How to write a study protocol

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How to write a study protocol

• EPIET, Lazareto, Menorca
• October 2009

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Objectives of this session

• Overview of the different elements to be
  included in a research protocol
• Guide for the Protocol exercise (week 2)

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Study protocol What?

• 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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Study protocol Why?

• 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 protocolHow 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. 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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1. Presentation

• Title
• short, accurate, concise
• 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
• 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 HCV infected patients

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3. Objectivesexample

• Non S.M.A.R.T objective
• To estimate mortality in Darfur
• To estimate the current mortality (1-30 July
  2004)
• among the Internally Displaced Population (IDP)
  present in the settlements at the time of the
  survey,
• in each of the three states of Greater Darfur

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Hypothesis

• The current crude mortality rate
  in IDPs in Darfur
  is above 1 death per 10,000 per
  day
• CMR gt 1/10,000/d

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Objectivesexample

• Non S.M.A.R.T objective
• - To identify protective factors for scrub typhus
• Principal Objective
• - To estimate the strength of the association
  between potential protection measures and scrub
  typhus (ST) among residents of peri-urban area of
  Darjeeling district.
• Secondary objective
• - Estimate the fraction of cases of ST that could
  be prevented through these measures

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Hypothesis

• The incidence of ST is lower in people using
  mite repellents on clothes than in people not
  using them

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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
• 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 sizee.g. Options for smoking and lung
cancer case-control study, England and Wales,
2009
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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 smoking ltgt lung cancer
• smoking definition, quantification, categories
• lung cancer case definition, control group
  definition

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CC study of sporadic cases
of Salmonella Enteritidis infections

• 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
  directory

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MethodsData 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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MethodsData 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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MethodsData analysis
Dummy table Food specific attack rates of
Salmonella infection in a day care centre,
Paris, May 1999
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MethodsData analysis

• CC study, risk factors for brucellosis in France

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4. MethodsData 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. MethodsData 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. MethodsPilot 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. MethodsLimitations

• Identification of potential sources of biases
• 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
• 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.ht
  ml

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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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Study protocoland now.

• Good Luck !