Study/Research protocol Introduction to Intervention Epidemiology Tunis, 4 November 2014 Presented by Dr Nada Ghosn Ministry of Public Health - Lebanon esumoh@moph.gov.lb

Sources FEM WIKI Writing a Study Protocol

Objectives Overview of different elements to include in a research protocol Understand the steps for writing a study protocol

The life cycle of an epidemiological study/investigation Needs for data Involving the programme Study question Recommendations Study objective(s) Conclusions Analysis plan Analyse data Data collection instruments Collect data 4

Protocol elements 1. Presentation 2. Background and justifications 3. Objectives 4. Methods 5. Ethical considerations 6. Project management 7. Timetable 8. Resources 9. References 10. Appendices

1. Presentation Title Short, accurate, concise Authors: Investigators Main centres Steering committee (if present) Summary of the protocol

2. Background and justification Statement of problem, study justification Importance of subject area: magnitude, frequency … Literature review: relevant ones, gaps in existing knowledge Study question: Principal questions to be addressed Expectation: contribution of results to existing knowledge, use of results, Information for action

3. Study objective(s) Study objective Formulate hypothesis Should answer the study question Formulate hypothesis

3. Study objectives S.M.A.R.T. objective Number of objectives Specific Measurable Action oriented Realistic Time related Number of objectives One objective or one principal + other secondary

3. Study objectives: the verb Written in epidemiological terms Verb: one verb per objetive “Determine” for hypothesis testing “Determine whether a contaminated product from bakery A caused an hepatitis A outbreak” “Estimate” for measuring indicator (s) “Estimate the prevalence of TB”

3. Study objectives: Hypotheses Hypothesis: Translation of the objectives in terms that allow statistical testing “Hospitalisations rates due to severe RV are lower in children vaccinated against RV than in unvaccinated children”

3. Study objectives: SMART Which one is SMART? By the end of this study … “To measure the effectiveness of rotavirus (RV) vaccine” “To estimate the effectiveness of full course of RV vaccine in reducing rates of hospitalizations of severe RV gastroenteritis”

3. Study objectives: SMART? By the end of this study … "To identify risk factors for HCV infection" "To determine if sharing a haemodialysis machine with a HCV infected patient is a risk factor for HCV infection“ "To identify failures in procedures designed to prevent cross-infection via haemodialysis machines" “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”

4. Methods The “Methods” section: Describes specific details of the procedures to achieve the study objectives What? And How? Judging the validity of the proposal: rely on the methodology

4. Methods Elements: Study design Study population Sampling procedure and sample size Definitions Analysis plan Data collection Data handling Pre-testing or pilot studies Limitations

4. Methods: a)Study design Choose design according to objectives Descriptive (cross-sectional …) or analytic (cohort, case control) Brief justification

4. Methods: b) Study population Definition By time, place and person Ex: “children < 5 years residents in the catchment area of participating hospitals” Selection Criteria for inclusion and exclusion Mechanisms of recruitment Follow up (if needed) Representativeness

4. Methods: c)Sample design & size Sampling design Sampling unit Frame: registry of all units of the population Sampling schema /method: simple random sampling, systematic, stratified, cluster … Randomisation procedures Replacement procedures (in case of refusal) Sample size Sample size and power calculations

4. Methods: d)Definitions Exposures: risk factors, protective factors, confounding factors Outcomes: case, control group

4. Methods: d)Definitions Cohort: ? "consumption of custard slices in June or July 1991, in South-West Wales “? ? "a person living in South-West Wales with a laboratory confirmed infection due to S. Enteritidis in June or July 1991“?

4. Methods: d)Definitions Case control ? “Persons reported from the weekly notifications from reference laboratory having S. Enteriditis infection”? ? “Persons living in SW Wales in same neighborhood as cases“ ? Random selection of people using telephone directory ?

4. Methods: e) Analysis plan Structured based on the objectives Descriptive and analytical Dummy tables = expected tables with empty cells Define indicators to be used Statistical tests to be used

4. Methods: e) Analysis plan CONTENT: Descriptive Cases: nb, %, rates, ratio Time, place, person Disease, exposure Analytical Crude analysis: 1 exposure & 1 outcome Stratified analysis: 2 exposures & 1 outcome Multivariable analysis: several exposures

Multivariable analysis 4. Methods: e) Analysis plan - content Descriptive Data description Generate / Recode New variables Descriptive analysis Time, place, persons Analytic Crude (univariate) analysis Stratified analysis Multivariable analysis

4. Methods: e) Analysis plan – dummy tables Dummy tables = expected tables with empty cells Descriptive results Comparison of groups (cohort, case control) Dose response relationship for key exposures (if appropriate) Stratification: possible confounding factors / effect modifiers (if appropriate)

Dummy table - Descriptive Males Females Age group Total Cases AR% < 10 y 10 – 19 y > 19 y Unknown

Dummy table – cohort studies Food specific attack rates

Dummy table - Case control studies Case control study risk factors for brucellosis in France, 1999 28

Dummy table – Dose response Cheese cake Total Cases AR% RR Reference 1 2 >= 2 Unknown

Dummy table – Stratified analysis Age < 30 y Cheese cake Total Cases AR% RR Yes No > 30 y

4. Methods – e) Analysis plan: Indicators List indicators to be generated Rates, ratio, proportions or quantitative variables E.g.: RV vaccine coverage, food specific attack rates Identify information to calculate indicators Numerators and denominators E.g.: children vaccinated / total children, eating cheese / total number of participants

4. Methods – f) Data collection How? Interview (face to face, telephone …), observation, record review, lab sample By whom? Interviewers: selection, training Supervision Tools Questionnaires, recording materials If questionnaires: self or interviewer administered Blind data collection? Procedures for taking specimens

4. Methods – f) Data collection Identify variables needed to reflect the needed information E.g.: “RV vaccination status”, “eat cheese Y/N” Identify data collection method for each variable Review vaccination cards or interview of the mother Interview participants

4. Methods – f) Data collection D) Exposure 11. Cheese 1. Yes 2. No 11. |__| 12. Ice cream 12. 13. Salad 13. 14. Cheese cake 14.

4. Methods – g) Data handling Coding During data collection, afterwards? By whom? Processing Software, hardware Data entry During the study, afterwards? Single entry, double entry? Validation and data cleaning

4. Methods – h) Pilot / pre test No study without pre-test To assess the feasibility of sampling To verify data collection methods and to test the questionnaire

4. Methods – i) Limitations Identification of potential sources of biases Selection bias Information bias How to deal with them Potential correction Expected impact on the results

5. Ethical considerations Informed consent Oral? written? Translated in local language Confidentiality Coding data and entering data without identifier Data storage and protection Ethical committee

6. Project management Participating institutions and persons Responsibilities and tasks of each partner Data ownership: Who can access the data? Who will provide clearance to publish the results?

7. Timetable Planning/organisation of the study of various activities and tasks: Writing the protocol, Permission, Obtain funding, Purchase of material, Recruitment of needed resources, Training staff, Data collection, Data entry, Data validation and cleaning, Data analysis, Report, article … Establishing milestones and deadlines

7. Timetable

8. Resources Resources: Human Equipment and material Laboratory tests Information, training Time Specify Available resources Requested resources Specify needed 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.shtml

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

Introduction to Intervention Epidemiology THANK YOU Introduction to Intervention Epidemiology Tunis, 4 November 2014 Presented by Dr Nada Ghosn Ministry of Public Health - Lebanon esumoh@moph.gov.lb