This document discusses clinical research and the placebo effect. It defines observational and interventional clinical studies. It describes the phases of clinical trials from Phase 0 to Phase IV. It explains that the word "placebo" comes from Latin meaning "I shall please." It discusses the placebo effect and nocebo effect, and the potential mechanisms of the placebo effect involving the release of endorphins. Examples of conditions responsive to the placebo effect include cancer, IBS, depression, and Parkinson's disease. A case study found that depressed people who responded to placebos also responded well to real antidepressants.

1. UNIVERSITY OF MUMBAI
Institute : Garware Institute Of Career Education and
Development, Kalina
Course : Post Graduate Diploma in Pharma
Management.
Name : Sneha Modak.

2. On

3. INTRODUCTION
 Clinical Research
 Phases of Clinical Trial
 Word Origin of Placebo
 Nocebo Effect
 Mechanism of Action of Placebo
 Examples
 Case Study

4. Clinical Research
There are 2 main types of clinical studies:
• Observational studies (cohort study, epidemiology)-
 It improves the knowledge of the disease and its evolution
over time. It are carried out within the framework of the
follow-up of the patients in the reference centers. It also
contains the natural history studies.
• Interventional studies or clinical trials –
 It provides scientific evidence of the efficacy and safety of a
new drug, a new care device or a new management in the
context of an illness. This is the necessary step for a new
molecule to become a drug or a new medical device to be
marketed.

5. Phases of Clinical Trials
• Phase 0- Human micro dosing studies (normally the doses
are 100 times less than the intended therapeutic doses)
 PK and PD parameter are derived
 No data on safety or efficacy
• Phase I – Human pharmacology trials.
 Healthy volunteers
 Size- 20 to 80
 PK & PD
 Maximum tolerated dose

6. Phase II – Therapeutic exploratory trials :-
 Effective dose and dosing regimen
 Size- 20-300
 Divided into:-
Phase IIA :- To assess dosing requirements.
Phase IIB :- To study efficacy
• Phase III – Therapeutic confirmatory trials:-
 Randomized, controlled, multi-centric trials.
 Also called pivotal trials.
 Effectiveness of drug in comparison with the current gold
standard treatment.
 Size- 300-3000

7. Phase IV- Post marketing surveillance studies :-
 More about the side effects and safety of the drug
 What the long term risks and benefits are
 To gather the information like use of drug in children
 Pregnant women, elderly patients
 Patient with renal failures.

8. Word Origin- Placebo
• The word "placebo" comes from the Latin and means "I shall
please."

9. Placebo effect :- A placebo is a substance with no known
medical effects, such as sterile water, saline solution, or a
sugar pill. A placebo is a fake treatment that in some cases can
produce a very real response

10. • Nocebo effect :- Nocebo effect is a term associated with the
placebo effect. It refers to negative effects that happen when
you're given a drug or other treatment that has been
ineffective, such as a pill with no active ingredients. If you're
given a placebo and experience side effects, that's the nocebo
effect in action.

11. Mechanism of Action of Placebo
( Neurobiological )

12. • Placebos May Trigger Hormone Responses
• One possible explanation is that taking the placebo triggered a
release of endorphins. Endorphins have a structure similar to
morphine and other opiate painkillers and act as the brain's
own natural painkillers.
• Researchers have been able to demonstrate the placebo effect
in action using brain scans, showing that areas that contain
many opiate receptors were activated in both the placebo and
treatment groups. Naloxone is an opioid antagonist that blocks
both natural endorphins and opioid drugs. Using naloxone,
placebo pain relief is reduced.

13. (A) Morphine causes pain relief by binding to opioid receptors in the brain.
(B) The reward pathways activated by placebos cause the release of
endorphins, which bind to opioid receptors. (C) Naloxone blocks opioid
receptors, preventing the binding of endorphins, thereby partially blocking
the placebo effect

14. Examples :- ( Placebo effect )
 Cancer :- Cancer treatment side effects like fatigue
and nausea
 Irritable Bowel Syndrome
 Depression
 Parkinson's
Disease

15. Case Study
• Placebo power: Depressed people who respond to
fake drugs get the most help from real ones
• The findings published in JAMA Psychiatry and
made at the University of Michigan Medical School.

16. Natural painkillers respond
• Placebo power: When the researchers gave depressed people a placebo
and told them it might help their symptoms, they saw changes in brain
chemistry (left) in patients who responded to the placebo pill, in the
areas of the brain involved in emotional regulation. Those same brain
changes were also observed in patients who responded to a real
antidepressant (right).

17. Conclusion:-
• Placebos present a unique opportunity to harness the power of
the mind in controlling pain.
• The placebo effect can have a powerful influence on how
people feel, but it is important to remember that they are not a
cure for an underlying condition.

18. REFERENCES:-
– http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-
real/
– Usha gupta and Menka Verma, doi: 10.4103/2229-3485.106383, US
National Library of Medicine National institute of Health,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601706
– Kendra cherry Author of Everything Psychology Book (2nd Edition) ,
https://www.verywellmind.com/what-is-the-placebo-effect-2795466
– Source: thecurbsiders.com, Updated December 17, 2018,
Reviewer Avia James,
https://www.betterhelp.com/advice/psychologists/placebo-effect-
psychology-definition- and- examples/
– https://www.uofmhealth.org/news/archive/201509/placebo-power-depressed-people-
who-respond-fake-drugs-get, The findings , published in JAMA Psychiatry and made at
the University of Michigan Medical School.

19. THANK YOU