Transcript 17-How to write a study protocol_2011

How to write a study protocol
Viviane Bremer
EPIET, Lazareto, Menorca
September 2011
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What is the study protocol?
• Every step of a study
• Answers relevant questions
- public health problem important?
- study question relevant to problem?
- objectives consistent with study question?
- study design achieves objectives?
- sufficient power?
- public health impact of the findings?
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Why write a study protocol?
• Check
- if objectives can be achieved
- feasibility of the study
• Prevent failure to collect crucial information
• Lays down the rules for all partners (quality)
• Obtain approval of ethical committee(s)
• Application for funds
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Study protocol
How to start ?
• Formulate the research question
• Get
– good examples of protocols
– ideas from similar published studies
– ideas from colleagues
• Use a checklist of items to include
• Get the requested format
(grant application)
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Protocol outline
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Presentation
Background and justifications
Objectives
Methods
Ethical considerations
Project management
Timetable
Resources
References
Appendices
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1. Presentation
• Title
– short, accurate, concise
•
•
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Investigators
Main centres
Steering committee (scientific board)
Summary of the protocol
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2. Background and justification
• Statement of problem, study justification
 importance of subject area
• magnitude, frequency
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gaps in existing knowledge
principal questions to be addressed
contribution of results to existing knowledge
use of results
dissemination of results
• Review relevant literature
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3. Objectives
• Should answer the study question
• Should be S.M.A.R.T.
– Specific
– Measurable
– Achievable/Accessible
– Realistic/Relevant
– Time-based/Timely
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3. Objectives
Principal objective
• Must be achieved
• Dictates design and methods
Secondary objectives
• Of interest, but not essential
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Hypotheses
• Translation of the objectives
in terms that allow statistical testing
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3. Objectives
example
• Non S.M.A.R.T objective
– To identify risk factors for HCV infection
Principal objective
• To determine if sharing a haemodialysis machine with
a HCV infected patient
is a risk factor for HCV infection
Secondary objective:
• To identify failures in procedures
designed to prevent cross-infection
via haemodialysis machines
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Hypothesis
“The incidence of HCV infection in
haemodialysis patients is higher in patients
sharing machines with HCV infected patients
than in patients not sharing machines with
an HCV infected patients”
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Protocol outline
1. Presentation
2. Background and justifications
3. Objectives
4. Methods
5. Ethical considerations
6. Project management
7. Timetable
8. Resources
9. References
10. Appendices
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4. Methods
• Procedures to achieve objectives
– what will be done?
– how?
• Information used to judge validity
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4. Methods
• Study design
 cohort, case control, cross-sectional…
 brief justification
• Study population
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definition
selection
criteria for inclusion and exclusion
mechanisms of recruitment
accessibility, follow-up, representativeness
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4. Methods
• Sampling design (ref: lecture sampling)
 frame: district, household, persons,…
 method: random, cluster, stratified,…
 randomisation procedures
 replacement procedures (in case of refusal)
• Sample size (ref: lecture sample calculation)
 sample size, power calculations
based on principal objective
 feasibility
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Sample size
e.g. Options for case-control study on sporadic campylobacter
and food exposure
Prevalence
of exposure
among
controls
Case:
control
ratio
Alpha
error/
power
Odds
ratio to
detect
Number
of
cases
Number
of
controls
10%
1:2
5%/ 80%
2
223
446
10%
1:2
5%/ 80%
3
81
162
10%
1:2
5%/ 80%
4
48
96
10%
1:2
5%/ 80%
5
34
68
10%
1:2
5%/ 80%
6
27
54
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4. Methods
• Selection and definition
 exposures:
risk factors, protective factors, confounding factors
 outcomes:
definition of case, of control group
• Items to be measured
– scales used
• e.g: legionella <=> car driving
- Driving exposure: definition, quantification, categories
- Legionella infection: case definition, control group definition
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CC study of sporadic cases
of Salmonella Enteritidis infections
• Exposure
– consumption of custard
• Case
– a person living in South-West Wales with
a laboratory confirmed infection due to S. Enteritidis
in June and July 2011
• Case finding
– through Public Health Laboratory; weekly notifications
• Control
– persons living in SW Wales
in same neighborhood as cases
• Control finding
– random selection of people using telephone directory
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Methods
Data analysis plan
• Structured in terms of objectives
• Hypotheses tested, dummy tables
 Comparison of groups
 risk factors
 protective measures
 Assessment of dose-response relationship
for key exposures
 Assessment of possible confounding factors / effect
modifiers
• Statistical tests used, adjustment, stratification
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Methods
Data analysis plan
• Define
– indicators you will need to reach objectives
– data you will need to collect
• Better estimates of sample size for analysis
of sub-groups
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Methods
Data analysis
Dummy table:
Food specific attack rates of Salmonella infection
in a day care centre, Paris, May 2009
ill
n
total
n
AR
%
RR
95%CI
ice-cream yes
ice-cream no
fruit cake yes
fruit cake no
pudding
pudding
yes
no
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4. Methods
Data collection
• How
 interview, observation, record review
• By whom
 interviewers: selection, training
 level of supervision
• Tools (ref: lecture “questionnaire design”)
 questionnaires, recording materials
 questionnaires: self or interviewer administered,
face-to-face or telephone interview
• Blind data collection
• Procedures for taking samples
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4. Methods
Data handling
• Coding (anonymisation)
 during data collection, afterwards?
 by whom?
• Processing
 software, hardware
 entry
• during the study, afterwards?
• single entry, double entry?
• Validation and data cleaning
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4. Methods
Pilot studies, pre-testing
• No study without pre-test
 Feasibility of sampling
 Data collection, measurement methods
 Questionnaire
• Describe how to test
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4. Methods
Limitations
• Identification of potential sources of biases
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selection bias
information bias
misclassification bias
interviewer bias
• How to deal with them
 possibilities for correcting
 how they will affect the results
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Protocol outline
1. Presentation
2. Background and justifications
3. Objectives
4. Methods
5. Ethical considerations
6. Project management
7. Timetable
8. Resources
9. References
10. Appendices
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5. Ethical considerations
• Informed consent
– translated in local lay language
• Confidentiality
– coding data collection instruments
without identifier
• Data storage and protection
• Ethics committee
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6. Project management
• Participating institutes and persons
• Responsibilities and tasks of each partner
• Data ownership
• (Authorship)
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7. Timetable
Planning/organisation of the study
• questionnaire design, recruitment, purchases
• permission
• obtain funding
Pilot study
• time to do adjustments
Final study
• data collection
• analysis
• presentation of results and write up
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8. Resources
• Extent of this section depends
on target audience
• Specify
 available sources
 requested sources
• Keep budget
 reasonable
 detailed
 well justified
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9. References
• Limit number of references to key articles
• Follow recommended style
• Vancouver
www.library.soton.ac.uk/infoskills/vancouver.shtml
www.transfusion.ca/new/bulletin/vancouver-style.html
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10. Appendices
• Methodological appendices
• List of definitions
• Questionnaires
• Introductory letters to study participants
• Informed consent forms
…..
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Common problems
• Too ambitious: too many questions
• Insufficient attention to literature
• Poor justification
 why is it important to answer this question?
 what impact does it have on public health?
• Poorly formulated objectives
• Inappropriate analysis
• Inadequate description
• Absence of pilot
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Your task next week
• Create a study protocol in small groups
• Present it to the plenary
• Read the references during the weekend