1. The document discusses various types of clinical research studies including observational studies like case reports, cross-sectional studies, and analytical studies like case-control and cohort studies. 2. Randomized controlled trials are described as the gold standard for clinical trials, with randomization and blinding methods explained to reduce bias. 3. Common study designs like parallel group, dose-ranging, cross-over, and factorial designs are summarized along with an example of the Physician's Health Study factorial design.

1. 1
Clinical Research Basics
Mohamed Fahmy Doheim
M.B.B.Ch Candidate

2. Previous lecture

3. Previous lecture

4. Study Designs

5. Type of studies
primary secondary
Observational interventional
AnalyticDescriptive
Reviews
Narrative Systematic

6. Observational Studies
Descriptive Analytic
1- Case reports/series
2- Cross sectional
1- Case control
2- Cohort
3- Cross sectional

7. Interventional studies
Clinical trials

9.  Randomized controlled trials
are the standards of excellence for
clinical trials.
 Other types:
• Uncontrolled trials.
• Non randomized trials
According to the study design

10. Randomization
• Allocation of treatments to participants is
carried out using a chance mechanism so
that neither the patient nor the physician
know in advance which therapy will be
assigned
• Simplest Case: each patient has the same
chance of receiving any of the treatments
under study

11. • We can not ensure comparability but
Randomization helps to balance all factors
between treatment groups
• If randomization “works” then groups will be
similar in all aspects except for the treatment
received

12. Blinding
• Masking the identity of the assigned
interventions
• Main goal: avoid potential bias caused by
conscious or subconscious factors
• Open-label.
• Single blind: patient is blinded
• Double blind: patient and assessing
investigator are blinded
• Triple blind: e.g. Statistician is also blinded

13. General Study Designs
• Many clinical trial study designs fall into the
categories of parallel group, dose-ranging,
cross-over and factorial designs
• There are many other possible designs and
variations on these designs

14. General Study Designs
• Parallel group designs
R
A
N
D
A
B
C
control

15. General Study Designs
• Dose-Ranging Studies
R
A
N
D
high dose
medium dose
low dose
control

16. General Study Designs
• Cross-Over Designs
R
A
N
D
A
B
B
A
WASH-OUT

17. General Study Designs
• Factorial Designs
R
A
N
D
A + B
A + c o n tro l
B + c o n tro l
c o n tro l + c o n tro l

18. Factorial Designs
• Example: Physician’s Health Study
• Physicians randomized to:
aspirin (to prevent cardiovascular disease)
beta-carotene (to prevent cancer)
aspirin and beta-carotene
neither (placebo)
Stampfer, Buring, Willett, Rosner, Eberlein and Hennekens
(1985) The 2x2 factorial design: it’s application to a randomized
trial of aspirin and carotene in U.S. physicians. Stat. in Med.
9:111-116.

20. Observational Designs
• Descriptive: used to formulate a
certain hypothesis: small / large scale.
Examples: case report,case-series;
correlation studies, cross-sectional
studies
• Analytical: used to test hypotheses:
small / large scale. Examples: case-
control, cross-sectional, cohort.

23. Cross-sectional studies
(Prevalence studies)
• Cross-sectional studies aim at describing
and quantifying the distribution of disease,
risk factors, or other characteristics in a
defined population at one particular time.
• Cross-sectional studies cover a selected
sample of a defined population
(surveys). If a cross-sectional study
covers the total population it is called a
census.

24. Cross-sectional studies
(Prevalence studies)
• Cross-sectional studies form a bridge
between simple descriptive studies
(case reports and case series) and
those that can test hypotheses
(analytic and intervention studies).
• They can suggest the presence of
relationships.

25. ANALYTICAL STUDIES
• Describe associations (between
exposure & outcome) and analyze
them for possible cause and effect.
• Attempt to establish causes or risk
factors for certain problems.

26. • This is done by comparing two or
more groups, some of which have
or develop the problem and some of
which have not.
Comparison
(Control)
Group

27. Types of analytical studies
• Case-control studies
• Cohort studies
•Cross sectional study

28. Case-control studies
• In a CASE-CONTROL STUDY the investigator
compares one group among whom the problem
that he wishes to investigate is present (e.g.
malnutrition) and another group called a control
or comparison group, where the problem is
absent, in order to find out what factors have
contributed to the problem.

29. Cohort studies
• In a COHORT STUDY, a group of individuals that
is exposed to a risk factor (study group) is
compared to a group of individuals not
exposed to the risk factor (control group).
• The researcher follows both groups over time and
compares the occurrence of the problem that
he expects to be related to the risk factor in the
two groups to determine whether a greater
proportion of those with the risk factor are indeed
affected.

30. Smoking
(varying from Not
smoking to Smoking >
3 packets/day)
Lung cancer
(yes, no)
Independent variable
(Exposure)
Dependent variable
(Outcome)
Study of smokers and non-smokers to determine the
importance of smoking as a risk factor for developing
lung-cancer.

31. SECONDARY RESEARCH
REVIEW
ARTICLES
(Narrative
reviews)
SYSTEMATIC
REVIEW
META-
ANALYSIS

32. REVIEW ARTICLES
(Narrative reviews)
Health care professionals have always used review articles as
a source of summarized evidence on a particular topic.
Review articles in the medical literature have traditionally
been in the form of ‘‘narrative reviews’’ where experts in a
particular field provide what is supposed to be a ‘‘summary of
evidence’’ in that field.
Narrative reviews, although still very common in the medical
field, have been criticized because of the high risk of bias,
and ‘‘systematic reviews’’ are preferred.
Systematic reviews apply scientific strategies in ways that
limit bias to the assembly, a critical appraisal, and
synthesis of relevant studies that address a specific
clinical question.

33. Systematic review & Meta-
analysis
• A systematic review is a comprehensive survey of a topic
in which all of the primary studies of the highest level of
evidence have been systematically identified, appraised
and then summarized according to an explicit and
reproducible methodology.
• A meta-analysis is a survey in which the results of all of
the included studies are similar enough statistically that
the results are combined and analyzed as if they
were one study.
In general, a good systematic review or meta-analysis will
be a better guide to practice than an individual article.

35. META-ANALYSIS
Following a systematic review, data
from individual studies may be pooled
quantitatively and reanalyzed using
established statistical methods.

36. The typical graph for displaying the results of
a meta-analysis is called a ‘‘forest plot’’.
The center of the diamond
represents the combined
treatment effect (0.37)

38. Hierarchy of evidence