2. TABLE OF CONTENTS
1. Clinical research Introduction
2. Protocols,
3. Objectives,
4. design.
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3. Clinical Research:
“ Clinical research is the key to the discovery of
latest diagnostic method and to develop modern
drugs for the treatment of diseases.’’
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5. What Are Clinical Trials?
According to WHO:-
It is systemic study on pharmaceutical product in
human subject in order to discover the effect & identify any
AR/to study ADME of product for their safety and efficacy.
There are interventional and observational types of
studies.
1. Interventional studies :- Are those in which the research
subjects are assigned by the investigator to a treatment or
other intervention, and their outcomes are measured.
2. Observational studies :- Are those in which individuals
are observed and their outcomes are measured by the
investigators.
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6. Why Are Clinical Trials
Important?
Clinical trials translate results of
basic scientific research into better ways to
prevent, diagnose, or treat disease
The more people take part, the faster we can:
- Answer critical research questions
- Find better treatments and ways to prevent
disease
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7. What are the benefits and risks of participating
in a clinical trial?
Benefits:-
Clinical trials that are well-designed and well-
executed are the best approach for eligible
participants to:
Patients will receive, at a minimum, the best
standard treatment (if one exists)
If the new treatment or intervention is proven to
work, patients may be among the first to benefit
Patients have a chance to help others and
improve patient care
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8. Risks:-
There are risks to clinical trials.
There may be unpleasant, serious or even life-
threatening side effects to experimental
treatment.
The experimental treatment may not be effective
for the participant.
The protocol may require more of their time and
attention than would a non-protocol treatment,
including trips to the study site, more treatments,
hospital stays or complex dosage requirements.
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9. Types of Clinical Trials
1. Treatment
2. Prevention
3. Early detection/screening
4. Diagnostic
5. Quality of life/supportive care
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10. Treatment Trials
What new treatments can help people with a
particular disease?
What is the most effective treatment for people
with that disease?
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11. Prevention Trials
Evaluate the effectiveness of ways to reduce the
risk of a particular disease
Enroll healthy people at high risk for developing
that disease
Include medicines, vitamins vaccines, minerals or
lifestyle change.
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12. Screening and
Early-Detection Trials
Find test for detecting a particular disease.
Detecting disease at an earlier stage, resulting in
improved outcomes
SUPPORTIVE CARE TRIAL
To improve comfort and quality of life for
individual with chronic illness.
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13. Diagnostic Trials
Develop better tools for diagnosing particular
condition or disease.
Possible benefits:
New technology may be better and less invasive
Earlier detection of recurrences
Possible risk:
May require people to take multiple tests
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14. Clinical Trial Phases
Conducted in four phases.
PHASE-1
How does the agent affect the human body?
What dosage is safe?
It is undertaken to find out –
The safety and toxicity
Biological activity and tolerability
Pharmacokinetic parameters
Researchers test a new drug or treatment in a small
group of people(20-80) for the first time.
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15. PHASE-2
Phase 2 trials continue to test the safety of the new
agent, and begin to evaluate how well it works against a
particular disease.
In phase 2 trials, the new agent is given to groups of
people with the disease in question, using the dosage
found to be safe in phase 1 trials.
If a new agent has demonstrated that it works against
the disease and is safe for people in phase 2 trials, it
enters a phase 3 trial.
Phase 2 trials usually have less than 100 participants.
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16. PHASE-3
It include controlled clinical trials where a new drug
therapy is compared with the previously established
therapy or placebo, under standardized conditions.
In this drug/treatment is given to a large group of peoples
(1000-3000) to conform its effectiveness monitor side
effect, compare it to commonly used treatment and
collect information that will allow drug or treatment to be
used safely.
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17. PHASE-4
POST MARKETING STUDY PHASE
The real clinical status and the nature and
frequency of adverse reaction often becomes
apparent only the drug is released for general use.
It include additional information like drug’s use ,
benefits and optimal use.
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18. Further trials
Clinical research continues throughout the lifetime of
the test article to include post marketing surveillance
where a periodic 'progress report' is submitted to the
regulatory authorities once every 2 years after the test
article is released into the market, and such as
pharmacovigilance where the safety of marketed
drugs, biologics or medical devices are monitored.
The focus of clinical research is wide enough to
include important items such as data management,
medical writing, regulatory consultation, and
biostatistics.
The clinical trials are regulated by country specific
Health Regulatory Agencies such as the Food and
Drug Administration (FDA) in the U.S. and the
European Medicines Agency (EMEA) in the European
Union.
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19. Summary of Phases I-III
# Length Purpose % Drugs
Successfully
Subjects Tested
Phase 20 – 100 Several Mainly Safety 70%
I months
Phase Up to Several Short term 33%
II several months- 2 safety; mainly
100 yrs. effectiveness
Phase 100s – 1-4 yrs. Safety, dosage & 25-30%
III several effectiveness
1000
20. Stage/Phase Time to Complete
Pre Clinical 4 Years
Phase I 1.3 Years
Phase II 2.1 Years
Phase III 1.5-Several Years
Phase IV
Total Time to Complete Testing 15 Years
21. Key Players in a Clinical Trial
Sponsor
Investigation Site Team
IRB/IEC
Regulatory Authority/Competent Authority
Subject/Participant
Contract Research Organization
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22. Clinical Trial Protocol
The contents of a trial protocol should generally
include the following topics:-
General Information:-
1. Protocol title, protocol identifying number, and
date. Any amendment(s) should also bear the
amendment number(s) and date(s).
2. Name and address of the sponsor and monitor
(if other than the sponsor).
3. Name and title of the person(s) authorized to
sign the protocol and the protocol
amendment(s) for the sponsor.
4. Name, title, address, and telephone number(s)
of the sponsor's medical expert (or dentist
when appropriate) for the trial.
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23. 5. Name and title of the investigator(s) who is (are)
responsible for conducting the trial, and the
address and telephone number(s) of the trial
site(s).
6. Name, title, address, and telephone number(s) of
the qualified physician (or dentist, if applicable),
who is responsible for all trial-site related
medical (or dental) decisions (if other than
investigator).
7. Name(s) and address(es) of the clinical
laboratory(ies) and other medical and/or
technical department(s) and/or institutions
involved in the trial.
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24. Background Information:-
1. Name and description of the investigational
product(s).
2. A summary of findings from nonclinical studies that
potentially have clinical significance and from
clinical trials that are relevant to the trial.
3. Summary of the known and potential risks and
benefits, if any, to human subjects.
4. Description of and justification for the route of
administration, dosage, dosage regimen, and
treatment period(s).
5. A statement that the trial will be conducted in
compliance with the protocol, GCP and the
applicable regulatory requirement(s).
6. Description of the population to be studied.
7. References to literature and data that are relevant
to the trial, and that provide background for the
trial.
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25. Protocol- Relevant components
General Information
Objectives and Justification
Ethical considerations
Study design
Inclusion, Exclusions & withdrawal of
subjects
Handling of products
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26. Protocol- Relevant components
Assessment of Efficacy
Assessment of safety
Statistics
Data handling & management
Quality control & quality assurance
Finance and Insurance
Publication policy
Evaluation
Supplementaries & Appendices
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27. Protocol- General Information
Protocol Title, identifying number & date.
Amendment number
Contact names, addresses
Name and title of Authorized signatory
Contact medical expert
Contact investigator(s)
Institution(s), Laboratories, department
contact
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28. Protocol- Objective & Justification
Aims & objectives, phase of study
Name & description of Inv product
Summary of non clinical & clinical studies
Summary of risks & benefits
Description of route of administration,
dosage
Statement of GCP compliance
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29. Protocol- Study Design
A Description of trial Design should include,
1. A description of design of trial to be
conducted,
Double blind
Placebo control
Parallel design
2. A description of measure taken to minimize
or avoid Bios
Randomization
Blinding 29
30. Protocol- Study Design
3. Packing/labeling description
4. Proposed date of initiation of study
5. Discontinuation criteria for subjects
6. Instructions on suspending or terminating the
study
7. Procedures for monitoring compliance
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31. PLACEBO CONTROLLED STUDY:
A method of investigation of drugs in which an
inactive substance (the placebo) is given to
one group of participants, while the drug being
tested is given to another group. The results
obtained in the two groups are then compared
to see if the investigational treatment is more
effective in treating the condition.
Endpoint:
A primary or secondary outcome used to
judge the effectiveness of a treatment.
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32. Clinical Trial Design
Randomization: A method used to prevent
bias in research; a computer or a table of
random numbers generates treatment
assignments.
Participants have an equal chance to be
assigned to one of two or more groups:
One gets the most widely accepted treatment
(standard treatment)
The other gets the new treatment being tested,
which researchers hope and have reason to
believe will be better than the standard
treatment
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33. Randomization
So all groups are as alike as possible
Provides the best way to prove the effectiveness
of a new agent or intervention
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34. Clinical Trial Design
Stratification: Categorizing subjects into
subgroups by specific characteristics
Enables researchers to look into separate
subgroups to see whether differences exist
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35. Protocol- Inclusion Exclusion criteria
Specifications of the subjects to be included
(age, gender, ethnic groups, prognostic
factors, diagnostic criteria)
Specify exclusion criteria
Subject withdrawal criteria & procedures
Protocol- handling of products
Safe handling and storage measures
System to be followed for labelling
Labeling specifications 35
36. Protocol- Efficacy assessment
Specifications of efficacy parameters
Descriptions of how these are measured and
recorded
Time & periodicity of recording
Description of special analysis/ tests(PK,
clinical, lab, radiology)
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37. Protocol- Safety assessment
Specifications of safety parameters
Procedures for eliciting reports of and
reporting ADR
Time &method of recording
Type, duration of follow up after adverse
events)
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38. Protocol- Statistics
Description of statistical methods employed
Details of enrollment plan
Significance level, power
Selection of subjects to be included in final
analysis
Procedure for reporting any deviation from
original plan should be described & justified in
protocol.
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39. Protocol- Finance & insurance
Budget, financial aspects
Sources of economic support
Subject payments
Reimbursement to team members
Insurance details of study subjects
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40. How Are Patients’ Rights
Protected?
1. Informed consent
2. Scientific review
3. Institutional review boards (IRBs)
4. Data safety and monitoring boards
(DSMBs)
Informed Consent:
• Purpose
• Procedures
• Potential risks and benefits
• Individual rights
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41. Scientific review
Institutional review boards (IRBs) are
required by federal law for trials that are:
--Federally funded
--Subject to FDA regulation
Data and safety monitoring boards:
Ensure that risks are minimized
Ensure data integrity
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42. Why Do So Few People Participate in
Clinical Trials?
Sometimes patients:
Don’t know about clinical trials
Don’t have access to clinical trials
May be afraid or suspicious of research
Can’t afford to participate
May not want to go against health care
provider’s wishes
Health care providers might:
Lack awareness of appropriate clinical trials
Be unwilling to “lose control” of a person’s care
Believe that standard therapy is best
Be concerned that clinical trials add administrative
burdens
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