clinical trials by thilak0505



•   Introduction on Drug Development Process
•   Understanding Clinical Trials
•   Types of clinical trials
•   Clinical trial protocol
•   Regulatory bodies governing clinical trials
•   Ethics in Clinical Drug Research
•   Phases of clinical trials
•   Study Designs
•   Clinical Trials in India
•   References

                   New chemical Entity

                    Preclinical studies

                      Investigational New
                      Drug Application

Clinical trials                                              Preclinical studies plus
Phase I                                                      Product formulation
Phase II                                                     Mfg & controls
Phase III                                                    Package & label design
                                                             LT animal toxicity
                  New Drug Application
                  FDA review
                  Pre approval plant inspection
                  FDA action

                   Post marketing
                   Phase IV,Clinical
                   pharmacology/toxicology, Adverse
                   drug reactions &product defects
                   reporting, product line extension

•Why participate in a clinical trial?
•Who can participate in a clinical trial?
•What happens during a clinical trial?
•What are the risks and benefits of participating
in a clinical trial?
•What should people consider before
participating in a trial?

•Treatment trials
•Prevention trials
•Diagnostic trials
•Screening trials
•Quality of life trials

•Statement of purpose and objective of the
•Outline of the investigational plan and design
including the kind of control group and
methods to minimize bias on the part of the
subjects, investigators and analysts.
•Estimate the number of patients to be involved.
•Basis for subject selection, including inclusion
and exclusion criteria
•Description of dosing plan, including dose
levels, route of administration and duration of
patient exposure.


•Description of the patients observations,
measurements and tests to be used
•Clinical procedures, lab tests and monitoring to
be used to minimize patient’s risk.
•Names, addresses and credentials of the principal
investigator and sub-investigators.
•Location and description of research facilities.
•Approval of authorized IRB

FDA-The Food, Drug and Cosmetics Act, as regulated through Title
21 of the U.S Code of Federal regulations, requires a new drug to be
approved by the Food and Drug administration.

Advisory Committee-The FDA often seeks the opinion of outside
experts to aid the agency in making decision on approvability of the
drug .
One or more advisory committee comprising scientific experts from
academic medicine, a consumer representative, biostatistician and
other members deemed to be important

Institutional Review Boards-A committee governing the conduct of
clinical trials at the local institution.
Members who have the professional competence in scientific, legal,
regulatory and moral perspective are included.

•Clinical trials in India are regulated by Schedule Y of the Drug and Cosmetics
Rules, 1945.

•The Central Drugs Standard Control Organization (CDSCO), headed by the Drugs
Controller General (India) (DCG(I)), discharges the functions allocated
to the Central Government (similar to the US Federal Government) under the
Drugs and Cosmetics Act,1940.

•DCG(I), along with the Indian Council of Medical Research (ICMR) have adopted
international regulatory guidelines and issued Indian versions of the same.

• ICMR issued the Ethical Guidelines for Biomedical Research on Human
Subjects in 2000 and Indian GCP guidelines were released by CDSCO in
December 2001. The Drug Technical Advisory Board (DTAB), the highest
technical body under the Drugs & Cosmetics Act, has endorsed adoption of GCP
guidelines for streamlining clinical studies in India.

•The clinical protocol must be reviewed and approved by an IEC of, at minimum,
seven members, including a medical scientist, a clinician, a statistician, a legal
expert, a social scientist and a common person from the community.

•Ethical principles
Informed consent
Distributive justice
•Ethical code:
The code of Nuremberg
The Helsinki code
•Ethical research questions
Drug testing in Healthy volunteers
Drug testing in pediatrics
Drug testing in women
Drug testing in prisoners
Drug testing in mentally disabled

              Phase I         Phase II        Phase III               Phase IV

Population    Healthy         Target          Target                  Mixed
              volunteers      diseased        diseased
                              patients        patients

Sample size   20-80           200-300         100-1000                >1000

Duration      Several         Several      Several years              Ongoing
              months          months-years

Conclusions   Safety,         Efficacy,short Safety,                  Long term
              tolerability,   term safety    effectiveness            adverse
              PK & PD                        and dosage               effects

•Study objective
•Sample size
•Study design

               -A method to reduce bias

•Blinded studies:
oSingle blind
oDouble blind
oTriple blind:

1.Surveys---------by simple questionnaire


 Parallel study design
 Simple parallel design
Stratified parallel design

 Cross over study design
Complete cross over design
 Balanced Incomplete Block Design
Latin Square Design

 Factorial design

3.Observational studies
 Case control studies
Cohort studies(prospective & retrospective)
 Cross sectional studies

•Subjects assigned as two groups.
• Treatment group & Control (or placebo) group.
•Treatment assigned to treatment group and no treatment or
placebo assigned to control group.
•The outcome measures are compared at the end of

•First all the subjects are divided into 2 specific groups (strata)
on the basis of some predefined factor.
So, 2 or more “Stratas” will be formed.

•Later, from the individual strata, the random samples will be
taken & assigned as study groups.

•Each study subject receives more than one study
treatment, one after the other.
• Each of the time intervals in which one of the study
treatments is administered is called a period.
• The continuation of the effect of one treatment into
the following period is referred to as carry over
•Washout period: The interval between end of a
treatment and beginning of the next is called as
wash out period.
 To eliminate the carry over effect.

                         SUBJECT          TREATMENT I   TREATMENT II

1.Each        subject    1                A             B
receives not more        2                B             A
than              two    3                A             C
formulations.            4                C             A
2.Each     pair     of   5                A             D
formulations    occur    6                D             A
together in the same     7                B             C
number of subjects.      8                C             B
3.Each formulation is    9                B             D
administered       the   10               D             B
same    number      of   11               C             D
times.                   12               D             C

1. Each subject receives just once each formulation
2. Each formulation is administered just once each period.

Two way cross over                                     Treatment
Group no               Subjects in group                             I                 II
   1                     1,2,3,4,5,6                                 A                 B
   2                      7,8,9,10,11,12                             B                 A
Three way cross over                                                 I        II            III
   1                   1,2,3,4,5,6                                   A        C             B
   2                   7,8,9,10,11,12                                B        A             C
   3                   13,14,15,16,17,18                             C        B             A
Four way cross over                                                  I   II        III      IV
   1                   1,2,3,4,5,6                                   A   B         C        D
   2                   7,8,9,10,11,12                                B   D         A        C
   3                   13,14,15,16,17,18                             C   A         D        B
    4                  19,20,21,22,23,24                             D   C         B        A

     Many times it is possible in one trial to
evaluate two or even three treatment regimens in
one study. Each drug could be compared to
placebo, and any interaction of the two drugs in
combination could also be evaluated.

    Investigator identifies a certain outcome in the
population, then matches the diseased group to a
healthy group and finally identifies differences in
exposure between the two groups .

Prospective cohort study: Cohort is identified before the
appearance of the disease.Follow a group of people who do
not have the disease for a period of time and see who
develop the disease.
•Assemble the Cohort
•Measure Predictor Variables and Potential Confounders
•Follow-up the Cohort and Measure Outcomes

Retrospective cohort study: Designs the grouping after the
data is collected.
•Identify a Suitable Cohort
•Collect Data about Predictor Variables
•Collect Data about Subsequent Outcomes

           In cross-sectional studies, one defines
and describes disease status (or outcome),
exposure(s), and other characteristics at a point
of time, in order to evaluate associations between

•There are numerous government funded medical and pharma
institutions facilitating multi-centered trials.
•India can boast of a large well trained & qualified manpower
that is well versed in English.
•Vast availability of clinical material.
•Cost efficiency.
•Alternative systems of medicine are practiced with equal
fervour as allopathy.
•Large patient population.

1.Biopharmaceutics and Pharmacokinetics BY V Venkateshwarlu(

2.Clinical Research in Pharmaceutical Development Edited by BarryBleidt, Michael

3.Clinical Trials A Practical Guide to Design, Analysis and Reporting. By Duolao Wang
and Ameet Bakhai, Editors

4.Designing Clinical Research Authors: Hulley, Stephen B.; Cummings, Steven R.;
Browner, Warren S.; Grady, Deborah G.; Newman, Thomas B

5.Essentials Of Clinical Trials. Edited by Stephen P.Glasser

6.Essentials of MEDICAL PHARMACOLOGY 6th Edition by KD Tripathi

7.Fundamentals Of Clinical Research by Antonella Bacchieri ,Giovanni Della Cioppa

8.Handbook Of PHASE I/II clinical Drug Trials edited by John O’Grady,Pieter

9. Pharmaceutical Dosage Forms by Howard C.Ansel.Loyd V.Allen, Nicholas
G.Popovich(pg no:23-58) Seventh Edition.

10. Pharmacology(Fifth edition) By H.P.Rang And M.M.Dale(

11.Text Book Of Clinical Trials Second Edition Edited by David Machin,Simon
Day, Sylvan Green

13.www. Clinical_trials.htm

14. www.clinical trials/irb.htm

15. www.clinical trials/Clinical-Trials-of-Drugs-and-Bio-Pharmaceuticals.htm


17. www.clinical trials/understand.htm

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