.

Our Center is dedicated to improving the health and safety of adults and children, and we do that by scrutinizing medical and scientific research to determine what is known and not known about specific treatments and prevention strategies, and to compare their safety and effectiveness. My personal expertise includes post-doctoral training in epidemiology at Yale Medical School; working as a faculty member and researcher at Vassar, Yale, and Harvard; and working in health policy in the U.S. Congress, the U.S. Department of Health and Human Services, and the White House. In addition to currently serving as president of the National Research Center for Women & Families, I am also a fellow at the University of Pennsylvania Center for Bioethics. And, I am on the board of two organizations that are working to increase the resources of the FDA, the Alliance for a Stronger FDA and the Reagan-Udall Foundation.

I am speaking today from my perspectives as a stockholder and as a public health researcher and policy expert, and from a bioethics perspective. I also have a historical perspective because in 1992 I conducted a Congressional investigation on the topic of children's cold medications that resulted in an oversight hearing that criticized the FDA's failure to appropriately regulate children's cold and cough medications. More than 16 years later, I am here to focus on some of the same questions we asked in Congress in 1992.

I will be addressing questions 2, 3, 5, 6, 7, 8 and 9.

Question 2: Should cough and cold products for the pediatric population continue to be available OTC, or should they be made available only by prescription?

The National Research Center for Women & Families' position is that cough and cold products for children should not continue to be available OTC because they are generally ineffective and pose unnecessary safety risks to our children.

The Products Don't Work
You have heard from Dr. Sharfstein and other experts that there is clear evidence that these OTC products do not work for children under 6. In fact, other studies indicate that they do not work for children under 12 and there is no evidence that they work for children of any age, but the risks are more substantial for younger children.

In August 2008, the journal Pediatrics published a study on cough and cold medication use by U.S. children from 1999-2006.¹ In the article, Dr. Louis Vernacchio of Boston University and his colleagues state that "Despite widespread parental belief that pediatric cough and cold medications are effective for treating coughs and colds, there are no data supporting the efficacy of cough and cold medications for such uses in young children; the few available randomized, controlled trials have found no significant benefits in this age group."

The authors also noted: "Exposure to antitussives, decongestants and antihistamines was highest among 2-5 year-olds…(this) is noteworthy, given concern about potential adverse effects and the lack of data on the efficacy of cough and cold medications in this age group."

Similarly, in the article, "Over-the-counter cough and cold medication use in young children," published earlier this year in Pediatric Nursing, researchers from Arizona State University stated the "Lack of evidence to support the use of OTC medications in young children is well documented in the literature."²

And, according to the American Academy of Pediatricians, "Several studies indicated that these products are not effective in children younger than 6 and can have potential serious side effects, even when given as directed."³

They are Unsafe
An estimated 7,000 children under the age of 12 (not under the age of 6) visited emergency departments for adverse drug events from cough and cold medications, according to a 2008 article by researchers at the Centers for Disease Control and Prevention that was published in August.⁴

Most of the children (64%) going to emergency departments were 2- to 5-year-olds. Unsupervised ingestions of cough and cold medications caused two-thirds of the estimated emergency department visits, which is a much higher proportion than for other medications (66% vs. 47%). Perhaps that is due to the packaging or the candy-like flavoring of these products, which will be discussed by Paul Brown in his testimony.

Adverse Events Underreported
The problem is worse than these statistics suggest because adverse drug events due to cough and cold medications taken by children are voluntary and therefore underreported. The reporting does not always include calls to poison control centers or visits to outpatient offices. Even deaths are under-reported.

The Toxic Exposure Surveillance System documented nearly 90,000 calls and three accidental deaths associated with cough and cold medicines among U.S. children in 2004.⁵ In a study of Arizona children published in August, researchers reported 10 deaths of children taking cough or cold medication in 2006 in just that one state alone.⁶

Yet the FDA states in the Federal Register for this hearing that "Based on the number of cases of serious adverse events reported to FDA and the number of serious adverse events in the CDC emergency room study, we believe that serious adverse events are relatively rare given the extensive use of the drug products." Obviously, the events are not rare. It's true that the denominator - the number of kids taking these drugs -- is huge. But these products don't save lives. They don't cure the common cold. And, in fact there is no evidence that they even reduce symptoms of the common cold. Why should we tolerate any serious adverse events for products that have not been proven effective? These products have risks without benefits.

The FDA also states in the Federal Register notice that: "Lack of safety and efficacy data for specific pediatric age groups also inhibits the conduct of meaningful risk benefit analysis." That statement is disingenuous.

It's true that we don't have solid data for each specific age group. However, FDA researchers reported that 54 children died from 1969 to 2006 after taking children's decongestants and 69 deaths of children were linked to antihistamines.⁷ However, the death toll is definitely higher, as shown in the previously cited Arizona study showing 10 children died in that one state in 2006 alone.

Besides death, other potential adverse events caused by the use and misuse of OTC children's cough and cold products include: Hypertension, rapid heart rate or slow heart rate, agitation, insomnia, lack of muscle control, psychosis, seizures, strokes, heart attacks, and coma.

Risks vs. Benefits
Are the risks of these severe adverse effects really worth it for products that have not been shown to be effective for the common cold?

I agree with the CDC study that states: "Removing OTC cough and cold products that are marketed for this age group (children) could reduce the number of adverse events."⁸

Rx Instead?
In the future, if companies can prove that children's cough and cold medications are effective under some circumstances for some children, these medications should be available only by prescription, with the effective uses clearly specified. Prescriptions should be necessary because of the widespread promotion and inevitable off label use of these drugs if they remain available OTC. When a doctor writes a prescription, he or she should use that time to educate parents about proper dosing and alert them about possible adverse reactions. If the doctor doesn't want to spend at least 5 minutes having that conversation, then he or she should not prescribe the medication.

Question 3: If children's OTC medications are no longer available, will caregivers substitute adult OTC cold medications?

If OTC cold and cough medications are labeled as not appropriate for children under the age of 6, children under 6 might continue to get the medications if they are labeled and promoted as effective for children between 6 and 12. For example, parents with a large 5-year-old are likely to think that since their child is the same size as some 6-year-olds, the medication would be safe and effective. Since there is no evidence that OTC children's medications work for children under 12, they should no longer be available OTC for children under 12.

Question #3 seems to indirectly acknowledge that, and asks only about whether adult OTC cold medications might be substituted. There is much less of a chance that parents will give adult OTC cold medication to children, especially if there are clear warnings of danger for children of taking a medication for adults. My colleague Paul Brown will talk more about that, especially the role of candy flavors and child-oriented packaging.

OTC adult cold and cough products should have prominent warning labels about the adverse effects these products can cause in children, and TV and magazine ads should state clearly that these products are not for children. I'm talking about real warnings, not the pseudo warnings in microscopic type in magazines or spoken at warp speed on TV ads while the visuals completely distract the TV viewer. Warning labels on adult OTC cough and cold products combined with a public education campaign by doctors and aimed at warning parents of the adverse events should mitigate the problem of some parents using an adult product on a child.

Educating the public to change health habits is always challenging, but public attitudes toward OTC children's medications are already changing. According to the Slone Survey, the use of cough and cold medications declined significantly from 1999 through 2006, from a high of 12% in 1999-2000 to a low of 8% in 2005-2006.

The Role of the FDA
In October 2007, The FDA's Nonprescription Drugs Committee and Pediatric Advisory Committee voted 21 to 1 that there was insufficient efficacy data to support the use of OTC children's cough and cold products for children under 6 years of age. We agree completely with that assessment, although we believe that the data are also insufficient to support use for children under the age of 12, and possibly teens as well.

Instead, in January, the FDA issued a Public Health Advisory, which recommended that these OTC products no longer be used to treat children under 2 because "serious and potentially life-threatening side effects can occur."

Although a step in the right direction, the decision to continue to allow the sale of these medications for children ages 2 and above has no foundation in science. It is a decision that is clearly aimed at placating the companies that make these products. That is not the role of the FDA.

As a stock holder, I am appalled that a company that I have substantial interest in continues to sell products that purport to help children but actually harm them. These products also contribute to the out of control health care costs in our nation. I am asking the FDA to do its job, but at the stockholders meeting next year, many of us will also ask for a vote to get these products off the shelves.

There is no evidence that these OTC cough and cold products are effective for children of any age. We said this at a Congressional hearing in 1992, and 16 years later it is still true. What is the FDA waiting for? How many Congressional hearings or Citizen's petitions are necessary to get the FDA to look at the data and do the right thing?

Despite cuts in many domestic programs, the FDA will receive a large increase in appropriations this year. The intent of Congress and those who lobbied for those increases is to give the FDA the resources it needs to do its job. However, the issue we're addressing today is not due to lack of resources.

It's a problem of lack of will. The FDA needs to put the science first, and the safety of our children, ahead of the $3.5 billion OTC cough and cold products' industry.

Question 5: Is it appropriate to recommend adult doses for children over 12, without requiring additional studies?

Of course it isn't appropriate to assume adult doses are safe and effective for children ages 12 and older. Metabolism rates are different for children, and weights vary greatly for children ages 12 and older. It is not logical to assume that a 200-pound child or adult should take the same dose as a 90-pound child. There are currently no data showing safety or effectiveness of adult OTC cold and cough medications for children over 12, so studies should be required before such labeling is allowed. Of course, studies should separately study and separately analyze boys and girls of various ages and weights.

Question 6: What is the most appropriate method for determining pediatric doses?

The most appropriate method for determining pediatric doses is scientifically analyzing sex, age, and weight. Guess work and speculation is not appropriate. First find out if there are safe and effective doses for children of any age or weight. Currently, we have no evidence to suggest that there are.

Question 7: Should monographs for topical or intranasal products for children be reconsidered as well?

Yes, all medications used by children should be tested to see if they actually work. And they should be tested to see if they are safe. FDA monographs should reflect science, not wishful thinking or logical assumptions. This should have been done years ago, but since it wasn't the companies will have to be patient while the studies are done and reviewed. Meanwhile, these products should not be sold.

Question 8: Should combination products be permitted for all pediatric age groups or should data be required to support each unique combination?

Combination cold medications are especially worrisome because there are risks associated with each ingredient and yet the person taking it might get no benefit at all from most of the ingredients. This is especially true for children's products, since there is no evidence that any of the ingredients work. These products should not be allowed for children of any age, except by prescription if proven effective and safe. When prescriptions are involved, the doctor will be responsible for choosing a combination product rather than a product that treats specific symptoms that the patient actually has.

Question 9: Can measurement errors be reduced by changes in measurement devices?

This question should only be relevant to prescription pediatric products that are proven safe and effective for specific populations, and therefore available by prescription. In that case, measurement devices, such as a plastic cup, should be clearly marked for the appropriate dosage for the child that the medication is prescribed for. Having several different measurements on the same cup or other device is confusing and would not be appropriate for a prescription drug.

Conclusions

The common cold is generally a mild, short-term illness. At best, an effective cold medication will reduce some symptoms, but there is no data indicating that any OTC children's cough and cold products are effective for children under 12. However, there is clear evidence that they can cause serious adverse reactions-including death. These products subject our children to unnecessary risks without any benefits. In short, the OTC cough and cold products "cure" is worse than the illness, and it is the FDA's responsibility to take them off the market and warn parents of their risks. Any concerns about dosages and labeling should be restricted to prescription products that are proven safe and effective for children.




Footnotes
¹ Vernacchio L, et al., (2008). Cough and Cold Medication Use by US Children, 1999-2006: Results from the Slone Survey, Pediatric, e323-9. Note: The Slone Survey is a telephone survey of medication use in the U. S. population and was conducted from February 1998 through April 2007. Participants were identified by random digit dialing and completed a brief confidential interview. For more information see http://www.bu.edu/slone/SloneSurvey/SloneSurvey.htm
² Ryan T., et al., (2008). Over-the-Counter cough and cold medication use in young children, Pediatr Nurs. (Mar-Apr; 34(2): 174-80, 184.
³ American Academy of Pediatrics (2008). American Academy of Pediatrics Urges Caution In Use of Over-The-Counter Cough and Cold Medicines, News Release.
⁴ Schaefer, M.K. et al., (2008). Adverse Events from Cough and Cold Medications in Children, Pediatrics. 121:4, 783-787.
⁵ Vernacchio L, et al., (2008). Op. Cit.
⁶ Rimsza ME and Newberry S. Unexpected Infant Deaths Associated with Use of Cough and Cold Medications, Pediatrics. 122:2 (August 2008) e318-e322.
⁷ Ryan T., et al., (2008). Op. Cit.
⁸ Schaefer, M.K. et al., (2008). Op. Cit.