Timelines of translational science: From technology initiation to FDA approval

Abstract

While timelines for clinical development have been extensively studied, there is little data on the broader path from initiation of research on novel drug targets, to approval of drugs based on this research. We examined timelines of translational science for 138 drugs and biologicals approved by the FDA from 2010-2014 using an analytical model of technology maturation. Research on targets for 102 products exhibited a characteristic (S-curve) maturation pattern with exponential growth between statistically defined technology initiation and established points. The median initiation was 1974, with a median of 25 years to the established point, 28 years to first clinical trials, and 36 years to FDA approval. No products were approved before the established point, and development timelines were significantly longer when the clinical trials began before this point (11.5 vs 8.5 years, p<0.0005). Technological maturation represents the longest stage of translation, and significantly impacts the efficiency of drug development.

Fig 1. The TIME^tm model technology growth cycle.

Top: Technology maturation is modeled as a best-fit, exponentiated logistic regression to the cumulative number of publications (N) over time. Bottom: The second derivative of this regression is used to identify the initiation point (point of greatest acceleration, d²log(N)/dx² = max) and established point (point of maximal deceleration, d²log(N)/dx² = min) for the technology. The initiation and established points bound a period of exponential growth, which subsequently slows as the technology approaches its limits.

Fig 2. Initation (Ti) years for technologies associated with NME approvals 2010–2014.

The distribution of technology initiation years for the drug target or biological entity associated with 102/138 NMEs approved by the FDA between 2010 and 2014.

Fig 3. Time interval between technology initiation and metrics of translational science.

(A) Time interval between technology initiation (Ti) and established (Te) years. (B) Time interval between technology initiation and start of clinical trials. (C) Time interval between technology initiation and first drug approval. The median and quartile boundaries are shown for all technologies with initiation after 1950.