Clinical Trails is the most important requirements to introduce a new medicine, Medical Devices and Vaccines in the market.

1. DAY-2
CLINICAL TRIALS
Overview, FDA Regulations for
Clinical Trials in India
Dr. S.B.Sinha—MD Regulatory
Consultant

2. CONTENT
S OF THE
MODULE
Introduction to Clinical Trials
Why Clinical Trials
Patients Interests
The Clinical Trail Process
Informed Consent
Rights and Protections
FDA Regulations for Clinical Trials In India

3. INTRODUCTION
TO CLINICAL
TRIALS
• Clinical Trials are best way to introduce
a new treatment/drug/equipment
/disgnostics to provide a patient with a
new safe and effective treatment.
• As a patient you may consider enrolling
for a clinical trail or you may be invited
by your doctor for the same.
Let‘s agree on words!
The process we are going to describe is
typical of new drug development, but
also applies to any other type of
intervention, such as diagnostic
strategies, surgical procedures, lifestyle
changes (diet, exercise, etc.) or
comparisons between new and existing
therapies in terms of effectiveness and
safety.
To make things easier, we will use the
word “treatment” to refer to any type of
intervention.

4. CLINICAL TRIALS
• An experiment or clinical trial in which two groups are used for
comparison purpose is known as Controlled Clinical Trials.
• In a controlled exposure study, one group of participants is exposed to a
substance (e.g. a pollutant) while those in the "control" group are not.
• In Uncontrolled trial there is only one group and there is no control group
for baseline comparison. Uncontrolled trials are often used in the early
phases of drug research, phases I and II, to determine pharmacokinetic
properties or to investigate tolerated dose ranges. They can also be
useful to study side effects, biochemical changes in long-term therapies,
tolerance, interactions or efficacy of drugs.

5. WHAT IS A
CONTROLLED
CLINICAL
TRIAL
Controlled clinical trials aim to improve
existing treatments or to replace them
with new and better ones.
Before a new treatment is made available
for patients, it must be tested in controlled
clinical trials for efficacy and safety.
Controlled clinical trials are designed to
help us learn more about the positive and
negative effects of treatments.
A treatment‘s efficacy and safety can only
be fully assessed after long-term use on
patients in everyday clinical practice

6. CONTROLLED
CLINICAL
TRIALS…
Before new drug treatments are tested in
patients in clinical trials they must be carefully
evaluated in laboratories.-This is known as Pre
Clinical Studies and are conducted on Animals
and Human Cells-
If the results of laboratory studies of a possible
treatment are promising, clinical trials are
designed to assess its possible beneficial and
adverse effects in patients and based on clinical
Trial data new Drugs are Introduced. An
application for Investigational New Drug IND is
made to FDA and after approval the CT is
initiated

8. Phases of Drug Development
Phase 1 Phase 2 Phase 3 Phase 4
No. of
Participants
20-50 100-300 300 to
thousands
Several
hundreds to
several
thousands
Purpose First in
humans
Find safe
dose For
pediatric
patients the
dose is 1/3
Determine
efficacy
Compare
new agent
with
standard
treatment
Post –market
Long-term
safety and
efficacy

9. PHASES IN
CLINICAL
TRIALS-
PRECLINICAL
STUDIES
Pharmacodynamics- What the drug do to
the body. Like reducing fever or improving
the liver profile.
Pharmacokinetics- What the body does
to the drug. Like absorption, distribution or
elimination by the body.
Toxicity Profile- Acute, sub acute or
chronic toxicity.
Therapeutic Index- Safety and Efficacy
evaluation.

10. IND
APPLICATION
Investigational New Drug
Application is required to be made to
CDSCO for approval for CT
It contains- Preclinical Safety Data,
Composition and source of drugs,
Chemical and Manufacturing
Information, Proposed Clinical Plans
and Proposal, Ethics Committee
Clearance.

11. TEA BREAK
11.15 AM
WE WILL MEET AT 11.30
AM

12. CLINICAL
TRIALS
PHASES-
PHASE-1
Phase 1 is the first stage of clinical trials on
humans to find safe dosage for CT
Primary goal is to assess safety, tolerance,
Pharmacokinetics and Pharmacodynamics
and select the dose by dose escalating.
Small number of 20-50 preferably Healthy
Volunteers participate in the Study and are
paid for their participation.
Dose escalating (Single and Multiple) is done
to determine safe and effective dose and is
fraction of dose that caused harm in Animals.

13. CLINICAL
TRIALS
PHASE-2
Primary goal is to evaluate the biological
activity or effect of the selected dose.
Designed to assess how well the drugs work.
Performed on a larger group of 100-300
Volunteers to determine efficacy of the Drug
To continue the safety studies of the Phase-1
Sometimes for Anticancer drugs Phase and
Ph-II are combined.
Split in Phase 2 a and Phase 2 b

14. CLINICAL
TRIALS
PHASE-2 A
Primary goal: To determine the therapeutic efficacy.
Pilot Trials- Determination of dose response, determine
dose regimen and determine the target population.
Subjects- fitting narrow eligibility criteria 100-300
Trial Design- Comparison with baseline status. Open
level or single/double blind.
Dose escalation
Parallel dose response.

15. TRIAL DESIGNS
Conducted on only one group of patient. OR
Conducted on two groups of similar patients.
Randomly the patients are selected to get the new/standard treatment. This is known as
Randomized Clinical Trials.
The Group which receive the new treatment is the Experimental Group OR The Active Group
and the Group receiving Standard Treatment is called Controlled Group/Comparison Group.
Both the groups are treated with same care.
Sometimes the patients (SINGLE) and the researchers(DOUBLE) don’t know which patients are
in which group and is known as BLIND trials. Others are open trials.

16. TRIAL
DESIGN
CONTD….
Sometimes there is no standard
treatments are available.
The Control group receives only
dummy treatment like sugar pills.
This is known as Placebo treatment.
Placebo treatments are not done if
there is a standard treatment
available.

17. CLINICAL
TRIAL
PHASE 2B
Pivotal Study- A pivotal clinical trial is
a clinical study seeking to demonstrate
the efficacy of a new drug in order to
obtain its marketing approval .
Objective- Continue trail of phase 2a
followed by Crossover trials and
multicenter and multisites.
Trial Design- Single/Double blinded in
Multicenter/multisites.

18. CLINICAL
TRIALS-
PHASE 3
Controlled Randomised trials in
Multicenters/ Multisites
Large number of patients 300-3000 and
more
Objective- Final Assessments of the New
Treatment with the Gold Standard
available.
Trial Design- Open level, Sigle or Double
blinded.
Dosage forms, formulations and
pharmacoeconomic evaluation is done.

19. CLINICAL
TRIALS
PHASE-4
Done after Drug has been put into market.
This is post market Surveillance for long term use to
evaluate the efficacy, dose modification and safety
profile for long term use
To evaluate ADR and also other uses of the Drug.
Report to be submitted at fixed intervals.
A part of Pharmacovigilance.
Drugs may be discontinued based on long term ADR.

20. INFORMED CONSENT BY PARTICIPANTS
• All the important information like benefits as well as side effects
and risks of the new treatment should be explained to the
participants by the researcher.
• Detailed written information should be provided after verbal
meeting.
• Participant should sign a written consent.
• Participant is free to walk out any time if he is not comfortable.
• Periodic updates should be provided to the participants to decide
whether he wishes to continue or quit the study.

21. GUIDELINES
FOR CT
PROTOCOLS
Drugs Control Act –Sch Y –
Requirements for permission to import
/ manufacture new drugs for Sale or
Conduct CT.
ICH- International Council for
Harmonization- Guidelines E6(R2)-
GCP Addendum to ICH, CT Protocols
and Protocols Amendments.
ICMR- National Ethical Guidelines for
Biomedical and Health research
involving human participants. These
deal with Ethical Considerations

22. LUNCH BREAK 1.00 PM
WE WILL MEET AT 2.00 PM

28. CLINICAL
TRIALS IN
INDIA
CDSCO- Central Drugs and Control Organization is the
body in India which lays down regulatory guidance for
Clinical Trials and New Drugs.
Its main objective is to standardize the Clinical Trials and
to assure Safety , efficacy and Quality of Drugs, Cosmetics
and Medical Devices.
DGCI-Drug Controller General of India (In CDSCO)-Is
responsible for giving regulatory permission for Clinical
Trials and approves marketing of Drugs in India and is
head of the Pharmacopeia Commission of India
DGCI-Is also responsible for inspection of sites for Clinical
Trials
DGCI is assisted by DTAB(Drug Technology Advisory
Board) and the DCC-(Drugs Consultative Committee)

29. IMPORTANT
RULES FOR
CLINICAL
TRIALS
UNDER
DRUGS AND
COSMETIC
RULES
122DA- Permission to conduct Clinical
Trails for New Drugs and Investigational
New Drugs
122DAA- Definition of Clinical Trials.
122DAB- Draft Guidelines for registration
of all Clinical Research Organisations
involved in Clinical Trials for 5 Years
122E- Definition of New Drug

30. CLINICAL TRIAL
REQUIREMENTS
IN INDIA
SCHEDULE Y
• Application for Permission.
• Clinical Trails
• Studies in specific population.
• Post Marketing Surveillance.
• Special Studies- BA/BE-
Bioavailability is defined as
relative amount of drug from an
administered dosage which enters
the systemic circulation and the
rate at which the drug appears in
the systemic circulation.
Bioequivalence studies are used
to assess the expected in vivo
biological equivalence of two
proprietary preparations of a drug.

31. APPLICATION
FOR
PERMISSION
Is made in FORM-44 with the Following Data
Chemical and Pharmaceutical information.
Animal pharmacology data.
Animal Toxicological Data
Human Clinical Pharmacology Data.
Regulatory Status in other Countries.
Prescribing Information.
Complete Testing Protocol for Quality Testing.

32. TEA BREAK
3.15 PM
WE WILL MEET AT 3.30
PM

33. R ESPON SIBILIT
Y OF TH E
SPONSOR
Implementation of Quality Assurance and
GCP-Good Clinical Practices and Protocols
of DGCI.
Submit the results of Clinical Trials at
periodic intervals.
Submit Serious Adverse Event (SAE)
Reports and action taken.
In case of premature discontinuation of the
study a summary report to be submitted
within 3 months of discontinuation.

34. R E S P O N S I B I L I T Y
O F
I N V E S T I G ATO R
Conduct of trails as per GCP and protocols of
DGCI.
SOP shall be documented.
During and follow ups on Clinical trails
adequate care and medications shall be
provided to the participants.
SAE and unexpected Adverse Events should
be reported within 24 hours to Sponsor and
within 7 days of occurance to Ethics
Committee.

35. ETHICS
COMMITTEE
It is an independent body comprising of
Medical, Non Medical, Scientific and non
scientific members whose responsibility is to
ensure protection of the rights, safety and
well being of all human subjects
participating in CT
An Institutional Ethics Committee is
mandatory requirement as per ICMR
Guidelines.

36. R E S P O N S I B I L I T I E S
O F E T H I C S
C O M M I T T E E
EC should approve the Clinical Trial
Protocols.
Ensure safety of all the participants.
Monitor the CT at periodic intervals.
Document SOP and record of all the
proceedings.
If EC revokes its approval shall give
reasons for such revokal.

37. APPENDICE
S
Appendix-I- Data to be submitted for CT for
marketing a new drug along with Application Form.
Appendix-II- Structure, contents and Formats for CT
Reports.
Appendix-III- Animal Toxicology
Appendix-IV-Animal Pharmacology
Appendix-V- Informed Consent
Appendix-VI- Fixed Dose Combination
Appendix-VII- Undertaking by Investigator.
Appendix-VIII-Ethics Committee

38. APPENDICE
S CONTD…
Appendix- IX- Stability Testing of New
Drugs.
Appendix-X- Contents of proposed
Protocols for CT.
Appendix-XI- Data elements for
reporting SAE and Unexpected
Adverse events occurring during a CT

39. THREE TIER
REVIEW
PROCESS-
NEW
REQUIREMENT
STEP-1- Review in SEC(Subject
Expert Committee)
STEP-2- Review by TRC(
Technical Review Committee)
STEP-3- Review by APEX
Committee.
If approved by all APEX Committee
Final Approval given by DGCI

40. SAE
C OMPEN SATION
- N EW
R EQU IR EMEN T
Gazette Notification GSR 53(E)
Jan 2013 Amended by Gazette
Notification GSR 889 (E) Dec
2014 effective June 2015
Clarifications regarding provision
of compensation for SAE.
Extended timelines for
submission of SAE.

41. OTHER NEW
PROVISIONS
Registration of EC with Licensing Authority is a must
and CDSCO approval is valid for three years.
Mandatory Audio Visual Recordings of Informed
Consent.
SUGAM Portal for online applications for CT
Pharmavision 2020 promises to make India a global
leader in CT
Regulations for conduct of CT introduced in 2017
with more clarity
ICMR Guidelines introduced in 2017

42. PLEASE FILL UP MCQ
SHEET
THANK YOU