Fundamentals of clinical research and experimental design

1. Fundamentals of Clinical research and experimental design
Usama M. Fouda
Professor of Obstetrics and Gynecology , Faculty of medicine, Cairo University .
Egypt

2. What is a clinical research?
• Clinical research involves the scientific investigation of the
etiology, prevention, diagnosis or treatment of human disease
using human subjects, human populations or materials of human
origin.

3. Classification of clinical studies

4. Some terms concerning observational studies
• Exposure: environmental or clinical factor, that could potentially
influence incidence in certain diseases or mortality. Smoking,
alcohol drinking, low birth weight, etc.
• Outcome: disease (cancer, cardiovascular diseases) or death.

5. Other classifications of clinical studies

6. Another way to classify clinical studies
• Retrospective studies
The study involves collecting data about events that happened
before the study was designed (surveys, archive data, etc.) and not
about events that will happen in future.
• Prospective studies
The study involves data collection about events that are going to
happen in the future.

7. A) Randomized controlled trial
• A randomized controlled trial is a type of scientific (often medical)
experiment which aims to reduce bias when testing a new
treatment.
• The people participating in the trial are randomly allocated to
either the group receiving the treatment under investigation or to
a group receiving standard treatment (or placebo treatment) as
the control.

8. • Randomized; the decision about whether a patient in the trial
receives the new treatment or the control treatment (or placebo)
is made randomly.
• Controlled; the trial uses a control group for comparison or
reference. In the control group, the patients do not receive the
new treatment being tested, but receive a reference treatment or
placebo instead.
• Trial; the drug or treatment is on trial during an RCT.

9. • RCTs are often used to test the efficacy or effectiveness of various
types of medical intervention.
• Randomization in a clinical trial helps to remove bias and to ensure
that the two groups being compared are truly similar, and that - as
far as possible - the only difference that could influence the
outcome in their disease is whether or not they are receiving the
new drug.

10. Double and single blind trials
A high-quality clinical trial is typically double-blind, or single-blind
where double-blinding is not possible.
Single-blind; the patients do not know if they are receiving the
active treatment or a placebo.
Double-blind; the patients and the physicians treating and
assessing those patients are unaware of who is in the active
treatment group.

13. B) Cross-sectional study (prevalence study)
• Cross-sectional study is an observational study that involves the
analysis of data collected from a population at one specific point in
time.
• They may be used to describe some feature of the population,
such as prevalence of an illness, or they may support conclusions
of cause and effect.

15. C) Cohort study
• Cohort study is an observational study used to investigate the
causes of disease, establishing links between risk factors and
health outcomes.
• Cohort studies typically observe large groups of individuals,
recording their exposure to certain risk factors to find clues as to
the possible causes of disease.

16. • The cohort study design is the best available scientific method for
measuring the effects of a suspected risk factor.
• Cohort studies are considered to be better than case-control
studies because they are usually "prospective" whereas the latter
being 'retrospective‘.

17. Limitations of Cohort study
1) Expensive to run and usually take many years to produce results.
2) Unsuitable for identifying the cause(s) of rare diseases or sudden
outbreak of disease.
3) Needs large number of people.
4) Offer clues (rather than definitive proof) about the causes of
disease.

18. Example for a cohort study
The Nurses’ Health Study was established in 1976, when a cohort of
121 700 US female registered nurses aged 30–55 years completed a
questionnaire on medical conditions and lifestyle practices. A total of
1799 newly diagnosed breast cancer cases occurred during the first
10 years of follow-up from mid-1976 to mid-1986.

19. • Analyses were then conducted to investigate the relationship
between oral contraceptive use and risk of breast cancer.
• Women who reported in the initial questionnaire in 1976 and in
subsequent ones to have never taken oral contraceptives were
considered as the ‘unexposed’ group in this analysis (Romieu et
al., 1989)

21. D) Case-control study
• A case-control study is a type of observational study in which
two existing groups differing in outcome are identified and
compared on the basis of some supposed causal attribute.
• Case-control studies are often used to identify factors that may
contribute to a medical condition by comparing subjects who
have that condition/disease (the "cases") with patients who do
not have the condition/disease but are otherwise similar (the
"controls").

22. Example for a case control study
• A case–control study was carried out in to assess the relationship
between cervical cancer and exposure to human papillomavirus
(HPV), smoking and selected aspects of sexual and reproductive
behavior.
• The study included 436 incident cases of cancer cervix and 387
controls of similar age randomly selected from the general
population that generated the cases (Muñoz et al., 1992).

24. Advantages of case control studies
1) Relatively quick and easy.
2) Does not need large numbers of people.
3) Suitable for identifying the cause(s) of rare diseases or sudden
outbreak of disease.
Limitations of case control studies
1) Recall bias.
2) Sampling bias.

25. A case-control study identifies cases of disease first and then
analyzes exposure to risk factors, whereas cohort studies follow
exposure data and watch for any emerging cases of disease.

27. Primary versus secondary research
• Primary research is defined as factual, firsthand accounts of the
study written by a person(s) who was a part of the study.
• Primary research tends to come first in the publication cycle.
• Primary research can be a conference paper, article published in a
journal or thesis.

28. • Secondary research is defined as an analysis and interpretation of
primary research.
• Secondary research tends to come second in the publication cycle.
• The method of writing secondary research is to collect primary
research that is relevant to a writing topic and interpret what the
primary research found.
• Secondary research can be a review or meta-analysis.

30. Systematic review
• A systematic review is a type of literature review that collects and
critically analyzes multiple research studies.
• The researchers use an organized method of locating, assembling,
and evaluating a body of literature on a particular topic using a
set of specific criteria [PRISMA].
• The systematic review may also include a quantitative pooling of
data, called a meta-analysis.

32. Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA)

34. Meta-analysis
• A meta-analysis uses a statistical approach to combine the results
from multiple studies in an effort to increase power (over
individual studies) and/or to resolve uncertainty when reports
disagree.

40. Practice guidelines ( clinical guidelines)
• A statement produced by a panel of experts that outlines current
best practice to inform health care professionals and patients in
making clinical decisions.
• The statement is produced after an extensive review of the
literature and is typically created by professional associations,
government agencies, and/or public or private organizations.

41. Good guidelines clearly define the topic; appraise and summarize
the best evidence regarding prevention, diagnosis, prognosis,
therapy, harm, and cost-effectiveness; and identify the decision
points where this information should be integrated with clinical
experience and patient wishes to determine practice.

42. Advantages
• Created by panels of experts.
• Based on professional published literature.
• Practical guidance for clinicians.
• Considered an evidence-based resource.
Disadvantages
• Slow to change or be updated.
• Not always available, especially for controversial topics.
• Expensive and time-consuming to produce.