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Study protocol

Study protocol. Jim teWaterNaude UCT Dept Public Health. Research. The process of asking and answering a question. Protocol. The reason for having for a study plan or protocol is efficiency

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Study protocol

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  1. Study protocol Jim teWaterNaude UCT Dept Public Health TRRM - 2005/6

  2. Research • The process of asking and answering a question TRRM - 2005/6

  3. Protocol • The reason for having for a study plan or protocol is efficiency • You want to be able to do the intended study quickly, cheaply, easily and ethically, and with no major oh-my-gosh-I-didn’t-think-of-that moments. • Here follow 3 examples of protocol outlines TRRM - 2005/6

  4. 1. Study protocol outline(This is the preferred style, as found in Hulley)

  5. Anatomy of research(what it’s made of) • Research question • Significance • Design • Subjects – Population – Sample size • Variables – Predictor – Outcome Physiology of research (how it works) Using measurements in a sample to draw inferences about phenomena in a population Hulley explains the process in familiar terms: TRRM - 2005/6

  6. 2. Major headings in a protocol(MRC approach) Title Investigators, institutional affiliations, & qualifications Summary/Abstract 1. Introduction • Literature review; Motivation for the study (problem); Purpose; Specific objectives; Implementation objectives 2. Methods • Definition of terms; Study design; Study population and sampling; Measurements; Pilot studies 3. Logistics and time schedule • Responsibilities of investigators and of staff; Time schedule 4. Data management and analysis 5. Resources • Available resources; Budget and budget motivation 6. Ethical and legal considerations 7. Reporting of results 8. Appendices

  7. 3. Components of a research proposal(Shi) • Title page • Table of contents • Abstract • Project Description • Introduction • Problem statement and significance • Goals and objectives • Methods and procedures • Evaluation • Dissemination • References • Budget and Justification • Human Subjects • Appendices TRRM - 2005/6

  8. The above protocol outlines have these as main elements: Population Question Relevance Study design and variables Timeframe To understand these, we need to revisit some epidemiology… Main protocol elements TRRM - 2005/6

  9. Epidemiology • The study of the distribution and determinants of health in humans • It is the science of the occurrence of disease in human populations TRRM - 2005/6

  10. … distribution and determinants… • Distribution • ‘What’ (the disease), plus ‘when’ + ‘where’ + ‘who’ or the disease described by TIME + PLACE + POPULATION • Determinants The ‘Why’ = the ‘causes’, or risk factors TRRM - 2005/6

  11. … distribution and determinants… • Distribution What, when, where, who • Descriptive studies • Determinants ‘Why’ What is associated with/ caused by • Analytic studies • Interventive studies TRRM - 2005/6

  12. Population • “a group sharing certain common characteristics” • Do not have to be people (most often are) • Can be records, institutions, farms, events • Does need to be clearly defined and specified TRRM - 2005/6

  13. Question Questions arise out of involvement in the field The research question occurs in 3 layers: • The conceptual research question is what the investigator wants to know about the world • The operational research question is what is deemed achievable though the deliberations of drawing up the study plan or protocol • The actual research question is what actually gets answered during the conduct of the study. TRRM - 2005/6

  14. Conceptual question Truth in the universe Operational question Truth in the study Actual question Findings in the study Design Implement Infer Infer The research cycle(after Hulley) TRRM - 2005/6

  15. Conceptual question Truth in the universe Operational question Truth in the study Actual question Findings in the study Design Implement Infer Infer The research cycle Target population Phenomena of interest Intended sample Intended variables Actual subjects Actual measurements TRRM - 2005/6

  16. Research – the process of asking and answering a question Asking your question ++++++++++++++++++++++++++++++++++++++ Answering your question TRRM - 2005/6

  17. Asking your question Background Methods +++++++++++++++++++++++++++++++++++++++++ Results Discussion Answering your question TRRM - 2005/6

  18. Asking your question General Specific +++++++++++++++++++++++++++++++++++++++++ Specific General Answering yourquestion TRRM - 2005/6

  19. Asking your question Conceptual Operational +++++++++++++++++++++++++++++++++++++++++ Operational Conceptual Answering your question TRRM - 2005/6

  20. Asking your question Background Literature review Objectives Methods Design Measurements ++++++++++++++++++++++++++++++ TRRM - 2005/6

  21. ++++++++++++++++++++++++++++++ Results Limitations Findings Discussion What this means Conclusion Answering your question TRRM - 2005/6

  22. Research questions using existing data • Choose a database • Become thoroughly familiar with all variables and how they were measured • Identify variables whose association may be of interest • Review the literature and consult experts to determine relevant research questions • Formulate specific hypotheses and settle on the statistical methods Table 13.1 in Designing Clinical Research Will you use existing, or generate your own data?

  23. “… but it doesn’t mean anything”(one of the children’s lament from Sound of Music) • Population • Question • Relevance (it has to mean something) • Study design and variables • Timeframe TRRM - 2005/6

  24. Relevance • FINER - Criteria for a Good Research Question • Table 2.1 in Hulley • Feasible Adequate number of subjects Adequate technical expertise Affordable in time and money Manageable in scope • Interesting To the investigator • Novel Confirms or refutes previous findings Extends previous findings Provides new findings • Ethical • Relevant To scientific knowledge To clinical and health policy To future research directions TRRM - 2005/6

  25. Study– design and variables There are 2 broad study design classes and 2 broad variable classes. Which is the best study design? “The question being asked determines the appropriate research architecture, strategy, and tactics to be used” This is quoted from the accompanying editorial: Sackett DL, Wennberg JE.Choosing the best research design for each question. Editorial. BMJ 1997;315:1636 TRRM - 2005/6

  26. Study designs- arranged in ascending order of credibility • Case reports • Case series • Correlational studies • Cross-sectional studies • Case-control studies • Cohort studies • Controlled trials TRRM - 2005/6

  27. 2 broad study design classes Descriptive and analytic • In descriptive epidemiology, we describe the distribution of an exposure or outcome, without overtly seeking to explain the distribution by looking for associations (distribution of health in humans) • In analytical epidemiology, we examine associations, often with the aim of identifying possible causes for an outcome (determinants of health in humans) TRRM - 2005/6

  28. Analytic study designs Observational and interventional • In observational epidemiology we examine the distribution or determinants of an outcome without any attempt to influence them (examples are smoking, drinking, sexual behaviours) • In interventional epidemiology we test a hypothesis by modifying an exposure within the study population and examining the effect on the outcome (examples are vaccine or drug trials) TRRM - 2005/6

  29. 2 broad variable classes Exposure and outcome variables • Exposures are also called risk factors, factors, predictor variables, independent variables. These may or may not be the cause of the outcome – we determine this through research • Outcomes are also called effects, dependent variables, diseases, events, or health-related states that we are interested in TRRM - 2005/6

  30. Time frame • “Rule of halves” • Spend half on Asking • ½ on Background • ½ on Methods • Spend half on Answering • ½ on Results • ½ on Discussion • ½ + ½ + ½ + ½ = 1 TRRM - 2005/6

  31. Epidemiological terms not covered • Quantitative and Qualitative • Validity and Variability • Causality/ Causal inference • Bias • Confounding • The 2x2 table • Occurrence and effect measures TRRM - 2005/6

  32. Protocol – more comments • The scientific thinking that goes into the protocol attempts to control the errors that commonly occur – these errors are either random (due to chance) or systematic (due to bias) • Developing a protocol is an iterative process of drafting and redrafting, visiting and revisiting, and is best approached initially by divergent rather than convergent thinking • The perfect study has yet to be done, as there are many trade-offs in the process of asking and answering your question TRRM - 2005/6

  33. An example of applying PQRST- the Dop system • Population • Productive farms in the Stellenbosch district • Question • What is the current prevalence of the Dop system (in 1995)? • Relevance • Never previously documented. Presumed health effects • Study design and variables • Cross-sectional descriptive. Frequency & amount of dop • Timeframe • ~ 4 months in all. 3-4 weeks for data collection, collected by nurses on their mobile clinic visits to the farms TRRM - 2005/6

  34. Apply PQRST: TRRM - 2005/6

  35. 1st Task at the lecture- task taken from Chapter 1 of the textbook For each of the following 4 abstracts: • State the research question in a single sentence that specifies the predictor and the outcome variables, as well as the population sampled • State the study design. Think also about the main inference that can be drawn from the study, to whom it can be generalised, and what the potential errors in drawing and applying these inferences are (Answers are given at the very end of this presentation) TRRM - 2005/6

  36. a. Giving vitamin D to patients with vitamin D deficiency can improve strength. To find out whether the ordinary weakness of aging could be treated with vitamin D, we selected 38 men and women 70 years of age and greater from a hypertension treatment clinic and randomly assigned them to receive either vitamin D3 or identical placebo. Muscle strength of the quadriceps, measured with an isokinetic dynamometer after 6 months of treatment, was similar in the two groups. The research question: The study design: TRRM - 2005/6

  37. b. To assess whether the sedative effects of psychotropic drugs might cause hip fractures, we studied 1021 men and women with hip fractures and 5606 without hip fractures among elderly Medicaid enrollees. Persons treated with short-acting tranquillizers had no increased risk of hip fracture. By contrast, there was an increased risk associated with current use of tranquillizers having half-lives of more than 24 hours (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.4). The research question: The study design: TRRM - 2005/6

  38. c. Knowledge about AIDS was studied among 893 teenaged boys and 633 girls drawn from 12 secondary schools in Zimbabwe. Ninety-three percent of the children thought that it was an infection caused by having sexual relations, and 10% believed that it could be contracted from toilet seats. The research question: The study design: TRRM - 2005/6

  39. d. We examined the use of estrogen replacement therapy in relation to breast cancer in postmenopausal women. During 367 187 person-years of follow-up, there were 722 new cases of breast cancer. The risk of breast cancer was significantly elevated among current estrogen users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67), but not among former users. The research question: The study design: TRRM - 2005/6

  40. 2nd Task at the lecture Write down your own Research Question in one sentence TRRM - 2005/6

  41. Task for September • Get the book • Get a research mentor in your department • Decide on your area of research. Will you use existing or generate new data? • Compose your one sentence Research Question • Flesh this out into a half-page study plan or protocol, using a structure that suits you. Start your literate review. • Submit this to jim@cormack.uct.ac.za for feedback TRRM - 2005/6

  42. Task for December • Complete your 5-page protocol(format outline in the next slide) • Submit this to jim@cormack.uct.ac.za for feedback TRRM - 2005/6

  43. 5-page protocol • Title • Abstract • Specific aims • Significance (limit to 1/2 page) • Design • Overview (time frame and nature of control) • Study subjects (selection criteria, plans for recruiting) • Measurements (predictors, confounders, outcomes) • Statistical issues (hypotheses and sample size) • Pretests, quality control, data management • Timetable Addendum: Ethical considerations (not part of the 5 pages) TRRM - 2005/6

  44. “It’s not how you start, it’s how you finish” 9 times winner Bruce Fordyce, describing the Comrades Marathon (but do please get to the start line) Many thanks UCT Dept Public Health TRRM - 2005/6

  45. a. Giving vitamin D to patients with vitamin D deficiency can improve strength. To find out whether the ordinary weakness of aging could be treated with vitamin D, we selected 38 men and women 70 years of age and greater from a hypertension treatment clinic and randomly assigned them to receive either vitamin D3 or identical placebo. Muscle strength of the quadriceps, measured with an isokinetic dynamometer after 6 months of treatment, was similar in the two groups. 1. Does treatment with vitamin D increase leg muscle strength in healthy people 70 years of age or greater? Audience comment: Healthy should read Hypertensive 2. Randomised blinded trial TRRM - 2005/6

  46. b. To assess whether the sedative effects of psychotropic drugs might cause hip fractures, we studied 1021 men and women with hip fractures and 5606 without hip fractures among elderly Medicaid enrollees. Persons treated with short-acting tranquillizers had no increased risk of hip fracture. By contrast, there was an increased risk associated with current use of tranquillizers having half-lives of more than 24 hours (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.4). 1. Do psychotropic medications increase risk for hip fracture among elderly men and women? 2. Case-control study Audience comment: Surely this could be a cross-sectional study? Response: Yes, but the wording seems to favour case-control, because they mention the hip fracture group as if they had been initially selected before the controls were selected, reflecting the conduct of a case-control study. Another clue is the use of odds ratio, which is synonymous with case-control studies TRRM - 2005/6

  47. c. Knowledge about AIDS was studied among 893 teenaged boys and 633 girls drawn from 12 secondary schools in Zimbabwe. Ninety-three percent of the children thought that it was an infection caused by having sexual relations, and 10% believed that it could be contracted from toilet seats. 1. What is the state of knowledge about AIDS among schoolchildren in Zimbabwe? 2. Cross sectional descriptive study TRRM - 2005/6

  48. d. We examined the use of estrogen replacement therapy in relation to breast cancer in postmenopausal women. During 367 187 person-years of follow-up, there were 722 new cases of breast cancer. The risk of breast cancer was significantly elevated among current estrogen users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67), but not among former users. 1. Does estrogen replacement therapy in postmenopausal women increase risk for breast cancer? 2. Cohort study TRRM - 2005/6

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