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  <front>
    <journal-meta>
      <journal-id journal-id-type="iso-abbrev">Pharmacophore</journal-id>
      <journal-id journal-id-type="publisher-id">pharmacophorejournal.com</journal-id>
      <journal-id journal-id-type="publisher-id">Pharmacophore</journal-id>
      <journal-title-group>
        <journal-title>Pharmacophore</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2229-5402</issn>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">pharmacophorejournal.com-6922</article-id>
      <article-id pub-id-type="doi">10.51847/m8LTGDHsIe</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original research</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Learning the Next Experiment: A Decision Architecture for Closed-Loop Drug Discovery under Cost, Uncertainty, and Scientific Value</article-title>
      </title-group>
                    <contrib-group>
                      <contrib contrib-type="author">
              <name>
                <surname>Osei</surname>
                <given-names>Daniel</given-names>
              </name>
                              <xref rid="aff1" ref-type="aff">1</xref>
                                                            <xref rid="cor1" ref-type="corresp" />
                          </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Janssens</surname>
                <given-names>Koenraad</given-names>
              </name>
                              <xref rid="aff2" ref-type="aff">2</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>Asare</surname>
                <given-names>Akua</given-names>
              </name>
                              <xref rid="aff3" ref-type="aff">3</xref>
                                        </contrib>
                      <contrib contrib-type="author">
              <name>
                <surname>El-Sayed</surname>
                <given-names>Mohammed</given-names>
              </name>
                              <xref rid="aff4" ref-type="aff">4</xref>
                                        </contrib>
                  </contrib-group>
                  <aff id="aff1">
            <label>1</label>Department of Closed-Loop Discovery and Experimental Design, Faculty of Pharmacy, University of Ghana, Accra, Ghana.
          </aff>
                  <aff id="aff2">
            <label>2</label>Department of Decision Architecture and Uncertainty Management, Faculty of Pharmaceutical Sciences, KU Leuven, Leuven, Belgium.
          </aff>
                  <aff id="aff3">
            <label>3</label>Department of Cost-Effective Experiment Planning, Faculty of Pharmacy, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
          </aff>
                  <aff id="aff4">
            <label>4</label>Department of Scientific Value Assessment in Drug Discovery, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
          </aff>
                          <author-notes>
            <corresp id="cor1">
              <bold>Address for correspondence:</bold> Prof. Wael Abu Dayyih, Department of
              Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Al-Karak 61710, Jordan.
                              E-mail: <email xlink:href="daniel.osei@ug.edu.gh">daniel.osei@ug.edu.gh</email>
                          </corresp>
          </author-notes>
                    <pub-date pub-type="epub">
        <day>28</day>
        <month>10</month>
        <year>2024</year>
      </pub-date>
      <volume>15</volume>
      <issue>5</issue>
      <fpage>100</fpage>
      <lpage>110</lpage>
      <permissions>
        <copyright-statement>
          Copyright: &#x000a9; 2026 Pharmacophore
        </copyright-statement>
        <copyright-year>2026</copyright-year>
        <license>
          <ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/"
            specific-use="textmining" content-type="ccbyncsalicense">
            https://creativecommons.org/licenses/by-nc-sa/4.0/</ali:license_ref>
          <license-p>This is an open access journal, and articles are distributed under the terms of
            the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
            others to remix, tweak, and build upon the work non-commercially, as long as appropriate
            credit is given and the new creations are licensed under the identical terms.</license-p>
        </license>
      </permissions>
      <abstract>
        <title>A<sc>BSTRACT</sc></title>
        <p>Closed-loop drug discovery seeks to connect computational inference, experiment selection, physical execution, measurement, and model updating into an iterative learning process. Yet the central decision in such a loop—what experiment should be performed next—cannot be resolved reliably by maximizing predicted activity, model confidence, expected improvement, or any other single performance measure. Candidate experiments differ not only in their likelihood of producing desirable outcomes but also in their capacity to reduce uncertainty, distinguish competing mechanisms, broaden chemical or biological coverage, reveal model failure, consume scarce resources, and delay other decisions. This article develops a proposed Next-Experiment Decision Architecture for organizing these non-equivalent considerations. The architecture treats experiment selection as a staged scientific decision comprising admissibility assessment, multidimensional value characterization, constrained portfolio assembly, and accountable authorization, execution, and adaptive control. It separates prediction from experimental confirmation, confidence from calibrated uncertainty, structural novelty from mechanistic learning, and data availability from decision suitability. It further introduces an evidence ledger that preserves model, assay, procedural, and human-decision provenance across iterations. The synthesis indicates that closed-loop value depends on the relationship between an experiment and the unresolved decision state, rather than on an intrinsic acquisition score. Important limitations include context dependence, incomplete uncertainty models, difficulty comparing heterogeneous value dimensions, and the absence of prospective validation across discovery stages and automated platforms. The proposed architecture is therefore not a deployment-ready decision tool. It is a conceptual and methodological framework intended to support testable experiment-selection policies, transparent failure handling, and more scientifically bounded implementation of active learning in pharmaceutical discovery.</p>
      </abstract>
      <kwd-group>
                <kwd>Active learning</kwd>
                <kwd>Closed-loop drug discovery</kwd>
                <kwd>Experiment selection</kwd>
                <kwd>Uncertainty quantification</kwd>
                <kwd>Scientific value</kwd>
                <kwd>Information asymmetry</kwd>
              </kwd-group>
    </article-meta>
  </front>
</article>