Clinical trials

A research study to answer specific

question (about drugs or new ways of
using known ‘treatments’).

 Usedto determine whether new

drugs or treatments are both safe
and effective .
DESIGN OF A CONTROLLED TRIAL-
1
 Protocol
 Definition of Study Population
 Estimate sample size (n)
 Inclusion and Exclusion
Criteria
DESIGN OF A CONTROLLED TRIAL-
2
 Randomization
 Intervention
 Follow-up
 Assessment of outcome
 CLINICAL TRIAL- PROTOCOL

A blue print or plan

 Consists of all the steps involved in
the trial
 Objectives of the study
 Size of the sample
 Procedure for allocation of subjects
 Treatment to be applied- when
,where, how, to what kind of patients
 CLINICAL TRIAL-PROTOCOL

 Standardization of working
procedures and schedules
 Fixing responsibilities of the
individuals involved in the trial
 Aims at preventing bias and to
reduce the source of errors in the
study .
 POPULATION
 Geographical limits
 Specific age groups
 Sex
 Occupational groups
 Social groups
 Specific diagnostic groups,etc.
 ESTIMATION OF SAMPLE
SIZE
 Proper
sample size saves time, effort
and money.

 Sizeof the sample depends on

precision

 Precisionconsists of significance
level and allowable error
 INCLUSION AND EXCLUSION
CRITERIA
 Whichsubjects are to be included
and which to be excluded.
 RANDOMISATION
 It is the ‘heart’ of a clinical trial.
 Is a process of eliminating “bias”
 Every individual gets an equal
chance of being allocated into either
group
 Best done by using a “random
number table”.
 INTERVENTIOIN

Intervention is an independent
variable.

E.g..Drugs , new procedure , vaccine,

etc
 FOLLOW-UP
 Examination of the study and control
subjects at
 A defined interval of time,
 In the standard procedure,
 Under the same circumstances,
 In the same time frame,
 Till final assessment.
 ASSESSMENT
 The final step

 Outcome of trial in terms of positive

and

negative results.
 POSTIVE RESULTS
 Reduced incidence of the disease

 Reduction in severity of the disease

 Cost of the health services. etc

 NEGATIVE RESULTS
 Severity and frequency of side
effects

 Complications if any , including

deaths.
 ELIMINATION OF BIAS
Some of the bias’s
 “Allocation bias”
 “Subject bias”
 “Investigator bias”
Randomization eliminates “allocation
bias” but does not eliminate
“investigator” or Subject’ bias
 BLINDING
 Eliminationof “investigator” or
“subject” bias can be done by a
technique called blinding.

 Three types:
Single blind trial
Double blind trial
triple blind trial
 SOME STUDY DESIGNS

Completely Randomised designs

 Subjects allocated randomly to study
and control groups.
 Applicable when subjects are
homogeneous in nature.
 COMPLETELY RANDOMISED DESIGNS
LAYOUT OF THE EXPERIMENT
TREATMENT A TREATMENT B
02 01
04 03
05 06
09 07
10 08
11 12
15 13
16 14
17 18
20 19
 RANDOMISED BLOCK
DESIGNS
 Thisdesign is applicable when the
subjects are heterogeneous in
nature.
E.g.. When the response is different
for different age groups, the age
groups are then stratified into blocks.
Following this subjects are allocated.
 LAYOUT OF THE EXPERIMENT
Age groups Treatment A Treatment B
<30 04 01
05 02
07 03
08 06
10 09
>or=30 05 01
06 02
07 03
09 04
10 08
 CROSS OVER DESIGN-PHASE I
TREATMENT A TREATMENT B
02 01
04 03
05 06
09 07
10 08
11 12
15 13
16 14
17 18
20 19
Phase I Clinical Pharmacology
(20-50)
 Health Volunteer or Patients
 Pharmacokinetics (Absorption,
Distribution, Metabolism, Excretion)
 Pharmacodynamics (Biological
Effects)
 Where Practicable, Tolerance, Safety,
Efficacy.
 Phase 2 Clinical Investigation
(50-300)
 Patients
 PK and PD
 Dose-ranging is expanding; Carefully
controlled studies for efficacy and
safety.
 Phase 3 Formal therapeutic
trials
(250-1000+)
 Efficacyon a substantial scale,
safety, comparison with other drugs.
Phase 4 Post Licensing
(Marketing) studies (2000-
10,000+)
 Surveillance
for safety and efficacy.
Further Formal therapeutic trials,
including comparisons with other
drugs.
 CROSS OVER DESIGN – PHASE
II
TREATMENT B TREATMENT A
02 01
04 03
05 06
09 07
10 08
11 12
15 13
16 14
17 18
 Ethical Considerations
 The research protocol should always
contain a statement of ethical
considerations involved and should
indicate that aspects under Helsinki
declaration are complied with.
 Ethical Considerations – three
principles
 Respect for persons – autonomous
individuals – informed consent
essential.
 Beneficience – minimize risks and
maximize benefits.
 Justice – benefits and burdens of
research be distributed fairly.
 Ethical Considerations
 An independent panel of reviewers is
given power to monitor preliminary
data and to determine whether to
terminate the study prematurely.
 Such procedures must be explained
to subjects during the consent
process.
 Ethical Considerations
 Is it ethical to plan a trial in which
people are not offered a intervention
measure ?
 Is it ethical not planning a
randomized trial ?
Failure to do so may result in
perpetuation of an ineffective
programme.
Under the circumstances – protection
of safety and rights of participating
persons becomes important.
 Ethical Considerations
 The process of obtaining informed
consent is more important than the
subject’s signature on a form.
 There is a need to disclose the
nature and procedures of the study
and the potential risks and benefits.
 This will help assure that the
participation is voluntary and results
confidential.
 Ethical Considerations

 Investigatorsneed to set their own

standards. Institutional review is
most important.

Investigators need to set their own

standards.
RISK APPROACH & EVALUATION OF
CONTROLLED TRIALS
THANK U