For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
42
views
62
references
 Top references
cited by
1
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    8
    shares
      231
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Quantifying and Communicating Uncertainty in Preclinical Human Dose-Prediction

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Human dose-prediction is fundamental for ranking lead-optimization compounds in drug discovery and to inform design of early clinical trials. This tutorial describes how uncertainty in such predictions can be quantified and efficiently communicated to facilitate decision-making. Using three drug-discovery case studies, we show how several uncertain pieces of input information can be integrated into one single uncomplicated plot with key predictions, including their uncertainties, for many compounds or for many scenarios, or both.

          Related collections

          Most cited references62

          • Record: found
          • Abstract: found
          • Article: not found

          Drug-like properties and the causes of poor solubility and poor permeability.

          C Lipinski (2001)
          There are currently about 10000 drug-like compounds. These are sparsely, rather than uniformly, distributed through chemistry space. True diversity does not exist in experimental combinatorial chemistry screening libraries. Absorption, distribution, metabolism, and excretion (ADME) and chemical reactivity-related toxicity is low, while biological receptor activity is higher dimensional in chemistry space, and this is partly explainable by evolutionary pressures on ADME to deal with endobiotics and exobiotics. ADME is hard to predict for large data sets because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Currently, screening for biological receptor activity precedes or is concurrent with screening for properties related to "drugability." In the future, "drugability" screening may precede biological receptor activity screening. The level of permeability or solubility needed for oral absorption is related to potency. The relative importance of poor solubility and poor permeability towards the problem of poor oral absorption depends on the research approach used for lead generation. A "rational drug design" approach as exemplified by Merck advanced clinical candidates leads to time-dependent higher molecular weight, higher H-bonding properties, unchanged lipophilicity, and, hence, poorer permeability. A high throughput screening (HTS)-based approach as exemplified by unpublished data on Pfizer (Groton, CT) early candidates leads to higher molecular weight, unchanged H-bonding properties, higher lipophilicity, and, hence, poorer aqueous solubility.
          Article 0 comments Cited 281 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The sciences of science communication.

            Baruch Fischhoff (2013)
            The May 2012 Sackler Colloquium on "The Science of Science Communication" brought together scientists with research to communicate and scientists whose research could facilitate that communication. The latter include decision scientists who can identify the scientific results that an audience needs to know, from among all of the scientific results that it would be nice to know; behavioral scientists who can design ways to convey those results and then evaluate the success of those attempts; and social scientists who can create the channels needed for trustworthy communications. This overview offers an introduction to these communication sciences and their roles in science-based communication programs.
            Article 0 comments Cited 112 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Improving communication of uncertainty in the reports of the intergovernmental panel on climate change.

              David Budescu, Stephen Broomell, Han-Hui Por (2009)
              The Intergovernmental Panel on Climate Change (IPCC) assesses information relevant to the understanding of climate change and explores options for adaptation and mitigation. The IPCC reports communicate uncertainty by using a set of probability terms accompanied by global interpretational guidelines. The judgment literature indicates that there are large differences in the way people understand such phrases, and that their use may lead to confusion and errors in communication. We conducted an experiment in which subjects read sentences from the 2007 IPCC report and assigned numerical values to the probability terms. The respondents' judgments deviated significantly from the IPCC guidelines, even when the respondents had access to these guidelines. These results suggest that the method used by the IPCC is likely to convey levels of imprecision that are too high. We propose an alternative form of communicating uncertainty, illustrate its effectiveness, and suggest several additional ways to improve the communication of uncertainty.
              Article 0 comments Cited 94 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): CPT Pharmacometrics Syst Pharmacol
                Journal ID (iso-abbrev): CPT Pharmacometrics Syst Pharmacol
                Journal ID (publisher-id): psp4
                Title: CPT: Pharmacometrics & Systems Pharmacology
                Publisher: BlackWell Publishing Ltd (Oxford, UK )
                ISSN (Print): 2163-8306
                ISSN (Electronic): 2163-8306
                Publication date (Print): April 2015
                Publication date (Electronic): 16 April 2015
                Volume: 4
                Issue: 4
                Pages: 243-254
                Affiliations
                [1 ]CVMD iMed DMPK, AstraZeneca R&D SE-431, 83, Mölndal, Sweden
                Author notes
                *Correspondence: M Sundqvist ( monika.sundqvist@ 123456astrazeneca.com )
                Article
                DOI: 10.1002/psp4.32
                PMC ID: 4429578
                SO-VID: b75761bc-95d4-49f5-85e2-097e8df691db
                Copyright © © 2015 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.
                License:

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 27 August 2014
                Date accepted : 26 February 2015
                Categories
                Subject: Tutorial

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content231

                See all similar

                Cited by1

                See all cited by

                Most referenced authors1,056

                See all reference authors