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Clinical Trials
Now the long stage in which the manufacturer has to prove the safety
and effectiveness of the potential drug has started. During the
different steps of clinical trials, the
experimental drug is given to different groups of people. Government
agencies regulate all phases of clinical development up to approval
of the new drug.
The United States Code of Federal Regulations is just one example
of the many official documents that outlines a code of conduct for
clinical trials. A major aspect of all clinical trials is informed
consent. Participants in clinical trials maintain their rights
to comprehensive information regarding the procedure, known risks,
potential benefits, and likely results of the study. After the physicians
and nurses have informed the patient fully about the trial, the
volunteer may choose to participate, and then signs the 'informed
consent form'. Informed consent is one of several protections that
a patient has; signing a consent form does not bind a participant
to the study, and the patient may still opt
to remove him/herself from the trial at any time.
Clinical trials are divided into different phases
and further divided into phase-specific aims. Primary human tests,
Phase I Trials, track the effects of
the new drug in healthy volunteers (20-80 people), but may be extended
to ill patients, especially cancer patients who have failed on current
therapies. Phase I trials are conducted to determine dose levels,
and weigh the tolerability, safety, how the body interacts with
the drug and what the drug does to the body. Pharmacokinetic findings
are influenced by the method of delivery used, the dosing frequency
(single doses, multiple doses, continuous infusion, daily, monthly,
etc.), the dosage form (powder, liquid, tablet, spray, ointment,
etc.), and the nature of the molecule (small synthetic molecule,
high-molecular-weight molecule, peptide, protein). On average, Phase
I lasts seven months. If safety problems don't arise, and indications
or markers of efficacy are found, further clinical studies can be
done in a Phase II setting.
Phase II studies require a larger testing pool of approximately
50 to 500 participants. Whereas Phase I examinations call for healthy
volunteers, participants in Phase II are patients diagnosed with
the ailment under study. The emphasis in Phase II is on finding
an effective dose and a dose that produces minimal side
effects. Initial Phase II tests commonly look at a variety of
doses to recognize the initial dosing plan.
Phase II trials usually have a double-blind design: the patients
are unaware of which group (placebo or new drug) they have been
assigned to, and the study investigators do not know, either.
Double-blinded studies supply evidence of the medicament's effect,
and it's 'therapeutic margin' (the difference between the maximum
effective dose and the dose at which side effects are observed).
Based on these results, the drug is advanced for a full development
decision, to determine its suitability for passage into Phase III.
Several hundreds or even thousands of volunteer patients give their
services for Phase III studies. Often
volunteers are recruited by advertisements in magazines or on websites.
Large-scale testing provides the pharmaceutical company and the
US Federal Drug Administration (FDA) with a more complete database
for understanding the drug's efficacy, advantages, and possible
unfavorable reactions. Phase III studies involve comparison of the
test drug with presently-available therapies. If the new drug demonstrates
improved activity and safety over current treatment, regulatory
approval to market it will be attained.
Phase III normally last several years. Over 3/4 of the drugs entering
Phase III successfully complete this phase. Then, the pharmaceutical
company can request regulatory approval from the appropriate authority
to market the drug - this is the FDA in the USA. Such approval is
based on the evidence from well-controlled, well-conducted clinical
studies, together with an adequate profile of the drug's side effects.
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Post-Marketing Studies
After the introduction of a new product, the pharmaceutical company
monitors the safety of the treatment in use, and also conducts what
are called Phase IV studies. The purpose
of Phase IV trials is to update data on safety and effectiveness
of the drug in special populations - children, the very-old, those
with organ failure, or other circumstances. If a new clinical indication
is sought, well-controlled clinical studies must be done along the
lines described for Phase II and Phase III, with positive results
of effectiveness compared with the side-effect profile in that particular
patient population.
Click
here to see a graphical presentation of the drug discovery process
designed by the FDA
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Progress
in the study of drugs and clinical research has been extensive since
the start of clinical experimentation over 1000 years ago. Twenty-first
century clinical trials and research are funded by private industry
(chiefly pharmaceutical and biotech companies); however, government-regulated
clauses and patient protection rights have become a prominent issue
and are just as critical as the trials themselves. New drug development
requires the combined efforts of specialists from many fields; members
of the drug discovery and development teams are as diverse as the
medications they produce.
