Clinical Literature

Evaluation
Charliemaign Stanley S. Cruz, R.Ph., MSc.

Content
Overview
Basic Elements of an Article

Overview
The Age of Information
There are tons of information available, some are true,
some are false
CRITICAL EVALUATION of this information is
highly required
Pharmacist are tasked to efficiently locate, critically
analyze, and effectively communicate data from
primary literature in the daily activities of patient care
and the medication use process.

Overview
Primary literatures are one of the most important
sources of information;
New medications
Clinical trial
New and innovative therapies
Errors can still be present and critical evaluation
of PR must be done

Overview
Control Clinical Trial
is the premier study design to measure and
quantify the difference in effect of the
intervention and control
the goal is the quantify effects both (e.g. efficacy
and safety)

Basic Element of an Article

Title
should reflect the work, unbiased, specific and
conscise, but not to general or detailed.
usually <10 words
should include keywords
randomized clinical trial should be identified in
the title

Title
Example:
Improved bronchodilation with levabuterol
compared with racemic albuterol in patients
with asthma.

Abstract
concise overview of the study or synopsis of the
major principles of the article
includes objectives, methods, results and
conclusions
Uses:
provides quick overview for readers
easy of publications in secondary resources

Introduction
Purpose:
discuss study rationale
discuss study purpose
educates readers on the issues that were the basis
for conducting the study
research purpose, objectives and shortcomings of
previous researches will be overcome in the
present

Introduction
Hypothesis must be established clearly
Null hypothesis
Alternative hypothesis
Must also be reviewed properly in case the author
is selective in the information or even use biased
wording

Methodology
methods are important in order for the results to
be valid as well
methodology sections provides information that is
requires very critical evaluation
well-planned methodology leads to higher
internal and external validity

Methodology
Validation
Internal Validity:
quality of study design
study must have a strong study design that
should translate into reliable results
External Validity:
ability to apply results into practice
results that are meaningful to practitioners and
can be used for patients

Methodology
Study Design
the research question dictates the study design to be
followed by researches
strengths and weaknesses of each design must be
considered efficiently
Controlled Clinical Trial
prospectively measures a difference in effect between two
or more therapies. Groups are treated similarly and each
subject is assigned and monitored in one of the groups.

Methodology
Patient Inclusion/Exclusion Criteria
results should be extrapolated to the patient type enrolled in
the study
Inclusion Criteria
list of subject demographics in order for them to enrol in a
study
Exclusion Criteria
characteristic that prevents a subject from enrolling or
requires withdrawal in the future from the study

Methodology
Patient Inclusion/Exclusion Criteria
subject selection may be affected by:
selection bias
gender bias
Run-in phase/Lead-in phase may also be
conducted by researchers

Methodology
Intervention/Control Groups
Intervention Group
intervention under investigation (e.g. medication/
procedure)
Control Group
can be placebo, active control, or historical data
both must be similar in all demographics

Methodology
Institutional Review Board/Subject Consent
IRB is tasked to make sure that subjects are not
exposed to unnecessary harm/unethical medical
procedure
It is also tasked to approve informed consent
forms for subjects

Methodology
Blinding
a technique where the subject/investigator is
unaware of who is the control/intervention
group to avoid further bias
specific blinding type usually is dictated by the
effect being measure during the trial

Methodology
Type of Blinding

Definition

No Blinding

subject/investigator are aware of the

study groups they belong to

Single Blinding

one of the investigator/subject is

unaware the group they belong to

both subject/investigator are unaware

Double Blinding
of the study groups they belong to
Triple Blinding

subject/investigator and personel for

data analysis are unaware of group
assignment

Methodology
Randomization
randomization is a unique differentiator of
controlled clinical trial from other study designs
simple to advance randomization techniques
can be employed in assigning subjects to study
groups

Methodology
Endpoints
should be appropriate for the study purpose and
measured using valid techniques and methods
Primary endpoints: the effect the that was
measure to answer the study objective
Secondary endpoint: other effects that are
important but are not considered the primary
purpose of the study

Methodology
Follow-up Schedule/Data Collection/Adherence
must have been designed to properly monitor
the effects of treatment both short and longterm
data collection/adherence should be monitored
effectively to ensure quality of data gathered
from subjects

Methodology
Statistical Analysis
Statistical analysis gives power to the results of
study.
its purpose is to collect data sufficient to reject
Ho and accept Ha

Methodology
Statistical Analysis
Inferential statistics
used to draw conclusions based on the sample
that can be applied to the population
Descriptive statistics
describes the characteristics of the sample and
results in some study design

Methodology
Type of Data

Definition

Examples

Nominal

categorical data;
exhaustive and exclusive

Yes/No; dead/alive; color of

cars

Ordinal

ranking, ordered

likert scale; visual analog

scale

Interval

data with measurable

equal distances; no true
zero

temperature in degress
fahrenheit

Ratio

data with measurable

equal distances;
absolute/true zero

temperature in kelvin, BP,

Cholesterol levels, RBC

Methodology
Type of
Data

Mode

Nominal

Ordinal

Interval/
Ratio

Median

Mean

Range

Interquar Standard
tile Range Deviation

Methodology
Inferential statistics is used to determine
difference between intervention and control
groups
P-value is computed from trial results and
statistical tests
Alpha level set before the beginning of the trial
(a priori)

Methodology
Hypothesis testing
Null hypothesis (Ho)
Opposing hypothesis, hypothesis of no difference
Results of study are used either to accept Ho or
reject Ho
Research hypothesis (Ha)
Aka alternative hypothesis
States that there are differences among groups of
comparison

Methodology
Random Errors
Type I or Alpha error
Ho is incorrectly rejected
false-positive result
sole reason: chance
Type II or Beta error
Ho is incorrectly accepted
false-negative result
reasons: chance and small sample size

Methodology

Methodology

Statistical Analysis
Non-Parametric Test
Chi-square test

Comparison of nominal data for

independent groups (2x2)

Fischers exact test

Comparison of nominal data for 2 groups

when expected frequency is <5

McNemars test

Comparison of nominal data for 2 matched

or paired groups

Contingency table analysis

(R x C)

Comparison of nominal data when there

are >2 groups or >2 possible outcomes

Cochran Mantel-Haenszel test

Comparison of nominal data for multiple

2x2 tables

Methodology
Non-Parametric Test
Wilcoxon Rank Sum test
Mann-Whitney U test

Comparison of continuous data taken from 2

independent groups

Wilcoxon signed rank test

Comparison of continuous data taken from 2

paired groups

Kruskal Wallis test

Comparison of continuous data taken from

>3 independent groups

Friedmans test

Comparison of continuous data taken from

>3 paired groups

Methodology
Parametric Test
Students T-test

Comparison of continuous data taken from 2

independent groups

Paired T-test

Matched/paired groups

1 Way ANOVA

Comparison of continuous data taken from >3

independent groups

Repeated measures

For paired / matched groups

2 Way ANOVA

Similar to 1 way ANOVA, but can be made for >2

factors

Statistical Analysis
Other Test
Pearson Regression

Determines if a linear correlation between 2

groups when data is normally distributed

Spearman Regression

Determines if a linear correlation between 2

groups when data is NOT normally distributed

Multivariate Regression

Determines relationship of variable with single

dependent continuous variable

Logistic Regression

Determines relationship of multiple variable with

single dependent dichotomous variable

Results
contains primary and secondary endpoint results and
other pertinent information related to the study purpose
Results will include:
subject demographics
subject dropouts/adherence
endpoint/safety
surrogate endpoints
subgroup analysis
monitoring ancillary & adjunctive therapies

Discussion/Conclusion
primary purpose is to evaluate/interpret the
results of the clinical trial
potential explanation about the results should be
made, in addition to discussing internal and
external validity of outcomes

Discussion/Conclusion
Association || Causation
Association: a connection or relationship
among things, people or variables.
Causation: when the expected outcome is a
d i r e c t l y p r ove n r e s u l t o f t h e a p p l i e d
intervention

Discussion/Conclusion
Example:
A study was conducted to know if Drug X causes colon cancer
among patients taking the medication. At the end of the
experiment, it was observed that patients taking Drug X were
twice as likely to develop colon cancer.

Discussion/Conclusion
Criteria in Determining Causation:
1. The strength of the association
2. The consistency of the association (reproducibility)
3. The specificity of the association
4. The temporal relationship between the presumed
cause and effect
5. The presence of a biological gradient or dose-response
relationship

Discussion/Conclusion
Criteria in Determining Causation:
6. The plausibility of the finding with respect to the biological
knowledge of the day
7. Coherence with current scientific theory
8. Use of experimental evidence to determine if the

frequency

of events is related
9. Judgment by analogy, where a finding may be more readily
accepted based on similar evidence
*may not be met in whole
*the more criteria are met, the more it is likely the association is a causation

Discussion/Conclusion
Statistical Significance
when computed p-value is < the determined a
priori alpha value, the results are statistically
significant
Clinical Significance
applicability of results into meaningful clinical
practice that would mean difference in the
outcomes for patients

Bibliography/References
provides a list of literature used to support the
information provided in the study and to also
acknowledge the work made by others
Bibliography
materials cited or not, or other literature that readers
need to refer to for background reading
References
materials that were cited within the text

Acknowledgement/Funding
Acknowledgment
section where recognition to individuals who
contributed to the study but do not meet
authorship requirements are stated
Funding
funding must be disclosed in order to assess
possible existence of bias and conflict of interest