Study protocols development
- 1. Field Epidemiology Training Program – Intermediate Standard Curriculum AFETP Intermediate, June, 2019 Study Protocols
- 2. 2 Study Protocols Objectives ▪ List the elements of a problem statement ▪ Describe the purpose of a study protocol ▪ List the basic sections of a protocol ▪ Critique a protocol
- 3. 3 Study Protocols Session Overview ▪ Purpose of study protocols ▪ Components of a study protocol ▪ Common problems with protocols
- 4. 4 Study Protocols Purpose of Study Protocols
- 5. 5 Study Protocols What is a Study Protocol? ▪ Document to guide the implementation and execution of the study ▪ Written by the study investigators ▪ Created during the planning stage
- 6. 6 Study Protocols Why Do We Need A Study Protocol? ▪ To clearly define the problem and study goals ▪ To ensure that study design is appropriate for research objectives ▪ To plan the study and ensure that it is feasible ▪ To provide technical details on study organization and procedures ▪ To obtain approval of ethical committee(s) and define the roles of all partners
- 7. 7 Study Protocols A Study Protocol Must… ▪ Be clearly written so that it can be understood by the study investigators and technical staff ▪ Provide sufficient detail on study procedures in order to achieve consistent results
- 8. 8 Study Protocols Where to Start? ▪ Use a protocol checklist – www.cdc.gov/niosh/nas/mining/pdfs/Protocol%20Checklist.pdf ▪ Use examples from other studies ▪ Ask your Instructors for examples
- 9. 9 Study Protocols Components of a Study Protocol
- 10. 10 Study Protocols Study Protocol Outline 1. Title page 2. Abstract 3. Introduction 4. Problem statement 5. Study objectives 6. Methods 7. Ethical considerations 8. Timeline 9. Resources 10. References 11. Appendices
- 11. 11 Study Protocols Title Page ▪ Title – Concise and specific ▪ Investigators – List all investigators and their affiliations – List the institutions associated with the study ▪ One page in length NB: May be specific guidelines for specific institutions
- 12. 12 Study Protocols Title Page (Example)
- 13. 13 Study Protocols Abstract ▪ Brief summary of the: – Problem – Study objectives – Methods to be used to address objectives – Expectations for how results will be used ▪ <1 page in length ▪ NB: Not the same as a manuscript abstract!
- 14. 14 Study Protocols Abstract (Example) Brief summary of the: Problem Childhood malaria is a problem in District X. The annual incidence of malaria among children<5 years in District X is 23/1000, with case-fatality rates of 9%. Bednets are widely available and free, and the reasons for the high rates of malaria are unknown. Study objectives We will evaluate risk factors for malaria and malaria deaths among children <5 years in District X. Methods to address objectives We will recruit children <5 years with confirmed malaria from Hospital Z, and compare them with age- matched children hospitalized for other reasons to identify malaria risk factors. Expectations for use of results These data will help us identify ways to reduce childhood malaria in District X.
- 15. 15 Study Protocols Introduction ▪ Background on the problem in the geographic region of study – Existing data about the problem in the area ▪ Brief review of relevant literature ▪ Justification and rationale for study ▪ 2-3 pages in length
- 16. 16 Study Protocols Problem Statement & Study Objectives What is your problem? How will you address it? PROBLEM STATEMENT OBJECTIVES
- 17. 17 Study Protocols There Are Two Problems in Every Problem Statement! The Knowledge Gap What is your problem? How will you address it? PROBLEM STATEMENT OBJECTIVES The Health Problem
- 18. 18 Study Protocols The Problem Statement: the Health Problem and the Knowledge Gap Health Problem The Knowledge Gap People with new diagnoses of HIV are not being linked into care at our targeted rates What factors (social, clinical, economical, etc.) influence linkage to care? Many people in our population are dying of tuberculosis We don’t know how prevalent it is or in what populations it’s most common Measles-containing vaccine uptake is lower than the recommended target What factors increase (or decrease) uptake of vaccines? Although there is a law to wear safety belts, people are still dying in accidents without wearing the belt What factors influence safety belt usage? To resolve these…. We need to study these!
- 19. 19 Study Protocols The Problem Statement Needs to Address Both of These ▪ Describing the Health Problem includes: – A specific description of the problem and its magnitude in your setting, in person/place/time – A brief explanation of why it’s a problem – A description of what it should be like (guidelines, national targets, etc.) ▪ Describing the Knowledge Gap includes: – A simple statement of what you don’t know! – The overall objective of your study
- 20. 20 Study Protocols Example of the simplest problem statement “Despite rollout of measles-containing vaccine in Country X during 2011, outbreaks of measles have continued. Measles-containing vaccine coverage is targeted to be >90% among 5-year-old children in Country X. However, a study during 2015 in District Y, showed coverage to be only 37% among children<5 years. The reasons for this poor coverage are unknown. We plan to evaluate reasons for low vaccine coverage in District Y.” The health problem What it should be like Why it’s a problem The Gap Overall objective
- 21. 21 Study Protocols Other Things You Can Put in a Problem Statement “Despite rollout of measles-containing vaccine in Country X during 2011, outbreaks of measles have continued. Measles-containing vaccine coverage is targeted to be >90% among 5-year-old children in Country X. However, a study during 2015 in District Y, showed coverage to be only 37% among children<5 years. The reasons for this poor coverage are unknown. We plan to evaluate reasons for low vaccine coverage in District Y.” The health problem What it should be like Why it’s a problem The Gap Overall objective Literature review: Data from other studies suggesting reasons for poor vaccine uptake Rationale: How the results of this study will benefit health in District Y Keep your problem statement to ~1 page or less!
- 22. 22 Study Protocols Problem Statement & Study Objectives What is your problem? How will you address it? PROBLEM STATEMENT OBJECTIVES
- 23. 23 Study Protocols Study Objectives ▪ General objective (usually one) – Derived from the research question(s) – Specifically addresses the Knowledge Gap ▪ Specific objectives (usually 2-5) – First one: Determining magnitude of problem – Next ones: Specific subsets of the General Objective – Note: Specific objectives may not be necessary for descriptive studies
- 24. 24 Study Protocols General Objective: Examples Health problem The Knowledge Gap General objective of your study People with new diagnoses of HIV are not linked into care at our targeted rates What factors (social, clinical, economical, etc.) influence linkage to care? Determine what factors are associated with linkage to care Many people in our population are dying of tuberculosis We don’t know how prevalent it is/ in whom it’s most common Determine the prevalence of tuberculosis in X population Measles-containing vaccine uptake is lower than the recommended target What factors increase (or decrease) uptake of vaccines? Determine what factors are associated with vaccine uptake Although there is a law to wear safety belts, people are still dying in accidents without wearing the belt What factors influence safety belt usage? Determine what factors are associated with use of a safety belt
- 25. 25 Study Protocols Specific Objectives: Example ▪ General objective: Determine what factors are associated with uptake of measles-containing vaccine in District Y ▪ Specific objectives: – Determine the uptake of measles-containing vaccine in District Y – Determine the association between social factors (perception of the vaccine, SES, vaccination history, number of children, educational level, etc.) and uptake of vaccine – Determine the association between proximity to a vaccination site and vaccine uptake – Determine the association between eligible vaccine candidates’ knowledge about the vaccine and uptake Specifically addresses Knowledge Gap Magnitude of problem Specific subsets of General Objective
- 26. 26 Study Protocols Methods ▪ Study design – Cross-sectional, case-control, cohort, etc. – Analytic vs descriptive – Justification for that design: how will it help you answer the main research question(s)? • We hypothesize that participating in school sports will improve school performance in primary-school children in Dar es Salaam, Tanzania • To test this hypothesis, we will conduct a ???? study
- 27. 27 Study Protocols Methods ▪ Study population – Subgroups targeted – Geographic location – Reasons for selection (representativeness, accessibility) – Inclusion and exclusion criteria (who is eligible, who cannot participate) • School-enrolled children ages 13-15 in Dar es Salaam • Current enrollment, and ages 13-15 years • Use a school assembly period for recruitment and enrollment • Consider role of teachers, administrators, parents • Scheduled follow-up survey at one year after exams
- 28. 28 Study Protocols Methods ▪ Sampling – Simple random, systematic random, convenience, etc. – Sampling frame, if appropriate – Recruitment and enrollment methods – Methods for follow-up / retention ▪ Sample size – Sample size or power calculations – Adjustment for non-response or loss to follow-up – Feasibility of recruitment of desired sample size
- 29. 29 Study Protocols Methods ▪ Data collection – Recruiting of participants – Self-administered questionnaires, interviews, clinical record reviews, etc. – Definitions of exposed/unexposed, outcomes, and key covariates – very important, and be specific • Primary exposure = self-reported participation in at least one school sport during the school year, adapted from a Global Youth and Sports Survey (reference author Name, Year) • Primary outcome = end of year exam score from school records • Covariates = age, gender, household members, alcohol use
- 30. 30 Study Protocols Methods ▪ Data handling and procedures – PDA, tablet, paper forms – Data entry and cleaning – Software used (Epi-Info, Excel, MS Access, etc.) – Data storage (password-protected computer?)
- 31. 31 Study Protocols Methods ▪ Laboratory procedures – Sample type, tests performed, location of testing – Quality control ▪ Data analysis plan – Descriptive analysis (provide dummy tables) – Procedures for coding your variables – e.g. we will create a summary score of physical activity based on responses to five questions – Procedures to handle missing data and outliers – Statistical methods to test your hypothesis
- 32. 32 Study Protocols Methods ▪ Training & project management – Who will run the study to ensure the work is done well – Training in standard operating procedures – Supervision and quality control ▪ Limitations – State the main design limitations and how you will address them – Sources of biases, weaknesses of study design What is a limitation of your study if you only sample public school children? How could you justify this?
- 33. 33 Study Protocols Ethical Considerations ▪ Describe informed consent process (if human subjects involved) ▪ Methods to ensure confidentiality – Use of identifying information – Data storage and protection ▪ Safety and protection of study participants
- 34. 34 Study Protocols Timeline ▪ Provides overview of timing of the different phases of the study: – Ethical approval – Subject recruitment and enrollment – Data collection – Data analysis – Presentation of results
- 36. 36 Study Protocols Resources ▪ Resources available – Personnel – Facilities – Materials ▪ Budget and justification – You would develop this section with a budget manager ▪ You need to show that you have the human and financial resources to conduct this study
- 37. 37 Study Protocols References ▪ Include in standard reference format ▪ Refer to ICJME guidelines: https://www.nlm.nih.gov/bsd/uniform_requirements.html ▪ Do NOT cite publications from organizations (such as WHO,CDC, etc.) or without a first author listed as ‘Anonymous’! – See ICJME guidelines for proper citation
- 38. 38 Study Protocols Appendices ▪ Include: – Questionnaires or other data collection instruments – List of variables with definitions – Dummy tables – Participant recruitment materials – Informed consent documents – Local approval letters, e.g. RMOs
- 39. 39 Study Protocols Common Problems With Study Protocols
- 40. 40 Study Protocols Potential Problems ▪ Research objectives are not specific ▪ Study objectives too ambitious, not feasible, poorly justified ▪ Insufficient details on study procedures ▪ Inappropriate analysis methods ▪ Inadequate resources available for completing the research objectives
- 41. 41 Study Protocols Non-Specific Research Objectives Example: “To gain a better understanding of the trends in influenza mortality in Country X.” How to correct? “To use sentinel surveillance data to compare weekly influenza mortality rates for the years 2000 through 2015 in Country X.”
- 42. 42 Study Protocols Study Objectives Too Ambitious, Not Feasible Example: “To determine the prevalence of HIV infection among all residents of County A, Liberia.” How to correct? “To estimate the prevalence of HIV infection among residents of County A, Liberia using cluster sampling methods.”
- 43. 43 Study Protocols Poor Justification Example: “This study is needed because previous studies on this topic were inadequate.” How to correct? “This study is needed because previous studies on this topic: (1) Did not use probability-based sampling methods, which limits the generalizability of their results, and (2) used non-validated methods to determine exposure, which may have resulted in misclassification of subjects.”
- 44. 44 Study Protocols Insufficient Details about Study Procedures Example: “Healthy control subjects will be recruited from local health clinics.” How to correct: “Control subjects will be recruited from health clinics X and Y. Persons aged 12 to 18 years who present for routine check-ups and who have no major complaint or illness will be eligible for the study.”
- 45. 45 Study Protocols Inappropriate Analysis Methods Example: “Risk ratios will be calculated for all risk factors to compare the probability of being a case or a control for each factor.” How to correct? “Odds ratios will be calculated for all risk factors to compare the odds of being a case or a control for each factor.”
- 46. 46 Study Protocols Unrealistic Timeline Example: “We will recruit and enroll 50 dengue hemorrhagic fever (DHF) patients per week to reach our goal of 200 subjects in one month.” How to correct? “Based on a average weekly incidence of 15 cases per week, we will recruit and enroll 10 dengue hemorrhagic fever (DHF) patients per week to reach our goal of 400 subjects in 20 weeks (5 months).”
- 47. 47 Study Protocols Inadequate Resources Example: “Face-to-face interviews will be conducted and blood samples will be drawn from all 200 subjects. A nurse will be hired to conduct this task.” How to correct? “Four teams each consisting of a nurse and an interviewer will be sent out in the field to conduct interviews and collect blood samples from 50 subjects each.”
- 48. 48 Study Protocols Group Protocol For The Course
- 49. 49 Study Protocols Study Protocol for FETP Trainees ▪ In this course, we will follow one protocol ▪ The topic is __________________________ ▪ You will develop your own analysis plan ▪ You will collect and analyze data specific to your field site, and submit a final report ▪ You and your colleagues will combine your results at the end of the course
- 50. 50 Study Protocols Stay Tuned! ▪ More discussion on course study protocol later in this Module
- 51. 51 Study Protocols Summary ▪ A comprehensive and well written study protocol is an invaluable tool to investigators before and during the study ▪ It should describe how you expect the study to proceed, including a clear and precise research plan ▪ Content must be sufficiently detailed so that any individual could perform the study
- 52. 52 Study Protocols References ▪ CDC. Developing a protocol. www.cdc.gov/niosh/nas/mining/pdfs/Protocol%2 0Checklist.pdf