Drug

Idea Development Launch

Synthesis PMS
Preclinical
Test New
CT I-III
indication/dose
Investigational
CT IV
New Drug
Drug Drug
Discovery Marketing
Any systematic study on medicinal products in human subjects whether in
patients or non patient volunteers in order to discover or verify the effects of
and/or to study their absorption, distribution, metabolism and excretion in
order to ascertain the efficacy and safety on the products.

The Goal:

Efficacy
SAFETY (Adverse Drug Reaction)
Dosage Regimen
 PRECLINICAL INFORMATION

- ACUTE/ SUBACUTE TOXICITY MUTAGENICITY PARTIAL ANTIGENICITY

- REPRODUCTIVE TOXICITY

- PRELIMINARY ADME
GENERAL INFORMATION ON DISCOVERY

DATA ON PHYSIOCHEMICAL PROPERTIES, STANDARD AND TEST METHODS

DATA ON STABILITY OF FORMULATIONS

DATA ON PHARMACOLOGICAL ACTIVITY

Phase I II III IV

Pre NDA trials Post Marketing trials

 Single/multiple dose

PK data
h
ADR profile
h
Max tolerated dose
h
h
h

Dose range and RoA

 Pre eliminary evidence of
efficacy
RESTRICTED PATIENTS
NUMBER 10 200 Pharmacodynamic/ Effective range of
effects in patients. dose
DESIGN:
SINGLE BLIND DESIGN
PRE POST DESIGN
CONTROLLED STUDIES (PLACEBO)
THE GOAL :
EFFICACY Decision
SAFETY
DOSE RANGING PILOT STUDIES IN DISEASED MEN
Yes No
(WIDE DOSE RANGE)
 Controlled studies; positive
control (standard)/placebo

Confirmation of efficacy;
Establishment of complete
safety profile; Base for
regulatory information
(labeling); Assessment of
risk/ benefit

Preparation of NDA
Post marketing drug surveillance

Retrospective

Epidemiology survey
ADR
Chronic SE
Efficacy in severe, multiple disease
Geriatry, Pediatri
New indication
New drug interaction
 The data are credible, and
A standard by
Implemented and that the right, integrity and
which clinical trials
reported confidentiality of subjects
are designed.
are protected.
I.
II.
III.
IV.
V.
VI.
STUDI DESIGN
 Interval of 7 days
or less

STUDI DESIGN
Figure 2.1 Schema with two study arms. This schema shows the step of enrollment, the interval of
time between enrollment and treatment, and the steps of treatment and evaluation of efficacy

Enrollment in
Study drug (dose on day 1 only) Evaluate disease on day 8
single arm study

Interval of 7 days
or less

Figure 2.2 Schema with one study arm. The schema shows the step of enrollment, the interval of
time from enrollment to beginning treatment, and the step of evaluating efficacy of treatment
STUDI
22 DESIGN
Clinical Trials

Exclude
subjects who
Run-in period Study team were not able
of, e.g., determines to follow the
3 months, which schedule
where all subjects had Daily
subjects followed placebo for
receive instructions
Include 5 years
placebo pills
subjects who
for taking on a Randomize
had followed
daily basis
the schedule
Daily study
drug for
5 years

Figure 2.3 Schema including a run-in period. The study design includes a run-in period that screens
for the ability of potential subjects to follow the treatment schedule
 Daily study
drug for
5 years

Figure 2.3 Schema including a run-in period. The study design includes a run-in period that screens
STUDI DESIGN
for the ability of potential subjects to follow the treatment schedule

Study drug. Once a day for 5 weeks Study drug. Twice a day for 5 weeks

Allocation Blood samples taken at baseline (on day 1, Blood samples taken at baseline (on day 1,
& randomi- before administering drug) and the first before administering drug) and the first
zation day of each 1 week cycle day of each 1 week cycle

Placebo. Once a day for 5 weeks Placebo. Twice a day for 5 weeks
Enrollment

Amendment to Clinical Study Protocol

Figure 2.4 Schema of a 2-arm study where the study design was changed during the study. The
schema shows the date when the study design was changed. Also shown are dates when blood sam-
ples were withdrawn