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M-08: Postmarketing Drug Dosage Changes of 413 FDA-approved New Molecular Entities, 2000-2014

Poster Presenter

      Anh Hoang Duong

      • Pharm D Student Summer Intern at FDA
      • Touro University
        United States


Post-marketing labeling changes are indicative of drug development quality as well as regulatory review and regulatory guidance. This study investigates drug labeling changes to dosing recommendations of 413 new molecular entities (NME) approved between 2000 and 2014.


Drug labels at the time of approval for all NMEs approved between 2000 and 2014 were compared to their most recent label. All drug labels were obtained from the drugs@FDA database. Changes in dosing recommendations were noted in different patient populations, drug-drug interaction, and etc.


Out of 413 approved NMEs, 411 were evaluated for dosage regimen changes. Two NMEs where excluded from the analysis due to unavailable label. Total number of NMEs with one or more dose changes was 96 (23.4%), 30 NMEs had two or more dose changes to their label. Amongst the therapeutic areas, Hematology/Oncology, had the largest number of post-marketing changes to the dose, (n=49). Genitourinary had the lowest number of changes with only one change to the label. The median time for dosage change was 4.8 years, (min: 0.62; max: 13.8). The most common dosing change to the label was due to extension of the indication to a pediatric population (n=32) and modification of the dose in the general population (n=30). The least common changes were in the geriatric population (n=2).


Compared to a previous study examining NMEs approved between 1980-1999, the percentage of NMEs with dose modifications between 2000-2014 is similar (23.4% versus 21%). However, most labeling changes in NMEs approved between 2000 and 2014 occurred due to indication expansions in the pediatric population. This is likely reflective of the passage of drug legislation and pediatric provisions (e.g., 1997 Food and Drug Administration Act [FDAMA], 2002 Best Pharmaceuticals for Children Act [BPCA], and the 2003 Pediatric Research Equity Act [PREA]), which incentivized and required the conduct of pediatric drug studies to obtain use information in product labeling. Adjusting for that discrepancy shows that the 2000-2014 NME cohorts had a smaller number of NMEs with labeling changes compared to the 1980-1999 cohorts (18.2% versus 21%).