http://bahrain.cochrane.org http://www.rt.ae The Bahrain Branch of the UK Cochrane Centre In Collaboration with Reyada Training & Management Consultancy, Dubai-UAE Cochrane Collaboration and Systematic Review Workshop, 20-21
Download ReportTranscript http://bahrain.cochrane.org http://www.rt.ae The Bahrain Branch of the UK Cochrane Centre In Collaboration with Reyada Training & Management Consultancy, Dubai-UAE Cochrane Collaboration and Systematic Review Workshop, 20-21
Slide 1
http://bahrain.cochrane.org
http://www.rt.ae
The Bahrain Branch of the UK Cochrane Centre
In Collaboration with
Reyada Training & Management Consultancy, Dubai-UAE
Cochrane Collaboration and Systematic
Review Workshop, 20-21 February 2007,
Dubai - UAE
W03
Dr. Zbys Fedorowicz, Dr. Dunia Al Hashimi, Dr. Ahmed Al Asfoor
Slide 2
Study Designs
Slide 3
Concepts to take home
• Recognize types of studies
• Recognize types of observational studies
• Strengths and weaknesses of case-control
and cohort study designs.
• Recognize a controlled trial
• Understand randomization,
blinding/masking, placebos
• Understand the ethics of clinical trials
Slide 4
Two Main Categories
• Observational
– Identify subjects first, then
– Observe and record characteristics
• Experimental
– Identify subjects
– Place in common context
– Intervention, then
– Observe effects of intervention
Slide 5
Types of studies
• Observational studies
– Case report/Case series
– Case control
– Cohort
• Experimental studies
Slide 6
Basic Definitions
• Retrospective - Any design that looks at
data that have already been gathered
• Prospective - Any design that collects
data on groups of subjects over time,
according to a carefully written protocol,
beginning at time zero; this design yields
data that enable comparisons of groups.
Slide 7
Basic Definitions
• Bias - A methodological problem resulting
from a selection process that is not
random
• Randomization - A process by which
subjects are assigned to experimental or
control groups so that the 2 groups are the
same in all characteristics.
Slide 8
Basic Definitions
• Population/target population - The total group
of people who are represented by the random
selection of members, usually connoting the
whole population but possibly connoting the
population of any subset, eg, women
• Sample - A subset of subjects from the
population of all who have a particular
characteristic, such as a disease
Slide 9
Basic Definitions
• Blinding - The process by which the identity of a
subject's group assignment (case or control) is
kept hidden from the subject
• Double blinding - A process that ensures that
both the subject and the caregiver or outcome
assessor are unaware of whether the subject is
assigned to the control or the experimental
group.
Slide 10
Case control studies
• Attempt to make inference from existing
observations (retrospective)
• Compares patients with outcome/disease
with those without and attempts to identify
factors that influenced that outcome (or
caused that disease)
• Important concept: start with the result
(disease) and work backwards for the
cause
Slide 11
Controls
• A control is a standard of comparison for
– Effects
– Variability
Slide 12
Case-control studies
• Controlled studies
• Retrospective
Slide 13
Case-control study design
Exposure
Disease
Observer
?
Choose groups with and without disease, look
back at what different exposures they may have
had
Slide 14
The logic of
Case-Control Studies
• Cases differ from controls only in having the
disease.
• If exposure does not predispose to having the
disease, then exposure should be equally
distributed between the cases and controls.
• The extent of greater previous exposure among
the cases reflects the increased risk that
exposure confers
Slide 15
Strengths of case-control
design
• Best study when have rare disease or
outcome
• Relatively quick and inexpensive
Slide 16
Weaknesses (potential biases)
• Selection (confounding) bias: controls must be
as similar to cases as possible
• Representativeness bias: cases should be
“typical”
• Recall bias: cases may be able to remember
events better because of its significance or
may be prompted to remember by investigators
• Survival bias: dead people don’t make it into
many case-cohort studies; and if they do, they
don’t remember things very well
Slide 17
Cohort studies
• Studies whether exposure to a “risk factor”
is associated with a subsequent “outcome”
• Select two populations who seem the
same except for the hypothesized risk
factor
• Follow them ahead in time and see how
many have the outcome or disease
• Important concept: Start with the risk, then
look for the outcome
Slide 18
Cohort studies
• Prospective
• Controlled
• Can determine causes and incidence of
diseases as well as identify risk factors
• Generally expensive and difficult to carry
out
Slide 19
Procedure for cohort study
• Identify groups of exposed subjects and
control subjects
• Match for other risk factors
• Follow over time
• Record the fraction in each group who
develop the condition of interest
• Compare these fractions using RR or OR
Slide 20
Logic of the cohort study
Differences in the rate at which exposed and
control subjects contract a disease is due to
the differences in exposure, since other
known
risk factors are equally present in the two
groups
Slide 21
Cohort study design
(Prospective)
Exposure
Observer
Disease
?
Start with two groups of people who are exposed
and unexposed, follow them to see who gets
disease.
Slide 22
Strengths of cohort study
• Not only can you look at risk, you can
calculate how many people actually get
the disease (incidence rates)
• Since you enroll subjects before the
outcome, you can measure multiple
exposures without recall bias
• Best for rare exposures
Slide 23
Potential biases in cohort
studies
• Selection (confounding) bias: have to
match similar groups – “Healthy worker
effect”
• Detection bias: measurement of
outcomes needs to be objective and
similar for both groups
• Length-time bias: study has to be long
enough for outcome to happen
• Excursion bias: subjects may disappear
or drop-out (lost to follow-up)
Slide 24
Some other problems
• Cohort studies may take a long time
• Cohort studies may require a large
number of people especially if the
outcome is uncommon
• Both of these make cohort studies
expensive
Slide 25
Experimental design
• Investigator controls exposure to the risk
or treatment by assigning subjects to one
group (experimental group) or another
(control group)
• Assignment to experimental or control
attempts to make sure both group are
similar in all ways except the experimental
manipulation
Slide 26
Randomization of subjects
• To help assure that groups are similar,
subjects are randomly assigned to
experimental or control groups
• Randomization is performed to increase
the likelihood that groups are matched in
other, non-experimental ways
• Randomization does not assure that the
groups are the same: still need to assess
whether they are
Slide 27
Randomised controlled trial
(RCT)
• Best form of healthcare evidence, or
the “gold standard” for evidence about
an intervention.
• lack of randomisation can give a 40 %
over or underestimate of treatment effect
synthesis of those trials statistical and
clinical heterogeneity.
Slide 28
Randomised controlled trial
intervention
group 1
Outcome
group 2
Outcome
population
control
Slide 29
RCT
RCT
SYSTEMATIC
REVIEW
RCT
Meta-analysis
“STRONGER” EVIDENCE
RCT
Slide 30
Randomization and
Confounding
• Randomization is supposed to have the
effect of distributing confounders both
known and unknown between the
intervention and control groups
Slide 31
Blinding
• Even after randomization, it is possible
that experimental subjects may be treated
differently than controls
• To combat this, “blinding” is often used
(also called masking)
• Blinding means that the subject,
investigator, or both (double-blind) do not
know what group the subject is assigned
to
Slide 32
Placebos
• Placebos are another way of trying to make
both groups similar
• A placebo is a biologically inactive substance
given to the control group so that they think
they are being treated
• “Placebo effect” is important: many patients in
the placebo group report getting better simply
because they are taking the placebo!
Slide 33
Are placebos ethical?
• When there is no known successful
therapy, a placebo is ethical (but
withholding a treatment known to be
effective is not!)
• Using a placebo instead of the
experimental drug is ethical since the
experimental drug is not known to be
beneficial and could actually be harmful
http://bahrain.cochrane.org
http://www.rt.ae
The Bahrain Branch of the UK Cochrane Centre
In Collaboration with
Reyada Training & Management Consultancy, Dubai-UAE
Cochrane Collaboration and Systematic
Review Workshop, 20-21 February 2007,
Dubai - UAE
W03
Dr. Zbys Fedorowicz, Dr. Dunia Al Hashimi, Dr. Ahmed Al Asfoor
Slide 2
Study Designs
Slide 3
Concepts to take home
• Recognize types of studies
• Recognize types of observational studies
• Strengths and weaknesses of case-control
and cohort study designs.
• Recognize a controlled trial
• Understand randomization,
blinding/masking, placebos
• Understand the ethics of clinical trials
Slide 4
Two Main Categories
• Observational
– Identify subjects first, then
– Observe and record characteristics
• Experimental
– Identify subjects
– Place in common context
– Intervention, then
– Observe effects of intervention
Slide 5
Types of studies
• Observational studies
– Case report/Case series
– Case control
– Cohort
• Experimental studies
Slide 6
Basic Definitions
• Retrospective - Any design that looks at
data that have already been gathered
• Prospective - Any design that collects
data on groups of subjects over time,
according to a carefully written protocol,
beginning at time zero; this design yields
data that enable comparisons of groups.
Slide 7
Basic Definitions
• Bias - A methodological problem resulting
from a selection process that is not
random
• Randomization - A process by which
subjects are assigned to experimental or
control groups so that the 2 groups are the
same in all characteristics.
Slide 8
Basic Definitions
• Population/target population - The total group
of people who are represented by the random
selection of members, usually connoting the
whole population but possibly connoting the
population of any subset, eg, women
• Sample - A subset of subjects from the
population of all who have a particular
characteristic, such as a disease
Slide 9
Basic Definitions
• Blinding - The process by which the identity of a
subject's group assignment (case or control) is
kept hidden from the subject
• Double blinding - A process that ensures that
both the subject and the caregiver or outcome
assessor are unaware of whether the subject is
assigned to the control or the experimental
group.
Slide 10
Case control studies
• Attempt to make inference from existing
observations (retrospective)
• Compares patients with outcome/disease
with those without and attempts to identify
factors that influenced that outcome (or
caused that disease)
• Important concept: start with the result
(disease) and work backwards for the
cause
Slide 11
Controls
• A control is a standard of comparison for
– Effects
– Variability
Slide 12
Case-control studies
• Controlled studies
• Retrospective
Slide 13
Case-control study design
Exposure
Disease
Observer
?
Choose groups with and without disease, look
back at what different exposures they may have
had
Slide 14
The logic of
Case-Control Studies
• Cases differ from controls only in having the
disease.
• If exposure does not predispose to having the
disease, then exposure should be equally
distributed between the cases and controls.
• The extent of greater previous exposure among
the cases reflects the increased risk that
exposure confers
Slide 15
Strengths of case-control
design
• Best study when have rare disease or
outcome
• Relatively quick and inexpensive
Slide 16
Weaknesses (potential biases)
• Selection (confounding) bias: controls must be
as similar to cases as possible
• Representativeness bias: cases should be
“typical”
• Recall bias: cases may be able to remember
events better because of its significance or
may be prompted to remember by investigators
• Survival bias: dead people don’t make it into
many case-cohort studies; and if they do, they
don’t remember things very well
Slide 17
Cohort studies
• Studies whether exposure to a “risk factor”
is associated with a subsequent “outcome”
• Select two populations who seem the
same except for the hypothesized risk
factor
• Follow them ahead in time and see how
many have the outcome or disease
• Important concept: Start with the risk, then
look for the outcome
Slide 18
Cohort studies
• Prospective
• Controlled
• Can determine causes and incidence of
diseases as well as identify risk factors
• Generally expensive and difficult to carry
out
Slide 19
Procedure for cohort study
• Identify groups of exposed subjects and
control subjects
• Match for other risk factors
• Follow over time
• Record the fraction in each group who
develop the condition of interest
• Compare these fractions using RR or OR
Slide 20
Logic of the cohort study
Differences in the rate at which exposed and
control subjects contract a disease is due to
the differences in exposure, since other
known
risk factors are equally present in the two
groups
Slide 21
Cohort study design
(Prospective)
Exposure
Observer
Disease
?
Start with two groups of people who are exposed
and unexposed, follow them to see who gets
disease.
Slide 22
Strengths of cohort study
• Not only can you look at risk, you can
calculate how many people actually get
the disease (incidence rates)
• Since you enroll subjects before the
outcome, you can measure multiple
exposures without recall bias
• Best for rare exposures
Slide 23
Potential biases in cohort
studies
• Selection (confounding) bias: have to
match similar groups – “Healthy worker
effect”
• Detection bias: measurement of
outcomes needs to be objective and
similar for both groups
• Length-time bias: study has to be long
enough for outcome to happen
• Excursion bias: subjects may disappear
or drop-out (lost to follow-up)
Slide 24
Some other problems
• Cohort studies may take a long time
• Cohort studies may require a large
number of people especially if the
outcome is uncommon
• Both of these make cohort studies
expensive
Slide 25
Experimental design
• Investigator controls exposure to the risk
or treatment by assigning subjects to one
group (experimental group) or another
(control group)
• Assignment to experimental or control
attempts to make sure both group are
similar in all ways except the experimental
manipulation
Slide 26
Randomization of subjects
• To help assure that groups are similar,
subjects are randomly assigned to
experimental or control groups
• Randomization is performed to increase
the likelihood that groups are matched in
other, non-experimental ways
• Randomization does not assure that the
groups are the same: still need to assess
whether they are
Slide 27
Randomised controlled trial
(RCT)
• Best form of healthcare evidence, or
the “gold standard” for evidence about
an intervention.
• lack of randomisation can give a 40 %
over or underestimate of treatment effect
synthesis of those trials statistical and
clinical heterogeneity.
Slide 28
Randomised controlled trial
intervention
group 1
Outcome
group 2
Outcome
population
control
Slide 29
RCT
RCT
SYSTEMATIC
REVIEW
RCT
Meta-analysis
“STRONGER” EVIDENCE
RCT
Slide 30
Randomization and
Confounding
• Randomization is supposed to have the
effect of distributing confounders both
known and unknown between the
intervention and control groups
Slide 31
Blinding
• Even after randomization, it is possible
that experimental subjects may be treated
differently than controls
• To combat this, “blinding” is often used
(also called masking)
• Blinding means that the subject,
investigator, or both (double-blind) do not
know what group the subject is assigned
to
Slide 32
Placebos
• Placebos are another way of trying to make
both groups similar
• A placebo is a biologically inactive substance
given to the control group so that they think
they are being treated
• “Placebo effect” is important: many patients in
the placebo group report getting better simply
because they are taking the placebo!
Slide 33
Are placebos ethical?
• When there is no known successful
therapy, a placebo is ethical (but
withholding a treatment known to be
effective is not!)
• Using a placebo instead of the
experimental drug is ethical since the
experimental drug is not known to be
beneficial and could actually be harmful