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Abstract

Background:

The application of regulatory informatics to identify trends in clinical trials is a new methodology with the potential to shape drug development programs. As an endpoint in hematologic malignancies, minimal residual disease (MRD) measures the depth of response to treatment, and has been given initial attention in draft regulatory guidelines and workshops by health authorities in the EU and US.

Methods:

In this paper, we analyze hematologic malignancy trials by searching for terms in Trialtrove, parsing the data sets with ActivePerl, and determining significance with the statistical package R.

Results:

We identify trends in the use of MRD compared to other endpoints and in different indications over time from 2005 to 2014. Results show that 2 trends of endpoint and MRD use emerge over time and the use of MRD as a primary endpoint is growing. We also take a case-study approach to investigate the functional context of MRD in chronic lymphocytic leukemia and show that it is predominantly used to determine MRD-negativity and also in correlation with other endpoints.

Conclusion:

The application of informatics tools to regulatory science can evaluate the role and context of MRD as it evolves in the changing pharmaceutical landscape.

Keywords

acute lymphocytic leukemia biomarker Committee for Medicinal Products for Human Use chronic lymphocytic leukemia chronic myelogenous leukemia Food and Drug Administration multiple myeloma

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Regulatory Informatics Reveals Minimal Residual Disease Trends in Hematologic Malignancies