Clinical research

1. Introduction To Clinical Research
Dr. S. R. Tiruvalavan, MBBS, MD, MBA
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 1

2. Introduction of myself delegates
Get to know each other!!!
August 20, 2022 The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop 2

3. Disclaimer about this usage of
few slides!!!
Dr Aamir Shaikh – My GURU
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 3

4. Session Outline
What Is Clinical Research?
What Is The Larger Purpose Of Clinical Research?
Clinical Research vs Clinical Practice
Clinical Research – The Perceptions
Knowledge / Resource Item
Open Forum – Q & A
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 4

5. Clinical Research - To Begin With…..A
Recap
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 5

6. What Is Clinical Research?
CR vs CT - Some Basic Terminologies...
Clinical Research: The class of all scientific approaches to evaluate
medical disease prevention, diagnosis, treatment, and cure, in
humans. Clinical Research is research conducted in the clinical
setting and involves human subjects (participants), unlike pre-
clinical (or non-clinical) research which typically involves in vitro
tests as well as in vivo testing in animals
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 6

7. What Is Clinical Research?
CR vs CT - Some Basic Terminologies...
Clinical Research: The class of all scientific approaches to evaluate
medical disease prevention, diagnosis, treatment, and cure, in
humans. Clinical Research is research conducted in the clinical
setting and involves human subjects (participants), unlike pre-
clinical (or non-clinical) research which typically involves in vitro
tests as well as in vivo testing in animals
Clinical Trials: A subset of those clinical studies that evaluates
investigational medicines in Phases I, II and III. Phase IV evaluations
of marketed medicines in formal clinical trials using the same or
similar types of protocols to those use in Phases I and III are also
referred to as clinical trials (Spilker B, 1991)
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 7

8. Locally Relevant, Cost-effective, Clinical Programs, In Traditional,
And Real World Settings…
Prevalence
CR / CP
Instruments
Screening
Risk -
Factors
Surveys
Clinical
Trials
HTA
HEOR
Diagnostics
Others…
Thus, Clinical Research Is More
Than Just Clinical Trials…
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 8

9. “The purpose of (clinical) research is to create the knowledge
essential for action to improve health. Without this knowledge,
action is impossible because it has no logical or empirical basis.
Indeed, ongoing action for health, if it does not contain an
imbedded program of research, frequently becomes irrelevant,
misleading or unnecessarily costly.”
Source: IUATLD booklet 2001
What Is The Larger Purpose Of CR?
Why Is It Important And Necessary?
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 9

10. “The purpose of (clinical) research is to create the knowledge essential for
action to improve health. Without this knowledge, action is impossible because
it has no logical or empirical basis. Indeed, ongoing action for health, if it does
not contain an imbedded program of research, frequently becomes irrelevant,
misleading or unnecessarily costly.”
“Research is an activity of perpetual questioning. While public health practice is
based on consensus, standardization and systematic practice, research requires
a sceptical mind, prepared to continuously evaluate and question. This
questioning and evaluating, when put into a systematic framework, creates the
new knowledge that is required to create and continually modify actions for
health. This is what research is and why it is important.”
Source: IUATLD booklet 2001
What Is The Larger Purpose Of CR?
Why Is It Important And Necessary?
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 10

11. Clinical Research Vs Clinical Practice
Clinical
Research
Clinical
Practice
?
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 11

12. Key Differences Between Clinical Practice
And Clinical Research
CLINICAL PRACTICE CLINICAL RESEARCH
Patient approaches physician Physician/ Researcher approaches
patient (hence, arguably greater onus of
responsibility on physician in this case)
Deductive i.e., from general to specific Inductive i.e., from specific to general
Primary goal is to provide medical
/clinical care to patients
Primary goal is to gather generalizable
knowledge
Individualized treatment of patients,
with many options
Systematic investigation with uniform
management of participants and few
options
Standard-of-care guidelines Research protocol
Source: Adapted Arbit HM, Journal of Clinical Research
Best Practices Vol. 4, No. 6, June 2008
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 12

13. Thus, Even As Some Essential “Clinical
Capabilities” Do Differ….
Clinical Practice
Clinical knowledge
Clinical judgment
Clinical therapeutics
Clinical care
Clinical management and
administration
Clinical Research
Basic knowledge and principles:
scientific and medical research
Basic research methodology:
approach, thinking, design
Research conduct: planning and
execution
Research communication:
publication and dissemination
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 13

14. From Animal to Man - Five Issues of Consideration
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 15

15. Human
Pharmacology
First in “Man”
PK
Safety
Therapeutic
Exploratory
First in Patients
Pilot
Proof of Concept
Therapeutic
Confirmatory
Proof of Efficacy
Pivotal
Phases Of Clinical Trials
Characteristics / Objectives Of Each Phase
Therapeutic Use / Phase IV / Post Marketing Commitments
Effectiveness and Safety in Close to Real World Setting
New Uses, Formulations, Doses, Regimes, Populations
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 16

16. Traditional Model
Safety, Efficacy, And Effectiveness Of New Medicines
Gradual, Visible Shift To Real World (Clinical Practice) Settings….
Post marketing Studies (Optional)
Phase
III
Preclinical
Studies
Phase I Phase II
Full Drug Approval
Study
Participants #
0 0-100 100-500 500-3000 3000 or More
Modified Traditional Model
Post marketing Studies
(Optional)
Phase
III
Preclinical
Studies
Phase I Phase II
Full Drug Approval
Study
Participants #
0 0-100 100-500 500-10000 10000 or More
Proposed/Current Model
Study
Participants #
0 0-100 100-500 500-3000 30000-300000
Post marketing
Studies (Optional)
Phase
III
Preclinical
Studies
Phase I Phase II
Full Drug
Approval
Post marketing
Studies (Required)
Conditional Drug
Approval
Time
300000 or More
Source: Adapted Storm B. JAMA 2006;295;17:2072-2075
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 17

17. The Opportunity - Indian CR Stakeholders Evolving assets
CR
Stak
e -
hold
ers
Subjects/
Participants
Society
Sponsors
Regulat
ors
Ethics
Committee
Clinicians/
Researchers/
Investigators
Institution
CROs /
SMOs
Stakeholder - A person or organization with a legitimate interest in a given
situation, action or enterprise
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 18

18. The Challenge - Every CR Stakeholder Has Own
Expectation, Interest, And Perception.
These Need To Be Managed….
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 19

19. How does one obtain information that is both
reliable and valid using methods that can be
fairly easily implemented across a variety of
clinical settings?
How does one conduct such research in a clinical
setting without adding undue constraints or
burdens on the existing clinical services?
How does one record, review, encode, and
analyze large amounts of data in an accurate and
timely manner?
Real World Clinical Practice Settings
Salient Questions To Address - 1
Source: Adapted Jensen P et al. J. Am. Acad. Child Adolesc. Psychiatry, 1996, 35(1 ):55-66.
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 20

20. Can clinical information be systematically
collected to conduct research on the types of
services people use, the nature of clinicians'
practices, and clinical outcomes?
Can projects be developed even in settings
where there is not a strong research climate,
for example, where clinicians feel they do not
have the appropriate skills and tools to conduct
such research?
Real World Clinical Practice Settings
Salient Questions To Address - 2
Source: Adapted Jensen P et al. J. Am. Acad. Child Adolesc. Psychiatry, 1996, 35(1 ):55-66.
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 21

21. “If we want more evidence-based
practice, we need more practice-
based evidence…”
Prof. Lawrence Green
Department of Epidemiology and
Biostatistics – University of California
Role and Relevance of The
Clinician-Researcher
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 22

22. Successful Clinician-Researchers
What do they require to succeed…
WILL – Want to? ABILITY- Able to?
The Clinic’les, Salem @ Research Protocol, Funding and Publication Workshop
August 20, 2022 23