Association between expedited review designations and the US or global burden of disease for drugs approved by the US Food and Drug Administration, 2010-2019: a cross-sectional analysis

Abstract

Objectives: Pharmaceutical innovation can contribute to reducing the burden of disease in human populations. This research asks whether products approved by the US Food and Drug Administration (FDA) from 2010 to 2019 and expedited review programmes incentivising development of products for serious disease were aligned with the US or global burden of disease.

Design: Cross-sectional study.

Outcome measures: Association of FDA product approvals (2010-2019), first approved indications, designations for expedited review with the burden of disease (disability-adjusted life years (DALYs)), years of life lost (YLL) and years of life lived with disability (YLD) for 122 WHO Global Health Estimates (GHE) conditions in US and global (ex-US) populations.

Results: The FDA approved 387 drugs in 2010-2019 with lead indications associated with 59/122 GHE conditions. Conditions with at least one new drug had greater US DALYs (p=0.001), US YLL (p<0.001), global DALYs (p=0.030) and global YLL (p=0.004) but not US YLD (p=0.158) or global YLD (p=0.676). Most approvals were for conditions in the top quartile of US DALYs or YLL, but <27% were for conditions in the top quartile of global DALYs or YLL. The likelihood of a drug having one or more designations for expedited review programmes was negatively associated (OR<1) with US DALYs, US YLD and global YLD. There was a weak negative association with global DALYs and a weak positive association (OR>1) with US and global YLL.

Conclusions: FDA drug approvals from 2010 to 2019 were more strongly aligned with US than global disease burden. Designations for expedited review were not aligned with either the US or global burdens of disease and may inadvertently disincentivise development of products addressing global disease burdens. These results may inform policies to better align pharmaceutical innovation with the burdens of disease.

Keywords: Health policy; PUBLIC HEALTH; Quality of Life.

Figure 1

Relationship between Food and Drug Administration (FDA) drug approvals and the US or global burden of disease of Global Health Estimates (GHE) conditions associated with their lead indications. The 122 GHE conditions in the GHE-2020 study were ranked by US disability-adjusted life years (DALYs). Bars indicate disease burden measured in US DALYs (left, blue) or global DALYs (right, orange). Bars are coloured by the number of products approved by the FDA, 2010–2019, with first approved indications for that condition. Empty bars indicate no approvals. Darker bars indicate larger numbers of approvals. Grid lines indicate quartiles of GHE conditions ranked by disease burden measured in DALYs with Q4 representing conditions with the highest disease burden and Q1 representing conditions with the lowest disease burden.

Figure 2

Association of Food and Drug Administration (FDA) drug approvals and designations for expedited review across quartiles of US and global burden of disease. (A) Number of FDA drug approvals, 2010–2019, is shown for quartiles of Global Health Estimates (GHE) conditions ranked by US (blue) or global (orange) burden of disease. The burden of disease is measured by DALYs, YLL or YLD as shown. The number of FDA approvals is shown for neoplastic (patterned fill) and non-neoplastic conditions (solid fill). (B) The proportion of drugs approved, 2010–2019, with at least one expedited designation across quartiles of GHE conditions ranked by disease burden. The burden of disease for 122 GHE conditions is measured by DALYs, YLL and YLD and was divided by quartile with Q1 representing conditions with the lowest disease burden and Q4 representing conditions the highest disease burden. DALYs, disability-adjusted life years; YLD, years of life lived with disability; YLL, years of life lost.

Figure 3

ORs representing the likelihood of receiving an expedited designation as a function of burden of disease. The OR of an approved drug having a designation for expedited review was calculated as a function of burden of disease metrics for Global Health Estimates conditions comprising the first approved indication. Data are shown for analyses of DALYs, YLL or YLD associated with the US burden of disease (A, B) or global burden of disease (C, D) using either the full data set (A, C) or excluding drugs indicated for neoplasm (B, D). Analyses were performed separately for accelerated, breakthrough, fast track or priority designations or at least one designation (‘1+designation’). (A) OR calculated for 387 products approved in 2010–2019 and US burden of disease metrics. (B) OR calculated for 290 products indicated for non-neoplastic conditions and US burden of disease metrics. (C) OR calculated for 387 products approved in 2010–2019 and global burden of disease metrics. (D) OR calculated for 290 products indicated for non-neoplastic conditions and global burden of disease metrics approved in 2010–2019. Data are shown as the average and 95% CI. Filled symbols represent data with p<0.0065 corresponding to the significance threshold of p=0.05 after a Bonferroni correction of 8 to account for multiple testing. DALYs, disability-adjusted life years; YLD, years of life lived with disability; YLL, years of life lost.