Abstract
The FDAs Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs / biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (&# ADR reports / &# shipping units) 1,000,000. MCASE / MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by ≥4 ADR reports and ≥20,000 shipping units during five years of marketing, and an RI ≥4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects.
Keywords: adr, adverse effect, fda, computational toxicology, predictive modeling, qsar, srs database, human clinical data
Current Drug Discovery Technologies
Title: Assessment of the Health Effects of Chemicals in Humans: II. Construction of an Adverse Effects Database for QSAR Modeling
Volume: 1 Issue: 4
Author(s): Edwin J. Matthews, Naomi L. Kruhlak, James L. Weaver, R. Daniel Benz and Joseph F. Contrera
Affiliation:
Keywords: adr, adverse effect, fda, computational toxicology, predictive modeling, qsar, srs database, human clinical data
Abstract: The FDAs Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs / biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (&# ADR reports / &# shipping units) 1,000,000. MCASE / MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by ≥4 ADR reports and ≥20,000 shipping units during five years of marketing, and an RI ≥4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects.
Export Options
About this article
Cite this article as:
Matthews J. Edwin, Kruhlak L. Naomi, Weaver L. James, Benz Daniel R. and Contrera F. Joseph, Assessment of the Health Effects of Chemicals in Humans: II. Construction of an Adverse Effects Database for QSAR Modeling, Current Drug Discovery Technologies 2004; 1 (4) . https://dx.doi.org/10.2174/1570163043334794
DOI https://dx.doi.org/10.2174/1570163043334794 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
Related Books

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Molecular Symmetry: A Structural Property Frequently Present in New Cytotoxic and Proapoptotic Drugs
Mini-Reviews in Medicinal Chemistry Cancer Stem Cells: The ‘Achilles Heel’ of Chemo-Resistant Tumors
Recent Patents on Anti-Cancer Drug Discovery Recent Advances in Ethnopharmacological and Toxicological Properties of Bioactive Compounds from <i>Aloe barbadensis</i> (Miller), <i>Aloe vera</i>
Current Bioactive Compounds Functions of Antimicrobial Peptides in Vertebrates
Current Protein & Peptide Science Interplay between DNA Methyltransferase 1 and microRNAs During Tumorigenesis
Current Drug Targets Editorial [Hot Topic: Hydrogen Sulfide: From Molecular Biology to Pharmacology Guest Editor: Stefano Fiorucci)]
Inflammation & Allergy - Drug Targets (Discontinued) Pharmacological Management of Type 2 Diabetes Mellitus: An Update
Current Diabetes Reviews MicroRNAs and Cancer: Towards a Personalized Medicine
Current Molecular Medicine Medicinal Plants from Peru: A Review of Plants as Potential Agents Against Cancer
Anti-Cancer Agents in Medicinal Chemistry Polymeric Radiotracers in Nuclear Imaging
Current Drug Delivery RNA Splicing: Basic Aspects Underlie Antitumor Targeting
Recent Patents on Anti-Cancer Drug Discovery Medicinal Plants and Cancer Chemoprevention
Current Drug Metabolism Epigenetic Regulation of Cytochrome P450 Enzymes and Clinical Implication
Current Drug Metabolism Telomerase Inhibitors: Potential Anticancer Agents
Mini-Reviews in Organic Chemistry Biomedical Applications of Gold Nanoparticles
Current Topics in Medicinal Chemistry Peptides Targeting Angiogenesis Related Growth Factor Receptors
Current Pharmaceutical Design Selective Inhibitors of Zinc-Dependent Histone Deacetylases. Therapeutic Targets Relevant to Cancer
Current Pharmaceutical Design Polysaccharide Based Formulations for Mucosal Drug Delivery: A Review
Current Pharmaceutical Design Ex Vivo Gene Transfer for Improvement of Transplanted Pancreatic Islet Viability and Function
Current Pharmaceutical Design Flavonoids in Atherosclerosis: An Overview of Their Mechanisms of Action
Current Medicinal Chemistry