1 How to write a study protocol EPIET, Lazareto, Menorca September 2011 Viviane Bremer

2 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?

3 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

4 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)

5 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

6 1. Presentation Title – short, accurate, concise Investigators Main centres Steering committee (scientific board) 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 questions to be addressed contribution of results to existing knowledge use of results dissemination of results Review relevant literature

8 3. Objectives Should answer the study question Should be S.M.A.R.T. – Specific – Measurable – Achievable/Accessible – Realistic/Relevant – Time-based/Timely

9 3. Objectives Principal objective Must be achieved Dictates design and methods Secondary objectives Of interest, but not essential

10 Hypotheses Translation of the objectives in terms that allow statistical testing

11 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

12 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

13 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

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

15 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

16 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

17 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%1:25%/ 80% %1:25%/ 80% %1:25%/ 80% %1:25%/ 80% %1:25%/ 80%62754

18 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

19 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

20 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

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 2009

23 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

24 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

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

26 4. Methods Limitations 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

27 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

28 5. Ethical considerations Informed consent – translated in local lay language Confidentiality – coding data collection instruments without identifier Data storage and protection Ethics committee

29 6. Project management Participating institutes and persons Responsibilities and tasks of each partner Data ownership (Authorship)

30 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

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

32 9. References Limit number of references to key articles Follow recommended style Vancouver

Appendices Methodological appendices List of definitions Questionnaires Introductory letters to study participants Informed consent forms …..

34 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