Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products

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btn-primary" href="/media/133660/download">Download the Draft Guidance Document</a> <a class="btn btn-primary" href="https://www.federalregister.gov/documents/2019/12/20/2019-27524/guidance-demonstrating-substantial-evidence-of-effectiveness-for-human-drug-and-biological-products">Read the Federal Register Notice</a> </div> <div class="lcds-statusbar text-center"> <span class="label label-default">Draft</span> </div> <p class="lcds-explainer-txt text-center">Not for implementation. Contains non-binding recommendations.</p> <div class="lcds-toolbar lcds-toolbar--social"> <ul class="lcds-share lcds-share--default"> <li class="lcds-share__item"> <a href="https://www.facebook.com/sharer/sharer.php?u=https://www.fda.gov%2Fregulatory-information%2Fsearch-fda-guidance-documents%2Fdemonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products" class="lcds-share__btn lcds-share--default__btn-facebook js-share" id="fb-share" target="_blank"><span class="fa icon-facebook" aria-hidden="true"></span>Share</a> </li> <li class="lcds-share__item"> <a href="https://x.com/intent/tweet/?text=Demonstrating%20Substantial%20Evidence%20of%20Effectiveness%20for%20Human%20Drug%20and%20Biological%20Products&url=https://www.fda.gov%2Fregulatory-information%2Fsearch-fda-guidance-documents%2Fdemonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products" target="_blank" class="lcds-share__btn lcds-share--default__btn-x-twitter js-share" id="twitter-share"> <svg class="icon-svg-inline" aria-hidden="true"> <use href="/themes/custom/preview/assets/images/fa-icons.svg#icon-x-twitter"> </svg> Post </a> </li> <li class="lcds-share__item hidden-xs"> <a href="https://www.linkedin.com/shareArticle?mini=true&url=https://www.fda.gov%2Fregulatory-information%2Fsearch-fda-guidance-documents%2Fdemonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products&title=Demonstrating%20Substantial%20Evidence%20of%20Effectiveness%20for%20Human%20Drug%20and%20Biological%20Products&source=FDA" class="lcds-share__btn lcds-share--default__btn-linkedin js-share" id="linkedin-share" target="_blank"><span class="fa icon-linkedin" aria-hidden="true"></span>Linkedin</a> </li> <li class="lcds-share__item"> <a href="mailto:?subject=Demonstrating%20Substantial%20Evidence%20of%20Effectiveness%20for%20Human%20Drug%20and%20Biological%20Products&body=https://www.fda.gov%2Fregulatory-information%2Fsearch-fda-guidance-documents%2Fdemonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products" class="lcds-share__btn lcds-share--default__btn-mail"><span class="fa icon-envelope" aria-hidden="true"></span>Email</a> </li> <li class=" lcds-share__item hidden-xs"> <a href="javascript:window.print();" title="Print this page" class="lcds-share__btn lcds-share--default__btn-print"><span class="fa icon-print" aria-hidden="true"></span>Print</a> </li> </ul> <div class="form-group"> </div> </div> </div> </section> </header> <div class="col-md-8 col-md-push-2" role="main"> <div class="inset-column"> <dl class="lcds-description-list--grid"> <dt class="cell-1_1">Docket Number:</dt> <dd class="cell-2_1"><a href="https://www.regulations.gov/docket/FDA-2019-D-4964">FDA-2019-D-4964</a></dd> <dt class="cell-1_2">Issued by:</dt> <dd class="cell-2_2"><a href="/regulatory-information/search-fda-guidance-documents/demonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products"></a> <div class="field field--name-field-issuing-office-taxonomy field--type-entity-reference field--label-above"> <div class="field--label">Guidance Issuing Office</div> <div class="field--items"> <div class="field--item">Center for Biologics Evaluation and Research</div> <div class="field--item">Center for Drug Evaluation and Research</div> </div> </div> </dd> </dl> </div> <div type="info"> <div class="alert alert-info"> <p><a href="https://www.federalregister.gov/documents/2020/01/27/2020-01322/demonstrating-substantial-evidence-of-effectiveness-for-human-drug-and-biological-products-draft">Federal Register Notice 1/27/2020: Extension of comment period</a></p> </div> </div> <p>This document is intended to provide guidance to applicants planning to file new drug applications (NDAs), biologics license applications (BLAs), or applications for supplemental indications on the evidence to be provided to demonstrate effectiveness. This guidance complements and expands on the 1998 guidance entitled Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products (the 1998 guidance).</p> <p>The 1998 guidance was issued in response to the Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L. 105–115), which stated that the substantial evidence requirement for effectiveness, which had generally been interpreted as calling for two adequate and well-controlled trials, could also be met by a single trial plus confirmatory evidence. The 1998 guidance, therefore, provided many examples of the types of evidence that could be considered confirmatory evidence, with a specific focus on adequate and well-controlled trials of the test agent in related populations or indications, as well as a number of illustrations of a single adequate and well-controlled trial supported by convincing evidence of the drug’s mechanism of action in treating a disease or condition.</p> <p>FDAMA thus introduced a specific new area of flexibility in the evidence needed to support effectiveness, but there are many other characteristics of the evidence supporting effectiveness that can vary (notably, trial designs, trial endpoints, statistical methodology), and evidence that varies in such ways potentially can provide substantial evidence of effectiveness but because of these characteristics may provide greater or lesser certainty. These characteristics also deserve consideration and were not discussed in the 1998 guidance. FDA’s consideration of these various designs, endpoints, and analyses which can differ in the strength of evidence they provide, reflects the Agency’s longstanding flexibility when considering the types of data and evidence that can meet the substantial evidence requirement.</p> <div class="inset-column"> <hr> <h2>Submit Comments</h2> <div class="row"> <div class="col-xs-12 col-sm-4"> <a class="btn btn-primary" <a href="https://www.regulations.gov/docket/FDA-2019-D-4964/document">Submit Comments Online</a> </div> <div class="col-xs-12 col-sm-8"> <p class="lcds-explainer-txt">You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))</p> <p class="lcds-explainer-txt">If unable to submit comments online, please mail written comments to:</p> <p class="lcds-explainer-txt"> Dockets Management<br/> Food and Drug Administration<br/> 5630 Fishers Lane, Rm 1061<br/> Rockville, MD 20852</p> <p class="lcds-explainer-txt"> All written comments should be identified with this document's docket number: <a href="https://www.regulations.gov/docket/FDA-2019-D-4964">FDA-2019-D-4964</a>. </p> </div> </div> </div> <h2>Questions?</h2>   </div> <aside class="col-md-2 col-md-push-2" role="complementary"> <section id="block-entityviewcontent-4" data-block-plugin-id="entity_view:node" class="block block-ctools block-entity-viewnode clearfix"> <div class="region region-"> <aside class="lcds-card lcds-card--border-top"> <ul role="menu" class="lcds-description-list"> <li role="menuitem" class="node-current-date lcds-description-list__item"> <div> <h2 class="lcds-description-list__item-heading">Content current as of:</h2> <p class="lcds-description-list__item-text"><time datetime="2020-01-27T00:00:00Z">01/27/2020</time> </p> </div> </li> <li role="menuitem" class="lcds-description-list__item"> <div> <h2 class="lcds-description-list__item-heading">Regulated Product(s)</h2> <ul role="menu" class="lcds-metadata-list"> <li role="menuitem">Biologics</li> 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