Journal Club (méthodologie) Introduction à la lecture d’articles médicaux (Partie 4)  

Journal Club (méthodologie) Introduction à la lecture d’articles médicaux (Partie 4)
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Introduction à la lecture d’articles médicaux (4)
« How to Read a Clinical Trial Paper »
Dr. Ioannis KOKKINAKIS
Chef de Clinique
Service de Médecine Interne - Hôpital du Valais Sion
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05.10.2017

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Qu’est-ce qu’on a déjà vu?
1. Grille de Lecture pour ERC
2. Autres Grilles des Lecture
3. Recommandations Int.
4. Types d’études
5. Etudes observationnels
6. Etudes expérimentales
7. Métanalyses
8. Rappel courte de la grille de lecture
9. PICOTS
10. Consort Statement
11. Rappels statistiques de base
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Lien pour télécharger les présentations:
https://www.dropbox.com/sh/
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?dl=0

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Qu’est-ce qu’on va voir …
Comment lire un article médical
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Les pièges à éviter

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380258/

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Are These Subjects Like My Patients?
Subjects in the study are representative of the patients a
clinician sees in his practice?
Were the study subjects sicker, or did they have more
complicated disease?
Did they fail more prior medications?
Did they have longer disease durations?
Shail, Higgins, Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

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Recruitment methods also influence the make-up of the study population and
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can lead to different response rates.
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Shail, Higgins, Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

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Oxygen Therapy in Suspected Acute Myocardial Infarction N Engl J Med 2017; 377:1240-1249
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Never mesure p-value for the baseline characteristics

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Multiplicity of analysis

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Acute
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What Happened to the Subjects?
Did They Drop Out? Why?
Reasons drop out:
Lack of benefit (they were too sick
to stay in the study)
Side effects (which made them
want to leave the study)
Personal beliefs
Bias
Oxygen Therapy in Suspected
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Myocardial Infarction N Engl J Med 2017; 377:1240-1249

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http://www.consort-statement.org

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Is the Study Design Biased?
Focus:
Comparator group
Allocation of subjects to treatment arms
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Blinding
Comparator: standard-of-care therapy.
Functional disease states: placebo group and/or a comparator that has
proven to be effective (placebo effect measured)
Studies of rifaximin (Xifaxan, Salix Pharmaceuticals) versus placebo for
treatment of IBS,
32% of the placebo-treated patients - relief of symptoms
41% of subjects in the treatment arm
Without the placebo comparator, the effect of rifaximin on IBS symptoms
would appear quite large.
Shail, Higgins, Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

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Is the Study Design Biased?
Focus:
Comparator group
Allocation of subjects to treatment arms
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Blinding
CONSORT diagram should be easy to follow and similarly detailed for each
arm.
ALLOCATION CONCEALMENT
Investigators cannot anticipate which arm the next subject will enter.
If the investigators knew a very sick patient would be likely to receive
placebo, they could avoid enrolling that patient, which could result in biased
enrollment.
Randomization
population level
clustered at the site level (all the subjects at 1 site are in a single arm)
Shail, Higgins, Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

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Is the Study Design Biased?
Focus:
Comparator group
Allocation of subjects to treatment arms
Blinding
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Single-blind - subject unaware of the allocation
Doubleblind - investigators are also unaware of the patient’s allocation.
Patients who are aware of their intervention may have lower compliance,
prone to reporting bias.
Investigators who are aware of the intervention may overestimate a
treatment effect.
Studies comparing outcomes with and without blinding have shown a
significant overestimation of the treatment effect in studies conducted without
blinding
Shail, Higgins, Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

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Study investigators rarely report whether the blinding process was successful.
In a 2007 analysis of 1,599 studies, only 2% reported the success of the
blinding process; of those, almost half determined that blinding was
unsuccessful (ie, patients could determine or guess whether they were
receiving active drug or placebo)
If patients in a placebo-controlled trial can deduce that they are in the placebo
arm, they could be less likely to report improvement, leading to underestimation
of the placebo effect and overestimation of the relative treatment effect.
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Shail, Higgins, Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

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Does the Study Include an Intention-to-Treat Analysis?
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Per protocol analysis biais?

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Is This a Test of Superiority? Equivalence?
Noninferiority?
In cases where a new therapy is more convenient or cheaper, an equivalence
or noninferiority study can be appropriate.
The sample size needed to determine noninferiority or equivalence is always
much higher than the size needed to determine superiority.
If a study is initially designed to test for superiority but this outcome is not
found, switching to an equivalence study would be inappropriate for 2 reasons:
the acceptable difference would not have been defined in advance
the sample size would be too small.
Shail, Higgins, Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

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Other
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considerations
Does the Measurement Matter?
Is It Reproducible? Accurate?
Dichotomous Outcomes, Continuous Outcomes, Correlations, Time-to-Event
Endpoints
How Are Missing Data Addressed?
Nonresponder imputation: consider any subject who has missing data as
one who would have failed to meet the endpoint
Lastobservation-carried-forward approach
Imputation: other data are used to estimate what the missing data would
have been
Do the Design and Methods Conform to the Prestudy Protocol?
Protocol registration
How big the effect is?
NNT

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How to read systematic reviews and meta-analyses
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http://www.prisma-statement.org

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Systematic reviews and meta-analyses
http://www.prisma-statement.org

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Systematic reviews and meta-analyses
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http://www.prisma-statement.org

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Systematic reviews and meta-analyses
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http://www.prisma-statement.org

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Systematic reviews and meta-analyses
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http://www.prisma-statement.org

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Systematic reviews and meta-analyses
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http://www.prisma-statement.org

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Systematic reviews and meta-analyses
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http://www.prisma-statement.org

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Forest plot

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http://www.equator-network.org

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http://www.equator-network.org

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How to evaluate a trial protocol
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http://www.spirit-statement.org

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http://www.spirit-statement.org

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http://www.spirit-statement.org

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GCP - Good Clinical Practice

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Parfois les études peuvent avoir des résultats qui nous surprennent

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Merci pour votre attention

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Further reading
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http://www.nejm.org/page/clinical-trials-series
© LE PEILLET Damien, Olaf et parentés    
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