What are Clinical Trials?
Clinical Trials – Why the Need?
The use of drugs is determined by the potential benefits
and side-effects; the benefits of drugs should outweigh the potential
side effects. The nature of the disease influences the importance
of these two factors e.g. while the use of chemotherapy to kill
cancer cells is considered to outweigh the side effect of temporary
hair loss, it would be unacceptable to regulatory authorities if
the same side effect occurred from a drug to treat a common cold.
The purpose of a clinical trial is to acquire further knowledge
of the properties of a drug while ensuring the safety of participants.
Phases of Clinical Trials
For a drug to progress from its initial laboratory molecule testing
to become licensed for human use can take up to 15 years and costs
millions of pounds. For every drug that becomes available on prescription
hundreds of drugs will fail. Often this is because they are not
found to have any additional benefits over similar drugs which are
already available.
Clinical trials are conducted in a series of phases that are controlled
and regulated under strict guidelines. Each phase increases in complexity
and the investigational drug must fulfil a series of criteria before
it can progress to the next phase. Clinical trials are usually divided
into phases I –IV.
Phase I
At this stage the trial drug is given to man for the first time
usually in healthy male volunteers to study the safety of the drug.
However, patients can also be recruited when there may be greater
risks involved in administering the trial drug to healthy volunteers
e.g. in certain cancer or AIDS studies. Phase I studies are designed
to establish primarily -
• How well the drug is tolerated
• Body’s effect on the drug (Pharmacokinetics)
• Whether any side effects occur
• Dose ranging (establishing the most effective dose)
• Drug’s effect on the body (Pharmacodynamics)
These studies usually involve small numbers of volunteers, and
don’t involve comparisons with other drugs.
Phase II
This involves the first testing of a drug in small numbers of patient
volunteers with the condition that the drug is intended for, eg
a potential asthma drug will be administered to patients who have
a diagnosed asthma condition. They are known as ‘Proof of
Concept’ studies and aim to assess the ‘dynamics’
of the investigational component i.e., does the trial drug work
in patients. They also focus on providing more information on drug
safety and associated side-effects. This phase can take up to two
years to complete and if results are favourable research of the
drug will only then move to the next phase.
Phase III
This is a ‘Programme of Studies’ involving a patient
population sample that is typically more than 1000. They further
explore the potential drug by focusing on dosage effects, safety
and how well the drug is tolerated.
They include Placebo (inactive substance) studies as a means of
assessing how effective the drug is and Comparator studies to compare
the safety against established and/or new products. 70-90% of drugs
tested at this stage are eventually licensed for sale.
A special certificate (CTX) is required from the Medicines HealthCare
Regulatory Agency (MHRA) to conduct phase II and III studies. The
MHRA considers data prior to a drug being tested in Phase II and
Phase III clinical trials data from previous studies must be provided
to the MHRA in order to apply for a Clinical Trial Certificate of
Exemption (CTX).
From May 1st 2004, all clinical trials (including Phase I healthy
volunteer trials) will require a new approval certificate (CTA)
from the MHRA.
Phase IV
These studies are performed once the product licence has been granted.
Again the drugs are given to the patients who have the condition
that the drug is intended for and are important to the marketing
strategy of the drug. They include comparative studies regarding
the effectiveness, side-effects and cost effectivess against other
marketed products.
Post Marketing Surveillance (PMS)
These studies:
• continue to monitor safety issues
• provide information on the marketed drug
• involve large numbers of patients
• are designed to identify side effects which occur very infrequently
Clinical Trial Regulation
There are many regulatory guidelines for clinical trials.
These ensure the safety and dignity of participants as well as ensuring
the benefits to subjects outweigh any potential risks .
Ethics Committee Approval
All studies must be submitted to a Research Ethics Committee
and approval granted before the study can take place. The Ethics
Committee are an independent body which consists of medical and
non medical lay people whose responsibility it is to ensure the
protection and rights, safety and well being of any subjects involved
in trial participation.
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