Study protocol

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Study protocol

• Jim teWaterNaude
• UCT Dept Public Health

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Research

• The process of asking and answering a question

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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-didnt-think-of-that
  moments.
• Here follow 3 examples of protocol outlines

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1. Study protocol outline(This is the preferred
style, as found in Hulley)
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Hulley explains the process in familiar terms

• Anatomy of research(what its 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

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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

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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

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Main protocol elements

• 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

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Epidemiology

• The study of the distribution and determinants of
  health in humans
• It is the science of the occurrence of disease in
  human populations

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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

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distribution and determinants

• Distribution
• What, when, where, who
• Descriptive studies
• Determinants
• Why
• What is associated with/ caused by
• Analytic studies
• Interventive studies

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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

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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.

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The research cycle(after Hulley)
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The research cycle
Target population Phenomena of interest
Intended sample Intended variables
Actual subjects Actual measurements
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Research the process of asking and answering a
question
Asking your question
Answering your question
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Asking your question Background Methods
Results
Discussion Answering your question
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Asking your question General Specific
Specific
General Answering your question
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Asking your question Conceptual Operational
Ope
rational Conceptual Answering your question
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• Asking your question
• Background
• Literature review
• Objectives
• Methods
• Design
• Measurements

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• Results
• Limitations
• Findings
• Discussion
• What this means
• Conclusion
• Answering your question

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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?

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but it doesnt mean anything(one of the
childrens lament from Sound of Music)

• Population
• Question
• Relevance (it has to mean something)
• Study design and variables
• Timeframe

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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

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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
  19973151636

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Study designs- arranged in ascending order of
credibility

• Case reports
• Case series
• Correlational studies
• Cross-sectional studies
• Case-control studies
• Cohort studies
• Controlled trials

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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)

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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)

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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

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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

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Epidemiological terms not covered

• Quantitative and Qualitative
• Validity and Variability
• Causality/ Causal inference
• Bias
• Confounding
• The 2x2 table
• Occurrence and effect measures

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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

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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

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Apply PQRST
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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)

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• 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

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• 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

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• 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

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• 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

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2nd Task at the lecture

• Write down your own Research Question in one
  sentence

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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_at_cormack.uct.ac.za for feedback

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Task for December

• Complete your 5-page protocol(format outline in
  the next slide)
• Submit this to jim_at_cormack.uct.ac.za for feedback

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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)

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Its not how you start, its 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

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• 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

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• 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

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• 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

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• 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