Study Acronym– Sponsor’s CodeVersion n°X.X of date
Version 1.0 du modèle de protocole
BIOMEDICAL DRUG RESEARCH PROTOCOL
Full length title of the study
Acronym(12 characters maximum)
Monocentric/ Multicentric study
Grenoble University Hospital (CHU de Grenoble)
Sponsor number: assigned by Easydore
EudraCT N°:
Inappropriate sections should be deleted.
COLOUR CODE
- HIGHLIGHTED IN BLUE: general instructions that must be deleted before issuing the final version of the protocol
- HIGHLIGHTED IN GREY: sections to fill-in and/or adapt for all types of study
Version N°X.Y- Date: DD-MMM-YYYY
Principal Investigator / Name and address of Principal InvestigatorSponsor / Grenoble University Hospital(CHU de Grenoble)
Department of Clinical Research and Innovation
Pavillon Dauphiné
CS 10217, 38043 Grenoble Cedex 09
This biomedical research has received funding from: source of funding
“This document the exclusive property of Grenoble University Hospital. It may not be copied, reproduced or transmitted, totally or partially, without written authorization.”
PRINCIPALSTAKEHOLDERS
Sponsor: / Grenoble University Hospital, Pavillon Dauphiné,CS 10217, 38043 Grenoble Cedex 09
Sponsor’s CRA:
Tel:
Fax: 04 76 76 52 21
eMail:
Principal Investigator / Family name, First name
Department
Grenoble University Hospital
Tel :
eMail:
Investigators / Family name, First name
Department
Grenoble University Hospital
Tel :
eMail:
Contact(s) investigator / Family name, First name
Department
Grenoble University Hospital
Tel :
eMail:
Person responsible for laboratory analyses / Family name, First name
Department
Grenoble University Hospital
Tel :
eMail:
All other services involved / Family name, First name
Department
Grenoble University Hospital
Tel :
eMail:
Pharmacy coordinator / Pharmaceutic supplier / Family name, First name
Department
Grenoble University Hospital
Tel :
eMail:
Clinical Research Vigilance / Edith SCHIR, Adeline PARIS, Marylaure GAVARD
CHU de Grenoble, Pavillon Dauphiné DRCI
Tel: 04 76 76 67 51
Fax: 04 76 76 83 54
eMail:
Methodologyand data management / Family name, First name
Department
Grenoble University Hospital
Tel :
eMail:
Page 1 of 47
Study Acronym– Sponsor’s CodeVersion n°X.X of date
Version 1.0 du modèle de protocole
HistorY OF protocol UPDATES
Mention only the final version submitted to the health authorities and later versions in case of amendments .
Version / Date / Reason for updateUpdate the table after completing the protocol
1SUMMARY OF THE RESEARCH
2SCIENTIFIC Justification and General DESCRIPTION OF the Research
2.1Current knowledge about the pathology
2.2Current knowledge about the drug
2.3Research hypotheses and expected results
2.4Benefit/risk ratio
2.4.1Benefits
2.4.2Risks
2.4.3Benefit/risk balance
2.5Expected Impact
3OBJECTIVES OF THE RESEARCH AND OUTCOMES
3.1Main Objective
3.2Primary Outcome/Endpoint
3.3Secondary Objectives
3.4Secondary Outcome(s)/ Endpoints
4Design/methodology of the study
5Eligibility criteria / Subject cHaractEristics
5.1Inclusion criteria
5.2Non-inclusion criteria
5.3Allowed treatment(s)/procedure(s)
5.4Method(s) of recruitment
6TREATMENT(S) USED IN THE STUDY
6.1Treatment(s) used in the study
6.2Reference treatment/placebo
6.3Drug / Product circuit
6.3.1Source of products
6.3.2Pharmacy circuit
7STUDY Procedure
7.1Provisional study calendar
7.2Course of study visits
7.3Summary of visits
7.4Pre-selection visit
7.5Sélection visit
7.6Inclusion visit
7.7Follow-up visits
7.8End of study visit
8PARAMETERS to be MESUREd and Measurement methods
8.1Clinical parameters
8.2Para-clinical parameters
8.3Laboratory Paramèters
8.3.1Parameters to be measured and methods used
8.3.2Labelling
8.3.3Site of analyses
9COLLECTION of biological samples
10PHARMACOVIGILANCE AND SAFETY
10.1Définitions
10.1.1Adverse Event (AE)
10.1.2Adverse Drug Reaction (ADR)
10.1.3Unexpected Adverse Drug Reaction (UADR)
10.1.4Serious Adverse Event or Reaction (SAE)
10.1.5Causality
10.1.6Severity
10.2Reference documents
10.3Responsibilities
10.3.1Responsibilities of the Investigator
10.3.2Responsibilities of the Sponsor
10.4Procedures and delays in reporting by the investigator
10.4.1Reporting procedure
10.4.2Reporting period
10.5Specific features of the protocol
10.5.1Reportable related adverse events/ Adverse events of special interest (AESI)
10.5.2Expected serious events and/or reactions
10.5.3Expected non-serious events
10.6Independent Data and Safety Monitoring Board
10.7In utero exposure
10.8Annual safety report
10.9Optionaltext
11DATA MANAGEMENT AND STATISTICAL ANALYSIS
11.1Collection and protection of data
11.2Calculation of number of subjects needed
11.3Randomization
11.4Statistical methods
12BLINDING
12.1Organization of blinding
12.2Unblinding
13Study stopping rules
13.1Study stopping criteria for a participating subject
13.2Early discontinuation of the experimental procedure by the subject
13.3Study stopped by the sponsor
13.4Study stopped by the investigator
13.5Inconveniance/constraints of the study and possible compensation of subjects /patients
14Rights of ACCESS to data and SOURCE documents
14.1Accèss to data
14.2Source data
14.3Confidentiality of data
15QUALITY CONTROLE and assurance
15.1Instructions for data collection
15.2Quality contrôl
15.3data management
15.4Audit and inspection
16ETHICAL and REGULATORY CONSIDERATIONS
17Archiving
18PUBLICATIONs
18.1Scientific communications
18.2Communication of the results to the subjects
18.3Cessation of the database
19References
20APPENDICES
PROTOCOL SIGNATURE PAGE
«Protocol title»
Acronym
This protocol was reviewed and approved at the date noted in the header.
The two parties undertake to carry out the research according to the protocol and the legislative and regulatory provisions
Principal Investigator
Title and name of investigator
Department
Sponsor: Grenoble University Hospital
(CHU de Grenoble)
Represented by:
Mme Hélène SABBAH-GUILLAUME
Director of Research and Partnerships
Department of Clinical Research and Innovation
List OF abrEviations Please check this list when you have finished writing your protocol
AESI / : / Adverse event of special interestANSM / : / Agence Nationale de Sécurité du Médicament et des produitsde santé= French health Authority for the Safety of medicines and health products
AMM / : / Autorisation de Mise sur le Marché = Marketing authorization
ATC / : / Classification Anatomique, Thérapeutique et Chimique = Anatomic, therapeutic and chemical classification
ARC / : / Attaché de Recherche Clinique = Clinical research assistant/ associate
BI / : / Brochure pour l’investigateur = Investigator’s Brochure
BPC / : / Bonnes Pratiques Cliniques = Good Clinical Practice
CCTIRS / : / Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé = Consultative committee on the treatment of information in Biomedical/Health research
CHU / : / Centre Hospitalier et Universitaire = University Hospital
CNIL / : / Commission Nationale Informatique et Liberté = National Commission on Informatiojn and Personal liberty
CPP / : / Comité de Protection des Personnes = Ethics Committee = institutional review board (IRB)
CRF / : / Case Report Form = Cahier d’observation
CSP / : / Code de la Santé Publique = Code of Public Health
CS / : / Comité Scientifique = Scientific Committee
CSI / : / Comité de Surveillance Indépendant = Independent Supervisory Board
DCI / : / Dénomination Commune Internationale = International Classiffication of Disease Code (ICD)
DM / : / Dispositif médical = Medical Device
DRCI / : / Délégation à la Recherche Clinique et à l’Innovation = Department of Clinical Research and Innovation
EI / : / Evènement Indésirable = Adverse Event
EIG / : / Evènement Indésirable Grave = Serious adverse Event
ICH / : / International Conference of Harmonization
MedDRA / : / Medical Dictionary for Regulatory Activities
MTI / : / Médicaments de thérapie innovante = Innovative therapymedicine
MTI-PP / : / Médicaments de thérapie innovante préparés ponctuellement = Innovative therapy medicine prepared punctually
PUI / : / Pharmacie à usage Intérieur = In house Pharmacy
RCP / : / Résumé des caractéristiques du produit = Product description
SPC : Summary of product characteristics / : / Summary of product characteristics
Page 1 sur 47
Study Acronym– Sponsor’s CodeVersion n°X.X of date
Version 1.0 du modèle de protocole
1SUMMARY OF THE RESEARCH
Title / Full title of the research studyShort title / Acronym
Investigateur principal / Name of principal investigator
Sponsor / GRENOBLE UNIVERSITY HOSPITAL (CHU de GRENOBLE)
Justification / context / Brief summary (scientificbackground, pathology, field of study)
méthodology / Type of study: retro/prospective study, mono/multicentric, controlled or not, randomized or not, open single/double blinded, case-control, cohortetc.
Principal objective / Principal objective of the study
Principal outcome/endpoint / Main outcome/endpoint
Secondary Objective(s) / Secondaryobjective(s) of the study
Secondary outcome(s)/endpoint(s) / List all the secondary outcome(s)/endpoint(s)
Inclusion criteria / List all the inclusion criteria
Non-inclusion criteria / List all the non-inclusion criteria
Conduct of the research / Brief description of the treatments/strategies/procedures
Number ofsubjects / Total number of subjects
Number ofcenters / Mono/multicentricstudy (XX centers)
+ List of centers participating in the study(Name of investigator + name of site)
provisionalcalendar of the study / Length of the inclusion period:
Length of treatment:
Length of participation of each subject:
Total length of the study:
Statistical analysis / Summary of the statistical methods
Expected impact / Describe the expected impact/benefits of the research
2SCIENTIFIC Justification and General DESCRIPTION OF the Research
2.1Current knowledge about the pathology
Description of the interest of the study in the context of current knowledge about the pathology.
The argument must be based primarily on indexed publications and pertinent data.
This justification should answer the following questions:
- What is the current state of knowledge about the disease (epidemiology of the disease to be treated with frequency and seriousness)
- Description of the study population
- Present treatment(s) of the pathology, if there are any
- What will be the strategy in the study? (please describe it)
- What is the purpose of the study?
- In what way is it new ?
2.2Current knowledge about the drug
Description of the interest of the study in the context of current knowledge about the pathology.
The argument must be based primarily on indexed publications and pertinent data.
This justification should answer the following questions:
- Description of the drug and its mode of action
- Description of its pharmacological interest and/or pharmacokinetic interest?
- What are the existing strategies and their functioning? What are their limits?
- What are the results of preclinical research?
- If the research concerns a drug, specify and justify the choice of conducting the research on healthy volunteers or on patients
2.3Research hypotheses and expected results
Precisely describe the hypothesis, physiopathological or other, which justifies the research, mentioning the treatment / the strategy / the procedure in the study, the target population (justify the choice of conducting the research on healthy volunteers/patients) and the criterion on which it will be judged.
2.4Benefit/risk ratio
2.4.1Benefits
Benefit(s) for the individual:
What will be the possible benefit for the subject? How will it be evaluated?
Group(s) Benefits:
If applicable, what are the expected benefits to society over current therapeutic methods?
2.4.2Risks
Risk(s) to the individual(s)
What are the risks related to the research for the subject? Are they serious?
What is their frequency?
Describe the risks linked to the treatment and to the study (1 or 2 maximum, the rest should appear in the “vigilance” chapter).
2.4.3Benefit/risk balance
Show how the benefit/risk balance is positive for the subject.
2.5Expected Impact
Give a detailed description of the expected benefits of this research.
3OBJECTIVES OF THE RESEARCH AND OUTCOMES
3.1Main Objective
The main objectivestems from themain hypothesis whichthe researchmust answer.This objectivemust be unique,simple and specificto the research;
Itmustbriefly describe:
-The study population,
-Whether it is an evaluationor a comparison,
-The timing oftheevaluation or comparison of the maincriterion,
- The treatments to be compared, ifapplicable.
3.2Primary Outcome/Endpoint
The main evaluation criterion or primary outcome must be clearly defined as it is using this criterion that the objective will be measured and it is on this tthat the statistical analysis depends.
It must be relevant to the main objective, direct, accurate, reproducible, and easy to collect.
Prefer a clinical endpoint, that is to say, a measure expressed in terms of quantity or quality of life; it is the measure by which we choose to evaluate the main objective to be assessed.
This criterion can be defined as:
- Quantitative variables (a numeric value (specify the units), mean, median etc.) or qualitative (response or not, success or not etc.)
- Tests/ procedures/methods of measurement, questionnaires to assess variables
- The conditions for the collection of this variable: time, frequency of collection
etc.
- Perhaps a single criterion or a combined one, if necessary
The characteristics of this variable (described in publications or in a previous study) will enable one to calculate the number of subjects needed for the research.
3.3Secondary Objectives
There may be several secondary objectives. They aim to document the main objective. They can correspond to exploratory or complementary analyzes of the main objective which will be tested later as part of a new biomedical research protocol.
They do not allow one to draw conclusions.
For each secondary objective, as for the main objective, one must specify:
- The study population,
- Whether it is an evaluation or a comparison,
- The timing of the evaluation or comparison,
- The treatments to be compared, if applicable.
3.4Secondary Outcome(s)/ Endpoints
List the secondary outcomes/endpoints that will meet the secondary objectives.
For each criterion, define:
- Quantitative variables (a numeric value (specify the units), mean, median etc.) or qualitative (response or not, success or not etc.)
- Tests/ procedures/methods of measurement, questionnaires to assess variables
- les conditions for the collection of these variables: time, frequency of collection
- etc.
4Design/methodology of the study
Describe the characteristics of the research using standard terms:
-Drug study (phase I, II, III, IV)
-Therapeutic / diagnostic / pronostic / experimental / determination of risk factors or etiological study
-Prospective / retrospective
-Randomized or not randomized
-Comparative or not comparative
-Open / single blind/ double blind
-Monocentric / multicentric
-National / European / International
Justify the choice of design.
5Eligibility criteria /Subject cHaractEristics
5.1Inclusion criteria
Criteria for the study population: age, sex, weight, lifestyle etc
- Criteria for diagnosis of the pathology: clinical signs and/or examinations needed to for diagnosis, clinical forms of the disease, etc.
- Severity criteria and progression of the pathology: stage(s) of the disease, clinical signs and/or examinations required to determine its stage of advancement etc.
- Criteria for treatments / strategies / procedures: criteria for compulsory previous treatments, current treatments, etc
- Criteria relating to the regulations: procedure for obtaining consent(adults, unemancipated minors, persons unable to give consent, research in emergency situations etc.), affiliation to a social security/health insurance system, entry in the national register of persons participating in biomedical research, etc.
Δ! A list that is too exhaustive can lead to difficulties in recruiting subjects, restrictive criteria should be justified (eg; no women, age limit etc.)
5.2Non-inclusion criteria
-Criteria concerning the population studied: age, sex, weight, lifestyle etc.
If women can be included, specify that they must not be pregnant or nursing.
The minimum age for inclusion must be 18 years unless it is not possible to conduct the research without including minor and in this case justify it.
-Criteria related to the pathology: stage and/or disease characteristics, etc.
- Criteria related to associated pathologies that could give rise to particular risks: known allergy to a drug, coagulation disorders when the treatment is injectable, previous pathology or pathology in progressiondisallowing the inclusion of the subject etc.
- Criteria related to contra-indications to one or other of the treatments / strategies / procedures studied:known allergy to a drug etc. you should list the cons-indications detailed in the SPC if treatment used is commercially available
- Criteria related to contra-indications to the examinations required by the protocol: coagulation disorders in case of invasive procedure, MRI etc
- Criteria related to treatments/procedures: period during which a treatment must have been stopped before the run-in phase, prohibited previous therapies, prohibited ongoing/associated treatments, foreseeable poor adherence to treatment/strategy/procedure, etc.
- Prohibited treatments and procedures:Define precisely the associatedtreatments/procedures that are forbidden as they may bias the study.
- Subject in exclusion period of another study,
- Subject under administrative or judicial control
- Subject who would receive over 4,500 euros in compensation due to their participation in other biomedical research in the 12 months prior to the study, if applicable
- Subject who cannot be contacted in an emergency
-Subject in exclusion period of another study,
-Subject under administrative or judicial control
-Subject who would receive over 4,500 euros in compensation due to their participation in other biomedical research in the 12 months prior to the study, if applicable
-Subject who cannot be contacted in an emergency
5.3Allowed treatment(s)/procedure(s)
Precisely define the allowed associated treatments/procedures, the circumstances and the terms of administration/implementation: treatments causing no cons-indication with the proposed study etc
5.4Method(s) of recruitment
Describe how subject recruitment is planned (consultations, hospitalizations, doctor network, patient files, advertisements, etc.) so as to demonstrate the feasibility of the study in terms of the recruitment of subjects.
Specify the departments from which recruitment will be made, the average number of subjects/patients available for inclusion per month or year in each center, the expected period of inclusion and procedures for determining the expected inclusion rate.
6TREATMENT(S)USED IN THE STUDY
6.1Treatment(s) used in the study
For each study treatment it is necessary to describe:
Name ofdrug/treatment and trade name, if applicable:XXX
Pharmaceutical form:XXX
Doseper administration:XXX
Number of tablets/capsulesperadministration: XXX
Specify the potential status of orphan drugs.
Do not forget to attach the SPC, if applicable, to this protocol.
Provide the operating procedure for preparing the treatment (if applicable)
6.2Reference treatment/placebo
For each reference treatmentor for the placebo it is necessary to describe:
Name of drug/treatment and trade name ,if applicable:XXX
Pharmaceutical form:XXX
Dose per administration:XXX
Number of tablets/capsules peradministration: XXX
Specify the potential status of orphan drugs.
Do not forget to attach the SPC, ifv applicable, to this protocol.
Provide the operating procedure for preparing the placebo (if applicable)
6.3Drug / Product circuit
6.3.1Source of products
State who will supply the product and the name of the participating pharmaceutical company.
Specify when orders of the product are to be made and by whom.
Give the terms of reprovision.
6.3.2Pharmacy circuit
A)Product reception
Who receives the product; who should they notify and how?
B)Product conditioning
Specify the type of packaging (blister, pill box, boxes, etc)
Specify who does the packaging.
C)Product labels and batch release
Study (Short title)
N°EudraCT: XXXXX
Coordinating Investigator: Dr/ Pr. XXXXX, Center n° X
Sponsor: Grenoble University Hospital
Product ( trade name®) x mg/mL or Placebo: XXX mL solution
Référence DCI: XXXXX
Route of administration: XXXXX
Subjectrandomization N°: Subject’s initials:
(Preparation made the: at (hour)/ Expires the: at (hour)
Batch N°:
Dispensed: Administered: at (hour)
Expiry date:
Store between XXX and XXX
FOR CLINICAL TRIAL ONLY
Keep out of reach of children
Δ‼ Complete the label template according to the specific characteristics of the study treatment.
In this paragraph also specify: rules for the release of product batches (drugs, cell therapy products) by the pharmacist in charge: give the name and address of the pharmacy et attach the procedures that already exist (see the release procedure for ITD or ITD-PP)
D)Product shipping and management
Give the shipping terms for research in which a certain amount of product is expected and is to be sent to pharmacies before the inclusions start in the investigators’ centers.
Define who is responsible for accounting of the product, checking the expiry date and its storage in the recommended conditions.
State how the centers will be replenished
E)Product Dispensation
Describe the methods of dispensing products: global issue, nominative dispensation, etc.
Define the methods for monitoring compliance (accountingof capsules, analysis of questionnaires, etc.)
F)Storage
Define the product storage conditions on the center’s pharmacy and if needed in the clinical unit.
Storage conditions at the pharmacy and in the clinical service.