Boris Jung Critical Care Medicine Montpellier - Sep, 14Th 2018 - Research Protocols Implying Human Beings, Master biologie santé
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Research Protocols Implying Human Beings,
Constitution Of Collections Of
Human Biological Samples
Boris Jung
Critical Care Medicine
Montpellier
1
Sep, 14Th 2018
1.The timeline of a study design 2.The consent to human research 3.The specifics of human research in the critically ill 4.How to constitute a human biological collection
1.The timeline of a study design 2.The consent to human research 3.The specifics of human research in the critically ill 4.How to constitute a human biological collection
Fact
Idea
Literature check ;-)
Quantitative hypothesis
Measured Parameters
Population of Interest
One example: Acidemia
5
Berend Et Al, N Engl J Med 2014
Metabolic Acidosis Is Associated With Physiological
Disturbances
Kraut Et Madias, Nat Rev Nephro 2010
Idea
Sodium Bicarbonate
Good ? Bad ?
NS ?
Should We Administer Sodium Bicarbonate
Idea
To Correct Severe Metabolic Acidosis
8
1999 French GuidelinesSodium Bicarbonate is used in French ICUs to treat
Fact
severe metabolic acidosis
9
Jung Et Al, Crit Care 2011Idea
Sodium Bicarbonate
Good ? Bad ?
NS ?Ph < 7.20
MortalitY = 57%
2011
Jung Et Al, Crit Care 201112 Jung Et Al, Crit Care 2011
Literature check
Physiological Studies : Ns
Observational Studies : Controversial
Prospective Trial: NoneLiterature check
Inclusion Criteria
Exclusion Criteria
Design Of The Study
• Prospective Vs Retrospective
• Interventional Vs Observational
• Single Intervention Vs Bundle
• Randomized Vs Before-After
• Single Center Vs Multiple CenterQuantitative hypothesis: Main endpoint
1) Day 28 Mortality and/or
2) Number of patients with at least one organ
failure at D7 (defined by SOFA ≥ 3)
Hypothesis
Better outcome
=
More survivors at D28 and/or
less patients with at least 1 organ failure at D7“Number
Needed To
Treat”
http://marne.u707.jussieu.fr/biostatgv/?module=etudes/sujets#Lancet 2018; 392: 31–40
Methodology
Departement De L’information Clinique (Dim)
1. Methodological Help
2. Statistical Plan
3. AnalysisDifférents types de recherches
Recherche sur données
Pas d’accès à la personne Recherche prospective
- Recueil rétrospectif ou prospectif et l’exploitation de données issues
de dossiers médicaux ou d’autres bases de données avec un
- Echantillons biologiques
- Banque d’images
accès direct à la personne
- Bases médico-administratives
Recherches qui bien qu’organisées et pratiquées sur l’être
humain n’ont pas pour finalité la production de connaissances
biologiques ou médicales
- Produits cosmétiques
- Enquêtes de satisfaction du consommateur (produits cosmétiques
ou alimentaires)
- Enquête de satisfaction auprès des patients Etude
Etude Non
- Expérimentations en science humaine et sociale dans le domaine de Interventionnelle
la santé interventionnelle
- Évaluation des pratiques professionnels de santé ou pratiques 1° ou 2°
3°
d’enseignement dans le domaine de la santé (RIPH 1 ou RIPH 2)
(RIPH 3)
Recherches DM ou HPS Médicament
2° 1° 1°
Avis CPP
Avis CEREES MR003 (MR002) Avis CPP CPP + ANSM
(ex CCTIRS) ou CNIL MR001 ou CNIL MR001 ou CNIL
et/ou
Autorisation CNIL “Minimal “Significant
Risks” Risks”
Avis Comité d’éthique Avis Comité de Protection de Personnes (CPP)IRB = Institutional Review Board
(Comité de Protection des Personnes)
✦ Doctors, Nurses And Research Technicians With A
Strong Experience In Research
✦ People With An Experience In French Law
✦ People From Patients Associations
✦ With No Conflicts Of Interest With The Protocol
✦ Sometimes Experts Can Be Invited To Review The
Scientific Aspect Of The ProtocolIRB = Institutional Review Board
(Comité de Protection des Personnes)
✦ Examine The Scientific Content Of The Protocol
✦ Examine The Researchers’ Curriculum
✦ Examine The Information To The Patients Content
✦ Make Sure The Protocol Fits With French Law
✦ Check Whether Insurances, Declarations To The
Authorities Have Been Made
✦ Protects The Patients And The SocietySafety If The Research Involves Any Medication The Ansm Will Review The Protocol ✦ Safety ✦ Indication ✦ Surveillance Of Any Side Effect
Data Management ?
RGPD 2018
“Règlement Général sur la Protection des
Données à caractère personnel “Data Managment
RGPD 2018
“Règlement Général sur la Protection des
Données à caractère personnel “1.The timeline of a study design 2.The consent to human research 3.The specifics of human research in the critically ill 4.How to constitute a human biological collection
Patient’s CONSENT ✦ Information As Clear As Possible ✦ Need Time To Think Before Signing ✦ Can Be Retracted Anytime With No Consequences ✦ Formal Meeting Between The Investigator / Patient ✦ Study With Or Without Direct Clinical Benefit
Recherche prospective
avec un
accès direct à la personne
Etude
Etude Non Interventionnelle
interventionnelle 1° ou 2°
3° (RIPH 1 ou RIPH 2)
(RIPH 3)
Recherches DM ou HPS Médicament
2° 1° 1°
Avis CPP
MR003 (MR002) Avis CPP CPP + ANSM
ou CNIL MR001 ou CNIL MR001 ou CNIL
Non- Signed
Consent Consent
Opposition1.The timeline of a study design 2.The consent to human research 3.The specifics of human research in the critically ill 4.How to constitute a human biological collection
What Is Critical Care Medicine ?
✦ Patients With At Least 2 ‘Organ Failure” Or With 1
Organ Failure And At High Risk
✦ Often Needing Organ Suppleance (Mechanical
Ventilation, Dialysis, Heart Assistance…)
✦ Constant Monitoring
✦ Multiple Specialities (Cardiology, Nephrology,
Anesthesia,…)
✦ High Tech
✦ Mortality Ranges: 10-30%
!32Patients Often Unable To Consent To Research
Renal Replacement Mechanical Plasma Exchange
Therapy Ventilation Therapy
Multiples Drugs Nitric Oxide
Inhalation
!33Patient’s CONSENT in the ICU
LIFE THREATENING NON-LIFE THREATENING
CONDITION CONDITION
✦ Inclusion With No
Consent
✦ Need Efforts In Trying ✦ Inclusion Needs
To Reach The Patient’S Consent By LEgal
Legal Representative Representative
✦ Legal Representative ✦ Follow-Up Consent By
Consent Asap The Patient Asap
✦ Follow-Up Consent By (Sometimes Tricky…)
The Patient Asap
(Sometimes Tricky…)Différents types de recherches
Recherche sur données
Pas d’accès à la personne Recherche prospective
- Recueil rétrospectif ou prospectif et l’exploitation de données issues
de dossiers médicaux ou d’autres bases de données avec un
- Echantillons biologiques
- Banque d’images
accès direct à la personne
- Bases médico-administratives
Recherches qui bien qu’organisées et pratiquées sur l’être
humain n’ont pas pour finalité la production de connaissances
biologiques ou médicales
- Produits cosmétiques
- Enquêtes de satisfaction du consommateur (produits cosmétiques
ou alimentaires)
- Enquête de satisfaction auprès des patients Etude
Etude Non
- Expérimentations en science humaine et sociale dans le domaine de Interventionnelle
la santé interventionnelle
- Évaluation des pratiques professionnels de santé ou pratiques 1° ou 2°
3°
d’enseignement dans le domaine de la santé (RIPH 1 ou RIPH 2)
(RIPH 3)
Recherches DM ou HPS Médicament
2° 1° 1°
Avis CPP
Avis CEREES MR003 (MR002) Avis CPP CPP + ANSM
(ex CCTIRS) ou CNIL MR001 ou CNIL MR001 ou CNIL
et/ou
Autorisation CNIL
Avis Comité d’éthique Avis Comité de Protection de Personnes (CPP)Advertising the Protocol
Nct02476253
The Protocol’s Abstract Is Declared On A Public Network
Before The First Patient Inclusion
The Full Extent Protocol And The Statistical Plan
Can Be Published In
Peer-Reviewed JournalsSteering Committee ✦ Independent Researchers With No Role In The Protocol ✦ Clinicians, Statisticians, (Pharmacologists) ✦ Interim Analysis ✦ Examine Safety Of The Study And Protocol Arms ✦ Avoid Futility ✦ Can Recommend The Study’s Interruption (Safety/Futility)
1.The timeline of a study design 2.The consent to human research 3.The specifics of human research in the critically ill 4.How to constitute a human biological collection
Biobank - Human samples • Human samples = cells, blood, plasma,…. • Aims of a biobank = Science
Biobank - Human samples ✦ Needs consent or non opposition (If “soins courants”) ✦ Needs declaration to Research Authorities / ARS ✦ Needs IRB/CPP approval ✦ If any potential risk related to patient sampling, need full approval and sometimes €€ compensation ✦ Can be an additional blood tube or even “rest of tubes” after routine of care phlebotomy ✦ Can need super-qualified skills to prepare and store the samples (ex: RNA)
Conclusion ✦ An idea is rarely that original but a non-sense protocol i useless and not ethic ✦ Checking the literature is a big issue in ethic assessment ✦ Methodology avoiding insufficient power is highly recommended ✦ Consent in the critically ill is not an easy process ✦ Several agencies, local and national watch the process
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