Transcript Document

Study protocol
Jim teWaterNaude
UCT Dept Public Health
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Research
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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-didn’t-think-of-that
moments.
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Here follow 3 examples of protocol outlines
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1. Study protocol outline
(This is the preferred style, as found in Hulley)
Element
Purpose
1. Research questions
What questions will the study address?
2. Significance (background)
Why are these questions important?
3. Design
Time frame
Epidemiologic approach
How is the study structured?
4. Subjects
Selection criteria
Sampling design
Who are the subjects and how will they be
selected?
5. Variables
Predictor variables
Confounding variables
Outcome variables
What measurements will be made?
6. Statistical issues
Hypotheses
Sample size
Analytic approach
How large is the study and how will it be
analyzed?
Hulley explains the process in familiar terms:
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Anatomy of research
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(what it’s made of)
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Physiology of research
(how it works)
• Research question
• Significance
• Design
• Subjects
– Population
– Sample size
• Variables
– Predictor
– Outcome
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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
3. Components of a research proposal
(Shi)
A.
B.
C.
D.
Title page
Table of contents
Abstract
Project Description
1.
2.
3.
4.
5.
6.
E.
F.
G.
H.
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:
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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
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It is the science of the occurrence of
disease in human populations
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… distribution and determinants…
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Distribution
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‘What’ (the disease), plus ‘when’ + ‘where’ + ‘who’
or the disease described by TIME + PLACE
+ POPULATION
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Determinants
The ‘Why’
= the ‘causes’, or risk factors
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… distribution and determinants…
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Distribution
What, when, where, who
• Descriptive studies
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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:
1. The conceptual research question is what
the investigator wants to know about the
world
2. The operational research question is what is
deemed achievable though the deliberations
of drawing up the study plan or protocol
3. The actual research question is what
actually gets answered during the conduct of
the study.
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The research cycle
(after Hulley)
Conceptual
question
Design
Operational
question
Truth in the
universe
Infer
Truth in the
study
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Implement
Infer
Actual
question
Findings in
the study
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The research cycle
Conceptual
question
Actual
question
Operational
question
Design
Implement
Target
population
Intended
sample
Actual
subjects
Phenomena
of interest
Intended
variables
Actual
measurements
Infer
Truth in the
universe
Infer
Truth in the
study
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Findings in
the study
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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
+++++++++++++++++++++++++++++++++++++++++
Operational
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
1.
2.
3.
4.
5.
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 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
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Relevance
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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
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Interesting
To the investigator
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Novel
Confirms or refutes previous findings
Extends previous findings
Provides new findings
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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 1997;315:1636
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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
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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
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In observational epidemiology we examine the
distribution or determinants of an outcome
without any attempt to influence them
(examples are smoking, drinking, sexual behaviours)
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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
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Outcomes are also called effects, dependent
variables, diseases, events, or health-related
states that we are interested in
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Time frame
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“Rule of halves”
– Spend half on Asking
• ½ on Background
• ½ on Methods
– Spend half on Answering
• ½ on Results
• ½ on Discussion
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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
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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
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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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st
1
Task at the lecture
- task taken from Chapter 1 of the textbook
For each of the following 4 abstracts:
1.
2.
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 shortacting 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
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Get the book
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Get a research mentor in your department
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Decide on your area of research. Will you use existing or
generate new data?
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Compose your one sentence Research Question
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Flesh this out into a half-page study plan or protocol, using
a structure that suits you. Start your literate review.
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Submit this to [email protected] for feedback
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Task for December
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Complete your 5-page protocol
(format outline in the next slide)
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Submit this to [email protected] for
feedback
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5-page protocol
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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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“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
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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 halflives 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
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