Fundamentals of Clinical research and experimental design

Usama M. Fouda

Professor of Obstetrics and Gynecology , Faculty of medicine, Cairo University .

Egypt

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.

Classification of clinical studies

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.

Other classifications of clinical studies

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.

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.

• 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.

• 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.

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.

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.

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.

• 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‘.

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.

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.

• 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)

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").

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).

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

4) Recall bias.

5) Sampling bias.

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.

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.

• 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.

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.

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

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.

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.

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.

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.