Journal Club (méthodologie) Introduction à la lecture d’articles médicaux (Partie 1)
Introduction à la lecture d’articles médicaux
Dr. Ioannis KOKKINAKIS
Chef de Clinique Adjoint
Service de Médecine Interne - Hôpital du Valais – Sion
23.03.2017
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Qu’est-ce qu’on va voir …
• 1. Types d’études
• 2. Grille de Lecture pour ERC
• 3. Autres Grilles des Lecture
• 4. Recommandations Int.
• Une prochaine fois…
– Types d’études en detail
– Statistiques d’études
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Classification - Clinical Trials
Phase I relates to the safety of the drug under
investigation in healthy volunteers. The aim is to
establish the appropriate doses of a drug to be
investigated in later trials and understand how the
drug is dealt with in the body.
Phase II usually involves a small (usually randomised)
trial investigating the potential benefits of a drug
among patients with a particular disease. These trials
are also used establish which therapies have the
potential to be investigated in full-scale, phase III
randomised trials.
Phase III trials are full-scale randomised controlled
trials evaluating the benefits of a drug against a
placebo or standard therapy in a substantial number of
patients. This is the key stage in establishing the
impact of a drug
Phase IV relates to the stage after a drug has been
approved and involves the long-term monitoring of the
safety of the drug. It sometimes refers to the
marketing process by which the drug is brought to the
attention of a large number of medical practitioners.
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Rev Mal Resp 2002, 19, 505-514
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Rev Mal Resp 2002, 19, 505-514
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Notre Grille de Lecture (SSMI)
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Validité des résultats
Méthodes
Validité interne
– Qualité méthodologique des essais
– Fiabilité
Validité externe
– Pertinence
– Generaliser?
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Allocation au traitement – randomisée?
A trial needs to be….
Controlled
– Any intervention needs to be compared to
one or more other interventions. This is often
a new treatment compared to standard
treatment. In drug therapy trials there will
often be a placebo control.
Unbiased
– There needs to be a fair comparison
between the treatments with no bias,
whether deliberate or accidental
– Randomisation is crucial: patients are
randomly allocated to a particular treatment
group.
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Follow up complet ?
Adjustments to Sample Size Calculations
Patients who are lost to follow up
Multiply the required sample size by 1/(1−Q)
where Q is the proportion expected to be lost to
follow-up.
Patients who receive the alternative
treatment
Multiply the required sample size by
where Q1 is the proportion in group 1 getting the
treatment for group 2, and Q2 = proportion in group 2
getting the treatment for group 1.
Patients who stop treatment
Multiply the required sample size by 1/(1-Q)2
where Q is the proportion on the active therapy who
stop taking their medication.
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Analyse finale?
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ITT vs PP
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As treated analysis
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Double aveugle?
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Groupes comparables?
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Intérêt pour P value?
March 17, 2017
DOI: 10.1056/NEJMoa1615664
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Groupes traités de la même manière ?
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http://www.consort-statement.org
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Resultats – Importance de l’effet
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March 17, 2017
DOI: 10.1056/NEJMoa1615664
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Précision de l’estimation
A trial needs to be…
Large
– Patients vary considerably in their
response to treatment. In order to
obtain a precise estimate of any
treatment effect, sufficiently large
numbers are require
de l’effet
du traitement?
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March 17, 2017
DOI: 10.1056/NEJMoa1615664
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p-value
the probability (ranging from 0 to 1) that the results observed in a trial
(or results more extreme) could have occurred by chance if the null
hypothesis is true. Therefore the smaller the p-value, the less likely the
null hypothesis is to be true. For example, a p-value=0.0001 indicates
the null hypothesis is very unlikely to be true whereas a p-value=0.53
indicates the observed results could easily have arisen by chance
Confidence interval
A confidence interval is an interval, constructed around an estimate from a
sample (e.g. the estimate of the size of effect of an intervention), that indicates
the uncertainty in the estimate because it was obtained from a sample. If
independent samples are taken repeatedly from the same population, and a
confidence interval calculated for each sample, then for example 95% (the
confidence level) of the intervals will include the unknown population parameter
95% of the time. Confidence intervals can be for other values e.g. 90%, 99%,
99.9%.
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Consider what conclusions you can draw from the table
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Résultats – applicables à mes patients?
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Inclusion/exclusion criteria
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Sample characteristics
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Autres issues importantes sur le plan clinique ?
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Bénéfices – risque/coût ?
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Autres types d’études ?
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Guidelines internationaux?
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fiabilit
http://
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Guidelines internationaux?
Consolidated Standards of Reporting Trials
– Premì re version en 1996 rédigée par le Groupe CONSORT, un panel
d’experts en méthodologie des essais cliniques
– Dernière version 2010
Objectifs du CONSORT
– Standardiser le contenu des articles traitant des essais thérapeutiques
randomisés en groupes parall̀ les
– Permettre une lecture critique des articles publiés: évaluer la
et la pertinence des résultats (validités interne et externe)
– Améliorer la méthodologie des essais cliniques
www.consort-statement.org
é
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http://www.consort-statement.org
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CONSORT 2010 checklist
http://www.consort-statement.org
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http://www.consort-statement.org
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Merci de votre attention …
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Further reading - bibliography
Text books
Wang D, Bakhai A. Clinical Trials: A Practical Guide to Design, Analysis, and
Reporting. London: Remedica; 2006. Chapter 1
Reviews
Pocock SJ, Stone GW. N Engl J Med 2016;375:861-870 and 971-979
NEJM:
http://www.nejm.org/page/clinical-trials-series
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http://www.nejm.org/page/clinical-trials-series
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Is the size of trials important?
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