Person:

Wang, Bo

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 nonapproval 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 3 sNDA. Improved communication may help translate the agency’s expert judgments to clinical practice.

BACKGROUND: Solid clinical evidence supports the effectiveness and safety of multiple drugs in treating diabetes, dyslipidemia, and hypertension, and numerous fixed-dose combination products (FDCs) containing such drugs have been developed for patients with more severe forms of these diseases. We sought to evaluate the extent to which utilization of treatment combinations for these conditions corresponded to the availability of FDCs. METHODS: Using claims data from a large national commercial insurer, we identified 2 cohorts of patients: those who filled multiple single-agent drugs to treat diabetes, dyslipidemia, and hypertension in 2012, and those who used FDCs containing these products during the same period. We determined the fill rate of single-agent pairs and FDCs, availability of FDCs for the most frequently filled single-agent and drug class pairs, and the number of conditions treated by frequently filled single-agent pairs and FDCs. RESULTS: During our study period, 848,082 patients filled prescriptions for 3,248 unique single-agent pairs (mean 4.7 per patient, standard deviation [SD] 5.0); and 568,923 patients received prescriptions for 43 unique FDCs (mean 1.1 per patient, SD 0.3). Three (15%) of the 20 most frequently filled single-agent pairs were available as FDCs, whereas 9 (45%) of the 20 most frequently filled drug class pairs were available as FDCs. Nearly all of the frequently filled FDCs had lower fill rates than the most frequently filled single-agent pairs. CONCLUSIONS: Utilization of drug combinations to treat cardiovascular conditions does not correspond well with availability of FDCs containing these agents. A concerted set of strategies should be implemented to streamline the development of useful combination products, including expedited approval pathways and increased investment in formulation studies.