1. A QUICK GUIDE TO
CLINICAL TRIALS

2. What is clinical trial?
 Methodological experimentation of
investigational drugs or devices (like
stents ) in human beings/
(volunteers/patients)

3. DRUG DEVELOPMENT PROCESS
Chemistry
Synthesis & Purification
Formulation
Animal Pharmacology
Animal Toxicity (Short / Long term)
Studies in Humans
Drug Authorities
Market

5. PHASE I TRIALS
1. Initial studies to determine the metabolism and
pharmacologic actions of drugs in humans, the side
effects associated with increasing doses, and to gain
early evidence of effectiveness; may include healthy
participants and/or patients.
2. In phase I trials, researchers test an experimental drug
or treatment in a small group of people (20-80) for the
first time to evaluate its safety, determine a safe
dosage range, and identify side effects.

6. PHASE II TRIALS
1. Controlled clinical studies conducted to evaluate the
effectiveness of the drug for a particular indication
or indications in patients with the disease or
condition under study and to determine the common
short-term side effects and risks.
2. In phase II trials, the experimental study drug or
treatment is given to a larger group of people (100-
300) to see if it is effective and to further evaluate its
safety.

7. PHASE III TRIALS
1. Intended to gather additional information to evaluate the overall
benefit-risk relationship of the drug and provide and adequate
basis for physician labeling.
2. In phase III trials, the experimental study drug or treatment is
given to large groups of people (1,000-3,000) to confirm its
effectiveness, monitor side effects, compare it to commonly used
treatments, and collect information that will allow the experimental
drug or treatment to be used safely.

8. PHASE IV TRIALS
 Post-marketing studies conducted to
describe additional information including
the drug's risks, benefits, and optimal use.

9. Randomized Controlled Trials
 Participants randomly allocated to either study drug OR
another like a different drug or placebo
 Follow up is for a specified period
 Analyses in terms of outcomes defined at the outset
 Objective of randomization is to rule out bias on part of
investigator ( doctor ) for a specific treatment.
1 2 3 4 5 6 7 8 9 10
A A B B B A A B B A

10. Cohort Studies
 Two or more groups of people are selected on the basis
of their exposure to a particular agent
 Subsequently followed up to see how many from each
group develop the ‘outcome’
 For example: smokers ( one group ) and non-smokers
( other group ) are selected and followed-up for a period
of say 5 years to see how many from the smoker group
and non-smoker group develop bronchitis( outcome )

11. Case Control Studies
 Patients with a particular disease are identified
and matched with controls
 Data is collected on past exposure to a possible
causal agent
 For example, diabetic patients (one group) and
non-diabetics (other group ) otherwise matching
with each other are selected and evaluated for a
risk factor (say obesity) for diabetes.

12. Cross-sectional Surveys
 Data are collected at a single time
e.g. Lipid profiles of 25 year old males in
Ahmedabad

13. Case Reports
 Medical history of a single patient
 Not very reliable as evidence
 Conveys information which might have
been lost

14. Terms :
 Systematic reviews: Summarize primary studies
according to a systematic scientific
methodology
 Meta-analyses: Integrate numerical data from
more than one study/trial on a single product
and analyze data
 Guidelines: Conclusions from primary studies on
clinical decisions
 For example JNC (Joint National Committee ) VII
Guidelines on hypertension, NCEP ATP III ( National
Cholesterol Education Program Adult Treatment
Plan ) Guidelines on dyslipidemia management

15. Terms (Cont…)
 Placebo controlled: Subjects in control group
receive a placebo whereas subjects in other
group receives drug
 Treatment controlled: Subjects in control group
receive a standard treatment whereas subjects
in other group receives drug under investigation.

16.  Single blind: Patients do not know which
treatment they are receiving
 Double blind: The investigators and the
patient both do not know which of the two
treatment options is being administered

17. Terms (Cont…)
 Multicenter trial: A clinical trial conducted
according to a single protocol at more
than one site and thus by more than one
investigator

18. Hierarchy of Evidence:
 In terms of clinical evidence ,Systemic
reviews & meta-analyses have rated as
the highest evidence followed by
randomized controlled trials.

19. Systematic reviews and meta-
analyses
Randomized controlled trials
Cohort studies
Case-control studies
Cross-sectional surveys
Case reports

20. WORKSHEET – 1

21. Q.1) What is clinical trial?
ANS :

22. Q. 2) ………… tops as a scientific
evidence in terms of clinical trials.
a) Case reports
b) Case-control study
c) Meta analysis & systemic review
d) None of above

23. Q. 3) What is randomized placebo-
controlled trial?
ANS :

24. Q. 4) State whether true or false.
1) Case report is considered to be the
reliable clinical evidence.
(__________)

25. Q. 5) What is cohort study?
ANS :

26. Q. 6) Define the following terms:
Meta-analysis:
Placebo-controlled study
Double-blind study:
Multi-centric study:

27. Absolute Risk Reduction (ARR ) &
Relative Risk Reduction (RRR) Absolute
Risk Reduction
 ARR is the difference in the event rate
between treatment group and control
groups

28. Relative Risk Reduction
 The proportional reduction in rates of bad
outcomes between experimental and
control participants in a trial

29. P Value
 P value: The probability of any particular
outcome having arisen by chance.
 Arbitrarily a P value of less than 1 in 20
(expressed as P<0.05, odds of 20 to 1) is taken
as "statistically significant" and a P value of less
than 1 in 100 (P<0.01) as "statistically highly
significant”.

30. Confidence Interval
 The range of numerical values in which we can be
confident (to a probability, such as 90 or 95%) that the
value being estimated will be found.
 A 95% CI is the range of values within which we can be
95% sure that the true value for the whole population lies.
RRR=26.9%, 95% CI,
Confidence intervals indicate the strength of evidence.
 The narrower the confidence interval, the more precise is
the estimate of effect.
 The larger the trial size, the narrower the interval.

31. Points to look for
 Who funded the research?
 Where was it published?
 How large was the patient population?
 How long was the population studied?
 How much at variance are the results of this
research with other studies?
 How sweeping did the study's findings appear to
be?
 What recommendations accompany the study,
and who is making them?

32. WORKSHEET - 2

33. Q. 2) What is relative risk
reduction ?
ANS :

34. Q. 3) What is the importance of “p
value” in clinical trials?
ANS :

35. Q.4) P value of …………is
considered as statistically
significant
a) > 0.5
b) <1
c) < 0.5
d) none of above

36. Q. 5) State whether the following
statement is true or false
1) Narrower is the confidence interval, the
more precise is the estimate of effect.
(_____________)