CLINICAL RESEARCH OVERVIEW

CLINICAL TRIALS

Clinical trials are studies performed with

human subjects to test new drugs or
combination of drugs, new approaches to
surgery or radiotheraphy or procedures to
improve the diagnosis of disease and quality
of life of the patients.
 CLINICAL RESEARCH
• Clinical research is
applied research.
• The purpose is to
evaluate whether the
medication is safe and
effective when it is used
for the disease under
question.
• Clinical trials also tell us
what is the appropriate
dose and route of
administration
 Types of Clinical Research
• Investigator Initiated (your idea; know-how;
study design)
– Federal Agency (NIH, ….)
– Contract research (Big/Small Pharma/Med Device
Co, …)
– Collaborative research (another institution)
• Sponsor Initiated (their ideas;
drug/device/biologic; protocol)
– Clinical trials (Phase I, II, III, IV)
– Contracted professional services
– Consulting services -tests & evaluations
• Clinical trials are studies in which people volunteer to test new drugs or
devices.
• Doctors use clinical trials to learn whether a new treatment works and is
safe for people.
• These kinds of studies are needed to develop new treatments for serious
diseases like cancer.
• Clinical trials are vital in studying all aspects of medicine, not just cancer.
• Every clinical trial in the must be approved and monitored by an
Institutional Review Board (IRB) to make sure the potential risks to
participants are as low as possible.
• Every institution that conducts clinical trials has an IRB.
• An IRB is a committee of health care professionals and community
members that do not have connections to the specific clinical trial.
• The IRB committee allows for unbiased decisions to be made about the
clinical trial and patient safety.
• The stakes may seem higher when researching medicines to treat cancer,
but all new treatments (drugs and medical devices) must go through
clinical trials before being approved by the FDA/OTHER REGULATORY
BODY.
 AIMS
Clinical trials aims to find the best ways to:
• prevent disease and reduce the number of
people who become ill
• treat illness to improve survival or increase the
number of people cured
• improve the quality of life for people living with
illness, including reducing symptoms of disease or
the side effects of other treatments, such as
cancer chemotherapy
• diagnose diseases and health problems.
 Core Components of Clinical trial
• Involve human subjects
• Move forward in time
• Most have a comparison a CONTROL group.
• Must have method to measure intervention
• Focus on unknowns – effects of medication
• Must be done before medication is part of
standard of care
• Conducted early in the development of therapies.
• Must review existing scientific data build on
that knowledge.
• Test a certain hypothesis
• Study protocol must be built on sound &
ethical science
• Control for any potential biases
 Regulations & Guidelines
• New Drug Act 2019
• Drugs & Cosmetics Act
• Schedule Y
• Indian GCP Guidelines
• Clinical Trial Permission
• Import License
• Export License
• BA BE Guidelines
• ICMR Guidelines for Medical Ethics
• ICH GCP Guidelines
• USFDA
• EU Directive
 Clinical Trial Eligibility
• Every clinical trial has guidelines and
requirements about who can participate.
• Some clinical trials may look only for people of
a certain age, gender, race, ethnicity, or
people with a specific disease, stage of
disease, or treatment history.
• Other clinical trials may be looking for people
without serious health conditions.
 STAGES OF
DRUG
DEVELOPMENT
 Phases of Clinical trial
• Before clinical trials, tests and treatments are
assessed in preclinical research.
• Preclinical research is not done with people. It
is done in animals.
• After preclinical research, tests and
treatments go through a series of clinical
trials.
• Clinical trials assess if tests or treatments are
safe for and work in people. Clinical trials have
five phases.
 Phase 0
1. Phase 0 is a recent designation for
exploratory trials.
2. First-in –human trials conducted in
accordance with U.S.FDA 2006 Guidelines on
Exploratory studies.
3. Also known as Micro-dosing trials
 Phase 0
1. The administration of single sub therapeutic
dose of study drug to a small number of
subjects (10to 15) to gather a preliminary
data on agents PK profile.
2. Phase 0 gives no data on safety or efficacy
3. Phase 0 is used to rank drug candidates in
order to decide which has best PK
parameters in humans to take forward into
development.
 Phase I
• Phase I trials aim to find the best dose of a new drug
with the fewest side effects.
• The drug will be tested in a small group of 15 to 30
patients.
• Doctors start by giving very low doses of the drug to a
few patients.
• Higher doses are given to other patients until side
effects become too severe or the desired effect is seen.
• The drug may help patients, but Phase I trials are to
test a drug’s safety.
• If a drug is found to be safe enough, it can be tested in
a phase II clinical trial.
 Phase 2

• Phase II trials further assess safety.

• Phase II trials are done in larger groups of
patients compared to Phase I trials.
• Often, new combinations of drugs are tested.
• Patients are closely watched to see if the drug
works.
• If a drug is found to work, it can be tested in a
phase III clinical trial.
 Phase 3

• Phase 3 trials are large and may include hundreds, or

sometimes many thousands, of patients from all over
the UK, and often from several countries.
• compare the effects of newer drugs with the standard
treatment,
• find out how well the drug works and how long the
effects last
• find out more about how common and serious any side
effects or risks are and about any possible longer term
problems that could develop.
 Phase 4

• Phase 4 trials are carried out after a new drug

has been shown to work and has been given a
licence.
• Phase 4 trials aim to find out: how well the
drug works when it is used more widely the
long-term risks and benefits more about the
possible rare side effects.
TOTAL TIME-
9-10 yrs
 Clinical Trial Designs
Controlled trials –
• are designed to compare different treatments.
• Most controlled trials compare a new treatment with
the standard or usual treatment by setting up two
groups of people.
• One group, known as the trial group or intervention
group, are given the new treatment.
• The other group is given the standard treatment and is
known as the control group.
• In situations where there is no standard treatment the
control group may not be given any treatment at all or
may be given a placebo.
 Blind trials
• In a blind trial, the participants are not told
which group they are in.
• This is because if they knew which treatment
they were getting, it might influence how they
felt or how they reported their symptoms.
• Some trials are double blind, which means that
neither the participants nor the doctors treating
them know which people are getting which
treatments.
• This also avoids the doctors’ hopes and
expectations influencing the results of the trial.
 Randomisation

• Many trials are randomised. This means that

people are allocated at random to the
treatment groups in the trial, usually by using
a computer programme.
• This is done so that each group has a similar
mix of people of different ages, sex and state
of health.
 Ethics in Clinical trials
3 ethical principles guide clinical research-
• Respect for persons- Treatment of person as
autonomous
• Beneficence- Issue re: potential conflict
between good of society vs. individual
• Justice- Treatment of all fairly & all equally
share benefits & risks.
 Ethical Issues:-Protection of Human
Subjects
• Rely highly on Investigator
• Participants right protected by IRB/IEC.
• An institutional review board (IRB), also known as an independent
ethics committee (IEC), ethical review board (ERB), or research
ethics board (REB), is a type of committee that applies research
ethics by reviewing the methods proposed for research to ensure that
they are ethical.
• Such boards are formally designated to approve (or reject), monitor,
and review biomedical and behavioral research involving humans.
• They often conduct some form of risk-benefit analysis in an attempt
to determine whether or not research should be conducted.
• The purpose of the IRB is to assure that appropriate steps are taken to
protect the rights and welfare of humans participating as subjects in a
research study.
 ICF- important part of Human Subject
protection
• To many, the term informed consent is mistakenly viewed as the same as
getting a research participant's signature on the consent form.
• FDA believes that obtaining a research participant's verbal or written
informed consent is only part of the process.
Informed consent involves providing a potential participant with:
• adequate information to allow for an informed decision about
participation in the clinical investigation.
• facilitating the potential participant's understanding of the information.
• an appropriate amount of time to ask questions and to discuss with family
and friends the research protocol and whether you should participate.
• obtaining the potential participant's voluntary agreement to participate.
• continuing to provide information as the clinical investigation progresses
or as the subject or situation requires.
The main purpose of clinical trials is to “study” new medical
products in people. It is important for people who are
considering participation in a clinical trial to understand their
role, as a “subject of research” and not as a patient.
• CAREER IN CLINICAL RESEARCH
Why A Career in Clinical Research?
• Sunrise Industry, Booming Market
• Huge Demand & Supply Gap,
• Easy Entry
• White Collared, Knowledge Intensive
• Good Career Prospects
• Quickies (quick money, growth on the ladder)
• National & International Travel, Cross-cultural Exposure
• Increased Contacts, Marketability
• Understanding of Drugs, Diseases & Management
• I Love Research, Documentation, Paper Work
 CR Career Pathway
• Pharmaceutical Companies
• Clinical CROs (Contract Research Organizations)
• BA/BE Centers
• SMOs (Site Management Organizations)
• Data Management CROs
• IT Companies in Healthcare / Clinical Domain
• EDC Service Providers
• Central Laboratories
• Packaging & Labeling & Contract Manufacturers
• Investigator & Site Staff • Training Centers.
Functions in Career Pathways

CRO/SMO

Quality
PV assurance

Sponsor
CR Site

Data
Mangeme DCGI
nt
 Career in CROs / Pharma / Biotech
Companies
CROs Pharma
Clinical Trial Assistant (CTA)
•Clinical Research Associate (CRA)
Phase I / II / III / IV Trial
• Senior CRA Project Management Drug
• Clinical Team Leader Development Planning
• Project Manager
• Senior Project Manager Monitoring Source Data
• Manager Medical & Regulatory Verification Safety
• Manager –Safety / Patents
• Manager Quality Assurance
Reporting Regulatory
• Medical Director Approval QA Audits
• Associate Director –Clinical Business Development
• Associate Director –Projects
• Director –Business Development
• Director / Head (Clinical Operations)
• General Manger / CEO / President
Career in SMO Career opportunities in DM
Clinical Research Coordinators (CRC) / Study Data Entry Operator
Coordinators
• Principal Investigators / Co-Investigators • Data Validation Executive
• Medical Monitors • QA Executive
• Project Manager / Senior Project • Data Manager
Manager
• Manager Medical & Regulatory • QA Manager
• Manager Quality Assurance • Statistical Programmer
• Manager –Business Development • Statistician
• Medical Director
• Associate Director –Clinical • Data Reviewer
• Associate Director –Projects • Data Base Designer
• Director / Head (Clinical Operations) • Medical Writer
• General Manager / CEO / President
• Head –Data Management
 Key Organizations into this area
• Companies into clinical research Sponsor companies:
Johnson & Johnson, Biocon, GlaxoSmithKline Beecham,
Allergan, Astra Zeneca, Ranbaxy Laboratories, Nicholas
Piramal, Dr.Reddys Laboratories, Novo Nordisk, Pfizer
etc.
• CROs: Quintiles, Manipal Acunova, ICON International,
Clintec, Clinigene International, Accenture, Paraxel,
Asian Clinical trials, Paragon, etc.

• Hospitals : St.Johns Hospital, M S Ramiah Memorial

Hospital, Kidwai Memorial Hospital, Bangalore Institute
of Oncology, Bangalore Diabetes Hospital, Wockhardt
Hospital, Apollo Hospitals etc.
Key Cities in India for Clinical Research
• Delhi & NCR Region
• Mumbai
• Pune
• Ahmedabad
• Vadodara
• Hyderabad
• Bangalore
• Chennai
• There are some new cities like Chandigarh; Bhopal,
Indore, Coimbatore; Vizag are emerging as new centres
for clinical trials
 IMPORTANT KNOWLEDGE AREAS
• Basic knowledge – Drug Development Process
• Clinical Trial Design & Statistics
• Adverse Events & Toxicology
• Regulatory & Ethics (GCP, GMP, GLP)
• Pharmacy, Pharmacokinetics, Pharmacology
• Disease, Diagnosis, Drugs
• Information Technology, Computing Skills
 To Conclude…
• A career in clinical research is definitely
challenging and satisfying.

• However success is ensured only when one

chooses the right course from the right
institution after thorough spadework.
• Questions??