How to write a study protocol
EPIET, Lazareto, Menorca
September 2005
Study protocol
What is it?
• Describes every step of a study
• Answer 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?
Study protocol:
Why do it?
• Check
- can objectives be achieved?
- is study feasible?
• Ensure collect crucial information
• Lay down rules for all partners (quality)
• Obtain approval of ethical committee(s)
• Apply for funds
Study protocol
How to start ?
• Get
– good examples
– ideas from similar published studies
– ideas from colleagues
• Use a checklist of items to include
• Obtain requested format
(grant application)
Protocol outline
1. Presentation (cover page)
2. Background and justification
3. Objectives
4. Methods
5. Ethical considerations
6. Project management
7. Timetable
8. Resources
9. References
10. Appendices
1. Presentation
• Title
– short, accurate, concise
• Investigators
• Main centres
• Steering committee
• Summary of the protocol
2. Background and justification
• Statement of problem, study justification
importance of subject area
• magnitude, frequency
gaps in existing knowledge
principal question(s) to be addressed
contribution of results to existing knowledge
public health use of results
• Review relevant literature
3. Objectives
• Should answer the study question
• S.M.A.R.T.
Principal objective
• Must be achieved
• Dictates design and methods
Secondary objectives
• Of interest, but not essential
3. Objectives
example 1
Principal objective
• To determine if sharing a haemodialysis
machine with an 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
3. Objectives
example 2
• To estimate the current mortality,
among the Internally Displaced
Population present in the settlements
at the time of the survey,
in each of the three states of Greater
Darfur region
Hypotheses
• Translation of the objectives
in terms that allow statistical testing
Hypotheses
• Translation of the objectives
in terms that allow statistical testing
“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 HCV infected patients”
Hypothesis
• The current crude mortality rate
in IDPs in Darfur
is above 1 death per 10,000 per day
CMR > 1/10,000/day
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
4. Methods
• Procedures to achieve objectives
– what will be done?
– how?
• Information used to judge validity
4. Methods
• Study design
cohort, case-control, cross-sectional…
brief justification
• Study population
definition
criteria for inclusion and exclusion
mechanisms of recruitment
accessibility, follow up, representativeness
4. Methods
• Sampling design
frame: district, household, persons,…
method: random, cluster, stratified,…
randomisation procedures
replacement procedures (in case of refusal)
• Sample size
sample size, power calculations based on
principal objective
feasibility
4. Methods
• Selection and definition
exposures:
risk factors, protective factors, confounding factors
outcomes:
definition of case and the control group
• Items to be measured
– scales used
• e.g: smoking ? lung cancer
- smoking: definition, quantification, categories
- lung cancer: case definition, control group definition
CC study of sporadic cases
of Salmonella Enteritidis infection
• Exposure
– consumption of custard slices
• Case
– a person living in South-West Wales with
a laboratory confirmed infection due to S.Enteritidis
in June and July 1991
• 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’s directory
Methods
Data analysis plan
• Structured in terms of objectives
• Hypotheses tested, dummy tables
• Statistical tests used, adjustment,
standardisation
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
Methods
Data analysis
Dummy table:
Food specific attack rates of Salmonella infection
in a day care centre, Paris, May 1999
ill total AR RR 95%CI
n n %
ice-cream yes
ice-cream no
fruit cake yes
fruit cake no
pudding yes
pudding no
Methods
Data analysis
Case-control study, risk factors for brucellosis in France
Cases Controls OR
Exposed Unexp Exposed Unexp
Age group
60
Sex
M
F
Occupation
Travel
Cheese
4. Methods
Data collection
• How
interview, observation, record review
• By whom
interviewers: selection, training
level of supervision
• Tools
questionnaires, recording materials
questionnaires: self or interviewer administered,
face to face or telephone interview
• Procedures for taking samples
4. Methods
Data handling
• Coding
during data collection, afterwards?
by whom?
• Processing
software, hardware
entry
• during the study, afterwards?
• single entry, double entry?
• Validation and data cleaning
4. Methods
Pilot studies, pre-testing
• No study without test
Feasibility of sampling
Data collection, measurement methods
Questionnaire
• Describe how to test
4. Methods
Limitations
• Identification of potential sources of biases
selection bias
information bias
• How to deal with them
possibilities for correcting
how they will affect the results
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
5. Ethical considerations
• Informed consent
• Confidentiality, record anonymity
• Data storage and protection
• Ethical committee
6. Project management
• Participating institutes and persons
• Responsibilities and tasks of each partner
• Data ownership
7. Timetable
Planning/organisation of the study
• questionnaire design, recruitment, purchases
• permission
• obtain funding
“Pilot study”
Final study
• data collection
• analysis
• presentation of results and write up
8. Resources
• Extent of this section depends on target
audience
• Specify
available sources
requested sources
• Keep budget
reasonable
detailed
well justified
9. References
• Limit number of references to key
articles
• Follow recommended style
• Vancouver
www.library.soton.ac.uk/infoskills/vancouver.shtm
l
10. Appendices
• Methodological appendices
• List of definitions
• Questionnaires
• Introductory letters to study participants
• Forms for informed consent
…..
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
Study protocol
and now….
• Good Luck !