CLINICAL TRIALS OF DRUG

SUBSTANCES
 Important Terminologies
 Principal Investigator: A person responsible for the conduct of the

clinical trial at a trial site. If a trial is conducted by a team of individuals

at a trial site, the investigator who is the responsible leader of the team
may be called the principal investigator.
 Sponsor: A person or an organization that manages and finances a

clinical trial.
 Clinical Investigator: A medical researcher in charge of carrying out a

clinical trial's protocol.

 Clinical Research Associate (CRA): Person employed by the study

sponsor or clinical research coordinator to monitor a clinical trial at one

or more participating sites. The CRA is responsible for ensuring all
clinical studies are conducted according to study protocol, within
regulations and ICH guidelines.3
 Important Terminologies
 Control:

 The treatment which has a predictable outcome. Research subjects in

the control group may receive a standard, commonly used treatment or

a placebo.
 Crossover:

 A study in which participants are randomly assigned one of two or more

treatment options for a specified time period. When that time period
ends, the participants "cross over" to one of the remaining treatments
for another specified time period.
 Double-blind:

 A study in which neither the participants nor the investigators who work

with them knows which treatment or placebo is being given to which

participant.
 Important Terminologies
 Informed consent:

 The required signed, written acknowledgement from a participant in a

clinical trial (or his or her legal representative), which states that he or
she understands what is going to happen in the trial and the risks
involved.
 Institutional Review Board (IRB):

 A group of people (including scientific experts as well as nonscientists)

that oversees the design of a clinical study and periodically reviews

clinical research to ensure there are no ethical violations. A clinical trial
must be approved by the IRB before it begins.
 Important Terminologies
 Placebo:

 A pill or treatment designed to have no effect on the person who takes it,

also called a "sugar pill."

 Placebo effect:

 Situation in which an individual feels an improvement in his or her

condition after taking an inactive substance or "sugar pill."

 Protocol:

 Procedures which must be followed. To protect the trial's scientific

accuracy, straying from protocol is seldom allowed.

 Important Terminologies
 Randomized:

 A study in which participants are assigned by chance (not by the

investigators' choice) to their particular groups.

 Single-blind:

 A study in which the investigators know which treatments each

participant is receiving, but participants do not.

 Open Label Trial:

 A trial in which the research staff and the trial participant know the

treatment that is assigned.

 Important Terminologies
 Interventions: Primary experimental treatments being studied. Types of

treatments may include drug, gene transfer, vaccine, behavior, device,

or procedure.
 Investigational New Drug Application (IND): The petition through

which a drug sponsor requests the FDA to allow human testing of a new
drug, antibiotic drug, or biological drug in a clinical investigation. This
includes an application for a biological product used in vitro for
diagnostic purposes.
 New Drug Application (NDA): An application submitted by a sponsor to

the FDA for approval to market a new drug (a new, non-biological

molecular entity) for human use.
 Introduction to Clinical Trials
 Clinical trial is a systematic investigation in human subjects for

evaluating the safety & efficacy of any new drug.

 Clinical trials are a set of tests in medical research and drug

development that generate safety and efficacy data for health

interventions in human beings
 Introduction to Clinical Trials

 Clinical trials are medical research studies in which people enrolled as

participants help to find out if a new treatment or procedure is safe and

effective. Clinical trials are used to test all types of medical interventions.
New drugs, treatment schedules, and surgical procedures are tested to
determine if they are safe and effective treatments for specific diseases.
Dietary, regimens, nutritional supplements, exercise programs, and
other interventions are tested to discover if they are able to prevent
disease safely and effectively. Most new medical interventions are
tested in clinical trials before being made available to the general public.
 Introduction to Clinical Trials
 Clinical trials cover a broad range of different types of research. For

example, trials are often used to test new medicines or vaccines but can
also be used to look at new combinations of existing medicines. They
can also be used to test whether giving a treatment in a different way
will make it more effective or reduce any side effects.
 Introduction to Clinical Trials

 Clinical trials are not always about testing medicines, they can be used

to test 'interventions' aimed at modifying a person's behaviour or

lifestyle. This could include an educational programme designed to
improve a person's understanding of their medical condition and help
them to manage it more effectively, or a psychological treatment, such
as the use of cognitive behavioural therapy for the treatment of anxiety
or depression.
 Aims of Clinical Trials
Clinical trials aim to find 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.
 Types of Clinical Trials
 The U.S. National Institutes of Health (NIH) organizes trials into

different types:
 Prevention trials: look for better ways to prevent disease in people

who have never had the disease or to prevent a disease from

returning. These approaches may include medicines, vitamins,
vaccines, minerals, or lifestyle changes.
 Screening trials: test the best way to detect certain diseases or

health conditions.
 Diagnostic trials: are conducted to find better tests or procedures

for diagnosing a particular disease or condition.

 Types of Clinical Trials
 Treatment trials test: experimental treatments, new combinations of

drugs, or new approaches to surgery or radiation therapy.

 Quality of life trials (supportive care trials): explore ways to improve

comfort and the quality of life for individuals with a chronic illness.
 Compassionate use trials or expanded access trials provide partially

tested, unapproved therapeutics to a small number of patients who have

no other realistic options. Usually, this involves a disease for which no
effective therapy has been approved, or a patient who has already failed
all standard treatments and whose health is too compromised to qualify
for participation in randomized clinical trials. Usually, case-by-case
approval must be granted by both the FDA and the pharmaceutical
company for such exceptions.
 Inclusion and Exclusion Criteria

 In a clinical trial, the investigators must specify Inclusion and

exclusion criteria for participation in the study.
 Inclusion criteria are characteristics that the prospective subjects must

have if they are to be included in the study, while exclusion criteria are
those characteristics that disqualify prospective subjects from inclusion
in the study. Inclusion and exclusion criteria may include factors such
as age, sex, race, ethnicity, type and stage of disease, the subject’s
previous treatment history, and the presence or absence (as in the case
of the “healthy” or “control” subject) of other medical, psychosocial, or
emotional conditions.
 Exclusion criteria

 Strongly Justified Reasons for Exclusion:

 Unable to provide informed consent

 Placebo or intervention would be harmful

 Lack of equipoise (intervention harmful)

 Effect of intervention difficult to interpret

 Potentially Justified Reasons for Exclusion:

 Individual may not adhere

 Individual may not complete follow up

 Individuals do not have reliable information

 Designing Clinical Trials
 Researchers design clinical trials to answer specific research questions

related to a medical product. These trials follow a specific study plan, called

a protocol, that is developed by the researcher or manufacturer. Before a
clinical trial begins, researchers review prior information about the drug to
develop research questions and objectives. Then, they decide:
 Who qualifies to participate (selection criteria)

 How many people will be part of the study

 How long the study will last

 Whether there will be a control group and other ways to limit research bias

 How the drug will be given to patients and at what dosage

 What assessments will be conducted, when, and what data will be collected

 How the data will be reviewed and analyzed

Types of Designs for Clinical Studies
 Treatment Studies:
 Randomized controlled trial
 Blind trial
 Non-blind trial
 Adaptive clinical trial
 Nonrandomized trial 
 Observational studies
 Cohort study
 Prospective cohort
 Retrospective cohort
 Time series study
 Case-control study
 Nested case-control study
 Cross-sectional study
 Community survey (a type of cross-sectional study)
 Ecological study
 Randomized controlled trial

 A randomized controlled trial (or randomized control trial; RCT) is a

type of medical experiment which aims to reduce bias when testing a

new treatment. The people participating in the trial are randomly
allocated to either the group receiving the treatment under investigation
or to a group receiving standard treatment (or placebo treatment) as the
control. Randomization minimises selection bias and the different
comparison groups allow the researchers to determine any effects of the
treatment when compared with the no treatment (control) group.
 Blind Trial

 A blind or blinded experiment is an experiment in which information

about the test is masked (kept) from the participant, to reduce or

eliminate bias, until after a trial outcome is known. It is understood
that bias may be intentional or unconscious, thus no dishonesty is
implied by blinding. If both tester and subject are blinded, the trial is
called a double-blind experiment.
 Open Label Trial

 An open-label trial or open trial is a type of clinical trial in which both

the researchers and participants know which treatment is being

administered. This contrasts with single blind and double
blind experimental designs, where participants are not aware of what
treatment they are receiving (researchers are also unaware in a double
blind trial).
 Adaptive Clinical Trial

 use existing data to design the trial, and then use interim results to
modify the trial as it proceeds. Modifications include dosage, sample
size, drug undergoing trial. In some cases, trials have become an
ongoing process that regularly adds and drops therapies and patient
groups as more information is gained. The aim is to more quickly
identify drugs that have a therapeutic effect.
 Fixed trials

 consider existing data only during the trial's design, do not

modify the trial after it begins and do not assess the results until
the study is complete
 PHASES OF CLINICAL TRIALS
 Clinical trials involving new drugs are commonly classified into four

phases. Each phase of the drug approval process is treated as a

separate clinical trial. The drug-development process will normally
proceed through all four phases over many years. If the drug
successfully passes through Phases 0, 1, 2, and 3, 4 it will usually be
approved by the national regulatory authority for use in the general
population. Before pharmaceutical companies start clinical trials on a
drug, they will also have conducted extensive preclinical studies,
Each phase has a different purpose and helps scientists answer a
different question.
 Preclinical study

 Preclinical study: A study to test a drug, a procedure, or another medical

treatment in animals. The aim of a preclinical study is to collect data in

support of the safety of the new treatment. Preclinical studies are
required before clinical trials in humans can be started.
 Deciding whether a drug is ready for clinical trials (the so-called move

from bench to bedside) involves extensive preclinical studies that yield

preliminary efficacy, toxicity, pharmacokinetic and safety information.
Wide doses of the drug are tested using in vitro (test tube or cell culture)
and in vivo (animal) experiments,
 Phases of Clinical Trials
 PHASE 0:

 PURPOSE:

Pharmacodynamics and pharmacokinetics in humans.

 EXPLANATION:

Phase 0 trials are the first-in-human trials. Single sub therapeutic

doses of the study drug or treatment are given to a small number of
subjects (10 to 15) to gather preliminary data on the agent's
pharmacodynamics (what the drug does to the body) and
pharmacokinetics (what the body does to the drugs). For a test drug,
the trial documents the absorption, distribution, metabolization, and
removal (excretion) of the drug, and the drug's interactions within the
body, to confirm that these appear to be as expected.
 Phases of Clinical Trials
 PHASE 1:

 PURPOSE:

Safety and Dosage.

 LENGTH OF STUDY:

 Several months.

 EXPLANATION:

Testing within a small group of people (20–80) to evaluate safety,

determine safe dosage ranges, and begin to identify side effects. A
drug's side effects could be subtle or long term, or may only happen
with a few of people, so phase 1 trials are not expected to identify all
side effects.
Approximately 70% of drugs move to the next phase.
 Phases of Clinical Trials
 PHASE 2:

 PURPOSE:

Establishing the efficacy and side effects of the drug.

 LENGTH OF STUDY:

 Several months to 2 years.

 EXPLANATION:

Testing with a larger group of people (100–300) to see if it is effective

and to further evaluate its safety. The gradual increase in test group
size allows less-common side effects to be progressively sought.
Approximately 33% of drugs move to the next phase
 Phases of Clinical Trials

 PHASE 3:

 PURPOSE:

Final confirmation of safety and efficacy and monitoring of ADRs

 LENGTH OF STUDY: 

1 to 4 years.
 EXPLANATION:

Testing with large groups of people (300–3,000) to confirm its

effectiveness, monitor side effects, compare it to commonly used
treatments, and collect information that will allow it to be used safely.
Approximately 25-30% of drugs move to the next phase
 Phases of Clinical Trials
 PHASE 4:

 PURPOSE:

studies during sales (Safety and efficacy).

 EXPLANATION:

post marketing surveillance (Pharmacovigilance) gives additional

information, including the treatment's risks, benefits, and optimal use.
As such, they are ongoing during the drug's lifetime of active medical
use. (Particularly relevant after approval under FDA Accelerated
Approval Program).