CLINICAL TRIAL

2. No intervention Intervention
Observational Experimental
Comparison
group
NoYes
Analytical
study (case
control,
cohort)
Descriptive
study
Random allocation
Yes No
Randomized
controlled
trial
Non-
Randomised

3. Typesofexperimentalstudies
Preventive or
prophylactic study –e.g.
Study of vaccines or risk
factor
Therapeutic or clinical trials
Community (field) trial -
Community wide basis e.g.
fluoridation trial for prevention
of tooth decay.

4.  Clinical Trials are the best way to test whether a treatment is
effective and better than other treatments (or no treatment).
 Randomized controlled trials are best suited for testing new
treatments.
STEPS OF A RCT
1.Preparing a protocol.
a)The medicine to be researched , selection of
patients , diagnostic criteria , dose of drug ,
duration of treatment , method of randomization ,
method of blinding , etc.
b)Developed and approved before enrollment of
subjects from the institutional ethics committee

5. 2.Selection of reference & experimental populations:
 Reference population –the population / group to whom an
investigator expects the result to be applicable.
all human beings or subgroups women , smokers etc
 Experimental population- actual population in which the study
will be carried out.

6. INFORMED CONSENT-
 Legally and ethically to inform
• Medicine its cost , possible toxic effects and benefits.
• By accepting to participate in the study he is willing to subjects
himself for new treatment that is under trial.
• He can withdraw from trial without giving any reason and without
any fear of loosing the benefits he has received till that time.

7. 3.Randomization –
Statistical procedure by which the participants are allocated in
to groups usually called ‘study’ and ‘control’ group.
Types
A]Simple randomization
B]Systematic randomization
C]Stratified randomization

8. 4.Intervention
Deliberate application or withdrawal or reduction of a suspected
causal factor.
5.Follow up
The period of follow up is predetermined and documented in
the protocol.
6.Assessment
Positive results-benefits –reduced incidence or severity.
Negative results –severity & frequency of side effects and
complication including death.

9.  Selection bias
 Bias due to subject variation
 Observer bias
 Investigator bias
 Attrition bias
Good study design - minimizing all
possible sources of bias

10.  Single blind
 Double blind
 Triple blinding
 Open label

11.  Randomized controlled trials
 Non randomized controlled trials
 Concurrent parallel design
Group getting new medicine continues to get the new medicine
and control group continues to get standard treatment
this is the usual format of rct.
Eligibility
assessed
Consent Randomized
Test drug
Control

12.  Cross over type design
a.Each patient gets both drugs the order in which the patient gets
each drug is randomized
b.Each patient serves as his own control
c.Avoids between participant variation in estimating intervention
effect
• Requires a small sample size

13. A(NEW
MEDICINE)
A
B(STANDARD MEDICINE) B
A followed by B
B followed by A
Run in
Wash
out
period

14.  Factorial design-
- two or more interventions.
- Allows study of interactive effects.
Disadvantages
1. Complexity of trial design
2. Complexity of statistical analysis

15.  Clinical trial using historical controls
A new intervention is used in a series of participants and results
are compared to the outcome in a previous series of
comparable population , the historical controls.
 Withdrawal study
Participant on particular treatment are taken off therapy or have
dosage reduced.
The study is used to assess response to discontinuation or
reduction.

16.  Group allocation design
Also called cluster randomisation design.
A group of individual , a clinic or community.
 Hybrid design
if substantial data is available from historical controls.
Smaller proportion of participants is allocated to either group and
study is conducted to see the effect of medicine.

17. Randomize
Placebo
Placebo
-refers to type of placebo
-drugs are adminstered by different routes (e.g.injection nd pills)
-In order to keep participants from knowing which treatment arm they
are in

18.  Clinical trial is an organized research , conducted on
human beings to investigate the safety and efficacy of a
drug.

19.  Clinical trial may be done for various purposes.
 Common types
• 1.prophylactic trial e.g immunization
• Safety trials e.g.side effects of oral contraceptics & injectacbles
• Therapeutic trials e.g drug treatment , surgical procedure
• Risk –factor trials ,e.g proving the etiology of a disease by
inducing it with the agent in animals / withdrawing the agent

20.  Drug discovery requires two basic steps , i.e. RESEARCH &
DEVELOPMENT.
 RESEARCH -3 Sequential activities –Target selection , drug
selection & product development.
 Target selection –a disease to treat and then developing a
model for that disease.
 Drug selection – finding a drug or group of drugs that work
within that model system.

21.  When the compounds with the desired activity are
discovered , the most promising among them are
optimized to produce one or two final compounds that may
eventually become drugs.
 DEVELOPMENT –
-Preclinical & Clinical development (clinical trial)

22.  Performed in the laboratory , using a wide array of
chemical and biochemical assays, cell culture models and
animal models of human disease.
 Develops -
Pharmacological profile
Acute toxicity
Short-term toxicity studies

23.  Phase -4 years.
 Investigational New drug application-test –human
 If regulatory body does not disapprove it within 30days ,
then this application becomes effective and at this stage
clinical trial can be initiated.

24.  Clinical trials on patients in different countries are
approved and monitored by different regulatory agencies ,
which in India , is monitored by Drug Controller of India
(DCGI) under Central Drug Standard Control
Organization(CDSCO).
 Duration – 8-9years

25. PHASE
l
PHASE
ll
PHASE
lll
PHASE
lV

26.  First stage of testing in human subjects (20-100).
 Designed to assess the initial safety ,maximum tolerance ,
Pharmacokinetics of the drug.
 Time period – 3 -6months

27.  Therapeutic Exploratory Trial. (20-300 Subjects).
 Efficacy in patients (primary objective)
 Safety issues (secondary objective)
 Dose and adverse reaction of drug.
 6months to 2years.
 Phase II
› Phase IIA: Designed to assess dosing requirements
› Phase IIB: Designed to study efficacy

28.  Therapeutic confirmatory trials. (300-3000 subjects).
 To establish efficacy of the drug against existing
therapy in larger number of patients, method of
usage etc.,.
 Subtypes
› Phase IIIA: to get sufficient and significant data.
› Phase IIIB: allows patients to continue the
treatment, Label expansion, additional safety data.

29.  Post Marketing Studies (PMS).
 Involves safety surveillance.
 Determine behavior of drug in real life situations.
 Evaluate action of drug in a situation of missed
dosage or over dosage.

30. 5,000-10,000
compounds
250
5
1 Approved by
FDA
Preclinical testing
Clinical testing

31.  International ethical and scientific quality standard for
designing , conducting , recording and reporting of clinical
trials
 International conference on harmonization of technical
requirement for registration of pharmaceuticals for human
use – good clinical practice : consolidated guidance (ICH-
GCP , 1997)
 Local regulatory requirements (DCGI)
 Indian council of medical research (ICMR code , 2000 )
 Local ethics review boards (ERBs)

32.  International ethical and scientific quality standard for
designing , conducting , recording and reporting of
clinical trials
Rationale Of Good Clinical Practice
 Legal requirement for conduction of the trial.
 Protects the rights , integrity and confidentiality of research
subjects.
 Provides assurance that the data and results are credible
and accurate.
 Global acceptance of the data.

33.  No clinical trial is initiated at any investigator site without
obtaining a written permission by the review board.
Sponsor /
CRO
Investigator
Study
subjects
REGULATORY
AUTHORITY
ERB

35. Conduction of clinical trial
 Different pharmaceutical companies , Biotechnology
companies , contract research organisation (CRO) ,
Research/ Academic Institutions and Cooperative Groups.
Sponsor /
CRO
InvestigatorRegulators

36.  The Clinical Trials Registry- India (CTRI), hosted at the ICMR's National
Institute of Medical Statistics (http://nims-icmr.nic.in), is a free and online
public record system for registration of clinical trials being conducted in India
that was launched on 20th July 2007 (www.ctri.nic.in).
 Initiated as a voluntary measure, since 15th June 2009, trial registration in the
CTRI has been made mandatory by the Drugs Controller General (India)
(DCGI) (www.cdsco.nic.in).

37.  Park’s textbook of preventive and social medicine
 Essentials of preventive and commuity dentistry –Soben
Peter.
 Principles and practice of medical research by dr.J.v.Dixit
 Mahajan & gupta textbook of preventive and social
medicine
 Online sources