protocol-writing-in-clinical-research#3

1. How to write a study protocol
EPIET, Lazareto, Menorca
September 2005

2. 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?

3. 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

4. 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)

5. 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

6. 1. Presentation
• Title
– short, accurate, concise
• Investigators
• Main centres
• Steering committee
• Summary of the protocol

7. 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

8. 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

9. 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 1

10. 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

11. Hypotheses
• Translation of the objectives
in terms that allow statistical testing

12. 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”

13. Hypothesis
• The current crude mortality rate
in IDPs in Darfur
is above 1 death per 10,000 per day
CMR > 1/10,000/day

14. 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

15. 4. Methods
• Procedures to achieve objectives
– what will be done?
– how?
• Information used to judge validity

16. 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

17. 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

18. 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

19. 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

20. Methods
Data analysis plan
• Structured in terms of objectives
• Hypotheses tested, dummy tables
• Statistical tests used, adjustment,
standardisation

21. 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

22. Methods
Data analysis
Dummy table:
Food specific attack rates of Salmonella infection
in a day care centre, Paris, May 1999
ill
n
total
n
AR
%
RR 95%CI
ice-cream yes
ice-cream no
fruit cake yes
fruit cake no
pudding yes
pudding no

23. Methods
Data analysis
Case-control study, risk factors for brucellosis in France
Cases Controls OR
Exposed Unexp Exposed Unexp
Age group
< 15
15 – 25
26 - 60
> 60
Sex
M
F
Occupation
Travel
Cheese

24. 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

25. 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

26. 4. Methods
Pilot studies, pre-testing
• No study without test
 Feasibility of sampling
 Data collection, measurement methods
 Questionnaire
• Describe how to test

27. 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

28. 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

29. 5. Ethical considerations
• Informed consent
• Confidentiality, record anonymity
• Data storage and protection
• Ethical committee

30. 6. Project management
• Participating institutes and persons
• Responsibilities and tasks of each partner
• Data ownership

31. 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

32. 8. Resources
• Extent of this section depends on target
audience
• Specify
 available sources
 requested sources
• Keep budget
 reasonable
 detailed
 well justified

33. 9. References
• Limit number of references to key
articles
• Follow recommended style
• Vancouver
www.library.soton.ac.uk/infoskills/vancouver.shtml

34. 10. Appendices
• Methodological appendices
• List of definitions
• Questionnaires
• Introductory letters to study participants
• Forms for informed consent
…..

35. 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

36. Study protocol
and now….
• Good Luck !