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Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

Wang B, Franklin JM, Eddings W, Landon J, Kesselheim AS - PLoS ONE (2016)

Bottom Line: FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63).Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).

View Article: PubMed Central - PubMed

Affiliation: Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT

Background: Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.

Methods: Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.

Results: During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).

Conclusions: The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

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Related in: MedlinePlus

Time-Series Analysis of New Users of Ziprasidone, 2003–2012.Patients were enrolled in UnitedHealth insurance. Adults were defined as ≥18 years old and pediatrics defined as <18 years of age. The first time interval ran from the third quarter of 2003 through the second quarter of 2009, when the US Food and Drug Administration’s Advisory Committee convened to discuss use of ziprasidone in the pediatric population. The skip period included the third and fourth quarters of 2009 to cover the aftermath of the FDA’s Psychopharmacologic Drugs Advisory Committee votes and the agency’s period of deliberation. The second time period ran from the first quarter of 2010 through the fourth quarter of 2012.
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pone.0152195.g003: Time-Series Analysis of New Users of Ziprasidone, 2003–2012.Patients were enrolled in UnitedHealth insurance. Adults were defined as ≥18 years old and pediatrics defined as <18 years of age. The first time interval ran from the third quarter of 2003 through the second quarter of 2009, when the US Food and Drug Administration’s Advisory Committee convened to discuss use of ziprasidone in the pediatric population. The skip period included the third and fourth quarters of 2009 to cover the aftermath of the FDA’s Psychopharmacologic Drugs Advisory Committee votes and the agency’s period of deliberation. The second time period ran from the first quarter of 2010 through the fourth quarter of 2012.

Mentions: There were 23,451 qualifying ziprasidone prescriptions. Fig 3 shows the trend for new ziprasidone prescriptions. Similar to quetiapine, we observed an increase in the rate of new prescriptions for the treatment of schizophrenia and bipolar disorder for children and adolescents during the period leading up to sNDA regulatory review, from 1.1 new users per 100,000 active pediatric enrollees in the third quarter of 2003 to a high of 3.4 in the second quarter of 2006. Following FDA non-approval, the rate of new prescription filling decreased to a low of 1.6 new users per 100,000 active enrollees in the fourth quarter of 2012. There was no statistically significant difference in the trend for these indications compared with the adult population (P = 0.61).


Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

Wang B, Franklin JM, Eddings W, Landon J, Kesselheim AS - PLoS ONE (2016)

Time-Series Analysis of New Users of Ziprasidone, 2003–2012.Patients were enrolled in UnitedHealth insurance. Adults were defined as ≥18 years old and pediatrics defined as <18 years of age. The first time interval ran from the third quarter of 2003 through the second quarter of 2009, when the US Food and Drug Administration’s Advisory Committee convened to discuss use of ziprasidone in the pediatric population. The skip period included the third and fourth quarters of 2009 to cover the aftermath of the FDA’s Psychopharmacologic Drugs Advisory Committee votes and the agency’s period of deliberation. The second time period ran from the first quarter of 2010 through the fourth quarter of 2012.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4816295&req=5

pone.0152195.g003: Time-Series Analysis of New Users of Ziprasidone, 2003–2012.Patients were enrolled in UnitedHealth insurance. Adults were defined as ≥18 years old and pediatrics defined as <18 years of age. The first time interval ran from the third quarter of 2003 through the second quarter of 2009, when the US Food and Drug Administration’s Advisory Committee convened to discuss use of ziprasidone in the pediatric population. The skip period included the third and fourth quarters of 2009 to cover the aftermath of the FDA’s Psychopharmacologic Drugs Advisory Committee votes and the agency’s period of deliberation. The second time period ran from the first quarter of 2010 through the fourth quarter of 2012.
Mentions: There were 23,451 qualifying ziprasidone prescriptions. Fig 3 shows the trend for new ziprasidone prescriptions. Similar to quetiapine, we observed an increase in the rate of new prescriptions for the treatment of schizophrenia and bipolar disorder for children and adolescents during the period leading up to sNDA regulatory review, from 1.1 new users per 100,000 active pediatric enrollees in the third quarter of 2003 to a high of 3.4 in the second quarter of 2006. Following FDA non-approval, the rate of new prescription filling decreased to a low of 1.6 new users per 100,000 active enrollees in the fourth quarter of 2012. There was no statistically significant difference in the trend for these indications compared with the adult population (P = 0.61).

Bottom Line: FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63).Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).

View Article: PubMed Central - PubMed

Affiliation: Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT

Background: Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.

Methods: Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.

Results: During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).

Conclusions: The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

Show MeSH
Related in: MedlinePlus