Types of Clinical Studies

Dr. Aya Hassan EL-Kadem, PhD

Lecturer of Pharmacology and Toxicology

Faculty of Pharmacy, Tanta University

 The safety of medicines is under evaluation
throughout the drug development cycle.
 This process starts before humans are exposed,
and continues during the clinical development
and post-marketing phases.
 Broadly, the safety of a medicine is tested in four
phases, each of which produces different types of
data.
These are as follows:

 • Pre-clinical (animal) studies

 • Healthy human volunteer studies (Phase I)

 • Clinical trials (Phases II and III)

 • Post-marketing surveillance (Phase IV)

Pre-clinical studies

 Pre-clinical studies are usually conducted in

rodents (rabbit, mouse, rat) and dogs.

 They aim to establish dosage levels below

which toxicity is not observed and to
identify the organs adversely affected by
higher doses.
The most important potential effects studied are:

 • Major organ toxicity

 • Chronic toxicity

 • Carcinogenicity

 • Mutagenicity (i.e. able to induce genetic mutation)

 • Teratogenicity (i.e. producing physical defects in the embryo)

 Even at this stage, some adverse effects might be acceptable depending on
the ultimate target population for the drug. For example, adverse
reproductive effects could be considered unimportant for a drug that is to be
used exclusively in an elderly population.

 When studies in animals demonstrate major toxicity, further drug

development is usually precluded and the level of toxicity in humans remains
unknown.

 When no major toxicity has been demonstrated in animals, development can

proceed into man.
 Clinical trials

• Clinical trials testing new treatments are divided into different stages,
called phases.

 They incorporate various design features to minimize bias such as

randomization to treatment groups, blinding of subjects and observers to
treatment allocation.
• The earliest phase trials may look at whether a drug is safe or the side
effects it causes.
 Phase I

 For most medicines, the first human exposure takes place in healthy
volunteers and participants are very closely monitored with clinical
supervision.

 Phase I clinical trials are done to test a new treatment for the first time in a
small group of people (e.g. 20-80) to evaluate safety (e.g. to determine a
safe dosage range and identify side effects).
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Phase II Clinical Trial

• Phase II clinical trials are done to study an intervention in

a larger group of people (several hundred) to determine
efficacy (that is, whether it works as intended) and to
further evaluate its safety.
 Phase III Clinical Trial

• Phase III studies are done to study the efficacy of an intervention

in large groups of trial participants (from several hundred to
several thousand) by comparing the intervention to other standard
or experimental interventions .

• Phase III studies are also used to monitor adverse effects and
to collect information that will allow the intervention to be used
safely.
 Phase IV Clinical Trial (Post-
marketing surveillance (PMS):

• Phase IV studies are done after an intervention has been marketed.

These studies are designed to monitor the effectiveness of the
approved intervention in the general population and to collect
information about any adverse effects associated with widespread
use over longer periods of time.

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 Clinical trials will identify most common adverse reactions but often have
important limitations, including:

 • The numbers of patients studied is generally not enough to identify rare but serious
ADRs.

 • The duration of follow-up is usually short.

 • Selection of patients – those at greatest risk of ADRs are often excluded.

 • The artificial conditions – patients are likely to be more closely monitored than in
real life.

 • Measurement of surrogate markers of effect rather than ‘hard’ end-points.