Study Protocol - Universiteit Stellenbosch University by gyvwpsjkko

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									Study protocol


       Jim teWaterNaude
   UCT Dept Public Health
        TRRM - 2005/6   1
                   Research

   The process of asking and answering a
    question




                   TRRM - 2005/6            2
                        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               3
              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                          How is the study structured?
 Time frame
 Epidemiologic approach
4. Subjects                        Who are the subjects and how will they be
 Selection criteria                selected?
 Sampling design
5. Variables                       What measurements will be made?
 Predictor variables
 Confounding variables
 Outcome variables
6. Statistical issues              How large is the study and how will it be
 Hypotheses                        analyzed?
 Sample size
 Analytic approach
    Hulley explains the process in familiar terms:


    Anatomy of research              Physiology of research
     (what it‟s made of)               (how it works)


    • Research question              Using measurements
    • Significance                    in a sample to draw
    • Design                          inferences about
                                       phenomena in a
    • Subjects                        population
    – Population
    – Sample size
    • Variables
    – Predictor
    – Outcome

                           TRRM - 2005/6                        5
     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.    Title page
B.    Table of contents
C.    Abstract
D.    Project Description
     1.   Introduction
     2.   Problem statement and significance
     3.   Goals and objectives
     4.   Methods and procedures
     5.   Evaluation
     6.   Dissemination
E.    References
F.    Budget and Justification
G.    Human Subjects
H.    Appendices

                            TRRM - 2005/6      7
      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…

                     TRRM - 2005/6               8
             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             9
… 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                 10
… 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   11
                                    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           12
                                   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.
                   TRRM - 2005/6                  13
               The research cycle
                           (after Hulley)




Conceptual               Operational                     Actual
  question     Design
                           question          Implement     question




Truth in the     Infer
                         Truth in the           Infer    Findings in
   universe                 study                           the study


                             TRRM - 2005/6                              14
                The research cycle

Conceptual                 Operational                     Actual
  question                   question                        question
                 Design                        Implement


   Target                    Intended                         Actual
 population                   sample                         subjects



 Phenomena                   Intended                         Actual
  of interest                variables                     measurements

                   Infer                          Infer
Truth in the               Truth in the                    Findings in
   universe                   study                           the study

                               TRRM - 2005/6                              15
                     Research
 – the process of asking and answering a question



Asking your question


++++++++++++++++++++++++++++++++++++++


Answering your question


                    TRRM - 2005/6               16
Asking your question

Background

                  Methods


+++++++++++++++++++++++++++++++++++++++++

                  Results

Discussion

Answering your question
                    TRRM - 2005/6           17
Asking your question

General

                  Specific


+++++++++++++++++++++++++++++++++++++++++

                  Specific

General

Answering your question
                    TRRM - 2005/6           18
Asking your question

Conceptual

                  Operational


+++++++++++++++++++++++++++++++++++++++++

                  Operational

Conceptual

Answering your question
                    TRRM - 2005/6           19
Asking your question

Background
Literature review
Objectives
                            Methods
                            Design
                            Measurements
++++++++++++++++++++++++++++++
                    TRRM - 2005/6          20
++++++++++++++++++++++++++++++

                         Results
                         Limitations
                         Findings
Discussion
What this means
Conclusion

Answering your question
                  TRRM - 2005/6        21
Research questions using existing data

1.   Choose a database
2.   Become thoroughly familiar with all variables and
     how they were measured
3.   Identify variables whose association may be of
     interest
4.   Review the literature and consult experts to
     determine relevant research questions
5.   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?
                                                         22
“… 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                 23
                                               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                 24
                                  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                   25
             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                   26
         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               27
                      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                   28
             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              29
                                           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           30
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       31
                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                   32
          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                       33
Apply PQRST:




               TRRM - 2005/6   34
 1st    Task at the lecture
 - task taken from Chapter 1 of the textbook

For each of the following 4 abstracts:
1.   State the research question in a single sentence
     that specifies the predictor and the outcome
     variables, as well as the population sampled
2.   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                    35
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               36
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                37
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                    38
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                39
2nd Task at the lecture

Write down your own Research
  Question in one sentence




             TRRM - 2005/6     40
             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                        41
              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         42
             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                    43
           “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                    44
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                     45
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                          46
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                      47
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                        48

								
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