EM1 When Are Breakthrough Therapies Cost-Effective?


      The US Food and Drug Administration (FDA)-designated breakthrough therapies offer substantial potential to improve health outcomes, but it is unclear whether their health gains represent favorable value for money.


      Using the Tufts Medical Center Cost-Effectiveness (CE) Analysis Registry we: (1) summarized the cost-effectiveness of breakthrough therapies (BT), as measured by the cost-per-quality-adjusted-life-year (QALY) metric; (2) compared the cost-effectiveness of BT and non-breakthrough therapies (NBT) in the US; and (3) identified factors associated with BT cost-effectiveness, using logistic regression models with a range of value benchmarks ($50K-$150K/QALY).


      Between 2013 and 2018, FDA approved 264 drugs, designating 84 (32%) as breakthrough therapies. We identified published US CE studies for 26% of BT drugs (48 studies, 227 CE ratios) and 23% of NBT drugs (60 studies, 96 CE ratios). Publications focused on hepatitis C (HepC) or other infectious diseases (38% of BT studies, 23% of NBT studies) and neoplasms (48% of BT studies, 11% of NBT studies). Median BT incremental costs and QALYs exceeded corresponding values for NBT ($29,231 vs. $20,263 and 0.7 vs. 0.2 QALYs, respectively), and CE ratios trended toward greater favorability for BT compared to NBT drugs (median values $38,000/QALY vs. $50,000/QALY, respectively). For BTs, HepC drugs had the most favorable CE ratios, as removing HepC studies increased the median CE ratio to more than $140,000 (with median $65,000 incremental cost and 0.61 QALYs gained). Further, BTs for new molecular entities (NME) had median CE ratios about 40% lower than non-NME BTs, reflecting their smaller incremental costs and greater QALY gains.


      Breakthrough drugs may confer greater health benefits than NBTs in terms of QALYs gained. However, nuances, such as target condition, NME, and choice of comparator greatly influence whether greater relative health gains represent favorable value for money.