Objectives: Breakthrough Therapy Designation (BTD) is an expedited drug pathway frequently used to bring oncology drugs to market. Historically, oncology drugs have high rates of adverse events (AEs). In this study, we compare post-marketing adverse events (PMAEs) in oncology medications approved with BTD vs. without BTD.

Methods: Data on all new drug applications (NDAs) 2012-2019 from the Drugs@FDA database was combined with PMAEs from the FDA Adverse Event Reporting System (FAERS) database. FAERS data reports PMAEs per year as the number of AEs divided by the duration of time the drug was on the market. Market share was estimated using publicly reported drug company earnings in 2019, and further categorized as high (n=7), medium (n=36), and low (n=49). Statistical comparisons were made using chi squared (X²), ANOVA, and logistical regression tests.

Results: Among the 92 oncology NDAs approved between 2012 and 2018, 36 (39%) received a BTD while 56 (61%) did not. Logistical regression and X² testing reveal no statistically significant differences in BTD by drug class, date of release, and number of PMAEs reported per year on market. However, when including duration on the market as a covariate, BTD association with PMAEs became significant. An ANOVA model with BTD, time on market, and market share effect on total PMAEs revealed a significant main effect model F (4,85) = 13.7, p <0.0001 and a significant interaction with BTD, F (1,2) = 5.18, p < 0.25 and high market share F (1,2) = 23.7, p= <0.0001. This indicates that BTD and high market share is associated with total PMAEs.

Conclusions: Oncology medications with BTD and high market share are associated with total PMAEs. BTD significance appears to be suppressed in statistical models when time on market is omitted.