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How to write a study protocol

EPIET, Lazareto, MenorcaSeptember 2011

Viviane Bremer

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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 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. References10. 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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• 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

3. Objectives example

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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. Presentation2. Background and justifications3. Objectives4. Methods5. Ethical considerations6. Project management7. Timetable8. Resources9. References10. 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 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

controls10% 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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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 2009

ill n

total n

AR %

RR 95%CI

ice-cream yes ice-cream no

fruit cake yes fruit cake no

pudding yes pudding no

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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. References10. 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.shtmlwww.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

Your task next week

• Create a study protocol in small groups• Present it to the plenary• Read the references during the weekend