V Clinical medicine is continuously changing

and expanding, therefore physicians need to

develop methods of seeking out and applying
new information

V Clinicians must therefore develop skills

allowing them to update and reevaluate their
knowledge, enabling them to provide optimal
patient care
V O 40-year-old accountant visited her family physician for a routine
checkup. The patient·s mother had been diagnosed with breast
cancer in the past year, and the patient wanted advice about what
she could do to reduce her own risk of developing this disease.
The patient had two children aged 6 and 8 years. She was in good
health, with regular menstrual cycles, and she had a recent normal
Papanicolaou smear and mammogram.
V In responding to the patient·s questions about breast cancer, the
physician confirmed that a positive family history increases the
risk of developing this disease. O number of other characteristics
are associated with a reduced risk of developing breast cancer,
such as early age at first full-term pregnancy and increasing
number of pregnancies. The physician was also aware of a
controversy regarding the relationship between intake of dietary
fat and occurrence of breast cancer.
V Searching the literature
‡ Must locate appropriate literature
V Reviewing the material
V Establishing causal relationship
V Systematic review
V =elpful resources include:
‡ Computer technology because automated
„ Medline: searches 4600 biomedical journals from 1966-
present
„ Part of the National library of medicine
‡ CD-ROMs
‡ Printed books and journals
‡ DVDs

The information is neither more nor less sound

because of medium by which it happens to come to
you
V It is important to have a uniform and thorough
approach to evaluate the articles
V Steps:
V 1. Consider the research hypothesis
V 2. Consider the study design
V 3. Consider the outcome variable
V 4. Consider the predictor variables
V 5. Consider the method of analysis
V 6. Consider the possible sources of bias
V 7. Consider the interpretation of results
V 8. Consider the utility of the results
V Oll of these should be considered before passing
judgment on an article
 V uirst a physician must determine the purpose of study and if it is clinically important
V There are various types of significance that may be ascribed to research findings

R
 



Statistical Exclusion of chance as an explanation for Statistical tests

findings

Clinical Importance of findings for change in current Magnitude of clinical response to an

clinical practice intervention

Biological uindings help to clarify the mechanism of Compare findings of information from
action invitro and invivo lab experimentation

V Is there a clear statement of the research hypothesis?

V Does the study address a question that has clinical relevance?
V If the study question is of interest, the reader should
then determine what type of study design was
employed:
‡ Case-control, Cohort, or Descriptive

‡ Depending on the disease the physician should determine

which study design would be appropriate

V Is the study design appropriate for the hypothesis?

V Does the design represent any advances over prior
approach?
V Does the study use an experimental or observational
design?
V =ere one looks for the outcome of interest
V Looking at the patient profile the outcome of interest
is the development of breast cancer
V It is important to specify how the presence or
absence of breast cancer was determined
V Possibilities:
‡ Death certificates limit information to deceased subjects.
Information may be incomplete or inaccurate
‡ Self-reports require that subjects be alive or have relatives that
could provide information on breast cancer.
‡ Medical records may provide more accurate information, but
diagnostic criteria may differ from physician to physician.
‡ =istopathologic diagnosis
V It is important to judge how precisely the investigator
defines the outcome
V Isthe outcome being studied relevant to
clinical practice?

V Whatcriteria are used to define the

presence of disease?

V Is
the determination of the presence or
absence of disease accurate?
V Risk factor or exposure under investigation
V More variables may limit the ability to collect
detailed info on exposure of interest (although it
may be more comprehensive)
‡ In a study of the cause of breast cancer, an investigator
may choose to examine a variety of exposure variables,
including reproductive factors such as age at first full-
term pregnancy, hormone levels, exposure to radiation,
and dietary fat intake.
V The reader must then determine whether the
methods used to characterize the presence or
absence of exposure are reliable and accurate
V Methods
‡ Subject or surrogate respondent reports
‡ Direct observations
‡ Measurement of biomarkers
V =ow many exposures or risk factors are being
studied?
V =ow is the presence or absence of exposure
determined?
V Is the assessment of exposure likely to be precise
and accurate?
V Is there an attempt to quantify the amount or duration
of exposure?
V Ore biological markers of exposure used in the
study?
V It is important to know which statistical test are important for
which types of analysis
V The type of statistical test that should be used is determined
by the goal of the analysis (e.g. to compare groups, to
explore an association and to predict an outcome) and the
types of variables used in the analysis (categorical, ordinal,
and continuous).
V Biomedical studies observe 5% level of statistical
significance
V Is the sample sized adequate to answer the research
question?
V =ave the assumptions underlying the statistical test been
met?
V =as chance been evaluated as a potential explanation of the
results?
 V Types of bias
º   

Selection bias Sample distorted by selection process

Case-control study³=ospital based
sample
Cohort studies
Information bias Misclassification of the variables
Systemic errors
Confounding On extraneous variable that accounts
for the observed result rather than the
risk factor of interest
 Number of
pregnancies

Dietary Breast
fat intake cancer
V Is the method of selection of subjects likely
to have biased results?
V Isthe measurement of the exposure or the
disease likely to be biased?
V =ave the investigators considered whether
confounders could account for the observed
results?
V What direction would each potential bias
influence the results?
V If the investigator reports a statistically significant result that
can·t be explained by bias the reader must then decide
whether the result is clinically important.
V Ex: O study concluding that a 50% decrease in dietary fat
intake is associated with a 5% decrease in risk of
developing breast cancer. With statistics like this the patient
may not be motivated to make the dietary change.
V =ow large is the observed effect?
V Is there evidence of a dose- response relationship?
V Ore the effects biologically plausible?
V If the findings are negative was there sufficient statistical
power to detect an effect?
V The usefulness of a study finding depends on
various factors, including the purpose of the
study, the limitations of the study population, the
clinical and biologic importance of the results,
and consistency with findings from other
published studies.
V Ore the findings consistent with other studies of
the same questions?
V Can the findings be generalized to other human
populations?
V Do the findings warrant a change in current
clinical practice?
R
 

    
 

Etiologic Can risk be reduced among

susceptible persons?

Diagnostic Can accuracy and timeliness of

diagnosis be improved?

Prognostic Can prognosis be determined more

definitively?

Therapeutic Can treatment be improved?

V Criteriafor evaluating a suspected
causal relationship
‡ Strength
‡ Presence of a dose-response relationship
‡ Correct temporal sequence
‡ Consistency of results across studies
‡ Biological plausibility
V Strength of observed association
‡ =elps in determining whether a risk factor causes a
disease
‡ Determined by the distance of risk ratio or odds
ratio from the null value
‡ Strong association is less likely due to chance or bias
V Dose-response relationship
‡ On increase in the risk factor and an increase in
developing disease good association
‡ But this doesn·t mean that the absence of a
progressive relation is bad association
 
2
1.8
1.6
1.4
1.2
1
Series 1
0.8
0.6
0.4
0.2
0
Low Moderate =igh Very high
V Temporal relationship
‡ Cause must always precede an affect in time
‡ Sometimes suspected factors are actually the result of the
disease
„ Ex: O person with an early undiagnosed cancer may make a
change in food choices and then later they are diagnosed.
‡ Case-control studies of chronic diseases with long latent
periods are particularly susceptible to this
V Consistency
V Biological plausibility
‡ The proposed causal relationship should be consistent
with what is currently known about biology and the
disease process
V meta-analysis is a type of quantitative systemic
review in which the results of multiple studies
that are considered combinable are aggregated
together to obtain a precise, and hopefully
unbiased, estimate of the relationship in question
‡ Combines a series of smaller studies each with a
statistically imprecise estimate of effect, a larger sample
size is obtained, with corresponding increase in statistical
precision
‡ Identifies the differences in findings across different
studies, sensitivity analyses can be conducted that may
lead to greater insight into the sources of heterogeneity
V 1. uormulate clear and meaningful question to be
addressed
‡ Things to consider:
„ Type of persons involved
„ Type of exposure
„ Type of control with which the exposure is compared
„ Outcome to be addressed
V 2. Search for studies of interest
V 3. extract the key data elements from the
included studies
V It is important when conducting meta-analyses
that selection of some studies and exclusions of
others do not lead to a distorted conclusion
V In2003 a meta-analyses of the
relationship between breast cancer and
dietary fat intake.
‡ The review included 45 studies (both case-
control and cohort) with a combined total of
25,000 breast cancer patients and 580,000
control subjects. On overall small increase in
risk of breast cancer was associated with
elevated total fat intake in both case control
(OR=1.14) and cohort studies(RR=1.11)