Investigating drug repositioning opportunities in FDA drug labels through topic modeling

BMC Bioinformatics

Proceedings

Halil Bisgin¹  Xiaowei Xu²  Zhichao Liu³  Weida Tong³  Hong Fang⁴  Reagan Kelly⁴ 

[1]Department of Information Science, University of Arkansas at Little Rock, 2801 S. University Ave., 72204-1099, Little Rock, AR, USA

[2]Department of Information Science, University of Arkansas at Little Rock, 2801 S. University Ave., 72204-1099, Little Rock, AR, USA

[3]Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079, Jefferson, AR, USA

[4]Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079, Jefferson, AR, USA

[5]ICF International Company at FDA's National Center for Toxicological Research, 3900 NCTR Rd, 72079, Jefferson, AR, USA

关键词: Atomoxetine;    Common Indication;    Topic Modeling;    Latent Dirichlet Allocation;    Auranofin;   

DOI  :  10.1186/1471-2105-13-S15-S6

来源: Springer

【 摘 要 】

BackgroundDrug repositioning offers an opportunity to revitalize the slowing drug discovery pipeline by finding new uses for currently existing drugs. Our hypothesis is that drugs sharing similar side effect profiles are likely to be effective for the same disease, and thus repositioning opportunities can be identified by finding drug pairs with similar side effects documented in U.S. Food and Drug Administration (FDA) approved drug labels. The safety information in the drug labels is usually obtained in the clinical trial and augmented with the observations in the post-market use of the drug. Therefore, our drug repositioning approach can take the advantage of more comprehensive safety information comparing with conventional de novo approach.MethodA probabilistic topic model was constructed based on the terms in the Medical Dictionary for Regulatory Activities (MedDRA) that appeared in the Boxed Warning, Warnings and Precautions, and Adverse Reactions sections of the labels of 870 drugs. Fifty-two unique topics, each containing a set of terms, were identified by using topic modeling. The resulting probabilistic topic associations were used to measure the distance (similarity) between drugs. The success of the proposed model was evaluated by comparing a drug and its nearest neighbor (i.e., a drug pair) for common indications found in the Indications and Usage Section of the drug labels.ResultsGiven a drug with more than three indications, the model yielded a 75% recall, meaning 75% of drug pairs shared one or more common indications. This is significantly higher than the 22% recall rate achieved by random selection. Additionally, the recall rate grows rapidly as the number of drug indications increases and reaches 84% for drugs with 11 indications. The analysis also demonstrated that 65 drugs with a Boxed Warning, which indicates significant risk of serious and possibly life-threatening adverse effects, might be replaced with safer alternatives that do not have a Boxed Warning. In addition, we identified two therapeutic groups of drugs (Musculo-skeletal system and Anti-infective for systemic use) where over 80% of the drugs have a potential replacement with high significance.ConclusionTopic modeling can be a powerful tool for the identification of repositioning opportunities by examining the adverse event terms in FDA approved drug labels. The proposed framework not only suggests drugs that can be repurposed, but also provides insight into the safety of repositioned drugs.

【 授权许可】

Unknown   
© Bisgin et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.