Episodes

  • Clinical Trials and Surrogate Outcomes (13)

    Clinical Trials and Surrogate Outcomes (13)
    Jul 27 2021

    Clinical Trials & Surrogate Outcomes

    Looking for clinical relevance means looking for a lot of details. 

    A crucial part of that is looking at WHAT is compared with WHAT

    But what if a comparison is not clinically relevant  - what do you do then?

    And how about studies using surrogate outcomes perhaps even approved by the FDA - they must be clinically relevant - but are they?

    In this episode, we talk about how to navigate this and find the best available research

    You don’t want to miss this episode

     

     Get the Precision Evidence Newsletter https://bit.ly/3tLBx3Z  

    LINKS:

    Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines Supplemental content, JAMA Oncology (2017) https://jamanetwork.com/journals/jamaoncology/fullarticle/2594542 

    FDA Approved Surrogate Endpoints: https://www.fda.gov/drugs/development-resources/table-surrogate-endpoints-were-basis-drug-approval-or-licensure  

    Virtual Reality Smartphone-Based Intervention for Smoking Cessation: Pilot Randomized Controlled Trial on Initial Clinical Efficacy and Adherence https://www.jmir.org/2020/7/e17571/ 

     

    NOTES: 

    • Finding clinically relevance in what is compared with what in a clinical trial 
    • How can we know what a relevant comparison is?
    • Different kinds of comparisons in clinical research
    • The pro and cons of surrogate endpoints
    • Examples of surrogate endpoints you should avoid
    • Outcomes in oncology research
    • FDA rules
    • When is information from placebo trials relevant - and when isn’t it relevant
    • Research with no comparator, when can that be useful?

     

    GET THE ABSTRACT SCREENING TOOL

    It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool to use when reading an abstract from a clinical research paper.

    Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at our website https://www.precision-evidence.com 

     

    Contact us at email: podcast@precision-evidence.com,

    Twitter @PrecisionEBM,

    You can learn more at our website, where you can also leave us a voice message.

    Website: www.precision-evidence.com

    Hosts:

    Dr. Kim Kristiansen, M.D: @KKristiansenMD   &  https://www.linkedin.com/in/kim-kristiansen 

    JG Staal: @HealthyEvidence

     Music thanks to mixkit.co 

     
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    18 mins
  • Addressing Clinical Relevance in Medical Papers (12)

    Addressing Clinical Relevance in Medical Papers (12)
    May 19 2021
    Addressing Clinical Relevance in Medical Papers Clinical trials and research should always aim to provide information that is meaningful and relevant for patients. In the last episode, we looked at how many - or rather - how few researchers mentioned and argued for what they would see as clinically relevant outcomes when setting up a study and listing it on clinicaltrials.gov In this episode, we go deeper to look at examples and why this is so important to improve the usefulness of the research   We want to make it mandatory to state the researchers' clinical relevance levels ahead of the trial, mentioning what they will consider clinically relevant when they pre-register their research on the clinicaltrials.gov website or similar websites. They then need to compare their findings in both the paper and abstract when publishing data from the study.    #clinicalrelevance   LINKS: Once-Weekly Semaglutide in Adults with Overweight or Obesity Paper https://www.nejm.org/doi/full/10.1056/NEJMoa2032183  ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/study/NCT03548935  10-Year Update on Study Results Submitted to ClinicalTrials.gov  https://www.nejm.org/doi/full/10.1056/NEJMsr1907644 FDA and NIH let clinical trial sponsors keep results secret and break the law https://www.sciencemag.org/news/2020/01/fda-and-nih-let-clinical-trial-sponsors-keep-results-secret-and-break-law  Compliance with the legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(19)33220-9.pdf  Our specific page on our website about requesting clinical relevance statement and evaluation https://www.precision-evidence.com/p/clinical-relevance/  Overview of clinical trials registers like clinicaltrials.gov: https://sites.google.com/a/york.ac.uk/yhectrialsregisters/home/clinicaltrials  Precision Evidence episode 11: “Clinical relevance - Looking at Recent Papers”  https://www.precision-evidence.com/11  NOTES:   Why is stating levels for clinical relevance important to make before a clinical trial starts?How should authors of clinical research papers refer and compare to clinical relevance statements?Looking at a specific study Importance of also looking at how the study is doneIn/exclusion criteriaCompliance with listing on clinicaltrials.govCompliance with publishing results on clinicaltrials.govChallenges to make a comprehensive review and analysis of a medical paper to make sure the information is both trustworthy and clinically relevant GET THE ABSTRACT SCREENING TOOL It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool to use when reading an abstract from a clinical research paper. Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at our website https://www.precision-evidence.com   Contact us at email: podcast@precision-evidence.com, Twitter @PrecisionEBM, You can learn more at our website, where you can also leave us a voice message. Website: www.precision-evidence.com Get the Precision Evidence Newsletter https://bit.ly/3tLBx3Z   Hosts: Dr. Kim Kristiansen, M.D: @KKristiansenMD   &  https://www.linkedin.com/in/kim-kristiansen  JG Staal: @HealthyEvidence  Music thanks to mixkit.co 
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    13 mins
  • Clinically Relevance - Looking at Recent Research (11)

    Clinically Relevance - Looking at Recent Research (11)
    Apr 29 2021

    Clinical trials and research should always aim to provide information that is meaningful and relevant for patients.

    • However, researchers are rarely addressing that topic when presenting results from trials.
    • In this episode, we look at published papers from high-ranking journals to get a sense of the extent of that problem. 
    • You may be surprised by our findings...

     

    We want to make it mandatory to state the researchers' clinical relevance levels ahead of the trial, mentioning what they will consider clinically relevant when they pre-register their research on the clinicaltrials.gov website or similar websites. They then need to compare their findings in both the paper and abstract when publishing data from the study.    #clinicalrelevance

     

    LINKS:

    Our specific page on our website about requesting clinical relevance statement and evaluation https://www.precision-evidence.com/p/clinical-relevance/ 

    Overview of clinical trials registers like clinicaltrials.gov: https://sites.google.com/a/york.ac.uk/yhectrialsregisters/home/clinicaltrials 

    Precision Evidence episode 10: “How to Get to Clinically Relevant Research” https://www.precision-evidence.com/10 

     

    NOTES: 

    • Statistical significance vs. clinical significance in clinical research
    • Clinical significance, clinical relevance, clinical meaningfulness, clinical evidence
    • Why researchers in the clinical field should always note ahead of starting a trial what they would consider clinically relevant and then refer back to that in the paper and abstract
    • Looking at 44 papers published in early 2021 in high ranking journals and analyzing the mentioning of clinical relevance
    • It is disappointing....
    • ALWAYS ASK FOR A CLINICAL RELEVANCE EVALUATION OF THE RESULTS - every time, all of us, whatever relation we have to produce, read and use information from clinical research
    • ASK FOR A CLINICAL RELEVANCE EVALUATION OF THE RESULTS - and let's make it just as normal as the p-value #doesitmatter 

     

    GET THE ABSTRACT SCREENING TOOL

    It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool to use when reading an abstract from a clinical research paper.

    Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at our website https://www.precision-evidence.com 

     

     Contact us at email: podcast@precision-evidence.com,

    Twitter @PrecisionEBM,

    You can learn more at our website, where you can also leave us a voice message.

    Website: www.precision-evidence.com

    Get the Precision Evidence Newsletter https://bit.ly/3tLBx3Z  

    Hosts:

    Dr. Kim Kristiansen, M.D: @KKristiansenMD

    JG Staal: @HealthyEvidence

     Music thanks to mixkit.co 

     
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    8 mins
  • How to Get to Clinically Relevant Research (10)

    How to Get to Clinically Relevant Research (10)
    Mar 26 2021
    How to Get to Clinically Relevant Research The default method to evaluate clinical research is by statistical significance  Unfortunately is statistical significance not related to the meaningfulness of the findings in the research and thereby to its meaningfulness for patients and healthcare If researchers stated ahead of starting the trial what they would consider clinically relevant,  the reader could relate to that and agree or disagree with the researcher It would come from focusing on using the provided information to help patients and improve healthcare - and not just publishing a paper We want to make it mandatory to state the researchers' clinical relevance levels ahead of the trial, mentioning what they will consider clinically relevant when they pre-register their research on the clinicaltrials.gov website or similar websites. They then need to compare their findings in both the paper and abstract when publishing data from the study.    #clinicalrelevance   LINKS: A specific page on our website about requesting clinical relevance statement and evaluation https://www.precision-evidence.com/p/clinical-relevance/  The history behind the chosen level for statistical significance with Ronald Fisher's book from 1925 "Statistical Methods for Research Workers." Precision Evidence Blog: https://www.precision-evidence.com/blog/the-p-value-and-sir-ronald-fischer/   96% of published studies mention a p-value at 0.05 or lower: "What Have We (Not) Learned from Millions of Scientific Papers with P Values?" https://www.tandfonline.com/doi/full/10.1080/00031305.2018.1447512  Overview of clinical trials registers like clinicaltrials.gov: https://sites.google.com/a/york.ac.uk/yhectrialsregisters/home/clinicaltrials  Only 15% of clinical research brings value: “Avoidable waste in the production and reporting of research evidence”  https://pubmed.ncbi.nlm.nih.gov/19525005/   Precision Evidence #8: "Critical Appraisal of the Moderna COVID19 Vaccine Trial"  https://www.precision-evidence.com/8   Precision Evidence #6: "Covid-19 Vaccines Trials: Understanding the First Published Results"  https://www.precision-evidence.com/6   Precision Evidence #5: "Covid-19 Vaccines Trials and Press Releases – Looking Beyond the Efficacy"  https://www.precision-evidence.com/5  TED talk with Sir Ken Robinson where he talks about two kinds of people  https://www.ted.com/talks/sir_ken_robinson_bring_on_the_learning_revolution    NOTES:  Statistical significance vs. clinical significance in clinical researchClinical significance, clinical relevance, clinical meaningfulnessShould clinical significance be used instead of statistical significance, or should they be used together?Problems with statistical significanceProblems with clinical significanceWhy researchers must state what they consider clinical relevant outcomes before starting a research project and refer back to that when evaluating their findings"Positive" vs. "negative" trials in terms of statistical significance and why all research mattersOverrepresentation in published research of statistically significant findings with p-values at 0.05 or lowerEfficacy measures with examples "Number Needed to Treat" (NNT) of "Number Needed to Harm" (NNH)The history behind the chosen level for statistical significance with Ronald Fisher's book from 1925 "Statistical Methods for Research Workers."  See also blog: Peer-reviewers responsibilityWe want to make it mandatory to state clinical relevance levels by the researchers ahead of the trial, mentioning what they will consider clinically relevant and essential when they pre-register their research on the clinicaltrials.gov website or similar websites. They then need to compare their findings with that both in the paper and abstract when publishing data from the researchALWAYS ASK FOR A CLINICAL RELEVANCE EVALUATION OF THE RESULTS - every time, all of us, whatever relation we have to produce, read and use information from clinical researchASK FOR A CLINICAL RELEVANCE EVALUATION OF THE RESULTS - and let's make it just as normal as the p-value #clinicalrelevance   GET THE ABSTRACT SCREENING TOOL It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool you can use when reading an abstract from a clinical research paper. Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at our website https://www.precision-evidence.com    Contact us at email: podcast@precision-evidence.com, Twitter @PrecisionEBM, You can learn more at our website, where you can also leave us a voice message Website: www.precision-evidence.com Get the Precision Evidence Newsletter https://bit.ly/3tLBx3Z   Hosts: Dr. Kim Kristiansen, M.D: @KKristiansenMD JG Staal: @HealthyEvidence   Music thanks...
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    18 mins
  • Russia's Sputnik COVID19 Vaccine Trial - Efficacy and Limitations #9

    Russia's Sputnik COVID19 Vaccine Trial - Efficacy and Limitations #9
    Feb 23 2021

    Russia's Sputnik COVID19 Vaccine Trial - Efficacy and Limitations

    • The Russian Sputnik COVID19 vaccine interim analysis has been published in the prestigious medical journal The Lancet
    • Efficacy is comparable to vaccines like the Pfizer/BioNTech and Moderna vaccines
    • But there are some serious concerns with the study and the published data reducing the usefulness of this vaccine and to whom it can be used
    • You don’t want to miss this episode

     GET THE ABSTRACT SCREENING TOOL

    It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool you can use when reading an abstract from a clinical research paper.

    Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at our website https://www.precision-evidence.com 

     LINKS:

    The Sputnik COVID19 Vaccine trial in the Lancet https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext 

    Precision Evidence #8: “Critical Appraisal of the Moderna COVID19 Vaccine Trial”

     https://www.precision-evidence.com/8 

    Precision Evidence #6: “Covid-19 Vaccines Trials: Understanding the First Published Results”

     https://www.precision-evidence.com/6 

    Precision Evidence #5: “Covid-19 Vaccines Trials and Press Releases – Looking Beyond the Efficacy”

     https://www.precision-evidence.com/5 

     

    NOTES:

    • The interim analysis of the Russian Sputnik COVID19 vaccine is published in The Lancet
    • It demonstrates efficacy at 94.6% which is comparable to the Pfizer/BioNTech and Moderna vaccine interim analysis
    • Safety is comparable as well
    • There are, however,  when scrutinizing the study, some serious concerns with impact on the usefulness of the vaccine and reducing the precision of the evidence

     Contact us at email: podcast@precision-evidence.com,

    Twitter @PrecisionEBM,

    You can learn more at our website, where you can also leave us a voice message 

    Website: www.precision-evidence.com

    Hosts:

    Dr. Kim Kristiansen, M.D: @KKristiansenMD

    JG Staal: @HealthyEvidence

     

    Music thanks to mixkit.co 
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    9 mins
  • Critical Appraisal of the Moderna COVID19 Vaccine Trial #8

    Critical Appraisal of the Moderna COVID19 Vaccine Trial #8
    Feb 2 2021

    Critical Appraisal of the Moderna COVID19 Vaccine Trial

    • There is a big interest in clinical research now due to the Covid19 pandemic
    • Especially the trails behind the Covid vaccines gain interest and is all over the news
    • In this episode, we take a look at the published paper on the Moderna vaccine trial using our last episode of this podcast (#7) about the precision of the evidence
    • We know from the news that the outcome in the Moderna vaccine trial is good with a reduction in risk at 94.1% by getting the vaccine
    • But is the study as a whole clinically relevant and trustworthy?
    • And how many people need to be given the vaccination to prevent one COVID19 infection? - Probably not what you would guess
    • We will cover this and much more in this episode

    GET THE ABSTRACT SCREENING TOOL

    It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool you can use when reading an abstract from a clinical research paper.

    Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at our website https://www.precision-evidence.com 

     LINKS:

    Moderna vaccine trial interim analysis paper (full access) https://www.nejm.org/doi/full/10.1056/NEJMoa2035389 

    Moderna vaccine trial interim analysis on clinicaltrials.gov  https://clinicaltrials.gov/ct2/show/NCT04470427 

    Evaluating clinical relevance in 2 x 2 matrix https://www.precision-evidence.com/matrix

    Precision Evidence #7 https://www.precision-evidence.com/7 

    Precision Evidence #6 https://www.precision-evidence.com/6 

    Precision Evidence #5 https://www.precision-evidence.com/5 

     

    NOTES:

     

    • Moderna vaccine trial has a somewhat confusing abstract
    • Efficacy is high at 94.1%  - and what that means in real life
    • It is statistically significant, but is it also clinically significant and relevant?
    • Stating what to be regarded clinically significant BEFORE stating the trial is important!
    • A closer look at study population and dropouts
    • A closer look at randomization and study period
    • The study on clinicaltrials.gov compared with paper, what can we learn?
    • How many persons need to be given the vaccination to prevent one COVID19 infection? - Probably not what you would guess
    • Safety and other vaccines
    • What we still need to know
    • Phase 3 vs Phase 4 trials
    • Conclusion
    • Future episodes of the Precision Evidence Podcast

     

     

     Contact us at email: podcast@precision-evidence.com,

    Twitter @PrecisionEBM,

    You can learn more at our website, where you can also leave us a voice message 

    Website: www.precision-evidence.com

    Hosts:

    Dr. Kim Kristiansen, M.D: @KKristiansenMD

    JG Staal: @HealthyEvidence

    PRECISION EVIDENCE ON TOP LIST

    Precision Evidence has been selected by Feedspot to the list of  

    Top 35 Clinical Trials Podcasts You Must Follow in 2021

    https://blog.feedspot.com/clinical_trials_podcasts/ 

     

    Music thanks to mixkit.co 

     
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    15 mins
  • The Precision of Clinical Research #7

    The Precision of Clinical Research #7
    Jan 15 2021
    • You’ve probably often heard that “Clinical trials show..” or “ evidence support that..”
    • Unfortunately, a research paper being published in a peer-reviewed medical journal is NOT a guarantee that it is clinically relevant  - even if it is a high ranking journal
    • As it is often the case the devil is in the details, so it is necessary to both read and evaluate the paper’s details and to put it into the context where you need the information
    • In this episode, we will talk about the details you need to look for

     

     

    GET THE ABSTRACT SCREENING TOOL

    It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool you can use when reading an abstract from a clinical research paper.

    Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at our website https://www.precision-evidence.com 

     

    LINKS:

    Evaluating clinical relevance in 2 x 2 matrix https://www.precision-evidence.com/matrix

    96% of published studies mention a p-value at 0.05 or lower: “What Have We (Not) Learned from Millions of Scientific Papers with P Values?” https://www.tandfonline.com/doi/full/10.1080/00031305.2018.1447512 

    Overview of clinical trials registers like clinicaltrials.gov: https://sites.google.com/a/york.ac.uk/yhectrialsregisters/home/clinicaltrials 

     

    PRECISION EVIDENCE ON TOP LIST

    Precision Evidence has been selected by Feedspot to the list of  

    Top 35 Clinical Trials Podcasts You Must Follow in 2021

    https://blog.feedspot.com/clinical_trials_podcasts/ 

     

    NOTES:

    • The conclusion in a clinical research paper is based on an analysis of data collected from a specific group of people: the study population
    • We have developed helpful tools to guide and help you with the process of screening afnf evaluate a paper from a clinical trial
      • The Abstract Screening Tool
      • The Precision Evidence Matrix for Clinical Relevance
      • Links to both above
    • The clinical usefulness depends on inclusion and exclusion criteria as well as the study design and method
    • The relevance of inclusion and exclusion 
    •  Can results be extrapolated to persons not included in a specific clinical trial?
    • What are the relevant outcomes?
    • Clinicaltrials.gov Why it is good and what is missing
    • Clinical relevance
    • P-values vs. clinical relevance
    • Precision of evidence
    • Using surrogate measurements as a stand-in for what we really want to know
    • How do you interpret the results from clinical trials?
    • Can researchers adjust the design and study population after data collection to improve outcomes?
    •  How to save time reading and evaluating clinical research papers

      Contact us at email: podcast@precision-evidence.com,

    Twitter @PrecisionEBM,

    website: www.precision-evidence.com

    Hosts:

    Dr. Kim Kristiansen, M.D: @KKristiansenMD

    JG Staal: @HealthyEvidence

     Music thanks to mixkit.co 

     
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    19 mins
  • Covid-19 Vaccines Trials: Understanding the First Published Results #6

    Covid-19 Vaccines Trials: Understanding the First Published Results #6
    Dec 15 2020

    Covid-19 Vaccines Trials: Understanding the First Published Results #6

    • With massive awareness in the media, we now have some detailed information about the first of the Covid19 vaccine trials
    • They differ in clinical usefulness
    • The efficacy measures of 95% are widely mentioned, but let's be clear about what it means and how can we use that information
    • In this episode, we go beyond the news coverage to find out and calculate how many persons need to be vaccinated to prevent one Covid19 infection both in general and for subgroups

     

    GET THE ABSTRACT SCREENING TOOL

    It can be a challenge to screen papers for clinical relevance. As we go beyond the abstract in this podcast, we have created a screening tool you can use when reading an abstract from a clinical research paper.

    Using that tool enables you to quickly screen an abstract from a medical journal for clinical relevance selecting only those you want to read. At the same time, you will know why you skipped the rest. Get it at https://www.precision-evidence.com/tool

    LINKS:

    Pfizer/BioNTech data from FDA https://www.fda.gov/media/144245/download

    Pfizer/BioNTech paper in NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa2034577?query=featured_home 

     

    AstraZeneca Paper in the Lancet https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

    Precision Evidence Podcast #5 https://www.precision-evidence.com/5

    Table with estimates of how many people need to be vaccinated to prevent one case of covid-19 https://www.precision-evidence.com/blog/covid19-and-the-first-clinical-trials-analyzing-the-details/

    NOTES:

    • In this episode, we follow up on the last episode of the Precision Evidence Podcast where we went beyond the press releases about the Covid19 vaccines
    • Now we have data from the first trials The Pfizer/BioNTech trial and the AstraZeneca Trial
    • They are different in many ways
    • How valid and useful is the data?
    • The meaning and clinical relevance of efficacy at 95%
    • How about clinical relevance and precision of the evidence
    • To find out, we calculate how many persons must get a vaccination to prevent one Covid19 infection, both in general and for age and comorbidity subgroups
    • Number Needed to Treat (NNT), or instead, Number Needed to Vaccinate
    • Safety of the vaccines
    • What is an mRNA vaccine
    • What do we still not know / and does it matter?
    • Conclusion and what to expect from other vaccine trials

     

    Contact us at email: podcast@precision-evidence.com,

    Twitter @PrecisionEBM,

    website: www.precision-evidence.com

    Hosts:

    Dr. Kim Kristiansen, M.D: @KKristiansenMD

    JG Staal: @HealthyEvidence

     

    Music thanks to mixkit.co 

     

     

     

     

     

     
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    14 mins