The role of placebo in clinical trials

1. Presented By…
Garima Saini
M.Pharm. (SEM-I)
Guided By…
Ms. Poonam Yadav
Department of Pharmaceutical Sciences,
Maharshi Dayanand University

2. THE ROLE OF PLACEBO
IN CLINICAL TRIALS

3. Definition
 Inert substance or treatment which is designed to have no
therapeutic value.
 Dummy medicine containing no active substance
 Patients who respond to placebo are termed as “Placebo
responders”

4. Placebo effect
Placebo effect is the psychological effect
Expectation to plays a potent role in the placebo effect.
The more a person believes they are going to benefit from a
treatment, the more likely it is that they will experience a
benefit

5. MECHANISM OF ACTION OF THE PLACEBO
Psychological mechanisms
• include expectations
• conditioning,
• memory,
• motivation,
• somatic focus,
• reward and reduction of
anxiety.
Neurobiological mechanisms
• responsiveness to placebo has
addressed placebo analgesia
• placebo effects can be completely
or partially reversed by the opioid
antagonist naloxone
• analgesic effects of placebo,
inhibited by the peptide
cholecystokinin(CCK)
• placebo operate by altering the
activity of both CCK and
endogenous opioids

6. placebo in clinical drug trials
for the following reasons:
Compare effects with those of the active drug
Comparison of active drugs validated by a placebo
Blind administration of two drugs that cannot be made
indistinguishable (Double Dummy technique)
Withdrawal period
Toxicity
Placebo responders to be excluded

7. Clinical equipoise in
placebo-controlled trials
 State where clinicians are unsure whether the new
treatment or intervention is as good as the
standard treatment.
 Violation of the therapeutic obligation of physicians
to offer optimal medical care.
 Right of the patient to receive the best care possible
is compromised .

8. Human research protection guidelines
The Office for Human Research Protection (OHRP) published
guidelines in 2008 for the use of placebo
“Placebos may be used in clinical trials where there is no known or
available (i.e., FDA-approved) alternative therapy that can be
tolerated by subjects.”
The use of placebos in controlled clinical trials must be justified by
a positive risk-benefit analysis
The subjects must be fully informed of the risks involved in the
assignment to the placebo group.
Continued assignment of subjects to placebo is unethical, once
there is good evidence to support the efficacy of the trial therapy

9. CONTINUE…
Subjects with an increased risk of harm from non- response may
be excluded.
Increased monitoring for deterioration of subjects and the use of
rescue medications may be included in the protocol.
‘Early escape’ mechanisms and explicit withdrawal criteria may
be built in so that subjects will not undergo prolonged placebo
treatment if they are not doing well.
The size of the population placed on placebo may be kept smaller
than the number in the active treatment arms.
Some drug trials involve a period during which all participants
receive only a placebo prior to the initiation of the study. This
period is called a ‘placebo washout’.

10. THE PURPOSE OF A WASHOUT PERIOD INCLUDE
:
Terminating the effects of any drug the subject may have been
taking before entering the clinical trial, so that the effects of the
trial drug may be observed.
Understanding whether the subjects co-operate with instructions
to take drugs.
 Understanding which subjects are ‘placebo responders’, in that
they experience a high degree of placebo effect.
In some protocols, the investigators plan to exclude those subjects
they find either poorly compliant or highly responsive to the
placebo

11. THE INFORMED CONSENT INFORMATION :
The subjects must be informed that they may be given a placebo.
A clear lay definition of the term ‘placebo’ must be given to the
subjects.
The rationale for using a placebo must be explained to the
subjects.
If applicable, the subjects must be informed of any viable medical
alternatives to being placed on placebo.

12. CONTINUE…
The duration of time that a subject will be on a placebo, degree of
discomfort, and potential effects of not receiving medication must
all be explained.
Any consequences of delayed active treatment must be explained
to the subjects
A statement in the risk section of the consent that the condition
of the subject may worsen while on placebo should be included.
A discussion in the benefits section that subjects who receive
placebo will not receive the same benefit as those who receive
active treatment if that treatment is effective should also be
included.

13. PROBLEMS ASSOCIATED WITH PLACEBO
Imperfect likeness
Impure placebos
Selecting placebo nonreactors
Overestimation of placebo effects