How were new medicines discovered? | Nature Reviews Drug Discovery

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Observations from this analysis — such as the fact that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches in an era in which the major focus was on target-based approaches — could have important implications for efforts to increase the productivity of drug research and development. Preclinical strategies that are used to identify potential drug candidates include target-based screening, phenotypic screening, modification of natural substances and biologic-based approaches. To investigate whether some strategies have been more successful than others in the discovery of new drugs, we analysed the discovery strategies and the molecular mechanism of action (MMOA) for new molecular entities and new biologics that were approved by the US Food and Drug Administration between 1999 and 2008. Out of the 259 agents that were approved, 75 were first-in-class drugs with new MMOAs, and out of these, 50 (67%) were small molecules and 25 (33%) were biologics. The results also show that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches — with 28 and 17 of these drugs coming from the two approaches, respectively — in an era in which the major focus was on target-based approaches. We postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development.","datePublished":"2011-06-24T00:00:00Z","dateModified":"2011-06-24T00:00:00Z","pageStart":"507","pageEnd":"519","sameAs":"https://doi.org/10.1038/nrd3480","keywords":["Drug discovery","Biomedicine","general","Pharmacology/Toxicology","Biotechnology","Medicinal Chemistry","Molecular Medicine","Cancer Research"],"image":["https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fnrd3480/MediaObjects/41573_2011_Article_BFnrd3480_Fig1_HTML.jpg","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fnrd3480/MediaObjects/41573_2011_Article_BFnrd3480_Fig2_HTML.jpg","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fnrd3480/MediaObjects/41573_2011_Article_BFnrd3480_Fig3_HTML.jpg","https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fnrd3480/MediaObjects/41573_2011_Article_BFnrd3480_Fig4_HTML.jpg"],"isPartOf":{"name":"Nature Reviews Drug Discovery","issn":["1474-1784","1474-1776"],"volumeNumber":"10","@type":["Periodical","PublicationVolume"]},"publisher":{"name":"Nature Publishing Group UK","logo":{"url":"https://www.springernature.com/app-sn/public/images/logo-springernature.png","@type":"ImageObject"},"@type":"Organization"},"author":[{"name":"David C. Swinney","affiliation":[{"name":"Roche Palo Alto","address":{"name":"Roche Palo Alto, Palo Alto, USA","@type":"PostalAddress"},"@type":"Organization"},{"name":"iRND3 (Institute for Rare and Neglected Diseases Drug Discovery)","address":{"name":"iRND3 (Institute for Rare and Neglected Diseases Drug Discovery), Belmont, USA","@type":"PostalAddress"},"@type":"Organization"}],"email":"david.swinney@irnd3.org","@type":"Person"},{"name":"Jason Anthony","affiliation":[{"name":"Roche Palo Alto","address":{"name":"Roche Palo Alto, Palo Alto, USA","@type":"PostalAddress"},"@type":"Organization"}],"@type":"Person"}],"isAccessibleForFree":false,"hasPart":{"isAccessibleForFree":false,"cssSelector":".main-content","@type":"WebPageElement"},"@type":"ScholarlyArticle"},"@context":"https://schema.org","@type":"WebPage"}</script> <link rel="canonical" href="https://www.nature.com/articles/nrd3480"> <meta name="journal_id" content="41573"/> <meta name="dc.title" content="How were new medicines discovered?"/> <meta name="dc.source" content="Nature Reviews Drug Discovery 2011 10:7"/> <meta name="dc.format" content="text/html"/> <meta name="dc.publisher" content="Nature Publishing Group"/> <meta name="dc.date" content="2011-06-24"/> <meta name="dc.type" content="OriginalPaper"/> <meta name="dc.language" content="En"/> <meta name="dc.copyright" content="2011 Springer Nature Limited"/> <meta name="dc.rights" content="2011 Springer Nature Limited"/> <meta name="dc.rightsAgent" content="journalpermissions@springernature.com"/> <meta name="dc.description" content="To investigate whether some strategies have been more successful than others in the discovery of new drugs, this article analyses the discovery strategies and the molecular mechanism of action for 259 new drugs that were approved by the US Food and Drug Administration between 1999 and 2008. Observations from this analysis — such as the fact that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches in an era in which the major focus was on target-based approaches — could have important implications for efforts to increase the productivity of drug research and development. Preclinical strategies that are used to identify potential drug candidates include target-based screening, phenotypic screening, modification of natural substances and biologic-based approaches. To investigate whether some strategies have been more successful than others in the discovery of new drugs, we analysed the discovery strategies and the molecular mechanism of action (MMOA) for new molecular entities and new biologics that were approved by the US Food and Drug Administration between 1999 and 2008. Out of the 259 agents that were approved, 75 were first-in-class drugs with new MMOAs, and out of these, 50 (67%) were small molecules and 25 (33%) were biologics. The results also show that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches — with 28 and 17 of these drugs coming from the two approaches, respectively — in an era in which the major focus was on target-based approaches. 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Out of the 259 agents that were approved, 75 were first-in-class drugs with new MMOAs, and out of these, 50 (67%) were small molecules and 25 (33%) were biologics. The results also show that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches — with 28 and 17 of these drugs coming from the two approaches, respectively — in an era in which the major focus was on target-based approaches. We postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development."/> <meta name="dc.creator" content="Swinney, David C."/> <meta name="dc.creator" content="Anthony, Jason"/> <meta name="dc.subject" content="Drug discovery"/> <meta name="citation_reference" content="citation_journal_title=Nature Rev. 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data-track-component="article body"> <article lang="en"> <div class="c-article-header"> <header> <ul class="c-article-identifiers" data-test="article-identifier"> <li class="c-article-identifiers__item" data-test="article-category">Analysis</li> <li class="c-article-identifiers__item">Published: <time datetime="2011-06-24">24 June 2011</time></li> </ul> <h1 class="c-article-title" data-test="article-title" data-article-title="">How were new medicines discovered?</h1> <ul class="c-article-author-list c-article-author-list--short" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-David_C_-Swinney-Aff1-Aff2" data-author-popup="auth-David_C_-Swinney-Aff1-Aff2" data-author-search="Swinney, David C." data-corresp-id="c1">David C. Swinney<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff2">2</a></sup> & </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Jason-Anthony-Aff1" data-author-popup="auth-Jason-Anthony-Aff1" data-author-search="Anthony, Jason">Jason Anthony</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup> </li></ul> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/nrd" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Nature Reviews Drug Discovery</i></a> <b data-test="journal-volume"><span class="u-visually-hidden">volume</span> 10</b>, <span class="u-visually-hidden">pages </span>507–519 (<span data-test="article-publication-year">2011</span>)<a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">48k <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="citation-count"> <p class="c-article-metrics-bar__count">1340 <span class="c-article-metrics-bar__label">Citations</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">108 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/nrd3480/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </header> <div class="u-js-hide" data-component="article-subject-links"> <h3 class="c-article__sub-heading">Subjects</h3> <ul class="c-article-subject-list"> <li class="c-article-subject-list__subject"><a href="/subjects/drug-discovery" data-track="click" data-track-action="view subject" data-track-label="link">Drug discovery</a></li> </ul> </div> </div> <div class="c-article-body"> <section aria-labelledby="Abs1" data-title="Key Points" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Key Points</h2><div class="c-article-section__content" id="Abs1-content"> <ul class="u-list-style-bullet"> <li> <p>We analysed the discovery strategies and the molecular mechanisms of action (MMOAs) for new molecular entities and new biologics that were approved by the US Food and Drug Administration (FDA) in the 10-year period between 1999 and 2008.</p> </li> <li> <p>Out of the total of 259 agents approved, 75 were first-in-class drugs with new MMOAs, and of these, 50 (67%) were small molecules and 25 (33%) were biologics.</p> </li> <li> <p>These results show that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches — with 28 and 17 of these drugs coming from these two approaches, respectively — in an era in which the major focus was on target-based approaches.</p> </li> <li> <p>There were 164 follower drugs, of which 83 (51%) were discovered with target-based approaches, 30 (18%) via phenotypic assays and 31 (19%) were biologics.</p> </li> <li> <p>Many different biochemical mechanisms mediated the drug response at the target. These included: reversible, irreversible and slow binding kinetics; competitive, uncompetitive and noncompetitive interactions between physiological substrates/ligands and drugs; and inhibition, activation, agonism, partial agonism, allosteric activation and induced degradation, among other mechanisms. We conclude that an affinity-driven 'one size fits all' approach to drug discovery does not account for the diversity of MMOAs of approved drugs.</p> </li> <li> <p>We postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development.</p> </li> <li> <p>We consider that technical risk — and, consequently, overall attrition in drug development — could be decreased for first-in-class drugs through the development and greater use of translational phenotypic assays and by considering diverse MMOAs when using a target-based, hypothesis-driven strategy.</p> </li> </ul> </div></div></section><section aria-labelledby="Abs3" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs3-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs3">Abstract</h2><div class="c-article-section__content" id="Abs3-content"><p>Preclinical strategies that are used to identify potential drug candidates include target-based screening, phenotypic screening, modification of natural substances and biologic-based approaches. To investigate whether some strategies have been more successful than others in the discovery of new drugs, we analysed the discovery strategies and the molecular mechanism of action (MMOA) for new molecular entities and new biologics that were approved by the US Food and Drug Administration between 1999 and 2008. Out of the 259 agents that were approved, 75 were first-in-class drugs with new MMOAs, and out of these, 50 (67%) were small molecules and 25 (33%) were biologics. The results also show that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches — with 28 and 17 of these drugs coming from the two approaches, respectively — in an era in which the major focus was on target-based approaches. We postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development.</p></div></div></section> <noscript> <div class="c-nature-box c-nature-box--side " data-component="entitlement-box"> <div class="js-access-button"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fnrd3480" class="c-article__button" data-test="ra21"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-buy-button"> <a href="#access-options" class="c-article__button c-article__button--inverted" data-test="ra21"> <span>Buy or subscribe</span> </a> </div> </div> </noscript> <div class="js-context-bar-sticky-point-mobile" data-track-context="article 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We specifically thank the members of the Biochemical Pharmacology Core led by A. Ford and the Virology Disease Biology Area led by N. Cammack for their support and encouragement. D.C.S. also wishes to thank the many scientists whose feedback, constructive criticism and desire to discover new medicines helped to provide the motivation for this work.</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, 94304, California, USA</p><p class="c-article-author-affiliation__authors-list">David C. Swinney & Jason Anthony</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">iRND3 (Institute for Rare and Neglected Diseases Drug Discovery), 951 Old County Road, PMB 316, Belmont, 94002-2760, California, USA</p><p class="c-article-author-affiliation__authors-list">David C. Swinney</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-David_C_-Swinney-Aff1-Aff2"><span class="c-article-authors-search__title u-h3 js-search-name">David C. Swinney</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=David%20C.%20Swinney" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=David%20C.%20Swinney" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22David%20C.%20Swinney%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li><li id="auth-Jason-Anthony-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Jason Anthony</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Jason%20Anthony" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Jason%20Anthony" data-track="click" data-track-action="author link - pubmed" data-track-label="link" rel="nofollow">PubMed</a><span class="u-hide"> </span><a class="c-article-identifiers__item" href="http://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Jason%20Anthony%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en" data-track="click" data-track-action="author link - scholar" data-track-label="link" rel="nofollow">Google Scholar</a></span></p></div></div></li></ol></div><h3 class="c-article__sub-heading" id="corresponding-author">Corresponding author</h3><p id="corresponding-author-list">Correspondence to <a id="corresp-c1" href="mailto:david.swinney@irnd3.org">David C. Swinney</a>.</p></div></div></section><section data-title="Ethics declarations"><div class="c-article-section" id="ethics-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="ethics">Ethics declarations</h2><div class="c-article-section__content" id="ethics-content"> <h3 class="c-article__sub-heading">Competing interests</h3> <p>David Swinney started this work while he was an employee of Roche Palto Alto, and is currently the CEO and co-founder of the Institute for Rare and Neglected Diseases Drug Discovery. </p> <p>Jason Anthony declares no competing financial interests.</p> </div></div></section><section data-title="Supplementary information"><div class="c-article-section" id="Sec6-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec6">Supplementary information</h2><div class="c-article-section__content" id="Sec6-content"><div data-test="supplementary-info"><div id="figshareContainer" class="c-article-figshare-container" data-test="figshare-container"></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM2"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary information (table s1)" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnrd3480/MediaObjects/41573_2011_BFnrd3480_MOESM2_ESM.xls" data-supp-info-image="">Supplementary Information (Table S1)</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Set of drugs analysed (XLS 81 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM3"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary information (box s2)" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnrd3480/MediaObjects/41573_2011_BFnrd3480_MOESM3_ESM.pdf" data-supp-info-image="">Supplementary Information (Box S2)</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Discovery of first-in-class medicines 1999-2008 (PDF 488 kb)</p></div></div></div></div></div></section><section aria-labelledby="appendices"><div class="c-article-section" id="appendices-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="appendices">Related links</h2><div class="c-article-section__content" id="appendices-content"><h3 class="c-article__sub-heading u-visually-hidden" id="App1">Related links</h3><h3 class="c-article__sub-heading" id="Sec5">FURTHER INFORMATION</h3><p> <a href="http://www.accessdata.fda.gov/scripts/cder/drugsatfda">Drugs@FDA</a> </p></div></div></section><section data-title="Glossary"><div class="c-article-section" id="glossary-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="glossary">Glossary</h2><div class="c-article-section__content" id="glossary-content"><dl class="c-description-list"><dt class="c-description-list__term u-text-bold" id="Glos1">New molecular entities</dt><dd class="c-description-list__description u-pl-32"> <p>(NME). 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How were new medicines discovered?. <i>Nat Rev Drug Discov</i> <b>10</b>, 507–519 (2011). https://doi.org/10.1038/nrd3480</p><p class="c-bibliographic-information__download-citation u-hide-print"><a data-test="citation-link" data-track="click" data-track-action="download article citation" data-track-label="link" data-track-external="" rel="nofollow" href="https://citation-needed.springer.com/v2/references/10.1038/nrd3480?format=refman&flavour=citation">Download citation<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-download-medium"></use></svg></a></p><ul class="c-bibliographic-information__list" data-test="publication-history"><li class="c-bibliographic-information__list-item"><p>Published<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2011-06-24">24 June 2011</time></span></p></li><li class="c-bibliographic-information__list-item"><p>Issue Date<span class="u-hide">: </span><span class="c-bibliographic-information__value"><time datetime="2011-07">July 2011</time></span></p></li><li class="c-bibliographic-information__list-item c-bibliographic-information__list-item--full-width"><p><abbr title="Digital Object Identifier">DOI</abbr><span class="u-hide">: </span><span class="c-bibliographic-information__value">https://doi.org/10.1038/nrd3480</span></p></li></ul><div data-component="share-box"><div class="c-article-share-box u-display-none" hidden=""><h3 class="c-article__sub-heading">Share this article</h3><p class="c-article-share-box__description">Anyone you share the following link with will be able to read this content:</p><button class="js-get-share-url c-article-share-box__button" type="button" id="get-share-url" data-track="click" data-track-label="button" data-track-external="" data-track-action="get shareable link">Get shareable link</button><div class="js-no-share-url-container u-display-none" hidden=""><p class="js-c-article-share-box__no-sharelink-info c-article-share-box__no-sharelink-info">Sorry, a shareable link is not currently available for this article.</p></div><div class="js-share-url-container u-display-none" hidden=""><p class="js-share-url c-article-share-box__only-read-input" id="share-url" data-track="click" data-track-label="button" data-track-action="select share url"></p><button class="js-copy-share-url c-article-share-box__button--link-like" type="button" id="copy-share-url" data-track="click" data-track-label="button" data-track-action="copy share url" data-track-external="">Copy to clipboard</button></div><p class="js-c-article-share-box__additional-info c-article-share-box__additional-info"> Provided by the Springer Nature SharedIt content-sharing initiative </p></div></div><div data-component="article-info-list"></div></div></div></div></div></section> </div> <section> <div class="c-article-section js-article-section" id="further-reading-section" data-test="further-reading-section"> <h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="further-reading">This article is cited by</h2> <div class="c-article-section__content js-collapsible-section" id="further-reading-content"> <ul class="c-article-further-reading__list" id="further-reading-list"> <li class="c-article-further-reading__item js-ref-item"> <h3 class="c-article-further-reading__title" data-test="article-title"> <a class="print-link" data-track="click" data-track-action="view further reading article" data-track-label="link:Protein target similarity is positive predictor of in vitro antipathogenic activity: a drug repurposing strategy for Plasmodium falciparum" href="https://doi.org/10.1186/s13321-024-00856-7"> Protein target similarity is positive predictor of in vitro antipathogenic activity: a drug repurposing strategy for Plasmodium falciparum </a> </h3> <ul data-test="author-list" class="c-author-list c-author-list--compact c-author-list--truncated u-sans-serif u-mb-4 u-mt-auto"> <li>Reagan M. 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