Clinical Trials: The Phases of Drug Testing and Approval

 Discovering and developing new medicines is a long, complex, and costly process,
but biopharmaceutical researchers devote (‫ )يكرسوا‬their careers to this often
frustrating but tremendously gratifying (interesting) task.

 The research and development (R&D) process is the road to new medicines—and
more often than not it entails ‫ ))يتضمن‬many turns, stops, and starts. Substantial
progress typically occurs in increments ‫ ))زيادات‬over time, as advances build on
each other

 Drug Discovery: The first step in developing a new medicine is to understand the
disease or condition as thoroughly as possible.

 Basic research provides clues ‫ ))أدلة‬about how to treat diseases and potential ways
to target the symptoms or underlying causes.

 A drug target can be a protein, RNA, DNA or other molecule that is somehow
involved in the disease.

 Researchers look for a lead compound—a promising molecule that could influence
the target and, potentially, become a medicine
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 Clinical Trials: The Phases of Drug Testing and Approval
 Preclinical Testing:
The drug discovery phase whittles down ‫ ))يتقلص‬thousands of compounds to a few
hundred promising possibilities that are ready for preclinical testing. In this stage,
scientists conduct laboratory (using cell lines) and animal studies to determine
whether a compound is suitable for human testing. At the end of this process, which
can take several years, a lead compound moves to the next stage, clinical trials in
humans. Before beginning a clinical trial, the pharmaceutical research company files an
Investigational New Drug Application with the Food and Drug Administration (FDA)-
USA & The European Medicines Agency (EMA).
 Pre-clinical investigations include animal studies and evaluations of drug
production and purity.
 Animal studies explore: 1) the drug’s safety in doses equivalent to approximated
human exposures, 2) pharmacodynamics (ie, mechanisms of action, and the
relationship between drug levels and clinical response), and 3) pharmacokinetics
(ie, drug absorption, distribution, metabolism, excretion, and potential drug–drug
interactions).

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 Clinical Trials: The Phases of Drug Testing and Approval
 Clinical Trials:
Clinical trials are the primary requirement for the development of novel,
innovative drug product, or high-risk medical devices
During this stage, a compound is tested in human volunteers (healthy or
patients). The clinical trials process occurs in several phases and takes on
average six to seven years. A potential medicine must successfully complete all
of the phases before being submitted to the FDA for review.
Because this process involves both benefits and risks, companies take great
care to protect the safety of trial participants and to ensure that they are
thoroughly informed about the trial and its potential risks and can give their
informed consent to participate, as required by federal regulations.
Companies also ensure that the trials are conducted correctly and with
integrity, including that the clinical trial results are disclosed at the appropriate
time.

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 Clinical Trials: The Phases of Drug Testing and Approval
 Clinical Trials:

The study design and the informed consent are reviewed, approved and monitored by
an Institutional Review Board (IRB). The IRB is made up of physicians, researchers, and
members of the community. Its role is to make sure that the study is ethical and the
rights and welfare ‫ ))رفاهية‬of participants are protected. This includes making sure that
research risks are minimized and are reasonable in relation any potential benefits.

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 Clinical Trials: The Phases of Drug Testing and Approval
 Following is a general description of the phases of clinical research or
trail:
Phases of Clinical Trial
Phase I: Purpose:

•To find a safe dose

•To decide how the new treatment should be given (by
mouth, in a vein, etc.)
•To see how the new treatment affects the human body and
fights disease such as cancer

Study Participants: 20 to 100 healthy volunteers or people

with the disease/condition
Approximately 70% of drugs move to the next phase

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 Clinical Trials: The Phases of Drug Testing and Approval
 Following is a general description of the phases of clinical research:

Phases of Clinical Trial

Phase II: Purpose:

•To determine if new drug has any beneficial activity and thus
worthy of further testing / investment of resources.
•Begin to focus on population (patients) for whom this drug
will likely show favorable effect (Efficacy and side effects)

Study Participants: Up to several hundred people with the

disease/condition
Approximately 33% of drugs move to the next phase

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 Clinical Trials: The Phases of Drug Testing and Approval
 Following is a general description of the phases of clinical research:
Phases of Clinical Trial
Phase III:Purpose:

•To compare the new treatment (or new use of a treatment)

with the current standard treatment or placebo.

Study Participants: 300 to 3,000 volunteers who have the

disease or condition

Length of Study: 1 to 4 years

Approximately 25-30% of drugs move to the next phase

“it is a key phase where the drug either make

or break its reputation with respect to safety
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 Clinical Trials: The Phases of Drug Testing and Approval
 Following is a general description of the phases of clinical research:

Phases of Clinical Trial

Phase IV or Post marketing study as the drug has

granted license or approval.

Evaluation in the real clinical setting, these studies

are crucial in gathering further safety information
from a larger group of patients in order to understand
the long term safety of the drug and address drug
interactions.

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 Clinical Trials: The Phases of Drug Testing and Approval
 FDA Review and Approval

If the results of all three clinical trials phases indicate that the compound is safe and
effective, the company submits a New Drug Application or Biologics License Application
to the FDA. This application, which includes reams ‫ ))رزم‬of data from all stages of
testing, is a request for FDA approval to market the new medicine.

Scientists at the FDA carefully review all the data from all of the studies on the
compound and, after weighing the benefits and risks of the potential medicine, decide
whether to grant approval. Occasionally, the FDA will ask for additional research before
granting approval or convene an independent expert panel‫دع وة لجن ة خ براء‬
‫ ) )مستقلة‬to consider data presented by the FDA and the company. The panel will then
advise the agency on whether to approve the application and under what conditions.

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 Clinical Trials: The Phases of Drug Testing and Approval
 Post-Approval Research and Monitoring (Phase IV trial)

Research on a new medicine does not end when the discovery and development phases
are over and the product is on the market. On the contrary, companies conduct extensive
post-approval research to monitor safety and long-term side effects in patients using the
medicine. The FDA requires that companies monitor a medicine for as long as it stays on
the market and submit periodic reports on safety issues. Companies must report any
adverse events that occur from use of the medicine.

FDA sometimes requires companies to conduct phase 4 clinical trials, which evaluate long-
term safety or effects in specific patient subgroups. Companies may conduct post-approval
studies to assess the benefits of a medicine for different populations or in other disease
areas. In some cases, they may also develop improved delivery systems or dosage forms.

This research phase is critical to improving researchers’ and clinicians’ understanding of a

medicine’s potential uses and its full benefits for health and quality of life. Continued
research can show whether a medicine has a greater impact on an outcome when it is
used earlier in a disease, in combination with other medicines, in different disease
indications, or in combination with specific biomarkers.

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Phase IV or Post marketing Surveillance
• No fixed duration / patient population
• Starts immediately after marketing
• Report all Adverse drug reaction (ADRs)
• Helps to detect
– rare ADRs
– Drug interactions
– Also new uses for drugs [Sometimes called Phase
V]

Adverse drug reaction: is an injury caused by taking a medication.

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 Clinical Trials: The Phases of Drug Testing and Approval

Some concepts to understand

Typically, clinical trials compare a new product or therapy with another that already
exists to determine if the new one is as successful as, or better than, the existing
one. In some studies, participants may be assigned to receive a placebo (an
inactive product that resembles the test product, but without its treatment value).

Comparing a new product with a placebo can be the fastest and most reliable
way to demonstrate the new product’s therapeutic effectiveness. However,
placebos are not used if a patient would be put at risk—particularly in the study of
treatments for serious illnesses—by not having effective therapy. Most of these
studies compare new products with an approved therapy. Potential participants
are told if placebos will be used in the study before they enter a trial.

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 Clinical Trials: The Phases of Drug Testing and Approval
Some concepts to understand

Randomization: the treatment each trial participant receives is often decided by a

process called randomization. This process can be compared to a coin toss that is
done by computer. During clinical trials, no one likely knows which therapy is
better, and randomization assures that treatment selection will be free of any
preference a physician may have. Randomization increases the likelihood that the
groups of people receiving the test drug or control are comparable at the start of
the trial, enabling comparisons in health status between groups of patients who
participated in the trial.

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 Clinical Trials: The Phases of Drug Testing and Approval
Some concepts to understand

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 Clinical Trials: The Phases of Drug Testing and Approval
Some concepts to understand

In single-or double-blind studies, also called single- or double-masked studies, the

participants do not know which medicine is being used, so they can describe what
happens without bias. "Blind" (or "masked") studies are designed to prevent members
of the research team or study participants from influencing the results. This allows
scientifically accurate conclusions. In single-blind ("single-masked") studies, only the
patient is not told what is being administered. In a double-blind study, only the
pharmacist knows; members of the research team are not told which patients are
getting which medication, so that their observations will not be biased. If medically
necessary, however, it is always possible to find out what the patient is taking.

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 Definitions
• Single Blind Study: A clinical trial where the
participant does not know the identity of the
treatment received

• Double Blind Study: A clinical trial in which

neither the patient nor the treating
investigators know the identity of the
treatment being administered.

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 Clinical Trials: The Phases of Drug Testing and Approval

Informed consent form:

-Voluntary
- Explained in simple nontechnical language
- Translated in the native language of the subject
- Comprehensive information regarding the trials
- Benefit of new therapy over existing ones
- Alternative treatments available
- All possible adverse reactions
- Freedom to withdraw from the trial at any time,
without giving any reason

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 Clinical Trials: The Phases of Drug Testing and Approval

Declaration of Helsinki (DoH): is a set of ethicals regarding human experimentation

developed for the medical community by the World Medical Association (WMA)

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 Clinical Trials: The Phases of Drug Testing and Approval

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This website supports the running of clinical trials for human medicines in the European
Union (EU) and European Economic Area (EEA).

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