• 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
    Small Innovators & Niche CROs

    Focus on Science

    Rapid and Data Rich Chromatographic Method Development

    Preparing Your Post Pandemic Talent Strategy

    How Modern Near-Infrared Came to Be
    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
    Frontage Expands Capabilities at its Clinical Site in Secaucus, NJ

    Ascendia Pharmaceuticals Poised for Expansion

    Bora Pharmaceuticals Adds Roller Compaction Capabilities

    Merck KGaA Selects PRA’s Remote Patient Monitoring Platform

    AGC Biologics Appoints Jun Takami GM of Chiba Site
    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

    Ascendia Pharmaceuticals Poised for Expansion

    Bora Pharmaceuticals Adds Roller Compaction Capabilities

    Alkermes, Merck Enter Clinical Trial and Supply Agreement

    Sterling Pharma Solutions Acquires ADC Biotechnology

    Moderna, Catalent Enter Long-Term Strategic Vax Pact
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Cryoport Acquires Critical Transport Solutions Australia

    PharmParts – This Makes Sense!

    Securing Your API Supply Chain: Three Keys to Success

    Enteris BioPharma: Custom Solutions – From Bench to Market

    The Benefits of Outsourcing Cold Storage
    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

    Frontage Expands Capabilities at its Clinical Site in Secaucus, NJ

    Ascendia Pharmaceuticals Poised for Expansion

    Merck KGaA Selects PRA’s Remote Patient Monitoring Platform

    Agilex Biolabs Acquires TetraQ for APAC Expansion Plans

    Alkermes, Merck Enter Clinical Trial and Supply Agreement
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    What Will Change at FDA for 2021?

    RBQM Comes of Age: COVID as a Catalyst for Change

    Post-Pandemic Regulations

    Enteris BioPharma: Custom Solutions – From Bench to Market

    Metrics Contract Services Completes Russian Regulatory Inspection
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    Adare Pharma Solutions

    Almac Group

    Syngene

    Emergent BioSolutions

    Baxter BioPharma Solutions
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    Baxter BioPharma Solutions

    Alcami

    PCI Pharma Services

    Almac Group

    Adare 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
    Columns

    Synthetic Control Arms

    In clinical trials, they don’t always capture the most important dimensions

    Synthetic Control Arms
    Related CONTENT
    • Mogene
    • Reed-Lane
    • Contracting And Outsourcing Agenda
    • Are We Embracing FDA’s Messages?
    • Drugs as...Fashion?
    Ben Locwin03.06.19
    Synthetic Control Arms: What are they? 
    If you haven’t heard of them, Synthetic Control Arms are control arms of a clinical trial—think treatment vs. control—which don’t actually involve enrolling patients into a trial to receive placebo against which to compare a legitimate therapeutic treatment.
     
    Why they’re not so good
    Using an idea to incorporate Real World Evidence (RWE) into clinical trials, the thinking goes that we can take the ‘idea’ of a control group and make a leap that this group can be artificially extracted from society.

    Where these data are intended to be pulled from: Electronic health records (EHR/EMR), administrative claims data, patient generated data from fitness trackers(!), home medical equipment, disease registries, and historical trial data. Keep in mind that much of these data aren’t validated.

    Expansion of the discussion
    Just because one is attempting to implement a concept in a new way doesn’t necessarily mean that it should be done. We can celebrate novel ideas executed well, and should ruthlessly and relentlessly controvert (falsify) those ideas which are ascientific. The impoverished thinking which forms the backbone of this synthetic control arm idea hasn’t adequately considered the most important parts of a control arm within clinical trials.

    When ‘control’ provides more control than you thought
    Far from being inert, a placebo treatment whether it’s a sugar pill, a sham interaction with a healthcare provider, or a sham surgery, is still a ‘treatment.’ Patients spontaneously get better when they take sugar pills, when a healthcare authority talks to them and listens to them, and when they undergo a surgical ‘non-procedure’ where the surgeon opens an incision, then closes it with no therapeutic surgery performed whatsoever. In each of these three cases, the patient experiences what we call an expectancy effect—that is, they ‘expect’ that their treatment modality will help them, and things get better. In every drug trial, there is a placebo group which responds directionally similarly with the actual treatment group (perhaps except for the overall magnitude (size) of the change). Don’t believe me? Check out this graphic:


     


    Where the red line is the actual performance of the drug therapy, and the green line is the actual performance of the placebo (sugar pill) treatment. This is NOT ‘no treatment,’ and the positive response is NOT trivial.

    We almost never run randomized controlled trials in the clinic where the control arm is actually ‘no treatment’—that is, the patient doesn’t undergo any exposure to a sugar pill, a positive discussion with the provider, nothing. In these cases, where there is admittedly a paucity of data, patients don’t perform the same as those in a placebo group—and of course also, then, much differently from the drug or device treatment group.

    So the synthetic control arm approach is comparing apples and oranges. We try to make the administration of a medical treatment and placebo treatment the same in as many ways as are practically controllable: same treatment center, same environmental/ambient administration conditions, same provider interactions, same diagnostic/prognostic discussions.*

    This approach allows us to see what exactly were the differences between the real treatment modality and the same rituals, but subtracting out the treatment modality.

    When we try to move this to having a treatment group, and a ‘no treatment-lazily-measured-out-in-the-wild’ control group, not only does the data variance skyrocket astronomically for that other group, making inferences difficult, but finding what is the ‘true’ treatment effect becomes all but impossible to determine.

    Of what value are increased trial speed and fewer patients recruited if the signals we need to detect for safety and efficacy and approval are impossible to confidently determine. This just shifts the uncertainty of well-run clinical trials to the Post-Marketing Surveillance phase to clean up the mess of poorly designed trials.

    To attempt to address some of this, FDA has appointed a new deputy commissioner to look into how to best tackle this challenge. Her role will undoubtedly be a difficult one, and include needing to develop various checklists or matrices to demonstrate the evidentiary value of different types of ‘real world’ data, most of which is nonsense. Another assumption within the synthetic control arm approach is that disease progressions are at best case linear, and at worst case, self-similar within disease states. This is another falsifiable assumption, and one made messier within RWE because of varying standard of care treatments. 

    *Of course, in this list when I say “same” I clearly mean “an attempt at no difference.” These terms are NOT synonymous! The environment and interactions will never be the same, and this adds to the necessary noise in the data across all patient-data-points and all clinical trials. If you hear yourself saying something is ‘the same’ as something else, please stop. The whole point of hypothesis testing is to test against the hypothesis of ‘no difference’ and no two things are exactly ‘the same.’ Except for subatomic particles, where as far as the universe is concerned, one electron or photon is indistinguishable from another, provided they are prespecified to have certain characteristics, such as “spin,” which are identical.

    References
    Kirsch, I. (2009). The emperor’s new drugs.
    Kaptchuk, T., Miller F. (2015). Placebo Effects in Medicine. New England Journal of Medicine; 373;1 8-9.
    Fisher, R. (1956). Statistical Methods and Scientific Inference.
    Locwin, B. (2019). I say placebo, you say potato: Misunderstandings and misgivings of the placebo phenomenon.


    Ben Locwin

    Ben Locwin, PhD, MBA, MS, MBB began his foray into healthcare decades ago after he started out as an astrophysicist. He is a popularizer and communicator of science, and has worked in a variety of pharmaceutical organizations (small molecule and biologics), medical device organizations, and within hospitals, clinics, and emergent care centers bringing better healthcare to the end user (i.e., the patients!).
    Related Searches
    • expansion
    • Testing
    • patients
    • it
    Suggested For You
    Mogene Mogene
    Reed-Lane Reed-Lane
    Contracting And Outsourcing Agenda Contracting And Outsourcing Agenda
    Are We Embracing FDA’s Messages? Are We Embracing FDA’s Messages?
    Drugs as...Fashion? Drugs as...Fashion?
    Aphena Ready for Opioid Crisis Response Act Aphena Ready for Opioid Crisis Response Act
    Akorn Receives FDA Warning Letter Akorn Receives FDA Warning Letter
    “Clinically Speaking” “Clinically Speaking”
    Janssen Receives FDA Approval for INVOKANA Janssen Receives FDA Approval for INVOKANA
    Alcami Collaborates with Medicines Development for Global Health Alcami Collaborates with Medicines Development for Global Health
    No, Your Neighbors and Facebook Friends Don’t Know Anything About Health and Wellness No, Your Neighbors and Facebook Friends Don’t Know Anything About Health and Wellness
    Reporting CPPs to FDA Reporting CPPs to FDA
    Marrying Suppliers & Sponsors! Marrying Suppliers & Sponsors!
     Symbiosis Secures FDA Approval Symbiosis Secures FDA Approval
    CDMOs and Drug Shortages CDMOs and Drug Shortages

    Related Columns

    • Clinical Trials | Serialization | Supply Chain
      Anti-Counterfeiting in the Pharmaceutical Industry: An Evolution

      Anti-Counterfeiting in the Pharmaceutical Industry: An Evolution

      Keeping up with counterfeitors in the pharmaceutical industry is no easy task, but patients’ lives depend on it.
      Ben Locwin, Healthcare Science Advisors 10.04.19

    • Clinical Trials | Process Development

      China Vaults to the Top of U.S. Biomanufacturers’ Off-Shoring Prospects

      A look at top destinations for future offshoring
      Eric S. Langer, BioPlan Associates 06.02.16

    • Clinical Trials

      Are More CRO Transactions Near?

      When will we see additional transactions involving the largest CROs?
      Chad Moore, Leerink Partners LLC 06.02.16


    • Biosimilars | Clinical Trials | Drug Discovery | Process Development

      Like the Temperature, It Feels Like Deal Activity is Heating Up

      A summary of 2016 transactions so far
      Chad Moore, Leerink Partners LLC 05.05.16

    • Analytical Services | Clinical Trials | Laboratory Testing | Supply Chain

      Analytical Instruments are On-Board with Outsourcing

      Newer process instruments are finally being designed with mobility in mind
      Emil W. Ciurczak, DoraMaxx Consulting 01.28.16

    • Biosimilars | Clinical Trials

      Outsourced Pharma Services: 2015 Review & 2016 Outlook

      ...
      Chad Moore, Leerink Partners 01.28.16


    • APIs | Biosimilars | Clinical Trials | Process Development | Vials

      2015 in Review: 6 Key Trends Affecting CMOs

      A look at major CMO trends ranging from budgets to growth opportunities
      Eric S. Langer, BioPlan Associates 11.17.15

    • Clinical Trials | Drug Development

      Recap of Notable Recent CRO Transactions

      Conditions are expected to remain favorable for M&A and capital markets activity in the pharmaceutical service and IT sector
      Chad Moore 10.07.15

    • Clinical Trials | Process Development

      Globalization Hits Biopharma Contract Manufacturing

      CMOs no longer need to be local, and some countries are set to benefit
      Eric S. Langer, BioPlan Associates 10.07.15


    • Clinical Trials

      Clinical Trial Participants: Why So Elusive?

      Looking at how some companies are improving clinical trial efficiency and speed to solve the clinical trial participant conundrum
      Chad Moore, Robert W. Baird & Co. Inc. 09.11.15

    • Clinical Trials | Drug Development

      Medical Affairs: The Next Wave of Outsourcing?

      Outsourcing of medical affairs is on the rise, creating opportunities for third-party providers
      Chad Moore, Robert W. Baird & Co. Inc. 07.14.15

    • Analytical Services | APIs | Bioanalytical Services | Biosimilars | Chemistry | Clinical Trials | Excipients | GMPs/GCPs | Laboratory Testing | Microbiology | QA/QC | R&D | Regulatory Affairs | Supply Chain | Toxicology | Validation

      Inventas vitam iuvat excoluisse per artes (Let us improve life through science and art)

      But Qui bono? (Who benefits?)
      Emil W. Ciurczak, DoraMaxx Consulting 07.14.15


    • Clinical Trials

      Why Do Americans Pay More for Cancer Treatments?

      The ever-increasing cost of cancer treatments globally is a constant cause for discussion and price negotiation between Pharma companies and health care providers
      Adele Graham-King, Contributing Editor 05.06.15

    • Clinical Trials | Drug Development

      M&A Activity Heats Up

      Last year was hot, but 2015 looks to be hotter.
      Chad Moore, Robert W. Baird & Co. Inc. 01.29.15

    • Capsules | Cleaning Validation | Clinical Trials | Extractables and Leachables | Facilities | Fill/Finish | GMPs/GCPs | Lyophilization | Process Development | R&D | Serialization | Supply Chain | Validation

      Sometimes, Even a Good Workman Can Blame His Tools

      A new generation of equipment will help generate products with less cost and effort, while being made more efficiently.
      Emil W. Ciurczak, DoraMaxx Consulting 01.29.15

    Trending
    • Sterling Pharma Solutions Acquires ADC Biotechnology
    • Sanofi To Build New $700M Flu Vaccine Facility In Canada
    • Alkermes, Merck Enter Clinical Trial And Supply Agreement
    • Ascendia Pharmaceuticals Poised For Expansion
    • Frontage Expands Capabilities At Its Clinical Site In Secaucus, NJ
    Breaking News
    • Bora Pharmaceuticals Adds Roller Compaction Capabilities
    • Ascendia Pharmaceuticals Poised for Expansion
    • Frontage Expands Capabilities at its Clinical Site in Secaucus, NJ
    • Merck KGaA Selects PRA’s Remote Patient Monitoring Platform
    • AGC Biologics Appoints Jun Takami GM of Chiba Site
    View Breaking News >
    CURRENT ISSUE

    April 2021

    • Small Innovators & Niche CROs
    • Focus on Science
    • Rapid and Data Rich Chromatographic Method Development
    • Preparing Your Post Pandemic Talent Strategy
    • How Modern Near-Infrared Came to Be
    • Securing Your API Supply Chain: Three Keys to Success
    • 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

    Kyowa Hakko Launches Heat-Treated Probiotic Strain for Eye Health
    CGA-7 Green Coffee Extract by Vidya Herbs Achieves Self-Affirmed GRAS Status
    Nutritional Complex Evidenced to Reduce Preterm Birth
    Coatings World

    Latest Breaking News From Coatings World

    Barentz Expands Canadian CASE Team
    Shepherd Color Company Opens Sales Office in China
    Chromaflo Technologies Awarded Gold Status CSR Rating by EcoVadis in EMEA
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    CMS Establishes New Payment for Pelvalon’s Eclipse System
    Varian, Google Cloud Partner to Bring Convenience to Cancer Therapy
    Resonetics Leases New Manufacturing Space in Costa Rica
    Contract Pharma

    Latest Breaking News From Contract Pharma

    Frontage Expands Capabilities at its Clinical Site in Secaucus, NJ
    Ascendia Pharmaceuticals Poised for Expansion
    Bora Pharmaceuticals Adds Roller Compaction Capabilities
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    Revlon Unveils New Fragrances Featuring Megan Thee Stallion & Sofia Carson
    Henkel Management Board Welcomes Wolfgang König
    Mielle Organics Gets a Major Investment
    Happi

    Latest Breaking News From Happi

    Nature’s Beauty Debuts Vegan Natural Body Care at Walgreens
    Estée Lauder Expands 'Beautiful' Fagrance Collection
    Mushrooms Are Key Ingredients in Beauty & Wellness
    Ink World

    Latest Breaking News From Ink World

    SE-DA Invests in Kornit Presto S
    Kumon North America Adds Speedmaster XL 106 from Heidelberg
    Iron Oxide Pigments Market to Register 4.7% CAGR from 2021 to 2028: GVR
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    Dantex elevates Joseph Sanchez to digital business development manager
    Mactac's Kevin Clunie joins TLMI panel
    MacDermid announces two new global sales roles
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    Precision Textiles Offers Biodegradable Medical Fabric
    Northshore Launches Megamax Briefs in New Colors
    Essity Acquires Distribution Rights to Sorbact in Australia and New Zealand
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    New Biosealant Could Stabilize Cartilage, Boost Healing After Injury
    Google Executive Joins SeaSpine's Board of Directors
    HSS and LimaCorporate Open Provider-Based 3D Design and Printing Facility
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    Tive Multi-sensor Tracker Solo 5G Relies on Sensirion SHT33
    VTT in 2020: Successful Year Despite Globally Challenging Times
    Lux Research: 3D Printing Market to Reach $51 Billion in 2030

    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