Download Legislative Advocacy: The Safety of Over-the

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Legislative Advocacy:
Why OTCs Go Over Parents’ Heads
Allison Baxterbeck
Elizabeth Chang
Amy DiPilato
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Case
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The mother of your 5 year old clinic patient brings her
daughter in for a walk-in appointment. The child has had 3
days of URI symptoms. On exam, she is afebrile with normal
vital signs for age. She is well appearing and in no distress,
but does have nasal congestion and a mild cough. Her
mother asks you, “What cough medicine is safe to give her?”
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Background
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Historically, lack of pediatric drug testing
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Smaller market
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Ethical considerations
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Logistical issues
Prior to 1990s, adult data was often extrapolated to children
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Trial and error approach to dosing drugs in children
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Occasionally disastrous results
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Background
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Pure Food and Drug Act of 1906
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Created the Food and Drug Administration (FDA)
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First set of consumer protection laws
Federal Food, Drug, and Cosmetic Act of 1938
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Passed in response to 107 deaths (many children) after ingestion
of legally marketed Elixir of Sulfanilamide, which contained
diethylene glycol
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Authorized FDA to demand evidence of drug safety
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1994 Pediatric Rule
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Allowed labeling of drugs for pediatric use based on
extrapolation of adult safety data assuming:
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Disease course similar in adults and children
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Response to drug similar in adults and children
Only a small number of drug studies resulted from this rule
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Food and Drug Administration
Modernization Act of 1997 (FDAMA)
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Financial incentives for pharmaceutical companies to
conduct studies on children
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Voluntary Pediatric Exclusivity Provision
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Additional 6 months marketing exclusivity if the drug is
voluntarily studied in children
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Applies to all formulations, dosages, and indications of drug
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Best Pharmaceuticals for Children Act
(2002)
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Main components
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Identify and prioritize drugs needing study
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Develop study requests in collaboration with experts from NIH,
FDA, etc
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Conduct studies on priority drugs if manufacturers do not
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Extended provisions from FDAMA
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Pediatric Trials Network
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2003 Pediatric Research Equity Act
(PREA)
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Allows FDA to require pediatric studies
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Required manufacturers of new drugs and biologic agents to
conduct pediatric studies
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FDA Amendments Act of 2007
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BPCA reauthorized
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Extended provision of offering additional patent exclusivity of onpatent drugs tested in children
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Expanded NIH research program in drug testing in children
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NIH priority list
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Proposed pediatric study requests allow trials that need
improved labeling to be tested by NIH if manufacturer
refuses to do so
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National Institute of Child Health
and Human Development
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Division of NIH
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Responsible for providing 25% BPCA funding annually
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Primarily responsible for studies to develop Investigational
New Drugs, label modifications for specific ages and
indications
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Started Pediatric Pharmacology Research Network (19942009)
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Specialized Centers in Research and Pediatric
Developmental Pharmacology Program (2010-present)
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Food and Drug Administration
Safety and Innovation Act of 2012
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Permanently reauthorized BPCA and PREA
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Encourages earlier pediatric study planning to ensure
expedited pediatric drug information to patients and parents
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Gives FDA authority to ensure PREA requirements met on
time
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Improves transparency of study data
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Increases focus on neonates
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AAP: Committee on Drugs
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One of 27 national Committees that develop AAP policies
and programs
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Reviews aspects of pediatric pharmacology [drug
indications, contraindications, absorption rates, routes of
administration, dosing, use precautions and mode of action
as they apply to children]
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Advises the Board of Directors in matters related to drug
labeling, safety and efficacy for Rx and OTC drugs
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Monitors federal legislation related to the drug approval
process
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Promotes the need for expanded pediatric drug trials
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Over-the-Counter (OTC) Monograph
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Established in 1972 by the FDA to evaluate safety and
effectiveness of OTC products
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Drugs go through a 3 phase process:
Advisory panel
looks at active
ingredients;
reviews claims,
recommends
labeling:
therapeutic
indications,
dosages, warnings
FDA reviews
ingredients based
on based on
panel’s reviews
Publication of final
regulations as
drug monograph
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Over-the-Counter (OTC) Monograph
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Essentially serves as a “cook book,” or list of recipes,
that include acceptable ingredients, formulations,
dosages and labeling for each category of drugs
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Products containing active ingredients or indications
not in the monograph require an approved “New Drug
Application”
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According to the FDA, OTC monographs are continually
updated as needed
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“The monograph process is no longer consistent
with current best practices in pediatric
pharmacology …While many monograph drugs are
safe and effective for use in children… others
continue to be labeled for children and heavily
marketed to parents despite safety concerns and
newer data showing a lack of efficacy in children.”
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AAP’s Position
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The OTC monograph system needs reform
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The New Drug Application (NDA) is the gold standard for the
review and approval of drugs based on robust clinical trials
and modern standards of evidence
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Only drugs submitted under the NDA process are subject to
the full scope of the pediatric drug laws, BPCA and PREA.
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AAP’s Position
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The FDA should have the authority to quickly require the
transition of a product from an OTC monograph  NDA when
significant concerns about safety and/or efficacy arise
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The FDA should remove a product from the monograph or
allow manufacturers a finite period to develop new data and
submit an NDA before ultimate removal of the drug from the
monograph
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Without new efficacy data, revision of monograph drugs
should include a de novo review of the appropriateness of
extrapolating adult efficacy to pediatric subpopulations.
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In Short…
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The need for more research looking at the unique physiology
of children: how drugs are absorbed, metabolized, and
eliminated
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Data on age-specific therapeutic data using modern
standards for safety and efficacy that are applicable to
children not just adults.
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Recommending pediatric dosing based on peds-specific
pharmacokinetic data AND efficacy data
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OTC Cough/Cold
Medications
1.
Current
recommendations/regulations
2.
Timeline leading to current state of
OTC cough/cold medications
3.
Future directions and improvements
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Current Recommendations and
Regulations for Cough/Cold Meds
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Regulated under the Cough, Cold, Allergy, Bronchodilator,
and Anti-asthmatic Drug Products monograph.
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1976 committee declared that “data on the use in children of
most drugs in [cough and cold preparations] are negligible
or nonexistent”
+ Current Recommendations
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AAP: Cough and cold medicines should not be prescribed or
recommended for children under 4 years of age.
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FDA: Strongly recommends that OTC cough and cold
products should not be used for infants and children under 2
years of age because serious and potentially life-threatening
side effects could occur.
Lack
of
Evidence
for
Efficacy
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Timeline of Changes:
 Early
2007: FDA review of 1969-2006 – 54 reported
child deaths decongestants and 69 from
antihistamines
 March
2007: Citizen petition for Relabeling of
Cough/Cold meds to advise against use in
children <6yo
 August
2007: Federal health officials recommended
“consult your physician”  Warning: Do not use in
children under 2 yr unless directed by your doctor
 October
2007: Manufacturers voluntarily recall
meds for children <2 and change labels
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Timeline of Changes
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October 2007: FDA joint mtg - Pediatric Advisory Committee
& Nonprescription Drug Advisory Committee:
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Unanimously vote: adult data should not be used
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Vote: 13 to 9 to Recommend FDA immediately take meds off
market for kids < 6yo
January 2008:
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FDA official statement against use of cough/cold meds in kids
<2yr
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Began working on revising OTC Monograph
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Timeline of Changes
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Fall 2008: Manufacturers voluntarily change labels to say:
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“Do not use” kids <4yr
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Warning on antihistamines: Do not use to sedate or make child
sleepy
October 2008: FDA Part 15 Hearing
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AAP recommended re-labeling against use <6yo, more studies on
pharmacokinetics and efficacy in children
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Effect of Changes:
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2013 Study by Hampton et al:
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<2yo: ED visits for Adverse drug events decreased by 41% after
market withdrawal
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2-3yo: ED visits for ADE decreased by 32% with labeling revision
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No significant change in ED visits for ADEs for patients 4-5yo or 611yo
FDA has not published a proposal to amend OTC monograph
despite recommendations from AAP and FDA’s own advisory
committee
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Future Directions
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Considering whether to regulate as New Drug Application
rather than via OTC Monographs.
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Modify the OTC Monograph for children
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New labeling: Against use in children <6yo
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Making label changes a requirement and not voluntary
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Education for families about OTC medications
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Case

The mother of your 5 year old clinic patient brings her
daughter in for a walk-in appointment. The child has had 3
days of URI symptoms. On exam, she is afebrile with normal
vital signs for age. She is well appearing and in no distress,
but does have nasal congestion and a mild cough. Her
mother asks you, “What cough medicine is safe to give her?”
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References
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2013-2014 National Committee Annual Report Committee on Drugs. N.d. MS. American Academy of
Pediatrics. Web. 27 Jan. 2015.
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"Background." Pediatric Trials Network. Eunice Kennedy Shriver National Institute of Child Health and Human
Development, 31 Oct. 2014. Web. 03 Feb. 2015.
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"Best Pharmaceuticals for Children Act." About the BPCA. Eunice Kennedy Shriver National Institute of Child
Health and Human Development, 13 May 2011. Web. 03 Feb. 2015.
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"Drug Research and Children." Drug Research and Children. U.S. Department of Health and Human Services, 24
Aug. 2011. Web. 03 Feb. 2015.
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Hampton LM, Nguyen DB, Edwards JR, Budnitz DS. Cough and cold medication adverse events after
market withdrawal and labeling revision. Pediatrics. 2013 Dec;132(6):1047-54.
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Legislation." Regulatory Information. U.S. Food and Drug Administration, 9 July 2012. Web. 03 Feb. 2015.

Neville, Katherine, MD. "Regulation of the Over the Counter Drug Products." US FDA Public Hearing. 24
Mar. 2014. Presentation.
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"Safe & Effective Drugs for Children." Federal Advocacy. American Academy of Pediatrics, n.d.Web. 03
Feb. 2015.
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"U.S. Food and Drug Administration." Over-the-Counter (OTC) Drug Monograph Process. N.p., 7 Jan.
2015. Web. 27 Jan. 2015.
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References
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Pappas, Diane et al. The common cold in children: Treatment and prevention. UpToDate. January 20, 2015.
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Pappas DE, Hendley JO. The common cold and decongestant therapy. Pediatr Rev 2011; 32:47.
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Paul IM, Yoder KE, Crowell KR, et al. Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal
cough and sleep quality for coughing children and their parents. Pediatrics 2004; 114:e85.
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Schroeder K, Fahey T. Should we advise parents to administer over the counter cough medicines for acute
cough? Systematic review of randomised controlled trials. Arch Dis Child 2002; 86:170.
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Taverner D, Latte J. Nasal decongestants for the common cold. Cochrane Database Syst Rev 2007; :CD001953.
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Hutton N, Wilson MH, Mellits ED, et al. Effectiveness of an antihistamine-decongestant combination for young
children with the common cold: a randomized, controlled clinical trial. J Pediatr 1991; 118:125.
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Clemens CJ, Taylor JA, Almquist JR, et al. Is an antihistamine-decongestant combination effective in
temporarily relieving symptoms of the common cold in preschool children? J Pediatr 1997; 130:463.
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Taylor JA, Novack AH, Almquist JR, Rogers JE. Efficacy of cough suppressants in children. J Pediatr 1993;
122:799.
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Paul IM, Beiler J, McMonagle A, et al. Effect of honey, dextromethorphan, and no treatment on nocturnal cough
and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med 2007; 161:1140.
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Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in
community settings. Cochrane Database Syst Rev 2014; 11:CD001831.