Академический Документы
Профессиональный Документы
Культура Документы
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Protocol is essentially….
a written plan of the study
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Protocol defined
ICH GCP 1.49
A document that describes the objective(s), design,
methodology, statistical considerations and
organization of a trial.
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Example of Research Protocol
Title of Project
Statement of Problem
Relevance of problem
Literature review
Statement of Objectives
Outcome variables
Statement of research hypothesis
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Health Research Methodology: A Guide for Training for Research Methods, WHO 2001
Research Methodology
Summary
Research Design – Research strategies & setting
Sampling
Use of controls
Study instruments
Short description of plans for data collection
Analysis and interpretation plan
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Health Research Methodology: A Guide for Training for Research Methods, WHO 2001
More Examples
1. TITLE PAGE
2. INVESTIGATORS AND STUDY
ORGANISATION
3. SIGNATURE PAGE
4. SYNOPSIS
5. TABLE OF CONTENTS
6. LIST OF ABBREVIATIONS
7. GLOSSARY OF TERMS
8. INTRODUCTION and BACKGROUND
9. OBJECTIVES
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ICH E6: Good Clinical Practice, Chapter 6
10. STUDY DESIGN
11. STUDY POPULATION & SUBJECTS
12. STUDY TREATMENT
13. ASSESSMENT OF EFFICACY
14. ASSESSMENT OF SAFETY & AE
15. CLINICAL ECONOMICS
16. STUDY CONDUCT
17. DATA MANAGEMENT
18. STATISTICAL METHODS
19. ETHICS & REGULATORTY
20. ADMINISTRATIVE MATTERS
21. REFERENCES
22. APPENDIX
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ICH E6: Good Clinical Practice, Chapter 6
2. Why a protocol?
Can’t we do without it?
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1. Justification
All research requires justification.
The protocol is testimony to the fact that the
investigators have sufficiently thought through the
proposed research concerning its justification,
scientific quality and ethical propriety.
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ICH GCP on trial justification
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2. Evaluation
All research requires review by both external and
internal parties.
The protocol provides the basis for review.
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Protocol reviewers
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4. Blueprint
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People involved
Many professions are involved in
Implementation:
1. CRA
CRF development and data collection mechanism, monitoring
convention.
2. CDM
data definition, database development, query generation
3. Site coordinator
site management, data collection, specimen/material handling etc
4. Statistician
randomisation, data monitoring, analysis
5. Investigator
techniques, schedule
6. Reference centres
techniques, schedule.
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3. How to write a protocol? Protocol
development
A protocol is a joint product of the different
professions involved
The best way to write an impressive protocol is to
“copy” another one.
Must have SOP and follow guideline.
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Protocol development- 1
1. TITLE PAGE
Protocol #
Author
Protocol Date
Amendment # and Date
Author’s and Reviewer’s signature and date
3. SIGNATURE PAGE
4. SYNOPSIS
5. TABLE OF CONTENTS
6. LIST OF ABBREVIATIONS
7. GLOSSARY OF TERMS
Definition of common and technical terms
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Protocol development- 3
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Protocol development- 4
9. OBJECTIVES
A. Primary question: the major question the investigators
are most interested in.
B. Secondary or subsidiary questions :
relate to subsidiary end points.
relate to subgroup hypotheses eg other than overall
contrast between each arm of trial.
C. Ancillary questions: questions that do not bear
directly on the intervention being tested but which are
nevertheless of interest; eg. natural history of disease
in the control group, risk factor analysis.
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Protocol development- 5
10. STUDY DESIGN
Study design, # patients & Duration
Schematic diagram of study design
Rx group
Control group
Discussion of study design: Justify decision
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Protocol development- 6
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Protocol development- 7
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Protocol development- 8
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Protocol development- 9
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Protocol development- 10
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Flowchart
Screenin Baseline PCI In Follow Follow Final
g hospital up up visit
Visit 1 2 3 3 4 5 6
Check eligibility X
Medical History X
Vital sign X
Efficacy assessment X X X X X
CompletePharmasri
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X X X X X X X
Protocol development- 12
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Protocol development- 13
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Protocol development- 14
21. REFERENCES
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Protocol development- 15
22. APPENDIX
A. DECLARATION OF HELSINKI
B. STUDY PROCEDURES
C. QUESTIONNAIRE and CRF
D. INVESTIGATIONAL PRODUCT LABELS
E. ELEMENTS OF INFORMED CONSENT
F. SAMPLE INFORMED CONSENT FORM
G. PATIENT INFORMATION SHEET
H. LETTER OF INDEMNITY
I. INVESTIGATORS’ CURRICULUM VITAE
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Case 1: To blind or not to blind
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Case 3: P value and p value
A trial was designed to compare the effect of a new
drug A, the standard drug B and placebo P. The p value for
treatment effect of A versus P was 0.001, for B versus P was 0.02 and for A
versus B was 0.45.
Questions for discussion
a) What is your take on the above results?
b) Drug A is efficacious?
c) Drug B is also efficacious?
d) There is no difference in treatment effect between drugs A and B in
that study?
e) However, since the p value for A vs P is much smaller than p value
of B vs P, A is likely to be more efficacious than B, though of
course the study did not show that?
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Case 4: It is not always possible to trial
Smoking is suspected to increase the risk of certain indolent
benign cancer (patients with the cancer don’t die quickly). The
best design is to randomise subjects to smoking or non-smoking, then follow
them up for many years to determine occurrence of the cancer. This is clearly
not ethically acceptable, even if one could afford to do the trial.
Questions for discussion
To address the above question, discuss the following design options:
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