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Lack of Evidence


 

In the late 1940s, Patricia Sanchez remembers sleeping on a cot in her oldest son’s bedroom most winter nights, listening for the vaporizer to run out of water so she could quickly refill it. The flu or even a bad cold invariably exacerbated his asthma, often causing him to wheeze and gasp for breath.

“We didn’t have any good medicines. It was a scary time,” she says. “I think we had to take him to the emergency department almost every winter.”

Today, with such medical advances as inhaled corticosteroids, many hospitalizations for asthma-related conditions can be avoided. Similarly, the use of ondansetron (Zofran) in children with gastroenteritis has decreased hospitalization rates. Many such medications originally developed for adults are helping to advance the treatment of childhood diseases, especially in oncology. But has the attraction of newer, stronger medications contributed to overuse for certain pediatric diseases?

A number of pediatric hospitalists think it has. Medication use in children has—for the most part—not received enough study. Therefore, hospitalists don’t always have enough evidence to guide their treatment decisions for young patients. Until the research catches up with the medications, hospitalists should be cautious.

HM physicians must stay abreast of the latest drug information and treatment guidelines. More importantly, they need to maintain clear lines of communication and outline reasonable expectations with their patients and their patients’ families.

Too Much, Too Soon?

Overuse of antibiotics and the growing threat of methicillin-resistant Staphylococcus aureus (MRSA) and other resistant strains frequently affect hospitalists in their practices, says Jack Percelay, MD, MPH, FAAP, FHM, a pediatric hospitalist with E.L.M.O. Pediatrics in New York City and a member of SHM’s board of directors. So does pressure from worried parents who want to employ whatever it takes to make their child better. “We want to be really careful about giving kids antibiotics,” he says, “and not use the biggest, newest guns in the hospital when they are not necessary.”

[Pediatric hospitalists] routinely use medications in children where the dosing is arbitrarily guessed at.

—Brian Alverson, MD, pediatric hospitalist, Hasbro Children’s Hospital, Providence, R.I.

Knowing how young and how much is safe and effective isn’t easy. Samir S. Shah, MD, MSCE, assistant professor of pediatrics and epidemiology at the University of Pennsylvania School of Medicine and attending physician in the divisions of infectious diseases and general pediatrics at The Children’s Hospital of Philadelphia, and his colleagues examined the use of adjuvant corticosteroids in children with bacterial meningitis. What they found was a worrisome upward trend of increased steroid administration, even though current evidence does not warrant the approach.1 When bacterial meningitis is caused by Haemophilus influenzae type B, adjuvant corticosteroids show a reduction in hearing loss in children, but studies conducted in the current era (when Streptococcus pneumoniae and Neisseria meningitidies are common causes of bacterial meningitis) do not show similar benefit.

In childhood cancer, oncology physicians and researchers have done an excellent job of refining treatment protocols, says Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center in Austin, Texas, and pediatric editor of The Hospitalist. Nearly 70% of all children with cancer in the U.S. are enrolled in clinical trials, which allows for expanded evidence on treatments and outcomes.

In other settings, it might be too early to tell whether children are being overmedicated, undermedicated, or appropriately medicated. The real question: What will the consequences of long-term medication be?

Direct-to-consumer advertising; expansion of the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for attention deficit hyperactivity disorder (ADHD), bipolar disorder, and autism spectrum disorder; and the acceptance of “biological psychiatry” as the theoretical basis for the etiology of behavioral and emotional disorders all contribute to the increased use of psychotropics, says Julie M. Zito, PhD, professor of pharmacy and psychiatry in the Pharmaceutical Health Services Research Department at the University of Maryland at Baltimore. Using Medicaid administrative claims data for Texas youth in foster care in 2004, Dr. Zito and colleagues found that more than a third of these children (37.9%) had been prescribed a psychotropic medication.2 Of those receiving medications, 41.3% were receiving at least three different classes of drugs, most frequently antidepressants, ADHD drugs, and anti-psychotic agents.

Although the foster child population is relatively small (513,000 children in the U.S. were in foster care in 2005, according to the Department of Health and Human Services), the trend seen in this population is concerning. Medco Health Solutions’ 2007 survey of drug trends predicts that prescriptions for medications to treat ADHD will continue to increase at a rate of about 3% per year.3

Another concern is that the use of atypical antipsychotic medications to treat behavioral or bipolar disorders in children could result in weight gain (as it does in adults), which can trigger metabolic syndrome and increased risk of diabetes.

A Florida study that Dr. Zito co-authored demonstrated increased cardiovascular visits to the ED in Medicaid-insured children who had received stimulants.4 “It’s clear that we need to know more about safety and efficacy [of these medications in children],” Dr. Zito says.

A Dose of Education

What can hospitalists do to best treat and inform their patients? Education is key for both the parent and the physician. Parents need the best information possible to make good decisions for their children. Physicians need to stay up-to-date with the research and drug warnings, and dedicate themselves to communicating with families during stressful situations. Here are some suggestions from the experts:

  • Reinforce the wise use of antibiotics. “Our job is good antimicrobial stewardship, and whenever we talk with parents or consult in the ER, we can try and emphasize the appropriate utilization—and not overutilization—of antibiotics,” Dr. Percelay says.
  • Reassure and educate parents that such symptoms as fever and cough are the body’s natural defense mechanisms; that the symptoms usually are self-limited; and that there are harms to overmedicating their children, Dr. Shen says. One FDA resource that can be helpful for parents: www.fda.gov/cder/drug/advisory/cough_cold_2008.htm.
  • Don’t “overinform” families and then feel as if your job is done, Dr. Coghlin advises. “You cannot disseminate patient education information in the same way each time—even for the same people. You must constantly reassess your level of communication with the family and understand how the information is being absorbed.”
  • Partner with community pediatricians to bridge the knowledge gap, especially in the management of common viral diseases. “It’s really my responsibility,” Dr. Shen says, “to carry back to the community the research knowledge and national guidelines on common inpatient conditions.”
  • Listen to the concerns of the people—parents and providers—you’re serving, Dr. Coghlin says. If you have a difference of opinion regarding the institution of therapies, do not just arbitrarily announce your dissent; show respect for the provider’s level of expertise. Expressed with tact, your opinion is more likely to be respected. You must realize, however, that changing beliefs and mind-sets on prescription medicine will not occur overnight.—GH

The Parent Trap

Daniel Coghlin, MD, a general pediatrician for eight years and now a pediatric hospitalist at Hasbro Children’s Hospital in Providence, R.I., believes parents’ expectations of their physicians—and medications—often are too high. Many think the doctor should provide a solution to all of their children’s illnesses, and the expected solution often entails a prescription.

Does parental pressure influence prescribing patterns? One study showed that pediatricians would prescribe antimicrobials 62% of the time if they thought the parents wanted them—even for a presumed viral illness.5

Dr. Shah points out that physicians might misunderstand the parents’ expectations; he suggests having a frank discussion about efficacy of antibiotics. “Studies have also shown that if the physician explains that antibiotics won’t work against viruses, that there is no benefit but there is potential harm, [then] that’s an answer that’s acceptable to most parents,” he says.

To be fair, says Brian Alverson, MD, also a pediatric hospitalist at Hasbro Children’s Hospital, physicians also contribute to overuse of antibiotics by ordering tests that drive up their inappropriate use. An X-ray might show small areas of lung atelectasis, which could be interpreted as pneumonia. A CBC test with an elevated white count could trigger an antimicrobial order. For the record, Dr. Alverson says neither test is indicated on a routine basis in the setting of bronchiolitis.

Over-the-Counter Risk

American consumers purchase 95 million packages of over-the-counter (OTC) cough and cold preparations for their sick children each year, according to the Consumer Healthcare Products Association. Many in the scientific community, including the American Academy of Pediatrics (AAP) and Wayne Snodgrass, MD, of the University of Texas Medical Branch’s department of pharmacology in Galveston, have pressed for more regulatory action, pointing to published evidence that ingredients such as brompheniramine are no more effective than a placebo in stopping a cough.6,7 Prompted by reports of two deaths in children, the FDA last October recommended that OTC cough-and-cold products not be given to infants or children under age 2. The FDA also is reviewing its recommendations for children ages 2 to 11.

Since initiation of the Pediatric Exclusivity Provision, which extends six months of patent exclusivity for products undergoing testing in children, and passage of the Best Pharmaceuticals for Children Act (BPCA) in 2002, more than 133 labeling changes have resulted from 300 pediatric-specific studies. (For a comprehensive list of the labeling changes, visit www.fda.gov/oc/opt/pediatriclabeling.html.)

In addition, National Institutes of Health prioritization of medications for future research studies in youth now consider frequency-of-use data from insured populations, Dr. Zito says. These changes have led to some improvements—for example, “black box” warnings against stimulants given for ADHD and selective serotonin reuptake inhibitors (SSRIs) prescribed for depression. The moves also underline the need for more research.

Key safety questions remain in the pediatric community. For example, is it acceptable to calculate smaller doses by weight of drugs approved safe for adults? On this subject, pediatric hospitalists “are woefully, inadequately armed with evidence,” Dr. Alverson says. “We routinely use medications in children where the dosing is arbitrarily guessed at.”

A 2007 study conducted by Dr. Shah and colleagues validates this point. The study found that most of the children hospitalized at 31 tertiary-care pediatric hospitals received at least one medication outside the FDA product license indication.8 Although the finding does not necessarily mean the medications were inappropriate, it highlights the dearth of studies establishing the proper dosages and uses of medications in children, and the long-term outcomes of their usage.

One way in which hospitalists can help is educating parents about the perils of OTC medicines, Dr. Shen says. An example of a safety concern is parents giving their children acetaminophen (Tylenol) and ibuprofen (Motrin) together; evidence shows that this kind of dosing error by parents is relatively common.

Fill the Knowledge Gap

When it comes to choosing medications and dosages for children, pediatric hospitalists often make treatment decisions based on their clinical experience, observational studies, or by extrapolating data from adult studies.

“There are countless examples of places where evidence-based physicians must still make educated guesses,” Dr. Alverson says.

However, experts point out that children are not “little adults.” Extrapolating from adult data can lead to unpredictable clinical responses and the possibility of overmedication. Going forward, the trick will be to tease out, with rigorous research, which medications—and at which dosages—are best for which kids.

Dr. Alverson suggests hospitalists stay on top of the literature, take advantage of all available CME, and plug into a listserv, such as the American Academy of Pediatrics’ HM listserv (download instructions and an enrollment form at www.aap.org/sections/hospcare/listservSOHM.pdf).

Above all, the key to dealing with families, he says, is to give them an open assessment of risks, benefits, and gaps in the scientific knowledge. TH

Gretchen Henkel is a freelance writer based in California.

References

  1. Mongelluzzo J, Mohamad Z, Ten Have TR, Shah SS. Corticosteroids and mortality in children with bacterial meningitis. JAMA. 2008;299(17):2048-2055.
  2. Zito JM, Safer DJ, Sai D, et al. Psychotropic medication patterns among youth in foster care. Pediatrics. 2008;121(1):e157-163.
  3. Drug Trend Report 2008. Medco Corporate Web site. Available at: www.medcohealth.com/medco/corporate/home.jsp?ltSess=y&articleID=DT_2008_Report_Pdf&ltSess=y. Accessed April 1, 2009.
  4. Winterstein AG, Gerhard T, Shuster J, et al. Cardiac safety of central nervous system stimulants in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics. 2007;120(6):e1494-1501.
  5. Mangione-Smith R, McGlynn EA, Elliott MN, Krogstad P, Brook RH. The relationship between perceived parental expectations and physician antimicrobial prescribing behavior. Pediatrics. 1999;103(4 Pt 1):711-718.
  6. Sharfstein JM, North M, Serwint JR. Over the counter but no longer under the radar—pediatric cough and cold medications. N Engl J Med. 2007;357(23): 2321-2324.
  7. Clemens CJ, Taylor JA, Almquist JR, Quinn HC, Mehta A, Naylor GS. Is an antihistamine-decongestant combination effective in temporarily relieving symptoms of the common cold in preschool children? J Pediatr. 1997;130(3):463-466.
  8. Shah SS, Hall M, Goodman DM, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007;161(3):282-290.

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