• Login
    • Join
  • FOLLOW:
  • Subscribe Free
    • Magazine
    • eNewsletter
    Checkout
    • Magazine
    • News
    • Manufacturing
    • Packaging
    • Development
    • Compliance
    • Top 25
    • Directory
    • Microsites
    • Events
    • More
  • Magazine
  • News
  • Manufacturing
  • Packaging
  • Development
  • Compliance
  • Top 25
  • Directory
  • Microsites
  • Events
  • Current / Back Issue
    Features
    Editorial
    Columns
    Digital Edition
    eNewsletter Archive
    Our Team
    Editorial Guidelines
    Subscribe Now
    Advertise Now
    Top Features
    High Drug Loading Amorphous Solid Dispersions

    Parenteral Drug Delivery Trends

    Selecting the Right Outsourcing Model for Emerging Biotech

    Inhaled Drug Delivery Technology

    The Future of Biologics: Accelerating Production, Reducing Costs
    Breaking News
    Online Exclusives
    Industry News
    Collaborations & Alliances
    Promotions & Moves
    Trials & Filings
    Financial Reports
    Bio News & Views
    Custom Sourcing News
    Packaging & Tracking
    CRO News
    Live From Shows
    Top News
    High Purity New England Bolsters Biopharma Solutions Services

    AMRI Contributes to Efforts to Increase COVID-19 Vax Supply

    CatSci Opens New Site in UK

    Pfizer Partners with Medicines Manufacturing Innovation Center

    Covectra Introduces Next-Gen Serialization Solution
    APIs
    Aseptic Processing
    Cleaning Validation
    Clinical Trial Materials
    Cytotoxics and High Potency Manufacturing
    Equipment
    Excipients
    Extractables and Leachables
    Facilities
    Fill/Finish
    Lyophilization
    Parenterals
    Process Development
    Process Validation
    Risk Management
    Scale-up/ Technology Transfer
    Solid Dosage/ Creams/ Ointments

    CatSci Opens New Site in UK

    Pfizer Partners with Medicines Manufacturing Innovation Center

    C2 Pharma Completes Multiple Regulatory Filings

    Bormioli Opens New Glass Research Center

    Why Increasing Solubility May Not Improve Bioavailability - In Vitro Predictions
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Covectra Introduces Next-Gen Serialization Solution

    Bormioli Opens New Glass Research Center

    Centrient Pharmaceuticals to Acquire Astral SteriTech

    Seasonal Vaccine Manufacturing

    PwC Joins Medicines Manufacturing Innovation Centre
    Analytical Services
    Bioanalytical Services
    Bioassay Developement
    Biologics, Proteins, Vaccines
    Biosimilars
    Chemistry
    Clinical Trials
    Drug Delivery
    Drug Development
    Drug Discovery
    Formulation Development
    Information Technology
    Laboratory Testing
    Methods Development
    Microbiology
    Preclinical Outsourcing
    R&D
    Toxicology

    AMRI Contributes to Efforts to Increase COVID-19 Vax Supply

    CatSci Opens New Site in UK

    Pfizer Partners with Medicines Manufacturing Innovation Center

    CrownBio & JSR Life Sciences Partner with Cambridge Quantum Computing

    Stevanato Group Launches AI Platform
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021

    Top BioPharma Form Accumulus Synergy

    Global Biosciences Co. Selects ValGenesis VLMS

    Gene Therapy Co. Selects ValGenesis' SaaS Platform

    The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    Alcami

    test company saurabh

    Reed-Lane

    PCI Pharma Services

    Aphena Pharma Solutions
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    Almac Group

    Adare Pharma Solutions

    test company saurabh

    Reed-Lane

    Aphena Pharma Solutions
    Webinars
    Live From Shows
    • Magazine
      • Current / Back Issue
      • Features
      • Editorial
      • Columns
      • Editorial Guidelines
      • Subscribe Now
      • Advertise Now
      • Enewsletter Archive
      • Digital Edition
    • Directory
      • Companies
      • Categories
      • Corporate Capabilities
      • Add Your Company
    • Manufacturing
      • APIs
      • Aseptic Processing
      • Cleaning Validation
      • Clinical Trial Materials
      • Cytotoxics and High Potency Manufacturing
      • Equipment
      • Excipients
      • Extractables and Leachables
      • Facilities
      • Fill/Finish
      • Lyophilization
      • Parenterals
      • Process Development
      • Process Validation
      • Risk Management
      • Scale-up/ Technology Transfer
      • Solid Dosage/ Creams/ Ointments
      • cGMP Manufacture
    • Packaging
      • Capsules
      • Cold Chain Management
      • Injectables
      • Logistics
      • Serialization
      • Solid Dosage / Semi-solids
      • Supply Chain
      • Vials
    • Development
      • Analytical Services
      • Bioanalytical Services
      • Bioassay Developement
      • Biologics, Proteins, Vaccines
      • Biosimilars
      • Chemistry
      • Clinical Trials
      • Drug Delivery
      • Drug Development
      • Drug Discovery
      • Formulation Development
      • Information Technology
      • Laboratory Testing
      • Methods Development
      • Microbiology
      • Preclinical Outsourcing
      • R&D
      • Toxicology
    • Compliance
      • Filtration & Purification
      • GMPs/GCPs
      • Inspections
      • QA/QC
      • Regulatory Affairs
      • Validation
    • Top 25 Pharma & BioPharma
    • Contract Pharma Direct
    • Breaking News
    • Online Exclusives
    • Slideshows
    • Experts Opinions
    • Surveys
      • Outsourcing Survey
      • Salary Survey
    • Glossary
    • Videos
    • Podcasts
    • White Papers
    • Infographics
    • Contract Pharma Conference
      • Contract Pharma Conference
      • Speakers
      • Exhibitors
      • Conference Sessions
    • Supplier Microsite
      • Companies
      • News Releases
      • Posters
      • Brochures
      • Services
      • Videos
      • Case Study
      • White Papers
    • eBook
    • Webinars
    • Events
      • Industry Events
      • Live from Show Events
      • Webinars
    • Classifieds / Job Bank
      • Classifieds
      • Job Bank
    • About Us
      • About Us
      • Contact Us
      • Advertise With Us
      • Privacy Policy
      • Terms of Use
    Expert's Opinion

    The Slow – But Desperately Needed – Evolution of Oncology Clinical Development Designs

    Appropriate adaptive designs in early stages of development can accelerate timelines and reduce costs, and help focus on the most promising agents.

    The Slow – But Desperately Needed – Evolution of Oncology Clinical Development Designs
    Related CONTENT
    • Altasciences Contributes to Vibegron Approval
    • ACG Launches ACG Laboratories
    • Aevitas Therapeutics Appoints President and CEO
    • Century Therapeutics Significantly Expands Capabilities
    • Lilly, Rigel Enter Exclusive CNS Development Collaboration
    Jürgen Hummel, MSc, Senior Director, Statistical Science, PPD, and Lead of PPD’s Adaptive Design Working Group01.07.21
    Oncology trials now make up more than one-third of today’s research pipeline, but conventional oncology development programs often are inefficient and have high failure rates. Of the oncology agents that enter Phase I trials, only about 3% eventually receive U.S. Food and Drug Administration (FDA) approval.1

    We can do better. The application of appropriate adaptive designs at the early stages of development can not only accelerate timelines and reduce costs, but also can help focus development on the most promising agents at the right doses in the right indications for the right patients.

    Adaptive designs potentially allow a trial to answer multiple questions at once, leveraging accumulating data so early findings can inform decisions in a flexible process. In contrast, traditional designs answer only one narrow scientific question at a time on a rigid sequential path in which answers to pivotal research questions are often obtained only at the end of the trial.

    Our experience in submitting protocols with adaptive designs in early stage oncology trials to U.S. and European regulators is that they not only accept these designs – they actively encourage them.

    Given that the methods are more efficient, well established and that regulators encourage their use – both through published guidance and in practice – why has adoption not occurred more quickly? To examine the question, let’s explore a specific example.

    Defining the maximum tolerated dose (MTD)
    Defining an accurate dose in early-phase oncology clinical trials is a common challenge. The MTD is estimated to be correct in only about 40% of trials,2 which may result in patients in subsequent trials being treated at subtherapeutic doses or doses that are too toxic. Selection of the wrong dose can not only disrupt the outcomes of all subsequent phases, it can, without a correction, ultimately lead to the development program’s failure.

    Most trials still identify MTD using the 3+3 design, a rule-based design that offers simplicity, convenience and familiarity. However, 3+3 has significant limitations. It relies on fixed cohort sizes, ignoring uncertainties, to define an MTD based only on data from the last dose. It also offers no ability to re-escalate or respond when late toxicities emerge. Several improved rule-based dose escalation designs have gained popularity in recent years, including the modified toxicity probability interval (mTPI) design and Bayesian optimal interval (BOIN) design.

    The continual reassessment model (CRM), an adaptive Bayesian model-based approach introduced in 1990, efficiently evaluates more doses – using all the data it collects – to estimate the MTD more precisely and with more confidence compared to 3+3 and other rule-based designs. The difference in accuracy becomes more obvious as more dose levels are tested. As a result, the CRM provides an increased chance of treating study patients around the MTD and a decreased chance of exposing patients dosed at levels greater than MTD. Several variants of the CRM have been developed, including the Neuenschwander, et. al., NCRM design with overdose control, which is the most-commonly used one (also referred to as Bayesian Logistic Regression Model [BLRM]).

    Even though the CRM has been shown to be more accurate in targeting the MTD than the 3+3 design, uptake has been slow. Lack of familiarity with the model and aversion to perceived risk has deterred adoption. But, in fact, many of the barriers impeding early adoption of the CRM have now been overcome. The following chart details common misconceptions that continue to linger.

    Thirty years of CRM in practice: Early barriers to adoption have now been addressed
    Misconceptions Truths
    CRM is operationally different compared to 3+3 Operationally, CRM is very similar to 3+3
    User-friendly simulation software is not available Powerful software now enables simulation of many common dose-escalation trials (e.g., Berry Consultants’ Fixed and Adaptive Clinical Trial Simulator (FACTS™)
    Dose recommendations from a model-based design cannot be overridden by clinicians CRM only provides a dose recommendation that can be overruled by a dose escalation committee
    Incorporating the CRM design into a study synopsis or protocol will delay the study start
     
    This is potentially true, but only if the study protocol is already near final. Otherwise, simulations can be performed in parallel.
    Moreover, even if the date of first patient in (FPI) is delayed, the study completion is still likely to be sooner due to a shorter study duration.
    The CRM design is cost prohibitive By potentially requiring fewer patients and allowing for more rapid progression through early dosing levels, the CRM often, in fact, reduces costs. Bigger picture, when you consider the potential costs of taking a suboptimal dose into the next phase, it becomes clear that identifying the right MTD in the dose-escalation phase could arguably generate the greatest cost savings – and advantage – that a program could gain.
     
     
    Part of the beauty of the CRM design is that simulations can compare the performance of the CRM design to the 3+3 and other designs. In our experiences, simulations typically inspire confidence in the CRM design, and then, in turn, the CRM design in practice inspires adoption. In subsequent trials, the CRM often is selected from the start as the go-to dose escalation design.

    In our experience, the key to adopting innovative designs is simple: try them. Once you have made a foray into these new ways of working, traditional methods may strike you as inflexible, slow and unclear compared to the flexibility and efficiency inherent in adaptive designs.
     
    1Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2):273-286.
    2North B, Kocher HM, Sasieni P. A new pragmatic design for dose escalation in Phase 1 clinical trials using an adaptive continual reassessment method. BMC Cancer. 2019;19(1):632.


    Jürgen Hummel, MSc, is the senior director of statistical science in biostatistics at  PPD. He’s been with the company since 2006 and currently leads its statistical science track within biostatistics and provides statistical consistency both internally and externally. He has been leading PPD’s cross-departmental Adaptive Design Working Group since its inception. During his 25-year career, he has held a variety of technical and managerial positions in biostatistics, predominantly within the CRO industry.
    Related Searches
    • Clinical Trials
    • Drug Development
    Suggested For You
    Altasciences Contributes to Vibegron Approval Altasciences Contributes to Vibegron Approval
    ACG Launches ACG Laboratories ACG Launches ACG Laboratories
    Aevitas Therapeutics Appoints President and CEO Aevitas Therapeutics Appoints President and CEO
    Century Therapeutics Significantly Expands Capabilities Century Therapeutics Significantly Expands Capabilities
    Lilly, Rigel Enter Exclusive CNS Development Collaboration Lilly, Rigel Enter Exclusive CNS Development Collaboration
    Patients as Partners in Clincial Trials Patients as Partners in Clincial Trials
    Kaneka Eurogentec Expands Capabilities Kaneka Eurogentec Expands Capabilities
    FUJIFILM Diosynth Hosts UK PM at COVID Vax Mfg. Site FUJIFILM Diosynth Hosts UK PM at COVID Vax Mfg. Site
    RotaChrom Technologies Partners with Cyclolab RotaChrom Technologies Partners with Cyclolab
    Anova Enterprises Acquires Corlexia Clinical Services Anova Enterprises Acquires Corlexia Clinical Services
    Vigene Plans Major Expansion in Maryland Vigene Plans Major Expansion in Maryland
    TCG Lifesciences Expands Footprint to the U.S. TCG Lifesciences Expands Footprint to the U.S.
    Inside a Vaccine Trial Inside a Vaccine Trial
    CureVac, UK Partner on Vaccines Against SARS-CoV-2 Variants CureVac, UK Partner on Vaccines Against SARS-CoV-2 Variants
    Imcyse, Pfizer Enter Autoimmune Research Alliance Imcyse, Pfizer Enter Autoimmune Research Alliance

    Related Expert's Opinion

    • Clinical Trials | Information Technology
      Top 5 Things to Know Before Selecting Clinical Trial Technology

      Top 5 Things to Know Before Selecting Clinical Trial Technology

      Look for a future-proof model, innovative vendors - not cutting-edge technology, and focus on user-centered design and interoperability.
      Andres Garcia, Co-founder and CTO Florence 02.08.21

    • Clinical Trials
      The Future of Clinical Trials Series: Part II

      The Future of Clinical Trials Series: Part II

      Greater awareness will ensure diversity is no longer an afterthought and patients will be at the center of every aspect of clinical research.
      Jena Daniels, Rasmus Hogreffe, Ingrid Oakley-Girvan, Dr. Michelle Longmire, Medable 01.26.21

    • Clinical Trials
      The Future of Clinical Trials Series: Part I

      The Future of Clinical Trials Series: Part I

      What will 2021 have in store for an industry in flux?
      Alison Holland, Head of Decentralized Trials, Medable, Maria Fotiu, Executive Vice President of Decentralized Solutions, Syneos Health 01.19.21


    • Clinical Trials | Drug Development | Information Technology
      Virtual Clinical Trials: The Future of Dermatology Studies

      Virtual Clinical Trials: The Future of Dermatology Studies

      COVID-19 has created lasting impacts for clinical trials and a host of benefits have arisen from the adoption of virtual and hybrid models.
      Sonja VanWye, RN, MSN, Director, Dermatology Strategy, IQVIA Biotech 01.15.21

    • Drug Development | Industry News | Regulatory Affairs
      The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021

      The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021

      A look at EUA standards and approvals, unavoidable pitfalls, Operation Warp Speed, FDA’s use of Real-World Evidence, and a slow return to "normalcy".
      Chad Landmon, Michelle Divelbiss and Alex Alfano, Axinn, Veltrop & Harkrider LLP's Intellectual Property and Food and Drug Administration Practice Groups 01.05.21

    • Clinical Trials | Information Technology
      Life Sciences Strive for Greater Agility

      Life Sciences Strive for Greater Agility

      Embracing real-time drug safety monitoring during and post COVID will continue to propel the industry forward.
      Ronan Brown, SVP of Integrated Technology & Compliance, and Joe Rymsza, VP, Global PV & Regulatory Technology Solutions, IQVIA 12.14.20


    • Clinical Trials | Drug Development | Information Technology
      Advances in Intelligent Automation

      Advances in Intelligent Automation

      The future of medicine relies on further digital transformation and automation-enabling solutions to improve drug development and monitoring.
      Updesh Dosanjh, Practice Leader, Technology Solutions, IQVIA 12.14.20

    • Drug Development
      Navigating Uncertainty: Considerations for Life Sciences 2021

      Navigating Uncertainty: Considerations for Life Sciences 2021

      With vaccines against COVID-19 on the horizon, our focus is shifting to 2021 and the major issues life sciences companies face and reasons for optimism.
      Arda Ural , EY Americas Health Sciences and Wellness Industry Leader, Ernst & Young LLP 12.11.20

    • Clinical Trials | Information Technology
      AI and Advanced Analytics

      AI and Advanced Analytics

      Equipped with the right tools, CROs are better positioned to develop optimal protocols, rapidly identify patients to enroll, and preempt study issues.
      Paul Oliver, Medidata 11.13.20


    • Clinical Trials | Information Technology
      eCOA: Addressing Barriers to Faster Deployment in Clinical Trials

      eCOA: Addressing Barriers to Faster Deployment in Clinical Trials

      Clinical Outcome Assessments are an increasingly important tool in clinical research.
      Paul O'Donohoe, Scientific Lead, eCOA and Mobile Health, Medidata 11.13.20

    • Clinical Trials | Information Technology
      Adding Remote Site Access to Sponsor Bids: What to Know as CRO

      Adding Remote Site Access to Sponsor Bids: What to Know as CRO

      Traditional monitoring has changed, CROs should build a portfolio of remote access solutions and have them ready.
      Ryan Jones, CEO, Florence Healthcare 10.13.20

    • Drug Development
      New York City is Not Dead, Our Life Sciences Sector is Thriving

      New York City is Not Dead, Our Life Sciences Sector is Thriving

      Amid the COVID-19 pandemic, life sciences is booming in NYC!
      Sara Jane Demy, CEO & Founder, Demy-Colton 10.01.20


    • Clinical Trials | Drug Development
      How to Balance Internal and External Staff Within Outsourcing Models

      How to Balance Internal and External Staff Within Outsourcing Models

      Strategies to consider in flexed staffing models.
      John Barry, SVP, Consulting Practice and Chief Strategy Officer, PRA Health Sciences, SSD 09.22.20

    • Biologics, Proteins, Vaccines | Drug Development
      The Importance of Global Collaboration in the Fight Against COVID-19

      The Importance of Global Collaboration in the Fight Against COVID-19

      Industry continues to join forces to find new treatments for COVID-19.
      Dohyun Cho, Chief Operating Officer, Enzychem Lifesciences 09.08.20

    • Clinical Trials | Drug Development
      FDA Response to COVID-19

      FDA Response to COVID-19

      A Discussion on Protocol Amendments and Clinical Study Reports in Affected Ongoing Trials.
      Jack Modell, M.D., Vice President and Senior Medical Officer, Rho 09.03.20

    Trending
    • Catalent Acquires Delphi Genetics
    • Inside A Vaccine Trial
    • Wavelength Pharmaceuticals Acquires Majority Stake In Vanamali Organics
    • Century Therapeutics Significantly Expands Capabilities
    • ICON Acquires Medpass
    Breaking News
    • High Purity New England Bolsters Biopharma Solutions Services
    • AMRI Contributes to Efforts to Increase COVID-19 Vax Supply
    • CatSci Opens New Site in UK
    • Pfizer Partners with Medicines Manufacturing Innovation Center
    • Covectra Introduces Next-Gen Serialization Solution
    View Breaking News >
    CURRENT ISSUE

    January/February 2021

    • High Drug Loading Amorphous Solid Dispersions
    • Parenteral Drug Delivery Trends
    • Selecting the Right Outsourcing Model for Emerging Biotech
    • Inhaled Drug Delivery Technology
    • The Future of Biologics: Accelerating Production, Reducing Costs
    • Business Intelligence For (and From) the Lab
    • Communicating Your Contracting Priorities to Your Drug Company Customers
    • COVID-19 Impact Report
    • The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021
    • View More >

    Cookies help us to provide you with an excellent service. By using our website, you declare yourself in agreement with our use of cookies.
    You can obtain detailed information about the use of cookies on our website by clicking on "More information”.

    • About Us
    • Privacy Policy
    • Terms And Conditions
    • Contact Us

    follow us

    Subscribe
    Nutraceuticals World

    Latest Breaking News From Nutraceuticals World

    Clinical Trial Finds Metabolic Benefits for Polyphenols Formula
    JRF Technology Debuts Elderberry Oral Film Strip
    Danone Adds to Plant-Based Portfolio with Acquisition of Follow Your Heart Brand
    Coatings World

    Latest Breaking News From Coatings World

    OQ Chemicals Increases Carboxylic Acids, Esters Prices
    Sensory Analytics Announces Issuance of Broad New Patent Covering Coating Thickness Measurement
    Arkema Reports Full-year 2020 Results
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    Japan to Lead APAC Assisted Reproductive Technology Devices Market
    Portescap Slotless Brushless DC Motors Receive ISO 13485 Certification
    FDA Breakthrough Device Designation Given to MI Transcatheter Heart Pump
    Contract Pharma

    Latest Breaking News From Contract Pharma

    High Purity New England Bolsters Biopharma Solutions Services
    AMRI Contributes to Efforts to Increase COVID-19 Vax Supply
    CatSci Opens New Site in UK
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    Christie Brinkley Joins SBLA Beauty
    Madison Reed Raises $52 Million in Financing Round
    The Estée Lauder Companies Closes Becca Cosmetics
    Happi

    Latest Breaking News From Happi

    Sales More Than Double at Madison Reed
    PBA Opposes House Bill 2325 in West Virginia
    J.R. Watkins Tackles Pain with New Lines
    Ink World

    Latest Breaking News From Ink World

    Etiflex Enters New Markets with Nilpeter FA-22 Installation
    Hydrocarbon Solvents Market to Surpass $8.1 Billion by 2030
    Lowe-Martin Adds 2 KODAK NEXFINITY Digital Presses
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    Amberley Labels turns to Kurz for embellishments
    Dantex set to install first PicoJet digital press in US
    Epson hosting workshop at Natural Products Expo virtual event series
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    H&V Announces Price Increase
    Fiber Bond VE3 Technology Inactivates SARS-CoV-2 in HVAC Filtration Systems
    Citizens Provides $325 Million Senior Credit Facility to Nice-Pak
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    First Implantation of CTL Amedica's Minimally Invasive Flex Tower
    NuVasive Nabs Simplify Medical for $150M
    SeaSpine Begins Limited Launch of WaveForm TA (TLIF Articulating) 3D-Printed Interbody
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    Comercial Kywi Improves Customer Service, Front-Store Operations with Zebra Mobile Solution
    Global Printed Circuit Board Market Projected to Reach $69.32 Billion by 2027
    RFID Locks Market to Reach $9.93 Billion by 2027: Allied Market Research

    Copyright © 2021 Rodman Media. All rights reserved. Use of this constitutes acceptance of our privacy policy The material on this site may not be reproduced, distributed, transmitted, or otherwise used, except with the prior written permission of Rodman Media.

    AD BLOCKER DETECTED

    Our website is made possible by displaying online advertisements to our visitors.
    Please consider supporting us by disabling your ad blocker.


    FREE SUBSCRIPTION Already a subscriber? Login