B.

Tech Biotechnology IV
Year

Clinical Trials and Regulatory Affairs

Introduction to
Clinical Trials
Unit I
PowerPoint Lecture Slide Presentation prepared by
R. Saicharan, Assistant Professor, DBT, SNIST

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

What Are Clinical Trials?

Research studies involving people
Try to answer scientific questions and find
better ways to prevent, diagnose, or treat
disease

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Definition of a clinical trial

A research activity that involves

administration of a test treatment to
some experimental unit in order to
evaluate the treatment.

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Key words

Treament

Experimental unit

Evaluate

Pharmaceutical, diet, procedure,

diagnostic, device, program,
placebo.
Subject from a target population.

Assessment of (clinical) effect, but

also adverse events, lab variables,
vital signs, quality of life, health
economy.

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

The Wheel of Science

Experiment

Research
question

Data

Conlusion

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Why Are Clinical Trials Important?

Clinical trials translate results of
basic
scientific research into better ways to
prevent, diagnose, or treat disease
The more people take part, the faster we
can:
Answer critical research questions
Find better treatments
prevent disease

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

and

ways

to

WHY ARE CLINICAL STUDIES

PERFORMED?
No chemical can be certified as completely
"safe". Every chemical is toxic at some
dosage
It is important to estimate the risk
associated with exposure to the chemical
under specified conditions by performing
appropriate tests.
Clinical trials may be required before the
national regulatory authority approves
marketing of the drug or device, or a new
dose of the drug, for use on patients.

7
Copyright R. Saicharan, Assistant Professor, DBT, SNIST

WHEN IS CLINICAL TRIAL NECESSARY?

1. Assess safety and efficacy of New Chemical
Entity
2. Assess safety and effectiveness of a different
dose
(e.g., 10mg dose instead of 5mg dose)
3. Assess safety and efficacy of an already
marketed medication or device for a new
indication i.e. a disease for which the drug is not
specifically approved
4. To compare the effectiveness in patients with a
specific disease of two or more already approved
or common interventions for that disease
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Copyright R. Saicharan, Assistant Professor, DBT, SNIST

History
Perhaps the first ever
clinical trial was James
Linds demonstration in
1753 that citrus fruits
cured
scurvy.
He
compared the effects of
various different acidic
substances ranging from
vinegar to cider, on
groups of sailors, and
found that the group who
were given oranges and
lemons
had
largely
recovered from scurvy
after 6 days.
Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Drug discovery/development process

discovery; refinement; chemical & biological

characterisation

safety & toxicity in animals; formulation development

volunteer studies; patient studies

Lessons &
development

regulatory process

marketing
post registration
monitoring

Discovery=find new active structure : Development=convert it to a useful drug

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

The path to a new medicine

Years 1

First patent
application
Drug Discovery
Target and lead Lead
identification
optimisation

Clinical trial
application

10

11

12

13

14

15

Product licence
application

Drug Development
Development
Concept testing for launch
Clinical Development
Phase I Phase II Phase III
12-150
50-1000 500-5,000
people
people
people

Product life
Launch cycle support

Phase IV studies continue

Toxicology and pharmacokinetic studies

(absorption, distribution, metabolism, excretion)
Pharmaceutical and analytical development
Process chemistry and manufacturing
Registration and regulatory affairs
Sales and marketing (preparation, promotion, advertising and selling)
No. of compounds
Up to
10,000
10-15

1-8

1-3

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

16

Phase I trials

Phase I
50-150
people

Phase II
100-200
people

Phase III
500-15000
people

Phase IV studies continue

Focused on tolerability and safety

12-30 (150) healthy people (often males)
Efficacy on biomarkers
Single and repeated doses
Increase dose levels
Interaction with other drugs
Pharmacokinetics
Explorative
Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Phase 2 trials
Phase I
50-150
people

Phase II Phase III

50-1000 500-5,000
people
people

Phase IV studies continue

50-1000 patients
Extensive monitoring
Safety and tolerability in patients
Often complicated design, explorative
Selection of optimal dose
Pharmacokinetics in patients
Effect in special populations
Explorative
Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Phase 3 trials
Phase I
50-150
people

Phase II
100-200
people

Phase III
500-15000
people

Phase IV studies continue

500-15000 patients
Effect is verified in the target population
Forms the basis of the NDA, New Drug
Application
Interactions between drugs start to become
measurable in the larger population
sub-groups start to be established
special features and problems show up
Confirmative
Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Summary of Phases I-III

#
Subs.

Length Purpose

Phase
I
Phase
II

20
100

Several Mainly Safety 70%

months

Up to
several
100

Several Short term

33%
months- safety;
2 yrs.
mainly
effectiveness

Phase
III

100s
several
1000

1-4 yrs. Safety,

25-30%
dosage &
effectiveness

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

% Drugs
Successfully
Tested

NY/VI AETC

Phase IV trials

Phase I
50-150
people

Phase II
100-200
people

Phase III
500-5,000
people

Phase IV studies
continue

Often large 500-15000 patients

Further investigation of efficacy and
safety post approval
Special populations
New indications
Marketing
Copyright R. Saicharan, Assistant Professor, DBT, SNIST

Observational studies

Data is collected for a set of patients

without any randomisation

Prospective: Data is collected after the objectives are s

data collection

analysis

interpretation
time

now

Retrospective: Data is collected before the objectives a

data collection

analysis
now

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

interpretation
time

Where to look for information

ICH (international Conference on Harmonisation)

http://www.ich.org/products/guidelines.html

FDA (Food and Drug Agency)

http://www.fda.gov/

EMEA (European Medicines Agency)

http://www.emea.europa.eu/

Cochrane Collaboration
http://www.cochrane.org/index.htm

Copyright R. Saicharan, Assistant Professor, DBT, SNIST

The Clinical Study Process

Preparation of
statistical
analysis
Outline

Clinical Study
Protocol
Study
Setup

Study Conduct
Data Capture

Statistical Analysis

Clinical Study
Report
Publication
s

Statistical Analysis Plan

Clean File Data base lock

Time
Copyright R. Saicharan, Assistant Professor, DBT, SNIST