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Digital twins in Alzheimer's trials enable smaller sample sizes
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trials enable smaller sample sizes</title> <meta name="description" content="Unlearn's digital twins show potential to reduce Alzheimer's phase 3 trial sizes by up to 33%, potentially saving millions." /> <link rel="canonical" href="https://www.drugdiscoverytrends.com/how-digital-twins-could-support-more-affordable-alzheimers-research/" /> <meta property="og:locale" content="en_US" /> <meta property="og:type" content="article" /> <meta property="og:title" content="Digital twins in Alzheimer's trials enable smaller sample sizes" /> <meta property="og:description" content="Unlearn's digital twins show potential to reduce Alzheimer's phase 3 trial sizes by up to 33%, potentially saving millions." /> <meta property="og:url" content="https://www.drugdiscoverytrends.com/how-digital-twins-could-support-more-affordable-alzheimers-research/" /> <meta property="og:site_name" content="Drug Discovery and Development" /> <meta property="article:publisher" 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class="entry-title">How digital twins could support more affordable Alzheimer’s research</h1> <div style="padding-bottom:5px;font-size:22px"></div><p class="entry-meta"><span class="entry-author">By <a href="https://www.drugdiscoverytrends.com/author/bbuntz/" class="entry-author-link" rel="author"><span class="entry-author-name">Brian Buntz</span></a></span> | <time class="entry-time">August 23, 2024</time></p></header><div class="entry-content"><div class="addtoany_share_save_container addtoany_content addtoany_content_top"><div class="a2a_kit a2a_kit_size_16 addtoany_list" data-a2a-url="https://www.drugdiscoverytrends.com/how-digital-twins-could-support-more-affordable-alzheimers-research/" data-a2a-title="How digital twins could support more affordable Alzheimer’s research"><a class="a2a_button_facebook" href="https://www.addtoany.com/add_to/facebook?linkurl=https%3A%2F%2Fwww.drugdiscoverytrends.com%2Fhow-digital-twins-could-support-more-affordable-alzheimers-research%2F&linkname=How%20digital%20twins%20could%20support%20more%20affordable%20Alzheimer%E2%80%99s%20research" title="Facebook" rel="nofollow noopener" target="_blank"></a><a class="a2a_button_x" href="https://www.addtoany.com/add_to/x?linkurl=https%3A%2F%2Fwww.drugdiscoverytrends.com%2Fhow-digital-twins-could-support-more-affordable-alzheimers-research%2F&linkname=How%20digital%20twins%20could%20support%20more%20affordable%20Alzheimer%E2%80%99s%20research" title="X" rel="nofollow noopener" target="_blank"></a><a class="a2a_button_linkedin" href="https://www.addtoany.com/add_to/linkedin?linkurl=https%3A%2F%2Fwww.drugdiscoverytrends.com%2Fhow-digital-twins-could-support-more-affordable-alzheimers-research%2F&linkname=How%20digital%20twins%20could%20support%20more%20affordable%20Alzheimer%E2%80%99s%20research" title="LinkedIn" rel="nofollow noopener" target="_blank"></a><a class="a2a_dd addtoany_share_save addtoany_share" href="https://www.addtoany.com/share"></a></div></div><div id="attachment_33487" style="width: 310px" class="wp-caption alignright"><img decoding="async" aria-describedby="caption-attachment-33487" class="size-medium wp-image-33487" src="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/07/AdobeStock_466014400-300x195.jpg" alt="Alzheimer's disease plaques" width="300" height="195" srcset="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/07/AdobeStock_466014400-300x195.jpg 300w, https://www.drugdiscoverytrends.com/wp-content/uploads/2024/07/AdobeStock_466014400-768x499.jpg 768w, https://www.drugdiscoverytrends.com/wp-content/uploads/2024/07/AdobeStock_466014400-368x238.jpg 368w, https://www.drugdiscoverytrends.com/wp-content/uploads/2024/07/AdobeStock_466014400.jpg 770w" sizes="(max-width: 300px) 100vw, 300px" /><p id="caption-attachment-33487" class="wp-caption-text">An artistic impression of amyloid plaques in Alzheimer’s disease [Adobe Stock]</p></div>Alzheimer’s clinical trials are among the most challenging and expensive studies to conduct with <a href="https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12450">a 2021 study pegging the total costs since 1995 at $42.5 billion</a>. Phase 3 trials are the biggest cost drivers, involving hundreds or thousands of participants.</p> <p>“We’re talking about studies with sometimes two thousand people per phase three clinical trial in Alzheimer’s,” said Charles Fisher, CEO of Unlearn, a company developing digital twins to streamline clinical trials. The phase 3 trial for solanezumab from Eli Lilly that completed in 2016 had 2,100 participants. More recently, the Clarity AD Phase 3 trial for lecanemab from Biogen and Eisai enrolled 1,795. Enrolling such large volumes isn’t a small undertaking. “Individual phase 3 clinical trials can cost hundreds of millions of dollars,” Fisher said.</p> <h2>The complexities of Alzheimer’s trial recruitment</h2> <p>The need for such large trials stems from a fundamental challenge: “Even though [Alzheimer’s] is really common, it’s actually really difficult to fully enroll those studies because you need so many participants coming from an elderly population that you don’t want to have too many comorbidities,” Fisher said.</p> <div id="attachment_33037" style="width: 310px" class="wp-caption alignright"><img decoding="async" aria-describedby="caption-attachment-33037" class="size-medium wp-image-33037" src="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/03/CharlesFisher-300x300.jpg" alt="Charles Fisher, Ph.D." width="300" height="300" srcset="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/03/CharlesFisher-300x300.jpg 300w, https://www.drugdiscoverytrends.com/wp-content/uploads/2024/03/CharlesFisher-150x150.jpg 150w, https://www.drugdiscoverytrends.com/wp-content/uploads/2024/03/CharlesFisher-238x238.jpg 238w, https://www.drugdiscoverytrends.com/wp-content/uploads/2024/03/CharlesFisher.jpg 540w" sizes="(max-width: 300px) 100vw, 300px" /><p id="caption-attachment-33037" class="wp-caption-text">Charles Fisher, Ph.D.</p></div> <p>“When you start a clinical trial and you don’t exactly know what to expect, you can make some mistakes,” Fisher said. Some trials focused on amyloid-lowering drugs encountered problems with dosing or side effects, leading to the need to make midstream adjustments. Such challenges underscore the need for novel approaches to optimize the trial process.</p> <h2>Digital twins offer hope for streamlining Alzheimer’s research</h2> <p>A pair of studies presented at the Alzheimer’s Association International Conference 2024, held July 28 to August 1, highlighted the potential of digital twins to optimize Alzheimer’s clinical trials. In a collaboration with Johnson & Johnson Innovative Medicine, Unlearn showed that incorporating participants’ digital twins could reduce control arm sizes by 33% when estimating the treatment effect on Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11-item (ADAS-Cog11) at 18 months or by 19% when estimating the effect on Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) at 12 months in Phase 3 studies. Additionally, digital twins could boost power by up to 10%.</p> <p>The significant costs of Alzheimer’s research, with phase 3 trials often reaching budgets of a quarter-billion dollars, are a significant hurdle in the field. Unlearn presented two studies at the Alzheimer’s Association International Conference 2024 highlighting the potential of digital twins to chip away at such costs while optimize Alzheimer’s clinical trial design. In collaboration with Johnson & Johnson Innovative Medicine, results showed that incorporating digital twins could cut control arm sizes by up to 33% in phase 3 studies, potentially saving tens of millions of dollars per trial. A separate study with AbbVie demonstrated that digital twins could reduce overall sample sizes by 10–15% in phase 2 studies, offering similar cost savings and potentially accelerating the pace of research.</p> <p>Beyond the substantial cost savings achieved through smaller sample sizes, digital twins promise faster enrollment, shorter trial durations, and potentially, faster access to potentially life-changing treatments for patients. “Anything that we can do to streamline, to decrease the cost of those studies, decrease the timeline, we think all of that is really important in areas like Alzheimer’s,” Fisher said.</p> <hr><span class="entry-categories">Filed Under: <a href="https://www.drugdiscoverytrends.com/category/machine-learning-and-ai/" rel="category tag">machine learning and AI</a>, <a href="https://www.drugdiscoverytrends.com/category/neurological-disease/" rel="category tag">Neurological Disease</a></span><br /><span class="entry-tags">Tagged With: <a href="https://www.drugdiscoverytrends.com/tag/ai-in-pharma/" rel="tag">AI in Pharma</a>, <a href="https://www.drugdiscoverytrends.com/tag/alzheimers-disease/" rel="tag">Alzheimer's disease</a>, <a href="https://www.drugdiscoverytrends.com/tag/clinical-trials/" rel="tag">clinical trials</a>, <a href="https://www.drugdiscoverytrends.com/tag/digital-twins/" rel="tag">digital twins</a>, <a href="https://www.drugdiscoverytrends.com/tag/phase-3-trials/" rel="tag">phase 3 trials</a>, <a href="https://www.drugdiscoverytrends.com/tag/sample-size-reduction/" rel="tag">Sample Size Reduction</a>, <a href="https://www.drugdiscoverytrends.com/tag/unlearn/" rel="tag">Unlearn</a></span><br /> <hr></div><footer class="entry-footer"></footer></article><section id="custom_html-10" class="widget_text widget widget_custom_html"><div class="widget_text widget-wrap"><div class="textwidget custom-html-widget"><div id="trendmd-suggestions"></div></div></div></section> <div class="author-box"><h4 class="block-header">About The Author</h4><div class="author-box-content"><img alt='' src='https://secure.gravatar.com/avatar/c46f07975579d6ea44d09cc4b8f2adb3?s=168&d=mm&r=g' srcset='https://secure.gravatar.com/avatar/c46f07975579d6ea44d09cc4b8f2adb3?s=336&d=mm&r=g 2x' class='avatar avatar-168 photo' height='168' width='168' loading='lazy' decoding='async'/><h5>Brian Buntz</h5><p>As the pharma and biotech editor at WTWH Media, Brian has almost two decades of experience in B2B media, with a focus on healthcare and technology. While he has long maintained a keen interest in AI, more recently Brian has made making data analysis a central focus, and is exploring tools ranging from NLP and clustering to predictive analytics. </p> <p>Throughout his 18-year tenure, Brian has covered an array of life science topics, including clinical trials, medical devices, and drug discovery and development. Prior to WTWH, he held the title of content director at Informa, where he focused on topics such as connected devices, cybersecurity, AI and Industry 4.0. A dedicated decade at UBM saw Brian providing in-depth coverage of the medical device sector. Engage with Brian on <a href="https://www.linkedin.com/in/brianbuntz/">LinkedIn</a> or drop him an email at bbuntz@wtwhmedia.com.</p> <p class="socials"><a href="https://www.linkedin.com/in/brianbuntz/" target="_blank" rel="noopener noreferrer"><i class="icon-url"></i></a></p></div></div><div class="related-articles"><h4 class="block-header">Related Articles <a href="https://www.drugdiscoverytrends.com/category/neurological-disease/">Read More ></a></h4><div class="article-listing"><div class="row"><article class="entry-summary"><a href="https://www.drugdiscoverytrends.com/miras-ketamir-2-shows-promise-in-preclinical-neuropathy-study/" class="entry-image-link"><img width="268" height="170" src="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/10/Mira-268x170.jpg" class="attachment-ea_summary size-ea_summary wp-image-33787 wp-post-image" alt="MIRA" decoding="async" loading="lazy" /></a><h5 class="entry-title"><a href="https://www.drugdiscoverytrends.com/miras-ketamir-2-shows-promise-in-preclinical-neuropathy-study/">MIRA’s Ketamir-2 shows promise in preclinical neuropathy study</a></h5></article><article class="entry-summary"><a href="https://www.drugdiscoverytrends.com/liraglutide-shows-promise-in-lessening-alzheimers-symptoms-in-phase-2b-trial/" class="entry-image-link"><img width="268" height="170" src="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/08/liraglutide-268x170.png" class="attachment-ea_summary size-ea_summary wp-image-33585 wp-post-image" alt="liraglutide" decoding="async" loading="lazy" /></a><h5 class="entry-title"><a href="https://www.drugdiscoverytrends.com/liraglutide-shows-promise-in-lessening-alzheimers-symptoms-in-phase-2b-trial/">Liraglutide shows promise in lessening Alzheimer’s symptoms in phase 2b trial </a></h5></article><article class="entry-summary"><a href="https://www.drugdiscoverytrends.com/alzheimers-drug-development-breakthrough-kisunla-approval/" class="entry-image-link"><img width="268" height="170" src="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/07/AdobeStock_466014400-268x170.jpg" class="attachment-ea_summary size-ea_summary wp-image-33487 wp-post-image" alt="Alzheimer's disease plaques" decoding="async" loading="lazy" /></a><h5 class="entry-title"><a href="https://www.drugdiscoverytrends.com/alzheimers-drug-development-breakthrough-kisunla-approval/">Could Kisunla approval mark a turning point in Alzheimer’s treatment?</a></h5></article><article class="entry-summary"><a href="https://www.drugdiscoverytrends.com/bioxcel-ai-platform-drug-repurposing-neuropsychiatric-disorders/" class="entry-image-link"><img width="268" height="170" src="https://www.drugdiscoverytrends.com/wp-content/uploads/2024/05/AdobeStock_218608484-268x170.jpeg" class="attachment-ea_summary size-ea_summary wp-image-33205 wp-post-image" alt="Abstract glowing digital business interface backdrop. 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ji=RegExp("^T?"+Ei.source+"$"),Pi=/^-?P(?:(?:(-?\d{1,9}(?:\.\d{1,9})?)Y)?(?:(-?\d{1,9}(?:\.\d{1,9})?)M)?(?:(-?\d{1,9}(?:\.\d{1,9})?)W)?(?:(-?\d{1,9}(?:\.\d{1,9})?)D)?(?:T(?:(-?\d{1,9}(?:\.\d{1,9})?)H)?(?:(-?\d{1,9}(?:\.\d{1,9})?)M)?(?:(-?\d{1,20})(?:[.,](-?\d{1,9}))?S)?)?)$/;function Yi(e){var t=e[0],n=e[1],r=e[2],i=e[3],o=e[4],s=e[5],u=e[6],a=e[7],l=e[8],c="-"===t[0],f=a&&"-"===a[0],d=function(e,t){return void 0===t&&(t=!1),void 0!==e&&(t||e&&c)?-e:e};return[{years:d(hr(n)),months:d(hr(r)),weeks:d(hr(i)),days:d(hr(o)),hours:d(hr(s)),minutes:d(hr(u)),seconds:d(hr(a),"-0"===a),milliseconds:d(mr(l),f)}]}var Wi={GMT:0,EDT:-240,EST:-300,CDT:-300,CST:-360,MDT:-360,MST:-420,PDT:-420,PST:-480};function qi(e,t,n,r,i,o,s){var u={year:2===t.length?br(dr(t)):dr(t),month:_r.indexOf(n)+1,day:dr(r),hour:dr(i),minute:dr(o)};return s&&(u.second=dr(s)),e&&(u.weekday=e.length>3?Cr.indexOf(e)+1:Fr.indexOf(e)+1),u}var 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Qi=Ti(/([+-]\d{6}|\d{4})(?:-?(\d\d)(?:-?(\d\d))?)?/,_i),Ki=Ti(/(\d{4})-?W(\d\d)(?:-?(\d))?/,_i),Xi=Ti(/(\d{4})-?(\d{3})/,_i),eo=Ti(Ni),to=Si((function(e,t){return[{year:zi(e,t),month:zi(e,t+1,1),day:zi(e,t+2,1)},null,t+3]}),Ai,Li,Zi),no=Si(Ii,Ai,Li,Zi),ro=Si(Vi,Ai,Li,Zi),io=Si(Ai,Li,Zi);var oo=Si(Ai);var so=Ti(/(\d{4})-(\d\d)-(\d\d)/,Fi),uo=Ti(Ci),ao=Si(Ai,Li,Zi);var lo={weeks:{days:7,hours:168,minutes:10080,seconds:604800,milliseconds:6048e5},days:{hours:24,minutes:1440,seconds:86400,milliseconds:864e5},hours:{minutes:60,seconds:3600,milliseconds:36e5},minutes:{seconds:60,milliseconds:6e4},seconds:{milliseconds:1e3}},co=gn({years:{quarters:4,months:12,weeks:52,days:365,hours:8760,minutes:525600,seconds:31536e3,milliseconds:31536e6},quarters:{months:3,weeks:13,days:91,hours:2184,minutes:131040,seconds:7862400,milliseconds:78624e5},months:{weeks:4,days:30,hours:720,minutes:43200,seconds:2592e3,milliseconds:2592e6}},lo),fo=gn({years:{quarters:4,months:12,weeks:52.1775,days:365.2425,hours:8765.82,minutes:525949.2,seconds:31556952,milliseconds:31556952e3},quarters:{months:3,weeks:13.044375,days:91.310625,hours:2191.455,minutes:131487.3,seconds:7889238,milliseconds:7889238e3},months:{weeks:30.436875/7,days:30.436875,hours:730.485,minutes:43829.1,seconds:2629746,milliseconds:2629746e3}},lo),ho=["years","quarters","months","weeks","days","hours","minutes","seconds","milliseconds"],mo=ho.slice(0).reverse();function yo(e,t,n){void 0===n&&(n=!1);var r={values:n?t.values:gn({},e.values,t.values||{}),loc:e.loc.clone(t.loc),conversionAccuracy:t.conversionAccuracy||e.conversionAccuracy};return new po(r)}function vo(e,t,n,r,i){var o,s=e[i][n],u=t[n]/s,a=!(Math.sign(u)===Math.sign(r[i]))&&0!==r[i]&&Math.abs(u)<=1?(o=u)<0?Math.floor(o):Math.ceil(o):Math.trunc(u);r[i]+=a,t[n]-=a*s}var po=function(){function e(e){var t="longterm"===e.conversionAccuracy||!1;this.values=e.values,this.loc=e.loc||xi.create(),this.conversionAccuracy=t?"longterm":"casual",this.invalid=e.invalid||null,this.matrix=t?fo:co,this.isLuxonDuration=!0}e.fromMillis=function(t,n){return e.fromObject({milliseconds:t},n)},e.fromObject=function(t,n){if(void 0===n&&(n={}),null==t||"object"!=typeof t)throw new Fn("Duration.fromObject: argument expected to be an object, got "+(null===t?"null":typeof t));return new e({values:Mr(t,e.normalizeUnit),loc:xi.fromObject(n),conversionAccuracy:n.conversionAccuracy})},e.fromDurationLike=function(t){if(or(t))return e.fromMillis(t);if(e.isDuration(t))return t;if("object"==typeof t)return e.fromObject(t);throw new Fn("Unknown duration argument "+t+" of type "+typeof t)},e.fromISO=function(t,n){var r=Mi(t,[Pi,Yi])[0];return r?e.fromObject(r,n):e.invalid("unparsable",'the input "'+t+"\" can't be parsed as ISO 8601")},e.fromISOTime=function(t,n){var r=Mi(t,[ji,oo])[0];return r?e.fromObject(r,n):e.invalid("unparsable",'the input "'+t+"\" can't be parsed as ISO 8601")},e.invalid=function(t,n){if(void 0===n&&(n=null),!t)throw new Fn("need to specify a reason the Duration is invalid");var r=t instanceof Rr?t:new Rr(t,n);if(li.throwOnInvalid)throw new In(r);return new e({invalid:r})},e.normalizeUnit=function(e){var t={year:"years",years:"years",quarter:"quarters",quarters:"quarters",month:"months",months:"months",week:"weeks",weeks:"weeks",day:"days",days:"days",hour:"hours",hours:"hours",minute:"minutes",minutes:"minutes",second:"seconds",seconds:"seconds",millisecond:"milliseconds",milliseconds:"milliseconds"}[e?e.toLowerCase():e];if(!t)throw new Cn(e);return t},e.isDuration=function(e){return e&&e.isLuxonDuration||!1};var t=e.prototype;return t.toFormat=function(e,t){void 0===t&&(t={});var n=gn({},t,{floor:!1!==t.round&&!1!==t.floor});return this.isValid?Ur.create(this.loc,n).formatDurationFromString(this,e):"Invalid Duration"},t.toHuman=function(e){var t=this;void 0===e&&(e={});var n=ho.map((function(n){var r=t.values[n];return ir(r)?null:t.loc.numberFormatter(gn({style:"unit",unitDisplay:"long"},e,{unit:n.slice(0,-1)})).format(r)})).filter((function(e){return e}));return this.loc.listFormatter(gn({type:"conjunction",style:e.listStyle||"narrow"},e)).format(n)},t.toObject=function(){return this.isValid?gn({},this.values):{}},t.toISO=function(){if(!this.isValid)return null;var e="P";return 0!==this.years&&(e+=this.years+"Y"),0===this.months&&0===this.quarters||(e+=this.months+3*this.quarters+"M"),0!==this.weeks&&(e+=this.weeks+"W"),0!==this.days&&(e+=this.days+"D"),0===this.hours&&0===this.minutes&&0===this.seconds&&0===this.milliseconds||(e+="T"),0!==this.hours&&(e+=this.hours+"H"),0!==this.minutes&&(e+=this.minutes+"M"),0===this.seconds&&0===this.milliseconds||(e+=yr(this.seconds+this.milliseconds/1e3,3)+"S"),"P"===e&&(e+="T0S"),e},t.toISOTime=function(e){if(void 0===e&&(e={}),!this.isValid)return null;var t=this.toMillis();if(t<0||t>=864e5)return null;e=gn({suppressMilliseconds:!1,suppressSeconds:!1,includePrefix:!1,format:"extended"},e);var n=this.shiftTo("hours","minutes","seconds","milliseconds"),r="basic"===e.format?"hhmm":"hh:mm";e.suppressSeconds&&0===n.seconds&&0===n.milliseconds||(r+="basic"===e.format?"ss":":ss",e.suppressMilliseconds&&0===n.milliseconds||(r+=".SSS"));var i=n.toFormat(r);return e.includePrefix&&(i="T"+i),i},t.toJSON=function(){return this.toISO()},t.toString=function(){return this.toISO()},t.toMillis=function(){return this.as("milliseconds")},t.valueOf=function(){return this.toMillis()},t.plus=function(t){if(!this.isValid)return this;for(var n,r=e.fromDurationLike(t),i={},o=Dn(ho);!(n=o()).done;){var s=n.value;(lr(r.values,s)||lr(this.values,s))&&(i[s]=r.get(s)+this.get(s))}return yo(this,{values:i},!0)},t.minus=function(t){if(!this.isValid)return this;var n=e.fromDurationLike(t);return this.plus(n.negate())},t.mapUnits=function(e){if(!this.isValid)return this;for(var t={},n=0,r=Object.keys(this.values);n<r.length;n++){var i=r[n];t[i]=Sr(e(this.values[i],i))}return yo(this,{values:t},!0)},t.get=function(t){return this[e.normalizeUnit(t)]},t.set=function(t){return this.isValid?yo(this,{values:gn({},this.values,Mr(t,e.normalizeUnit))}):this},t.reconfigure=function(e){var t=void 0===e?{}:e,n=t.locale,r=t.numberingSystem,i=t.conversionAccuracy,o={loc:this.loc.clone({locale:n,numberingSystem:r})};return i&&(o.conversionAccuracy=i),yo(this,o)},t.as=function(e){return this.isValid?this.shiftTo(e).get(e):NaN},t.normalize=function(){if(!this.isValid)return this;var e=this.toObject();return function(e,t){mo.reduce((function(n,r){return ir(t[r])?n:(n&&vo(e,t,n,t,r),r)}),null)}(this.matrix,e),yo(this,{values:e},!0)},t.shiftTo=function(){for(var t=arguments.length,n=new Array(t),r=0;r<t;r++)n[r]=arguments[r];if(!this.isValid)return this;if(0===n.length)return this;n=n.map((function(t){return e.normalizeUnit(t)}));for(var i,o,s={},u={},a=this.toObject(),l=Dn(ho);!(o=l()).done;){var c=o.value;if(n.indexOf(c)>=0){i=c;var f=0;for(var d in u)f+=this.matrix[d][c]*u[d],u[d]=0;or(a[c])&&(f+=a[c]);var h=Math.trunc(f);for(var m in s[c]=h,u[c]=(1e3*f-1e3*h)/1e3,a)ho.indexOf(m)>ho.indexOf(c)&&vo(this.matrix,a,m,s,c)}else or(a[c])&&(u[c]=a[c])}for(var y in u)0!==u[y]&&(s[i]+=y===i?u[y]:u[y]/this.matrix[i][y]);return yo(this,{values:s},!0).normalize()},t.negate=function(){if(!this.isValid)return this;for(var e={},t=0,n=Object.keys(this.values);t<n.length;t++){var r=n[t];e[r]=0===this.values[r]?0:-this.values[r]}return yo(this,{values:e},!0)},t.equals=function(e){if(!this.isValid||!e.isValid)return!1;if(!this.loc.equals(e.loc))return!1;for(var t,n=Dn(ho);!(t=n()).done;){var r=t.value;if(i=this.values[r],o=e.values[r],!(void 0===i||0===i?void 0===o||0===o:i===o))return!1}var i,o;return!0},pn(e,[{key:"locale",get:function(){return this.isValid?this.loc.locale:null}},{key:"numberingSystem",get:function(){return this.isValid?this.loc.numberingSystem:null}},{key:"years",get:function(){return this.isValid?this.values.years||0:NaN}},{key:"quarters",get:function(){return this.isValid?this.values.quarters||0:NaN}},{key:"months",get:function(){return this.isValid?this.values.months||0:NaN}},{key:"weeks",get:function(){return this.isValid?this.values.weeks||0:NaN}},{key:"days",get:function(){return this.isValid?this.values.days||0:NaN}},{key:"hours",get:function(){return this.isValid?this.values.hours||0:NaN}},{key:"minutes",get:function(){return this.isValid?this.values.minutes||0:NaN}},{key:"seconds",get:function(){return this.isValid?this.values.seconds||0:NaN}},{key:"milliseconds",get:function(){return this.isValid?this.values.milliseconds||0:NaN}},{key:"isValid",get:function(){return null===this.invalid}},{key:"invalidReason",get:function(){return this.invalid?this.invalid.reason:null}},{key:"invalidExplanation",get:function(){return this.invalid?this.invalid.explanation:null}}]),e}();var go=function(){function e(e){this.s=e.start,this.e=e.end,this.invalid=e.invalid||null,this.isLuxonInterval=!0}e.invalid=function(t,n){if(void 0===n&&(n=null),!t)throw new Fn("need to specify a reason the Interval is invalid");var r=t instanceof Rr?t:new Rr(t,n);if(li.throwOnInvalid)throw new _n(r);return new e({invalid:r})},e.fromDateTimes=function(t,n){var r=gs(t),i=gs(n),o=function(e,t){return e&&e.isValid?t&&t.isValid?t<e?go.invalid("end before start","The end of an interval must be after its start, but you had start="+e.toISO()+" and end="+t.toISO()):null:go.invalid("missing or invalid end"):go.invalid("missing or invalid start")}(r,i);return null==o?new e({start:r,end:i}):o},e.after=function(t,n){var r=po.fromDurationLike(n),i=gs(t);return e.fromDateTimes(i,i.plus(r))},e.before=function(t,n){var r=po.fromDurationLike(n),i=gs(t);return e.fromDateTimes(i.minus(r),i)},e.fromISO=function(t,n){var r=(t||"").split("/",2),i=r[0],o=r[1];if(i&&o){var s,u,a,l;try{u=(s=ps.fromISO(i,n)).isValid}catch(e){u=!1}try{l=(a=ps.fromISO(o,n)).isValid}catch(e){l=!1}if(u&&l)return e.fromDateTimes(s,a);if(u){var c=po.fromISO(o,n);if(c.isValid)return e.after(s,c)}else if(l){var f=po.fromISO(i,n);if(f.isValid)return e.before(a,f)}}return e.invalid("unparsable",'the input "'+t+"\" can't be parsed as ISO 8601")},e.isInterval=function(e){return e&&e.isLuxonInterval||!1};var t=e.prototype;return t.length=function(e){return void 0===e&&(e="milliseconds"),this.isValid?this.toDuration.apply(this,[e]).get(e):NaN},t.count=function(e){if(void 0===e&&(e="milliseconds"),!this.isValid)return NaN;var t=this.start.startOf(e),n=this.end.startOf(e);return Math.floor(n.diff(t,e).get(e))+1},t.hasSame=function(e){return!!this.isValid&&(this.isEmpty()||this.e.minus(1).hasSame(this.s,e))},t.isEmpty=function(){return this.s.valueOf()===this.e.valueOf()},t.isAfter=function(e){return!!this.isValid&&this.s>e},t.isBefore=function(e){return!!this.isValid&&this.e<=e},t.contains=function(e){return!!this.isValid&&(this.s<=e&&this.e>e)},t.set=function(t){var n=void 0===t?{}:t,r=n.start,i=n.end;return this.isValid?e.fromDateTimes(r||this.s,i||this.e):this},t.splitAt=function(){var t=this;if(!this.isValid)return[];for(var n=arguments.length,r=new Array(n),i=0;i<n;i++)r[i]=arguments[i];for(var o=r.map(gs).filter((function(e){return t.contains(e)})).sort(),s=[],u=this.s,a=0;u<this.e;){var l=o[a]||this.e,c=+l>+this.e?this.e:l;s.push(e.fromDateTimes(u,c)),u=c,a+=1}return s},t.splitBy=function(t){var n=po.fromDurationLike(t);if(!this.isValid||!n.isValid||0===n.as("milliseconds"))return[];for(var r,i=this.s,o=1,s=[];i<this.e;){var u=this.start.plus(n.mapUnits((function(e){return e*o})));r=+u>+this.e?this.e:u,s.push(e.fromDateTimes(i,r)),i=r,o+=1}return s},t.divideEqually=function(e){return this.isValid?this.splitBy(this.length()/e).slice(0,e):[]},t.overlaps=function(e){return this.e>e.s&&this.s<e.e},t.abutsStart=function(e){return!!this.isValid&&+this.e==+e.s},t.abutsEnd=function(e){return!!this.isValid&&+e.e==+this.s},t.engulfs=function(e){return!!this.isValid&&(this.s<=e.s&&this.e>=e.e)},t.equals=function(e){return!(!this.isValid||!e.isValid)&&(this.s.equals(e.s)&&this.e.equals(e.e))},t.intersection=function(t){if(!this.isValid)return this;var n=this.s>t.s?this.s:t.s,r=this.e<t.e?this.e:t.e;return n>=r?null:e.fromDateTimes(n,r)},t.union=function(t){if(!this.isValid)return this;var n=this.s<t.s?this.s:t.s,r=this.e>t.e?this.e:t.e;return e.fromDateTimes(n,r)},e.merge=function(e){var t=e.sort((function(e,t){return e.s-t.s})).reduce((function(e,t){var n=e[0],r=e[1];return r?r.overlaps(t)||r.abutsStart(t)?[n,r.union(t)]:[n.concat([r]),t]:[n,t]}),[[],null]),n=t[0],r=t[1];return r&&n.push(r),n},e.xor=function(t){for(var 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n=(void 0===t?{}:t).separator,r=void 0===n?" – ":n;return this.isValid?""+this.s.toFormat(e)+r+this.e.toFormat(e):"Invalid Interval"},t.toDuration=function(e,t){return this.isValid?this.e.diff(this.s,e,t):po.invalid(this.invalidReason)},t.mapEndpoints=function(t){return e.fromDateTimes(t(this.s),t(this.e))},pn(e,[{key:"start",get:function(){return this.isValid?this.s:null}},{key:"end",get:function(){return this.isValid?this.e:null}},{key:"isValid",get:function(){return null===this.invalidReason}},{key:"invalidReason",get:function(){return this.invalid?this.invalid.reason:null}},{key:"invalidExplanation",get:function(){return this.invalid?this.invalid.explanation:null}}]),e}(),wo=function(){function e(){}return e.hasDST=function(e){void 0===e&&(e=li.defaultZone);var t=ps.now().setZone(e).set({month:12});return!e.isUniversal&&t.offset!==t.set({month:6}).offset},e.isValidIANAZone=function(e){return Kr.isValidZone(e)},e.normalizeZone=function(e){return 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e({ts:i,zone:o,loc:xi.fromObject(n)}):e.invalid($o(o))},e.fromMillis=function(t,n){if(void 0===n&&(n={}),or(t))return t<-864e13||t>864e13?e.invalid("Timestamp out of range"):new e({ts:t,zone:ni(n.zone,li.defaultZone),loc:xi.fromObject(n)});throw new Fn("fromMillis requires a numerical input, but received a "+typeof t+" with value "+t)},e.fromSeconds=function(t,n){if(void 0===n&&(n={}),or(t))return new e({ts:1e3*t,zone:ni(n.zone,li.defaultZone),loc:xi.fromObject(n)});throw new Fn("fromSeconds requires a numerical input")},e.fromObject=function(t,n){void 0===n&&(n={}),t=t||{};var r=ni(n.zone,li.defaultZone);if(!r.isValid)return e.invalid($o(r));var i=li.now(),o=ir(n.specificOffset)?r.offset(i):n.specificOffset,s=Mr(t,hs),u=!ir(s.ordinal),a=!ir(s.year),l=!ir(s.month)||!ir(s.day),c=a||l,f=s.weekYear||s.weekNumber,d=xi.fromObject(n);if((c||u)&&f)throw new Vn("Can't mix weekYear/weekNumber units with year/month/day or ordinals");if(l&&u)throw new Vn("Can't mix ordinal dates with 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e({invalid:r})},e.isDateTime=function(e){return e&&e.isLuxonDateTime||!1};var t=e.prototype;return t.get=function(e){return this[e]},t.resolvedLocaleOptions=function(e){void 0===e&&(e={});var t=Ur.create(this.loc.clone(e),e).resolvedOptions(this);return{locale:t.locale,numberingSystem:t.numberingSystem,outputCalendar:t.calendar}},t.toUTC=function(e,t){return void 0===e&&(e=0),void 0===t&&(t={}),this.setZone(ei.instance(e),t)},t.toLocal=function(){return this.setZone(li.defaultZone)},t.setZone=function(t,n){var r=void 0===n?{}:n,i=r.keepLocalTime,o=void 0!==i&&i,s=r.keepCalendarTime,u=void 0!==s&&s;if((t=ni(t,li.defaultZone)).equals(this.zone))return this;if(t.isValid){var a=this.ts;if(o||u){var l=t.offset(this.ts);a=ts(this.toObject(),l,t)[0]}return Ko(this,{ts:a,zone:t})}return e.invalid($o(t))},t.reconfigure=function(e){var t=void 0===e?{}:e,n=t.locale,r=t.numberingSystem,i=t.outputCalendar;return Ko(this,{loc:this.loc.clone({locale:n,numberingSystem:r,outputCalendar:i})})},t.setLocale=function(e){return this.reconfigure({locale:e})},t.set=function(e){if(!this.isValid)return this;var t,n=Mr(e,hs),r=!ir(n.weekYear)||!ir(n.weekNumber)||!ir(n.weekday),i=!ir(n.ordinal),o=!ir(n.year),s=!ir(n.month)||!ir(n.day),u=o||s,a=n.weekYear||n.weekNumber;if((u||i)&&a)throw new Vn("Can't mix weekYear/weekNumber units with year/month/day or ordinals");if(s&&i)throw new Vn("Can't mix ordinal dates with month/day");r?t=Ro(gn({},Uo(this.c),n)):ir(n.ordinal)?(t=gn({},this.toObject(),n),ir(n.day)&&(t.day=Math.min(gr(t.year,t.month),t.day))):t=Go(gn({},Ho(this.c),n));var l=ts(t,this.o,this.zone);return Ko(this,{ts:l[0],o:l[1]})},t.plus=function(e){return this.isValid?Ko(this,ns(this,po.fromDurationLike(e))):this},t.minus=function(e){return this.isValid?Ko(this,ns(this,po.fromDurationLike(e).negate())):this},t.startOf=function(e){if(!this.isValid)return this;var t={},n=po.normalizeUnit(e);switch(n){case"years":t.month=1;case"quarters":case"months":t.day=1;case"weeks":case"days":t.hour=0;case"hours":t.minute=0;case"minutes":t.second=0;case"seconds":t.millisecond=0}if("weeks"===n&&(t.weekday=1),"quarters"===n){var r=Math.ceil(this.month/3);t.month=3*(r-1)+1}return this.set(t)},t.endOf=function(e){var t;return this.isValid?this.plus((t={},t[e]=1,t)).startOf(e).minus(1):this},t.toFormat=function(e,t){return void 0===t&&(t={}),this.isValid?Ur.create(this.loc.redefaultToEN(t)).formatDateTimeFromString(this,e):"Invalid DateTime"},t.toLocaleString=function(e,t){return void 0===e&&(e=An),void 0===t&&(t={}),this.isValid?Ur.create(this.loc.clone(t),e).formatDateTime(this):"Invalid DateTime"},t.toLocaleParts=function(e){return void 0===e&&(e={}),this.isValid?Ur.create(this.loc.clone(e),e).formatDateTimeParts(this):[]},t.toISO=function(e){var t=void 0===e?{}:e,n=t.format,r=void 0===n?"extended":n,i=t.suppressSeconds,o=void 0!==i&&i,s=t.suppressMilliseconds,u=void 0!==s&&s,a=t.includeOffset,l=void 0===a||a,c=t.extendedZone,f=void 0!==c&&c;if(!this.isValid)return null;var d="extended"===r,h=os(this,d);return h+="T",h+=ss(this,d,o,u,l,f)},t.toISODate=function(e){var t=(void 0===e?{}:e).format,n=void 0===t?"extended":t;return this.isValid?os(this,"extended"===n):null},t.toISOWeekDate=function(){return is(this,"kkkk-'W'WW-c")},t.toISOTime=function(e){var t=void 0===e?{}:e,n=t.suppressMilliseconds,r=void 0!==n&&n,i=t.suppressSeconds,o=void 0!==i&&i,s=t.includeOffset,u=void 0===s||s,a=t.includePrefix,l=void 0!==a&&a,c=t.extendedZone,f=void 0!==c&&c,d=t.format,h=void 0===d?"extended":d;return this.isValid?(l?"T":"")+ss(this,"extended"===h,o,r,u,f):null},t.toRFC2822=function(){return is(this,"EEE, dd LLL yyyy HH:mm:ss ZZZ",!1)},t.toHTTP=function(){return is(this.toUTC(),"EEE, dd LLL yyyy HH:mm:ss 'GMT'")},t.toSQLDate=function(){return this.isValid?os(this,!0):null},t.toSQLTime=function(e){var t=void 0===e?{}:e,n=t.includeOffset,r=void 0===n||n,i=t.includeZone,o=void 0!==i&&i,s=t.includeOffsetSpace,u="HH:mm:ss.SSS";return(o||r)&&((void 0===s||s)&&(u+=" "),o?u+="z":r&&(u+="ZZ")),is(this,u,!0)},t.toSQL=function(e){return void 0===e&&(e={}),this.isValid?this.toSQLDate()+" "+this.toSQLTime(e):null},t.toString=function(){return this.isValid?this.toISO():"Invalid DateTime"},t.valueOf=function(){return this.toMillis()},t.toMillis=function(){return this.isValid?this.ts:NaN},t.toSeconds=function(){return this.isValid?this.ts/1e3:NaN},t.toUnixInteger=function(){return this.isValid?Math.floor(this.ts/1e3):NaN},t.toJSON=function(){return this.toISO()},t.toBSON=function(){return this.toJSDate()},t.toObject=function(e){if(void 0===e&&(e={}),!this.isValid)return{};var t=gn({},this.c);return e.includeConfig&&(t.outputCalendar=this.outputCalendar,t.numberingSystem=this.loc.numberingSystem,t.locale=this.loc.locale),t},t.toJSDate=function(){return new Date(this.isValid?this.ts:NaN)},t.diff=function(e,t,n){if(void 0===t&&(t="milliseconds"),void 0===n&&(n={}),!this.isValid||!e.isValid)return po.invalid("created by diffing an invalid DateTime");var r,i=gn({locale:this.locale,numberingSystem:this.numberingSystem},n),o=(r=t,Array.isArray(r)?r:[r]).map(po.normalizeUnit),s=e.valueOf()>this.valueOf(),u=bo(s?this:e,s?e:this,o,i);return s?u.negate():u},t.diffNow=function(t,n){return void 0===t&&(t="milliseconds"),void 0===n&&(n={}),this.diff(e.now(),t,n)},t.until=function(e){return this.isValid?go.fromDateTimes(this,e):this},t.hasSame=function(e,t){if(!this.isValid)return!1;var n=e.valueOf(),r=this.setZone(e.zone,{keepLocalTime:!0});return r.startOf(t)<=n&&n<=r.endOf(t)},t.equals=function(e){return this.isValid&&e.isValid&&this.valueOf()===e.valueOf()&&this.zone.equals(e.zone)&&this.loc.equals(e.loc)},t.toRelative=function(t){if(void 0===t&&(t={}),!this.isValid)return null;var n=t.base||e.fromObject({},{zone:this.zone}),r=t.padding?this<n?-t.padding:t.padding:0,i=["years","months","days","hours","minutes","seconds"],o=t.unit;return Array.isArray(t.unit)&&(i=t.unit,o=void 0),ys(n,this.plus(r),gn({},t,{numeric:"always",units:i,unit:o}))},t.toRelativeCalendar=function(t){return void 0===t&&(t={}),this.isValid?ys(t.base||e.fromObject({},{zone:this.zone}),this,gn({},t,{numeric:"auto",units:["years","months","days"],calendary:!0})):null},e.min=function(){for(var t=arguments.length,n=new Array(t),r=0;r<t;r++)n[r]=arguments[r];if(!n.every(e.isDateTime))throw new Fn("min requires all arguments be DateTimes");return ar(n,(function(e){return e.valueOf()}),Math.min)},e.max=function(){for(var t=arguments.length,n=new Array(t),r=0;r<t;r++)n[r]=arguments[r];if(!n.every(e.isDateTime))throw new Fn("max requires all arguments be DateTimes");return ar(n,(function(e){return e.valueOf()}),Math.max)},e.fromFormatExplain=function(e,t,n){void 0===n&&(n={});var r=n,i=r.locale,o=void 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Why..."),console.error(e)}},ws.open("GET","https://medtech100.com/md100/json/pricing",!0),ws.send(); </script> </head> <body> <div id="md-tech-ad"> <table class="md-table" align="center" cellpadding="0" cellspacing="0" width="100%"> <tr> <td width="100%"> <div class="md-align"> <img id="md-logo" class="md-margin" src="https://images.designworldonline.com/newsletters/images/ee034d8d8274c1ee5e8111f11cf1be49.png" alt="Medtech 100 logo"> </div> </td> </tr> <tr> <td width="100%"> <div class="md-align"> <div class="margin-text"> <span style="font-weight:600;color:#e06636!important;font-size:16px!important;line-height:14px!important"> Market Summary > Current Price </span> </div> </div> </td> </tr> <tr> <td width="100%"> <div class="md-align" id="md-content-container"> <div id="md-current-price"></div> <div id="md-current-time"></div> <div id="md-chart-container"> <div id="md-intraday-chart"></div> </div> </div> </td> </tr> <tr> <td width="100%"> <div class="md-align"> <div class="md-margin-text"> <span style="font-size:13px;line-height:15px!important"> The MedTech 100 is a financial index calculated using the BIG100 companies covered in Medical Design and Outsourcing. </span> </div> </div> </td> </tr> <tr> <td width="100%"> <div class="md-margin-text"> <a href="https://medtech100.com/?utm_source=DDT&utm_medium=BOXAD&utm_campaign=boxad&utm_id=MD100"> <button class="md-btn"> <span style="font-size:13px;font-weight:600"> Click for Index Details >> </span> </button> </a> </div> </td> </tr> </table> </div> </body> </html></div></div></section> <section id="custom_html-6" class="widget_text widget widget_custom_html"><div class="widget_text widget-wrap"><div class="textwidget custom-html-widget"><center><div id='div-gpt-ddt_sidebar1'> <script> googletag.cmd.push(function() { googletag.display('div-gpt-ddt_sidebar1'); }); </script> </div></center></div></div></section> <section id="custom_html-14" class="widget_text widget widget_custom_html"><div class="widget_text widget-wrap"><h4 class="widget-title widgettitle">AI Meets Life Sci</h4> <div class="textwidget custom-html-widget"><a href="https://www.drugdiscoverytrends.com/category/podcast/"><img src="/wp-content/uploads/2023/12/AiLS_700x466_11-23_Vs3.jpg" alt=""></a></div></div></section> </aside></div></div></div><div class="footer-socials"><div class="wrap"><label style="color:#ffffff">Connect with Drug Discovery & Development</label> <a href="https://www.facebook.com/DrugDiscoveryDev/" target="_blank" rel="noopener noreferrer"><i class="icon-facebook"></i></a><a href="https://twitter.com/DrugDiscoverDev" target="_blank" rel="noopener noreferrer"><i class="icon-twitter"></i></a><a href="https://www.linkedin.com/authwall?trk=bf&trkInfo=AQHXj5nc_XABCwAAAXk4_G5QGUfHQiD86N23ZbyzSbsmnyyim2VzO8i1014RSfZgnVrQe5QzBNowe1plc0fhUz33ExdBejRNtpVV9k-MDg8XcY3qeUGsxPpdVW_k44H1_bfWg2M=&originalReferer=&sessionRedirect=https%3A%2F%2Fwww.linkedin.com%2Fcompany%2Fdrug-discovery-%26-development" target="_blank" rel="noopener noreferrer"><i class="icon-linkedin"></i></a></div></div><footer class="site-footer"><div class="wrap"><div class="row"><div class="footer-logo"><a href="https://www.drugdiscoverytrends.com">Drug Discovery and Development</a></div><div class="footer-menu"><div class="menu-footer-menu-container"><ul id="menu-footer-menu" class="menu"><li id="menu-item-21963" class="menu-item"><a href="https://www.massdevice.com/">MassDevice</a></li> <li id="menu-item-21959" class="menu-item"><a href="https://www.devicetalks.com/">DeviceTalks</a></li> <li id="menu-item-21960" class="menu-item"><a href="https://medtech100.com/">Medtech100 Index</a></li> <li id="menu-item-21964" class="menu-item"><a href="https://www.medicaldesignsourcing.com/">Medical Design Sourcing</a></li> <li id="menu-item-21961" class="menu-item"><a href="https://www.medicaldesignandoutsourcing.com/">Medical Design & Outsourcing</a></li> <li id="menu-item-21962" class="menu-item"><a href="https://www.medicaltubingandextrusion.com/">Medical Tubing + Extrusion</a></li> <li id="menu-item-14868" class="menu-item"><a href="https://www.drugdiscoverytrends.com/sign-up-for-the-drug-discovery-development-enewsletter/">Subscribe to our E-Newsletter</a></li> <li id="menu-item-14870" class="menu-item"><a href="https://www.drugdiscoverytrends.com/contact-us/">Contact Us</a></li> <li id="menu-item-21956" class="menu-item"><a href="https://www.drugdiscoverytrends.com/about-us/">About Us</a></li> <li id="menu-item-14890" class="menu-item"><a target="_blank" href="https://www.rdworldonline.com/">R&D World</a></li> <li id="menu-item-14902" class="menu-item"><a href="https://www.drugdeliverybusiness.com/">Drug Delivery Business News</a></li> <li id="menu-item-14889" class="menu-item"><a target="_blank" href="https://www.pharmaceuticalprocessingworld.com/">Pharmaceutical Processing World</a></li> </ul></div></div><div class="footer-copyright"><p>Copyright © 2024 WTWH Media LLC. 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