Transcript Case control studies: - Tehran University of Medical Sciences

How to Write
Introduction Section?
Dr. Gholamreza Khalili
Department of Epidemiology & Biostatistics
School of public health
Tehran University of Medical Sciences
Introduction
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Before you begin, answer the basic questions:
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What do I have to say?
Is it worth saying?
What is the right format?
What is the audience?
What is the right journal?
Introduction
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General, concise description of problem
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Where that work is deficient
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background to the work
previous research
how your research will be better
State the hypothesis
About 3 to 4 paragraphs
Paragraph1:
What we know
Paragraph2:
What we don’t know
Paragraph3:
Why we did this study
Introduction
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Existing state of knowledge
Gaps in knowledge which research will fill.
State what you Intend to do & the purpose of
article
Give pertinent references
Summarize the rationale for study or observation
Define specialized terms or abbreviations you
want to use
Inverted pyramid
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The structure should funnel down from a
broad perspective to a specific aim
Oxidative stress plays an important role in....
When LDL particles are oxidized ...
Antioxidants are important...
...Paraoxonase...
Introduction
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Don’t make it a review article
Don not include methods, results and
discussion
Don’t put down every all previous studies &
their data gaps
Don’t explain pathophysiology irrelevant to
your study
Introduction
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Tell why you have undertaken the study
Clarify what your work adds
Follow the best advice
Keep it short
Make sure you are aware of earlier studies
Tell about importance of your study
Don’t baffle your readers
Give the study design
Think about using journalistic tricks
Introduction
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To write an effective introduction you must:
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Know your audience
Keep it short
Tell readers why you have done the study
Explain why it is important
Convince readers that it is better than others
Try to hook them!
Types of study designs
Dr. Gholamreza Khalili
Department of Epidemiology & Biostatistics
School of public health
Tehran University of Medical Sciences
Types of Studies
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Descriptive Studies
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Observational Analytic Studies
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Cross Sectional studies
Ecologic studies
Case Control studies
Cohort studies
Experimental Studies
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Randomized controlled trials
Hierarchy of Study Types
Descriptive
•Case report
•Case series
•Survey
Analytic
Observational
•Cross sectional
•Ecologic
•Case-control
•Cohort studies
Experimental
•Randomized
controlled trials
•Field Trials
•Community
Trials
Strength of evidence for causality between a risk factor and outcome
Descriptive studies
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Getting a “lay of the land”
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Surveys (NHIS, MCBS)
Describing a novel phenomena
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Case reports or case series
Descriptive studies
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Cannot establish causal relationships
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Still play an important role in describing trends and
generating hypotheses about novel associations
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The start of HIV/AIDS research
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Squamous cell carcinoma in sexual partner of Kaposi sarcoma patient.
Lancet. 1982 Jan 30;1(8266):286.
New outbreak of oral tumors, malignancies and infectious diseases
strikes young male homosexuals. CDA J. 1982 Mar;10(3):39-42.
AIDS in the "gay" areas of San Francisco. Lancet. 1983 Apr
23;1(8330):923-4.
Analytic Studies
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Attempt to establish a causal link between a
predictor/risk factor and an outcome.
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You are doing an analytic study if you have any of the
following words in your research question:
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greater than, less than, causes, leads to, compared with,
more likely than, associated with, related to, similar to,
correlated with
Hierarchy of Study Types
Descriptive
•Case report
•Case series
•Survey
Analytic
Observational
•Cross sectional
•Ecologic
•Case-control
•Cohort studies
Experimental
•Randomized
controlled trials
•Field Trials
•Community
Trials
Strength of evidence for causality between a risk factor and outcome
Research Question
Is the regular consumption of Red Bull
associated with improved academic
performance among U.S. medical students?
Background
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Alford C, Cox H, Wescott R. The effects of red bull energy drink on human
performance and mood. Amino Acids. 2001;21(2):139-50.
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Warburton DM, Bersellini E, Sweeney E. An evaluation of a caffeinated taurine
drink on mood, memory and information processing in healthy volunteers without
caffeine abstinence. Psychopharmacology (Berl). 2001 Nov;158(3):322-8.
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Seidl R, Peyrl A, Nicham R, Hauser E. A taurine and caffeine-containing drink
stimulates cognitive performance and well-being. Amino Acids. 2000;19(3-4):63542.
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Horne JA, Reyner LA. Beneficial effects of an "energy drink" given to sleepy
drivers. Amino Acids. 2001;20(1):83-9.
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Kennedy DO, Scholey AB. A glucose-caffeine 'energy drink' ameliorates subjective
and performancedeficits during prolonged cognitive demand. Appetite. 2004
Jun;42(3):331-3.
Great idea, but how do you get started….
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Interesting, novel, and relevant, but…
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You only have 25,000 dollars to start
investigating this question.
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What is feasible?
Study Design #1
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Cross-sectional study of UCSF medical students taking
USMLE Step 2
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Questionnaire administered when registering for USMLE 2
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Primary predictor: self-report of >3 cans Red Bull per week for the
previous year
Covariates: Age, sex, undergraduate university, place of birth
Outcome: Score on USMLE Step 2
Cross-sectional study: structure
Red Bull consumption
USMLE Score
time
Cross-sectional Study:
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Descriptive value:
 How many UCSF medical students drink Red Bull?
 What is the age and sex distribution of UCSF medical
students who drink Red Bull?
Analytic value:
 Is there an association between regular Red Bull consumption
and test scores among UCSF med students?
Cross-sectional Study: Pluses
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Prevalence (not incidence)
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Fast/Inexpensive - no waiting!
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No loss to follow up
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Associations can be studied
Measures of association
Risk ratio
(relative risk)
Disease
Yes
No
Yes
A
B
No
C
D
Risk
Factor
A
A+B
C
C+D
Cross-sectional study: minuses
- Cannot determine causality
Red Bull consumption
USMLE Score
time
Cross-sectional study: minuses
- Cannot determine causality
•ACE inhibitor use and hospitalization rates among
those with heart failure
time
Cross-sectional study: minuses
- Cannot determine causality
- Cannot study rare outcomes
What if you are interested in the rare
outcome?
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The association between regular Red Bull
consumption and…
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A perfect score on the USMLE – Step 2
Graduating top 1% of the medical school class
Acceptance into a highly selective residency
ANSWER: A Case-Control study
Study Design #2
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A case-control study
Cases: med students accepted to residency in “highly
selective specialty X”.
Controls: med students who applied but were not accepted.
Predictor: self-reported regular Red Bull consumption
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Additional covariates (age, sex, medical school, undergraduate
institution)
Case control studies
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Investigator works “backward” (from
outcome to predictor)
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Sample chosen on the basis of outcome
(cases), plus comparison group (controls)
Study multiple exposures in a
Case-control Study
C
B
C
B
Exposed
to A
Not Exposed
to A
Disease
C
B
C
B
Exposed
to A
Not Exposed
to A
No Disease
Case-control study structure
present
ACTUAL CASES
students
who matched in “highly
selective specialty X”
Red Bull consumption
YES
Red Bull consumption
NO
ACTUAL CONTROLS
students who failed
to match in “highly selective
specialty X”
time
Case control studies
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Determines the strength of the association
between each predictor variable and the
presence or absence of disease
Cannot yield estimates of incidence or
prevalence of disease in the population
(why?)
Odds Ratio is statistics
Case-control Study: pluses
+ Rare outcome/Long latent period
+ Inexpensive and efficient: may be only feasible option
+ Establishes association (Odds ratio)
+ Useful for generating hypotheses (multiple risk factors
can be explored)
Case-control study-minuses
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Causality still difficult to establish
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Selection bias (appropriate controls)
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Recall bias: sampling (retrospective)
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Cannot tell about incidence or prevalence
Where are we?
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Preliminary results from our cross-sectional and casecontrol study suggest an association between Red Bull
consumption and improved academic performance among
medical students
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What’s missing? - strengthening evidence for a causal link
between Red Bull consumption and academic performance
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Use results from our previous studies to apply for funding
for a prospective cohort study!
Study design #3
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Prospective cohort study of UCSF medical
students Class of 2009
All entering medical students surveyed regarding
consumption and variety of other potential
covariates
Survey updated annually to record changes in
Red Bull consumption
Outcomes: USMLE Step 1 score, USMLE Step
2 score, match in first choice residency
Cohort studies
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A cohort (follow-up, longitudinal) study is a comparative,
observational study in which subjects are grouped by their
exposure status, i.e., whether or not the subject was
exposed to a suspected risk factor
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The subjects, exposed and unexposed to the risk factor, are
followed forward in time to determine if one or more new
outcomes (diseases) occur
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Subjects should not have outcome variable on entry
The rates of disease incidence among the exposed and
unexposed groups are determined and compared.
Study multiple outcomes in a
cohort Study
Not Exposed
Exposed
Develop
Disease A
B
C
Do not
Develop
Disease A
Develop
Disease A
B
C
B
C
Do not
Develop
Disease A
B
C
Elements of a cohort study
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Selection of sample from population
Measures predictor variables in sample
Follow population for period of time
Measure outcome variable
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Famous cohort studies
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Framingham
Nurses’ Health Study
Physicians’ Health Study
Olmsted County, Minnesota
Prospective cohort study structure
The present
The future
Top USMLE scorers
Everyone else
time
Strengths of cohort studies
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Know that predictor variable was present before
outcome variable occurred (some evidence of
causality)
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Directly measure incidence of a disease outcome
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Can study multiple outcomes of a single
exposure (RR is measure of association)
Weaknesses of cohort studies
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Expensive and inefficient for studying rare outcomes
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Often need long follow-up period or a very large population
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Loss to follow-up can affect validity of findings
Other types of cohort studies
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Retrospective cohort
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Identification of cohort, measurement of predictor
variables, follow-up and measurement of outcomes
have all occurred in the past
Much less costly than prospective cohorts
Investigator has minimal control over study design
Other types of cohort studies
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Nested case-control study
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Case-control study embedded in a cohort study
Controls are drawn randomly from study sample
Case cohort Study
Hierarchy of Study Types
Descriptive
•Case report
•Case series
•Survey
Analytic
Observational
•Cross sectional
•Ecologic
•Case-control
•Cohort studies
Experimental
•Randomized
controlled trials
•Field Trials
•Community
Trials
Strength of evidence for causality between a risk factor and outcome
What distinguishes observational studies from
experiments?
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Ability to control for confounding
Confounder
Predictor
Outcome
Examples:
sex (men are more likely to drink red bull and men are
more likely to match in neurosurgery)
Undergraduate institution (students from northwest school are more likely
to drink red bull and also more likely to score higher on
USMLE)
But we measured all of the potential
confounders…….
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In a prospective cohort study you can (maybe)
measure all potential known confounders,
but…
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You can’t control for unmeasured
confounders
Study design # 4
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Randomized controlled trial of daily Red Bull consumption
among entering UCSF medical students Class 2009
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Randomized to daily consumption of Red Bull vs. daily
consumption of placebo
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Outcomes: USMLE Step 1 score, USMLE Step 2 score,
match in first choice residency
Randomized controlled trials
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Investigator controls the predictor variable
(intervention or treatment)
Major advantage over observational studies is
ability to demonstrate causality
Randomization controls unmeasured
confounding
Only for mature research questions
Basic Trial Design
Population
Sample
Treatment
Dx
No Dx
Randomization
Control
Placebo
Dx
No Dx
Steps in a randomized controlled
trial
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Select participants
Measure baseline variables
Randomize
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Eliminates baseline confounding
Types (simple, stratified, block)
Steps in a randomized controlled
trial
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Blinding the intervention
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As important as randomization
Follow subjects
Measure outcome
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Clinically important measures
Adverse events
Comparing Cohort Studies with
Randomized Trials
Interventional Study
Observational Study
Study group
Study group
Random Allocation
No Allocation
Group A
Group B
Group A
Group B
Hierarchy of Study Types
Descriptive
•Case report
•Case series
•Survey
Analytic
Observational
•Cross sectional
•Ecologic
•Case-control
•Cohort studies
Experimental
•Randomized
controlled trials
•Field Trials
•Community
Trials
Strength of evidence for causality between a risk factor and outcome
How to Write Methods &
Material Section?
Dr. Gholamreza Khalili
Department of Epidemiology & Biostatistics
School of public health
Tehran University of Medical Sciences
Methods
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Allows reader to judge the quality of the work
Identifies weaknesses
Allows repetition of the study
State the study design & specifications
Methods
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WWWWWH (who, what, where, why, when &
how?)
Define variables
Patient/Participants inclusion
Dates
Randomisation/Placebo/Blindness
Ethics/consent
Treatments
Outcomes and endpoints
Statistical methods & power
Check list for Methods
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Study design mentioned?
Who, what, where, why, how, when?
Inclusion/exclusion criteria?
logical & chronological order?
Measurements defined? justified? detailed?
referenced?
Check list for Methods
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Sample size justified?
Transformations and statistical analyses clear?
New techniques validated properly?
Could the reader reproduce your study from
the details provided?
Methods
What subjects/patients/animals/specimens
techniques were used?
 Reason for selecting the experimental design
of the study.
 Statistical methods used for analysis
 The section should be called "Material and
Methods” only if inanimate specimens have
been used.
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(continue)
Methods
Patient / Animals / Specimens
• Numbers
• How are they grouped
• Criteria
• Informed consent obtained
Techniques
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Give enough details for readers to assess the
validity of the results, and repeat the study
If standard techniques is used, give
appropriate reference, any modifications
should be clearly explained
If drug trial, clear description of trial
CONSORT Statement
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CONSORT stands for Consolidated Standards of
Reporting Trials.
It is developed by the CONSORT Group to alleviate
the problems arising from inadequate reporting of
randomized controlled trials (RCTs).
The website: http://www.consort-statement.org
Methods
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Study design
Participants
Ethical approval
Sample size
Questionnaires
Interventions
Clinical assessments
Statistical methods
What to include in the methods section (1)
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How the study was designed:
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Keep the description brief
Say how randomization was done
Use names to identify parts of study sequence
What to include in the methods section (2)
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How the study was carried out:
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How the participants were recruited and chosen
Give reasons for excluding participants
Consider mentioning ethical features
Give accurate details of materials used
Give exact drug dosages
Give exact form of treatments
What to include in the methods section (3)
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How the data were analysed:
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Use a P value to disprove the null hypothesis
Give an estimate of power of the study
Give the exact tests used for statistical analysis
How to Write
Abstract Section?
Dr. Gholamreza Khalili
Department of Epidemiology & Biostatistics
School of public health
Tehran University of Medical Sciences
The Abstract
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The function of the abstract is to provide an
overview of the paper.
The overview should present the main story and a
few essential details of the paper for readers who
read only the abstract and should serve as both a
clear preview and a clear, accurate recapitulation of
the main story for readers who read the paper.
Thus, the abstract should make sense both when
read alone and when read with the paper .
Abstract
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Summarizes the major findings in the broad
context of the work
Consists of two or three sentences of topic
introduction
Selected results (not all but the most
important)
Concludes with implications of work
Abstracts
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The abstract should be neither vague and
general on the one hand nor fussily
detailed on the other. It should be specific
and selective.
Abstracts
The abstract of a paper should state concisely:
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the question that was asked,
what was done to answer the question,
what was found that answers the question,
and
the answer to the question.
Abstracts
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Most journals limit the length of the abstract
(usually to 250 words or less) “Uniform
Requirements for Manuscripts Submitted to
Biomedical Journals”
For un-structured abstracts, limit the abstract to
150 words or less.
If no limit is stated, make your abstract no
longer than the abstracts in recent issues of the
journal.
In summary:
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The abstract should provide an overview of
the main story and a few essential -details.
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The abstract should be clear both to readers
who read the paper and to readers who do not
read the paper.
Abstract Writing
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Write the abstract as one paragraph.
Use the techniques of continuity to
make the paragraph flow. Use signals to
indicate the parts of the abstract:
Signal what you found by "We found
that" or something similar.
Abstract Writing
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Signal the answer by "We conclude that" or "Thus"
or something similar. Signal implications by "We
suggest that" or something similar.
The question and what was done can usually be
written in one sentence in “the form "To determine
X, we. ..." If the question and what was done are in
separate sentences, use signals such as "We asked
whether. .." (question) and "To answer this question,
we. .." (what was done).
Abstract Writing
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Use present tense verbs for the question and the
answer.
Use past tense verbs to state what was done and
what was found.
Be careful not to omit the question, not to state
the question vaguely, and not to state an
implication instead of the answer .
Abstract Writing
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To ensure that the question is specific
rather than vague, check the question
against the answer: use the same key terms
for the independent and dependent
variables; keep the same point of view;
and, to anticipate the answer , use the same
verb in the question as in the answer .
If you give a p value, also give data (for
example, mean(SD) and the sample size
(n).
Abstract Writing
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Write short sentences.
Use simple words. Avoid jargon. Avoid
abbreviations. Keep the abstract short.
Omit less important information (experimental
preparation, confirmatory results, comparisons
with previous results, data for less important
variables, definitions, background,
implications).
Abstract Writing
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Omit details [unnecessary details of
methods, exact data (give percent
change), p values, "significantly"].
Avoid repetition (use a category term in
what was done and name the variables in
what was found; state "mean ::t SD" only
once).
Use active voice instead of passive voice.
Abstract Writing
Omit unnecessary words (use "Thus"
instead of "We conclude that"; use an
adjective or an apostrophe instead of an "of'
phrase: for example, "ductal rings" instead
of "rings of ductus arteriosus," "rings'
sensitivity" instead of "sensitivity of the
rings"; but do not omit "a," "an," or "the"
when they are necessary).
Exceptions
 If the journal to which you are submitting a
paper requests a different form for the
abstract, follow the requested form.
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Keywords
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Select terms that you would look up to find your own
paper and that would attract the readers you hope to
reach.
Select current, specific terms, preferably medical
subject headings (MeSH), that name important topics
in your paper .
Use phrases as well as single words.
If the journal asks you to supply only terms that are
not in the title of the paper, do so
If necessary, include a term as an indexing term even
if the term does not appear in your paper .
Check list for Abstract
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Background, methods, results, discussion?
Key features mentioned?
Anything that does not appear in full text?
Results in words?
Conclusion: justified? objective?
Meaningful interpretation
Follows the guidelines