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. 2014 Sep 23;111(7):1305-9.
doi: 10.1038/bjc.2014.448. Epub 2014 Aug 12.

The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?

P Blumenfeld  1 , R M Pfeffer  2 , Z Symon  2 , R B Den  3 , A P Dicker  3 , D Raben  4 , Y R Lawrence  5
Affiliations

The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?

P Blumenfeld et al. Br J Cancer. .

Abstract

Background: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT-drug development programmes before patent expiration.

Methods: We identified novel drug-radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: date the initial phase I trial with/without RT was opened/published, date of the published positive phase III trials, and patent expiration dates. Lag time was defined as the interval between opening of the phase I trial without RT and the opening of the phase I with RT. Linear regression was used to model how the lag time has changed over time.

Results: The median lag time was 6 years. The initial phase I trial with RT was typically published 2 years after the first published positive phase III trial and 11 years before patent expiration. Using a best-fit linear model, lag time decreased from 10 years for phase I trials published in 1990 to 5 years in 2005 (slope significantly non-zero, P<0.001).

Conclusions: Clinical drug development with RT commences late in the life cycle of anti-cancer agents. Taking into account the additional time required for late-phase clinical trials, the delay in initiating clinical testing of drug-RT combinations discourages drug companies from further pursuing RT-based development. Encouragingly, lag time appears to be decreasing. Further reduction in lag time may accelerate RT-based drug development, potentially improving patient outcomes.

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Figures

Figure 1
Figure 1
Flow diagram of the process used to Identify trials for analysis.
Figure 2
Figure 2
Typical time line of drug development with radiation. Time intervals refer to median values derived from the study of 66 drugs, as detailed in Table 2.
Figure 3
Figure 3
Lag time-P as a function of the publication year of phase I without RT.
See this image and copyright information in PMC

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