2. Definition
Objective
Key Word
Protocol
Scientific Aspect of Clinical Trial
Participating Parties in Clinical Trial
3. The great tragedy of science.. the slaying of a beautiful
hypothesis by an ugly fact.
Thomas Henry Huxley
4. WHAT EXACTLY ARE CLINICAL TRIALS?
Clinical trials are scientific investigations that examine
and evaluate safety and efficacy of different therapies
in human subjects.
.
5. Objectives:-
Developing/Writing a protocol.
Developing an Investigator Site File (ISF) –
Regulatory Binder.
Screening, Recruitment, Enrollment and Retention.
Safety reporting .
Interim and Annual Reports.
End of Study Visit.
6. THE THREE IMPORTANT KEY WORDS
Experimental Unit
An experimental unit is usually referred to as a subject from a targeted
population under study. For example, the intended population could be
patients with certain diseases at certain stages or healthy human subjects.
Treatment
In clinical trials a treatment can be a placebo or any combinations of a new
pharmaceutical identity (e.g., a compound or drug), a new diet, a surgical
procedure, a diagnostic test, a medial device, a health education program,
or no treatment.
Evaluation
In addition to the traditional evaluation of effectiveness and safety of a test
treatment, clinical trials are also designed to assess quality of life,
pharmacogenomics, and pharmaco-economics such as cost-minimization,
cost-effectiveness, and cost-benefit analyses to human subjects associated
with the treatment under study.
7. Monitoring visits
Serology
CRF
Data analysis +
Development Plan
Preparation of trial
Study report
Registration file
Scientific publications
IP
Pre-Study
Activities
BEFORE
DURING
AFTER
End of study
activity
Clinical Trials
8. Title & Abstract
Introduction
General statement of purpose
Complete Preclinical results on animal study
Clinical data if available
Time frame
Goals: Primary & secondary objectives
Study Design:
Type of study
Recruitment criteria : Exclusion & Inclusion criteria
Randomisation criteria and Sample size
Duration of study
Data Analysis:
Case report forms, Statistical Analysis, Bibliography
9. SPONSORS FOR CLINICAL TRIALS IN THE U.S.
Pharmaceutical and Biotechnology companies – which
must prove the safety and effectiveness of their medicines
before they can be marketed
National Institutes of Health (NIH) – which are funded by
the US Government. The National Cancer Institute (NCI),
which is a part of the NIH, sponsors a good portion of the
thousands of cancer clinical trials going on at any point of
time.
10. Other government agencies, including parts of the
Department of Veterans Affairs and the Department
of Defence, also sponsor cancer clinical trials.
University Medical Schools and Hospitals, or any
other medical research centers.
Some non-profit organizations and even individual
or group of physicians also sometimes sponsor clinical
trials.
11. Phases of Clinical Trial
Preclinical trial
Phase I : First in man safety
Phase II : First in patient dose, dosage form
Phase III : Efficacy, ADRs
Post marketing surveillance or Phase IV : Evaluation in the real
clinical setting
12. Research on a new drug or a new
medical device , usually done on
animals, to learn about mechanisms of
action, determine how well the
treatment works, and see if it is safe to
test on humans.
13. Objectives
1. To assess a safe & tolerated dose
2. To see if pharmacokinetics differ much
from animal to man
3. To see if kinetics show proper absorption,
bioavailability
4. To detect effects unrelated to the expected
action
5. To detect any predictable toxicity
14. Healthy volunteers : Uniformity of subjects:
age, sex, nutritional status [Informed consent
a must]
Exception: Patients only for toxic drugs
eg:- Anti HIV, Anticancer
– Exclusion criteria
Women of child bearing age, children,
15. First in patient [ different from healthy volunteer]
Early phase [20 – 200 patients with relevant disease]
Therapeutic benefits & ADRs evaluated
Establish a dose range to be used in late phase
Single blind [Only patient knows] comparison with
standard drug
Late phase [ 50 – 500]
Double blind
Compared with a placebo or standard drug
16. Assesses efficacy against a defined therapeutic
endpoint
Detailed Pharmacokinetic & Pharmacodynamic
data
Establishes a dose & a dosage form for future
trials
Takes 6 months to 2 years [ 35% success rate]
17. Large scale, Randomised, Controlled trials
Target population: 250 – 1000 patients
Performed by Clinicians in the hospital
Minimises errors of phases I and II
Methods
Multicentric Ensures geographic & ethnic variations
Diff patient subgroups Eg pediatric, geriatric, renal impaired
Randomised allocation of test drug /placebo / standard drug
Double blinded:
Cross over design
Vigilant recording of all adverse drug reactions
Rigorous statistical evaluation of all clinical data
Takes a long time: up to 5 years [25% success]
18. Group Week 1 Week2 Week3
I Standard Placebo Test
II Placebo Test Standard
III Test Standard Placebo
* A wash out period of a week between two weeks of
therapy
19. No fixed duration / patient population
Starts immediately after marketing
Report all ADRs
Helps to detect
rare ADRs
Drug interactions
Also new uses for drugs [Sometimes called Phase V]
20. Below are some estimates on the amount of time it takes
for this process in treatment research.
Pre-clinical Trials - 4.5 years
Phases I-III - 8.5 years
FDA Approval - 1.5 years
Phase IV - Ongoing for the duration of the use of the drug
21. 1. Patient / Healthy volunteer
2. Clinical Pharmacologist, Clinical
Investigator & team: [Qualified and
competent]
3. Institution where trials are held :
[Approval required]
4. Ethical Review Board or Institutional
Ethical Committee:
5. Sponsor
6. Regulatory Authorities
22. Patient / Healthy volunteer : Subject of
the trial
Clinical Pharmacologist, Clinical
Investigator & team:
– Conducts the clinical trial; reports all
adverse events
–
Institution where trials are held :
– Provides all facilities [Approval required]