CLINICAL STUDY

A. Alfia MT

Department of Pharmacology
Faculty of Medicine
Tadulako University
 Development

Preclinical studies
The R&D Clinical studies
process
Discovery Early Clinical Development
CHEMISTRY/ IND* PHASE I PHASE II PHASE III NDA** PHASE IV
 PHARMA­
COLOGY
Regulatory  Efficacy  Clinical  Comparativ Regulatory  Continued 
Search for 
review studies on  studies on a  e studies on  review comparative 
active 
healthy  limited scale a large  studies
substances *Investigational 
New Drug volunteers number of  KNOWLEDGE
Toxicology,  Application for  patients
50–150 100–200 LEVEL
efficacy  permission to  Registration, 
administer a new  persons patients
studies on  market 
various types 
drug to humans 500–5,000
introduction
of animals KNOWLEDGE patients
**New Drug 
LEVEL Application
Application for 
permission to market
a new drug

TIME SPAN

2–4 yrs. 2–6 months 3–6 yrs. 1–3 yrs. 

Approximately 10–15 years from idea to marketable drug

6/3/19
 What Are Clinical Trials?
 Research studies involving people
 Try to answer scientific questions and
find better ways to prevent, diagnose, or
treat disease
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
Do Many People Take Part in
Clinical Trials?
 Few people participate
What Are the Different Types
of Clinical Trials?
 Treatment
 Prevention
 Early detection/screening
 Diagnostic
 Quality of life/supportive care
 Treatment Trials

 What new treatments can help people

with a particular disease?

 What is the most effective treatment for

people with that disease?
Randomized Trials
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
Randomization
Why is Randomization
Important?
 So all groups are as alike as possible
 Provides the best way to prove the
effectiveness of a new agent or
intervention
Treatment Trials
Placebos are almost never used:
 Placebos are used only when no
standard treatment exists
 Patients are told of this possibility
before deciding to take part
Clinical Trial Protocol
 A recipe or blueprint
 Strict scientific guidelines:
--Purpose of study
--How many people will participate
--Who is eligible to participate
--How the study will be carried out
--What information will be gathered about
participants
--Endpoints
Benefits of Participation
Possible benefits:
 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
Risks of Participation
Possible risks:
 New treatments or interventions under study
are not always better than, or even as good as,
standard care
 Even if a new treatment has benefits, it may not
work for every patient
 Health insurance and managed care providers
do not always cover clinical trials
Patient Protection
 There have, unfortunately, been past
abuses in patient protection

 Ensure that people are told about the

benefits, risks, and purpose of
research before they agree to
participate
How Are Patients’ Rights
Protected?

 Informed consent
 Scientific review
 Institutional review boards (IRBs)
 Data safety and monitoring boards
(DSMBs)
How Are Patients’ Rights
Protected?
Informed Consent:
Purpose
Procedures
Potential risks and
benefits
Individual rights
Data and safety monitoring boards:
 Ensure that risks are minimized
 Ensure data integrity
 Stop a trial if safety concerns arise or
objectives have been met
 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
Safety in Clinical Trials

 First consideration is the

protection of the rights,
safety and well-being of
the study subject.
Groups concerned with clinical
research
Ethics
Committees

Patients & healthy

Sponsors volunteers

clinical
research
Drug
Clinical regulatory
investigators authorities
 Clinical Trial Phases

Phase 1 trials
 How does the agent affect the human body?
 What dosage is safe?
 Phase I Testing
 Description:
 Establishes safety and toxicity in humans
 Short term (up to 1 month)
 Few healthy volunteers (20 – 80)

 Evaluates:
 Pharmacodynamics (physiologic effects)
 Pharmacokinetics
 Bioavailability
 Bioequivalance
 Dose proportionality
 Metabolism
Phase I Studies: Participant Issues

 Less information for informed consent

 Generally requires over night stays
 Frequent blood draws for lab work.
 Least likely to receive therapeutic dose.
 No therapeutic benefit to healthy
volunteers.
Clinical Trial Phases
Phase 2 trials
 Does the agent or intervention have an effect
on the disease?
 Phase II Studies
 Description
 Well-defined subject eligibility criteria
 Controlled comparisons with either placebo or active
control
 Short-medium duration (weeks to months long)
 Larger number of subjects (100-300)
 Establishes effectiveness of drug for a specific
population and disease
 First to use subjects with the disease or
condition (not healthy volunteers)
 Evaluates:
 Safety in patients
 Efficacy/pharmacologic effects
 Pharmacokinetics (single and multi dose
optional)
 Bioavailability
 Drug-disease interactions
 Drug-drug interactions
 Efficacy at different doses
 Phase II Studies
Participant Issues:
 Slightly more information for informed
consent
 Greater chance of therapeutic dose
 Study maybe placebo controlled
 Frequent visits with blood draws
Clinical Trial Phases
Phase 3 trials
 Is the new agent or intervention (or new use
of a treatment) better than the standard?
 Participants have an equal chance to be
assigned to one of two or more groups
Phase III Studies

 Description
 Broader patient eligibility criteria than in
Phase II studies
 Studies may have two or three treatment
groups
 Longer duration (months to years)
 Involves hundreds to thousands of subjects
 Evaluates
 Efficacy and safety evaluation in population
subgroups
 Dosing intervals
 Drug-drug interactions
 Drug-disease interactions
 Risk/benefit information
Phase III Studies
Participant Issues
 More Information for making informed
consent
 Visits are less frequent and shorter in
duration
 May or may not receive active drug
 FDA can stop the study from proceeding
or stop a trial that has started:
 For safety reasons
 If the company fails to disclose accurately
the risks of the study to the investigators
 If protocol design is clearly deficient in
meeting stated objectives (Phase II and III)
 Phase IV Studies
Description
Post-marketing studies
May involve additional age or ethnic groups
Monitors continued safety in large groups
Must be conducted if the FDA approves the drug on the
“fast track” before all premarketing data is collected
Evaluates
Adverse events
Other efficacy or pharmacoeconomic data

Epidemiologic date
 Phase IV Studies
Participant Issues
 Most information available for the informed consent
 Most likely to receive therapeutic dosage
 Less rigid inclusion criteria
 Study drug may or may not be free
 May be done at their primary care providers office
Cost of Developing New Drugs

 It costs $500,000,000
to develop one new
medication from the
laboratory to FDA
approval.
Thank You